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Sample records for active endocrine organ

  1. Organization versus activation: the role of endocrine-disrupting contaminants (EDCs) during embryonic development in wildlife.

    PubMed Central

    Guillette, L J; Crain, D A; Rooney, A A; Pickford, D B

    1995-01-01

    Many environmental contaminants disrupt the vertebrate endocrine system. Although they may be no more sensitive to endocrine-disrupting contaminants (EDCs) than other vertebrates, reptiles are good sentinels of exposure to EDCs due to the lability in their sex determination. This is exemplified by a study of alligators at Lake Apopka, Florida, showing that EDCs have altered the balance of reproductive hormones resulting in reproductive dysfunction. Such alterations may be activationally or organizationally induced. Much research emphasizes the former, but a complete understanding of the influence of EDCs in nature can be generated only after consideration of both activational and organizational alterations. The organizational model suggests that a small quantity of an EDC, administered during a specific period of embryonic development, can permanently modify the organization of the reproductive, immune, and nervous systems. Additionally, this model helps explain evolutionary adaptations to naturally occurring estrogenic compounds, such as phytoestrogens. PMID:8593864

  2. Endocrine-Active Pharmaceuticals: An Environmental Concern?

    EPA Science Inventory

    Recently, there has been growing interest in pharmaceuticals that are specifically designed to have endocrine activity, such as the estrogens used in birth control pills, exerting unintended effects on fish and other aquatic organisms. These pharmaceuticals may not be persistent...

  3. Human skin: an independent peripheral endocrine organ.

    PubMed

    Zouboulis, C C

    2000-01-01

    The historical picture of the endocrine system as a set of discrete hormone-producing organs has been substituted by organs regarded as organized communities in which the cells emit, receive and coordinate molecular signals from established endocrine organs, other distant sources, their neighbors, and themselves. In this wide sense, the human skin and its tissues are targets as well as producers of hormones. Although the role of hormones in the development of human skin and its capacity to produce and release hormones are well established, little attention has been drawn to the ability of human skin to fulfil the requirements of a classic endocrine organ. Indeed, human skin cells produce insulin-like growth factors and -binding proteins, propiomelanocortin derivatives, catecholamines, steroid hormones and vitamin D from cholesterol, retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert their biological effects on the skin through interaction with high-affinity receptors, such as receptors for peptide hormones, neurotransmitters, steroid hormones and thyroid hormones. In addition, the human skin is able to metabolize hormones and to activate and inactivate them. These steps are overtaken in most cases by different skin cell populations in a coordinated way indicating the endocrine autonomy of the skin. Characteristic examples are the metabolic pathways of the corticotropin-releasing hormone/propiomelanocortin axis, steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of biological activities on the skin, with major effects caused by growth hormone/insulin-like growth factor-1, neuropeptides, sex steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor ligands, and eicosanoids. At last, human skin produces hormones which are released in the circulation and are important for functions of the entire organism, such as sex hormones, especially in aged individuals, and insulin-like growth

  4. Purinergic signalling in endocrine organs.

    PubMed

    Burnstock, Geoffrey

    2014-03-01

    There is widespread involvement of purinergic signalling in endocrine biology. Pituitary cells express P1, P2X and P2Y receptor subtypes to mediate hormone release. Adenosine 5'-triphosphate (ATP) regulates insulin release in the pancreas and is involved in the secretion of thyroid hormones. ATP plays a major role in the synthesis, storage and release of catecholamines from the adrenal gland. In the ovary purinoceptors mediate gonadotrophin-induced progesterone secretion, while in the testes, both Sertoli and Leydig cells express purinoceptors that mediate secretion of oestradiol and testosterone, respectively. ATP released as a cotransmitter with noradrenaline is involved in activities of the pineal gland and in the neuroendocrine control of the thymus. In the hypothalamus, ATP and adenosine stimulate or modulate the release of luteinising hormone-releasing hormone, as well as arginine-vasopressin and oxytocin. Functionally active P2X and P2Y receptors have been identified on human placental syncytiotrophoblast cells and on neuroendocrine cells in the lung, skin, prostate and intestine. Adipocytes have been recognised recently to have endocrine function involving purinoceptors.

  5. Endocrine activity of persistent organic pollutants accumulated in human silicone implants--Dosing in vitro assays by partitioning from silicone.

    PubMed

    Gilbert, Dorothea; Mayer, Philipp; Pedersen, Mikael; Vinggaard, Anne Marie

    2015-11-01

    Persistent organic pollutants (POPs) accumulated in human tissues may pose a risk for human health by interfering with the endocrine system. This study establishes a new link between actual human internal POP levels and the endocrine active dose in vitro, applying partitioning-controlled dosing from silicone to the H295R steroidogenesis assay: (1) Measured concentrations of POPs in silicone breast implants were taken from a recent study and silicone disks were loaded according to these measurements. (2) Silicone disks were transferred into H295R cell culture plates in order to control exposure of the adrenal cells by equilibrium partitioning. (3) Hormone production of the adrenal cells was measured as toxicity endpoint. 4-Nonylphenol was used for method development, and the new dosing method was compared to conventional solvent-dosing. The two dosing modes yielded similar dose-dependent hormonal responses of H295R cells. However, with the partitioning-controlled freely dissolved concentrations (Cfree) as dose metrics, dose-response curves were left-shifted by two orders of magnitude relative to spiked concentrations. Partitioning-controlled dosing of POPs resulted in up to 2-fold increases in progestagen and corticosteroid levels at Cfree of individual POPs in or below the femtomolar range. Silicone acted not only as source of the POPs but also as a sorption sink for lipophilic hormones, stimulating the cellular hormone production. Methodologically, the study showed that silicone can be used as reference partitioning phase to transfer in vivo exposure in humans (silicone implants) to in vitro assays (partition-controlled dosing). The main finding was that POPs at the levels at which they are found in humans can interfere with steroidogenesis in a human adrenocortical cell line.

  6. Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

    PubMed

    Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

    2014-12-01

    This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds.

  7. Biochemistry of adipose tissue: an endocrine organ.

    PubMed

    Coelho, Marisa; Oliveira, Teresa; Fernandes, Ruben

    2013-04-20

    Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance.

  8. Biochemistry of adipose tissue: an endocrine organ

    PubMed Central

    Coelho, Marisa; Oliveira, Teresa

    2013-01-01

    Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of nutritional intake (leptin, angiotensin), control of sensitivity to insulin and inflammatory process mediators (tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), resistin, visfatin, adiponectin, among others) and pathways (plasminogen activator inhibitor 1 (PAI-1) and acylation stimulating protein (ASP) for example). This paper reviews some of the biochemical and metabolic aspects of adipose tissue and its relationship to inflammatory disease and insulin resistance. PMID:23671428

  9. The skeleton as an endocrine organ.

    PubMed

    DiGirolamo, Douglas J; Clemens, Thomas L; Kousteni, Stavroula

    2012-11-01

    Surprising new discoveries in the field of skeletal biology show that bone cells produce endocrine hormones that regulate phosphate and glucose homeostasis. In this Review, we examine the features of these new endocrine pathways and discuss their physiological importance in the context of our current understanding of energy metabolism and mineral homeostasis. Consideration of evolutionary and comparative biology provides clues that a key driving force for the emergence of these hormonal pathways was the development of a large, energy-expensive musculoskeletal system. Specialized bone cells also evolved and produced endocrine hormones to integrate the skeleton in global mineral and nutrient homeostasis. The recognition of bone as a true endocrine organ represents a fertile area for further research and should improve the diagnosis and treatment of metabolic diseases such as osteoporosis and diabetes mellitus.

  10. Spatial and temporal patterns of endocrine active chemicals in small streams indicate differential exposure to aquatic organisms

    USGS Publications Warehouse

    Lee, K.E.; Barber, L.B.; Schoenfuss, H.L.

    2014-01-01

    Alkylphenolic chemicals (APCs) and hormones were measured six times from February through October 2007 in three Minnesota streams receiving wastewater to identify spatial and temporal patterns in concentrations and in estrogen equivalency. Fish were collected once during the study to evaluate endpoints indicative of endocrine disruption. The most commonly detected APCs were 4-tert-octylphenol and 4-nonylphenol and the most commonly detected hormones were estrone and androstenedione. Chemical concentrations were greatest for nonylphenol ethoxycarboxylates (NPECs) (5,000-140,000 ng/l), followed by 4-nonlylphenol and 4-nonylphenolethoxylates (50-880 ng/l), 4-tert-octylphenol and 4-tert-octylphenolethoxylates with concentrations as great as 130 ng/l, and hormones (0.1-54 ng/l). Patterns in chemicals and estrogen equivalency indicated that wastewater effluent is a pathway of APCs and hormones to downstream locations in this study. However, upstream contributions can be equally or more important indicating alternative sources. This study indicates that aquatic organisms experience both spatially and temporally variable exposures in the number of compounds, total concentrations, and estrogenicity. This variability was evident in fish collected from the three rivers as no clear upstream to downstream pattern of endocrine disruption endpoints emerged.

  11. Potency matters: thresholds govern endocrine activity.

    PubMed

    Borgert, Christopher J; Baker, Stephen P; Matthews, John C

    2013-10-01

    Whether thresholds exist for endocrine active substances and for endocrine disrupting effects of exogenous chemicals has been posed as a question for regulatory policy by the European Union. This question arises from a concern that the endocrine system is too complex to allow estimations of safe levels of exposure to any chemical with potential endocrine activity, and a belief that any such chemical can augment, retard, or disrupt the normal background activity of endogenous hormones. However, vital signaling functions of the endocrine system require it to continuously discriminate the biological information conveyed by potent endogenous hormones from a more concentrated background of structurally similar, endogenous molecules with low hormonal potential. This obligatory ability to discriminate important hormonal signals from background noise can be used to define thresholds for induction of hormonal effects, without which normal physiological functions would be impossible. From such thresholds, safe levels of exposure can be estimated. This brief review highlights how the fundamental principles governing hormonal effects - affinity, efficacy, potency, and mass action - dictate the existence of thresholds and why these principles also define the potential that exogenous chemicals might have to interfere with normal endocrine functioning.

  12. EADB: An Estrogenic Activity Database for Assessing Potential Endocrine Activity

    EPA Science Inventory

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body’s endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many ...

  13. Endocrine active chemicals and endocrine disruption in Minnesota streams and lakes: implications for aquatic resources, 1994-2008

    USGS Publications Warehouse

    Lee, Kathy E.; Schoenfuss, Heiko L.; Barber, Larry B.; Writer, Jeff H.; Blazer, Vicki; Keisling, Richard L.; Ferrey, Mark L.

    2010-01-01

    Although these studies indicate that wastewater-treatment plant effluent is a conduit for endocrine active chemicals to surface waters, endocrine active chemicals also were present in surface waters with no obvious wastewater-treatment plant effluent sources. Endocrine active chemicals were detected and indicators of endocrine disruption in fish were measured at numerous sites upstream from discharge of wastewater-treatment plant effluent. These observations indicate that other unidentified sources of endocrine active chemicals exist, such as runoff from land surfaces, atmospheric deposition, inputs from onsite septic systems, or other groundwater sources. Alternatively, some endocrine active chemicals may not yet have been identified or measured. The presence of biological indicators of endocrine disruption in male fish indicates that the fish are exposed to endocrine active chemicals. However indicators of endocrine disruption in male fish does not indicate an effect on fish reproduction or changes in fish populations.

  14. Endocrine-active chemicals in mammary cancer causation and prevention.

    PubMed

    Jenkins, Sarah; Betancourt, Angela M; Wang, Jun; Lamartiniere, Coral A

    2012-04-01

    Endocrine-active chemicals alter or mimic physiological hormones. These compounds are reported to originate from a wide variety of sources, and recent studies have shown widespread human exposure to several of these compounds. Given the role of the sex steroid hormone, estradiol, in human breast cancer causation, endocrine-active chemicals which interfere with estrogen signaling constitute one potential factor contributing to the high incidence of breast cancer. Thus, the aim of this review is to examine several common endocrine-active chemicals and their respective roles in breast cancer causation or prevention. The plastic component, bisphenol A (BPA), the synthetic estrogen, diethylstilbestrol (DES), the by-product of organic combustion, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the soy component, genistein, and the red grape phytoalexin, resveratrol, have some degree of structural similarities to each other and estradiol. However, despite these structural similarities, the in vitro and in vivo properties of each of these chemicals vary greatly in terms of breast cancer causation and prevention. Early life exposure to BPA and DES increases rodent susceptibility to chemically induced mammary carcinogenesis, presumably through retardation of normal mammary gland maturation and/or disrupting the ratio of cell proliferation and apoptosis in the mammary gland. On the other hand, early exposures to genistein and resveratrol protect rodents against chemically induced and spontaneous mammary cancers. This is reported to occur through the ability of genistein and resveratrol to accelerate mammary gland maturation. Interestingly, TCDD, which is the most structurally dissimilar to the above chemicals and functions as an anti-estrogen, also increases chemically induced mammary carcinogenesis through retardation of mammary gland maturation. This article is part of a Special Issue entitled 'Endocrine disruptors'.

  15. EADB: an estrogenic activity database for assessing potential endocrine activity.

    PubMed

    Shen, Jie; Xu, Lei; Fang, Hong; Richard, Ann M; Bray, Jeffrey D; Judson, Richard S; Zhou, Guangxu; Colatsky, Thomas J; Aungst, Jason L; Teng, Christina; Harris, Steve C; Ge, Weigong; Dai, Susie Y; Su, Zhenqiang; Jacobs, Abigail C; Harrouk, Wafa; Perkins, Roger; Tong, Weida; Hong, Huixiao

    2013-10-01

    Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the body's endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.

  16. Endocrine Activity of Extraembryonic Membranes Extends beyond Placental Amniotes

    PubMed Central

    Albergotti, Lori C.; Hamlin, Heather J.; McCoy, Michael W.; Guillette,, Louis J.

    2009-01-01

    Background During development, all amniotes (mammals, reptiles, and birds) form extraembryonic membranes, which regulate gas and water exchange, remove metabolic wastes, provide shock absorption, and transfer maternally derived nutrients. In viviparous (live-bearing) amniotes, both extraembryonic membranes and maternal uterine tissues contribute to the placenta, an endocrine organ that synthesizes, transports, and metabolizes hormones essential for development. Historically, endocrine properties of the placenta have been viewed as an innovation of placental amniotes. However, an endocrine role of extraembryonic membranes has not been investigated in oviparous (egg-laying) amniotes despite similarities in their basic structure, function, and shared evolutionary ancestry. In this study, we ask whether the oviparous chorioallantoic membrane (CAM) of chicken (Gallus gallus) has the capability to synthesize and receive signaling of progesterone, a major placental steroid hormone. Methodology/Principal Findings We quantified mRNA expression of key steroidogenic enzymes involved in progesterone synthesis and found that 3β-hydroxysteroid dehydrogenase, which converts pregnenolone to progesterone exhibited a 464 fold increase in the CAM from day 8 to day 18 of embryonic development (F5, 68 = 89.282, p<0.0001). To further investigate progesterone synthesis, we performed explant culture and found that the CAM synthesizes progesterone in vitro in the presence of a steroid precursor. Finally, we quantified mRNA expression and performed protein immunolocalization of the progesterone receptor in the CAM. Conclusions/Significance Collectively, our data indicate that the chick CAM is steroidogenic and has the capability to both synthesize progesterone and receive progesterone signaling. These findings represent a paradigm shift in evolutionary reproductive biology by suggesting that endocrine activity of extraembryonic membranes is not a novel characteristic of placental

  17. Endocrine activity of mycotoxins and mycotoxin mixtures.

    PubMed

    Demaegdt, Heidi; Daminet, Britt; Evrard, Annick; Scippo, Marie-Louise; Muller, Marc; Pussemier, Luc; Callebaut, Alfons; Vandermeiren, Karine

    2016-10-01

    Reporter gene assays incorporating nuclear receptors (estrogen, androgen, thyroid β and PPARγ2) have been implemented to assess the endocrine activity of 13 mycotoxins and their mixtures. As expected, zearalenone and its metabolites α-zearalenol and β- zearalenol turned out to have the strongest estrogenic potency (EC50 8,7 10-10 ± 0,8; 3,1 10-11 ± 0,5 and 1,3 10-8 ± 0,3 M respectively). The metabolite of deoxynivalenol, 3-acetyl-deoxynivalenol also had estrogenic activity (EC50 3,8 10-7 ± 1,1 M). Furthermore, most of the mycotoxins (and their mixtures) showed anti-androgenic effects (15-acetyldeoxynivalenol, 3-acetyl-deoxynivalenol and α-zearalenol with potencies within one order of magnitude of that of the reference compound flutamide). In particular, deoxynivalenol and 15-acetyl-deoxynivalenol acted as antagonists for the PPARy2 receptor. When testing mixtures of mycotoxins on the same cell systems, we showed that most of the mixtures reacted as predicted by the concentration addition (CA) theory. Generally, the CA was within the 95% confidence interval of the observed ones, only minor deviations were detected. Although these reporter gene tests cannot be directly extrapolated in vivo, they can be the basis for further research. Especially the additive effects of ZEN and its metabolites are of importance and could have repercussions in vivo.

  18. Effects of Two Endocrine-active Pharmaceuticals, Tamoxifen and Anastrozole, on Reproduction in a Marine Fish, Tautogolabrus adspersus

    EPA Science Inventory

    Endocrine-active pharmaceuticals entering the aquatic environment through sewage effluent may have unintended, adverse impacts on the reproduction of aquatic organisms, which in turn may affect the sustainability of exposed populations. Laboratory experiments were conducted with ...

  19. Fate of steroid hormones and endocrine activities in swine manure disposal and treatment facilities.

    PubMed

    Combalbert, Sarah; Bellet, Virginie; Dabert, Patrick; Bernet, Nicolas; Balaguer, Patrick; Hernandez-Raquet, Guillermina

    2012-03-01

    Manure may contain high concern endocrine-disrupting compounds (EDCs) such as steroid hormones, naturally produced by pigs, which are present at μgL(-1) levels. Manure may also contain other EDCs such as nonylphenols (NP), polycyclic aromatic hydrocarbons (PAHs) and dioxins. Thus, once manure is applied to the land as soil fertilizer these compounds may reach aquifers and consequently living organisms, inducing abnormal endocrine responses. In France, manure is generally stored in anaerobic tanks prior spreading on land; when nitrogen removal is requested, manure is treated by aerobic processes before spreading. However, little is known about the fate of hormones and multiple endocrine-disrupting activities in such manure disposal and treatment systems. Here, we determined the fate of hormones and diverse endocrine activities during manure storage and treatment by combining chemical analysis and in vitro quantification of estrogen (ER), aryl hydrocarbon (AhR), androgen (AR), pregnane-X (PXR) and peroxysome proliferator-activated γ (PPARγ) receptor-mediated activities. Our results show that manure contains large quantities of hormones and activates ER and AhR, two of the nuclear receptors studied. Most of these endocrine activities were found in the solid fraction of manure and appeared to be induced mainly by hormones and other unidentified pollutants. Hormones, ER and AhR activities found in manure were poorly removed during manure storage but were efficiently removed by aerobic treatment of manure.

  20. Endocrine Activity of AVB, 2MR, BHA, and Their Mixtures.

    PubMed

    Klopcic, Ivana; Dolenc, Marija Sollner

    2017-03-01

    Personal care products are used increasingly, resulting in growing concern concerning their potential disruption of normal hormonal functions. Recent results on the bioaccumulation of cosmetic ingredients in wildlife and humans point to the need for an in-depth analysis for endocrine activity, in particular with respect to their influence on the androgen (AR), glucocorticoid (GR), and thyroid hormone receptors (TRs). Furthermore, humans are commonly exposed simultaneously to complex mixtures of endocrine active compounds. We have therefore examined 3 frequently used cosmetic ingredients: 2-methylresorcinol (2MR), butylated hydroxyanisole (BHA) and avobenzone (AVB), for (anti)-androgen-, (anti)-glucocorticoid-, and (anti)-thyroid hormone-like activities. Their binary and ternary mixtures at EC50 or IC50 concentrations have also been examined for anti-androgen-, glucocorticoid-, and thyroid hormone-like activities. In the MDA-kb2 reporter cell line, compounds possessed anti-androgen-, glucocorticoid-, and anti-glucocorticoid-like activities (except AVB). A new cell line, GH3.TRE-Luc, was used to evaluate anti-thyroid and thyroid hormone-like activities. The combinations 2MR + BHA and 2MR + BHA + AVB have glucocorticoid-like activity: only 2MR + AVB has anti-androgen-like activity. On the other hand, binary and ternary mixtures of compounds showed no thyroid hormone-like activity. Thus, in addition to identifying new endocrine disrupting compounds, it is also necessary to determine the effects of their mixtures in order to assess fully their risk to human health.

  1. Mysid crustaceans as potential test organisms for the evaluation of environmental endocrine disruption: a review.

    PubMed

    Verslycke, Tim A; Fockedey, Nancy; McKenney, Charles L; Roast, Stephen D; Jones, Malcolm B; Mees, Jan; Janssen, Colin R

    2004-05-01

    Anthropogenic chemicals that disrupt the hormonal systems (endocrine disruptors) of wildlife species recently have become a widely investigated and politically charged issue. Invertebrates account for roughly 95% of all animals, yet surprisingly little effort has been made to understand their value in signaling potential environmental endocrine disruption. This omission largely can be attributed to the high diversity of invertebrates and the shortage of fundamental knowledge of their endocrine systems. Insects and crustaceans are exceptions and, as such, appear to be excellent candidates for evaluating the environmental consequences of chemically induced endocrine disruption. Mysid shrimp (Crustacea: Mysidacea) may serve as a viable surrogate for many crustaceans and have been put forward as suitable test organisms for the evaluation of endocrine disruption by several researchers and regulatory bodies (e.g., the U.S. Environmental Protection Agency). Despite the long-standing use of mysids in toxicity testing, little information exists on their endocrinology, and few studies have focused on the potential of these animals for evaluating the effects of hormone-disrupting compounds. Therefore, the question remains as to whether the current standardized mysid endpoints can be used or adapted to detect endocrine disruption, or if new procedures must be developed, specifically directed at evaluating hormone-regulated endpoints in these animals. This review summarizes the ecological importance of mysids in estuarine and marine ecosystems, their use in toxicity testing and environmental monitoring, and their endocrinology and important hormone-regulated processes to highlight their potential use in assessing environmental endocrine disruption.

  2. The Gut Microbial Endocrine Organ: Bacterially-Derived Signals Driving Cardiometabolic Diseases

    PubMed Central

    Brown, J. Mark; Hazen, Stanley L.

    2015-01-01

    The human gastrointestinal tract is home to trillions of bacteria, which vastly outnumber host cells in the body. Although generally overlooked in the field of endocrinology, gut microbial symbionts organize to form a key endocrine organ that convert nutritional cues from the environment into hormone-like signals that impact both normal physiology and chronic disease in the human host. Recent evidence suggests that several gut microbial-derived products are sensed by dedicated host receptor systems to alter cardiovascular disease (CVD) progression. In fact, gut microbial metabolism of dietary components results in the production of proatherogenic circulating factors that act through a meta-organismal endocrine axis to impact CVD risk. Whether pharmacological interventions at the level of the gut microbial endocrine organ will reduce CVD risk is a key new question in the field of cardiovascular medicine. Here we discuss the opportunities and challenges that lie ahead in targeting meta-organismal endocrinology for CVD prevention. PMID:25587655

  3. Prosobranch snails as test organisms for the assessment of endocrine active chemicals--an overview and a guideline proposal for a reproduction test with the freshwater mudsnail Potamopyrgus antipodarum.

    PubMed

    Duft, Martina; Schmitt, Claudia; Bachmann, Jean; Brandelik, Cornelius; Schulte-Oehlmann, Ulrike; Oehlmann, Jörg

    2007-02-01

    Recently, prosobranch snails have been recommended as promising candidates for test organisms for the assessment of endocrine active chemicals. Three prosobranch snail species, the freshwater mudsnail Potamopyrgus antipodarum, the freshwater ramshorn snail Marisa cornuarietis, and the marine netted whelk Nassarius reticulatus are portrayed and their respective biotests are presented together with results of laboratory experiments and biological effect monitoring surveys in the field. All characterized species are highly sensitive toward xeno-androgens [triphenyltin (TPT), tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN)], and xeno-estrogens [bisphenol A (BPA), octylphenol (OP), ethinylestradiol], and show effects at environmentally relevant, rather low concentrations in laboratory experiments. For exposure to the xeno-androgen TPT, EC(10) values range between 15.9 and 29.0 ng as Sn/L (sediment 0.03 mug as Sn/kg), for TBT, EC(10) values are found between 3.42 and 37.8 ng as Sn/L (sediment 2.98 microg as Sn/kg) and effect concentrations for FEN are calculated as 18.6 ng/L (EC(10)) and 0.19 microg/kg (EC(50) sediment; EC(10) not calculable). Exposure to xeno-estrogens yielded EC(10 )values of 13.9 ng/L (0.19 microg/kg) for BPA, a NOEC of <1 microg/L (EC(10) of 0.004 microg/kg) for OP and a NOEC of 1 ng/l (EC(10) sediment of 2.2 microg/kg) for ethinylestradiol. Responses to androgens comprised the development of imposex and the reduction of fertility or embryo production, effects of estrogens included the stimulation of egg production and embryo production, and the increased weight of glands. Also, biological effect monitoring studies with P. antipodarum and N. reticulatus in several rivers or estuarine areas revealed the capacity of the biotests to detect an androgenic or estrogenic potential of sediment samples. A comparison of the three test species with regard to sensitivity and practical aspects in routine application favors the freshwater mudsnail P

  4. Skeletal muscle as an endocrine organ: PGC-1α, myokines and exercise

    PubMed Central

    Schnyder, Svenia; Handschin, Christoph

    2015-01-01

    An active lifestyle is crucial to maintain health into old age; inversely, sedentariness has been linked to an elevated risk for many chronic diseases. The discovery of myokines, hormones produced by skeletal muscle tissue, suggests the possibility that these might be molecular mediators of the whole body effects of exercise originating from contracting muscle fibers. Even though less is known about the sedentary state, the lack of contraction-induced myokines or the production of a distinct set of hormones in the inactive muscle could likewise contribute to pathological consequences in this context. In this review, we try to summarize the most recent developments in the study of muscle as an endocrine organ and speculate about the potential impact on our understanding of exercise and sedentary physiology, respectively. PMID:26453501

  5. Early Outgrowth Cells Release Soluble Endocrine Antifibrotic Factors That Reduce Progressive Organ Fibrosis

    PubMed Central

    Yuen, Darren A.; Connelly, Kim A.; Zhang, Yanling; Advani, Suzanne L.; Thai, Kerri; Kabir, Golam; Kepecs, David; Spring, Christopher; Smith, Christopher; Batruch, Ihor; Kosanam, Hari; Advani, Andrew; Diamandis, Eleftherios; Marsden, Philip A.; Gilbert, Richard E.

    2017-01-01

    Adult bone marrow-derived cells can improve organ function in chronic disease models, ostensibly by the release of paracrine factors. It has, however, been difficult to reconcile this prevailing paradigm with the lack of cell retention within injured organs and their rapid migration to the reticuloendothelial system. Here, we provide evidence that the salutary antifibrotic effects of bone marrow-derived early outgrowth cells (EOCs) are more consistent with an endocrine mode of action, demonstrating not only the presence of antifibrotic factors in the plasma of EOC-treated rats but also that EOC conditioned medium (EOC-CM) potently attenuates both TGF-β- and angiotensin II-induced fibroblast collagen production in vitro. To examine the therapeutic relevance of these findings in vivo, 5/6 subtotally nephrectomized rats, a model of chronic kidney and heart failure characterized by progressive fibrosis of both organs, were randomized to receive i.v. injections of EOC-CM, unconditioned medium, or 106 EOCs. Rats that received unconditioned medium developed severe kidney injury with cardiac diastolic dysfunction. In comparison, EOC-CM-treated rats demonstrated substantially improved renal and cardiac function and structure, mimicking the changes found in EOC-treated animals. Mass spectrometric analysis of EOC-CM identified proteins that regulate cellular functions implicated in fibrosis. These results indicate that EOCs secrete soluble factor(s) with highly potent antifibrotic activity, that when injected intravenously replicate the salutary effects of the cells themselves. Together, these findings suggest that an endocrine mode of action may underlie the effectiveness of cell therapy in certain settings and portend the possibility for systemic delivery of cell-free therapy. PMID:23922321

  6. Occurrence, fate, and ecosystem implications of endocrine active compounds in select rivers of Minnesota

    NASA Astrophysics Data System (ADS)

    Writer, J.; Keefe, S.; Barber, L. B.; Brown, G.; Schoenfuss, H.; Kiesling, R.; Gray, J. L.

    2009-12-01

    Select endocrine active compounds (EACs) were measured in four rivers in southern Minnesota. Additionally, caged and wild fish were assessed for indication of endocrine disruption using plasma vitellogenin and histopathology. Low concentrations of EACs were identified in all rivers, as was elevated plasma vitellogenin in caged and wild fish, indicating potential endocrine disruption. To evaluate the persistence of these compounds in small rivers, a tracer study was performed on one of the rivers (Redwood River) using Lagrangian sampling coupled with hydrologic modeling incorporating transient storage. Mass exchange (transient storage, sorption) and degradation were approximated as pseudo first order processes, and in-stream removal rates were then computed by comparing conservative tracer concentrations to organic compound concentrations. Production of estrone and 4-nonylphenol in the studied reach as a result of biochemical transformation from their parent compounds (17β-estradiol and alkylphenolpolyethoxylates, respectively) was quantified. The distance required for 17β-estradiol and nonylphenol to undergo a 50% reduction in concentration was >2 km and >10 km, respectively. These results indicate that EACs are transported several kilometers downstream from discharge sources and therefore have the potential of adversely impacting the lotic ecosystem over these distances.

  7. MYSID CRUSTACEANS AS POTENTIAL TEST ORGANISMS FOR THE EVALUATION OF ENVIRONMENTAL ENDOCRINE DISRUPTORS: A REVIEW

    EPA Science Inventory

    Verslycke, Tim A., Nancy Fockedey, Charles L. McKenney, Jr., Stephen D. Roast, Malcolm B. Jones, Jan Mees and Colin R. Janssen. 2004. Mysid Crustaceans as Potential Test Organisms for the Evaluation of Environmental Endocrine Disruption: A Review. Environ. Toxicol. Chem. 23(5):12...

  8. ENDOCRINE ACTIVE SUBSTANCES AND DOSE-RESPONSE FOR INDIVIDUALS AND POPULATIONS

    EPA Science Inventory

    Endocrine Active Substances and Dose-Response for Individuals and Populations
    Hugh A. Barton

    Abstract for IUPAC-SCOPE article

    Dose-response characteristics for endocrine disruption have been major focuses in efforts to understand potential impacts on human and ec...

  9. Toxicity and Estrogenic Endocrine Disrupting Activity of Phthalates and Their Mixtures

    PubMed Central

    Chen, Xueping; Xu, Shisan; Tan, Tianfeng; Lee, Sin Ting; Cheng, Shuk Han; Lee, Fred Wang Fat; Xu, Steven Jing Liang; Ho, Kin Chung

    2014-01-01

    Phthalates, widely used in flexible plastics and consumer products, have become ubiquitous contaminants worldwide. This study evaluated the acute toxicity and estrogenic endocrine disrupting activity of butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), bis(2-ethylhexyl) phthalate (DEHP), diisodecyl phthalate (DIDP), diisononyl phthalate (DINP), di-n-octyl phthalate (DNOP) and their mixtures. Using a 72 h zebrafish embryo toxicity test, the LC50 values of BBP, DBP and a mixture of the six phthalates were found to be 0.72, 0.63 and 0.50 ppm, respectively. The other four phthalates did not cause more than 50% exposed embryo mortality even at their highest soluble concentrations. The typical toxicity symptoms caused by phthalates were death, tail curvature, necrosis, cardio edema and no touch response. Using an estrogen-responsive ChgH-EGFP transgenic medaka (Oryzias melastigma) eleutheroembryos based 24 h test, BBP demonstrated estrogenic activity, DBP, DEHP, DINP and the mixture of the six phthalates exhibited enhanced-estrogenic activity and DIDP and DNOP showed no enhanced- or anti-estrogenic activity. These findings highlighted the developmental toxicity of BBP and DBP, and the estrogenic endocrine disrupting activity of BBP, DBP, DEHP and DINP on intact organisms, indicating that the widespread use of these phthalates may cause potential health risks to human beings. PMID:24637910

  10. Recommended approaches to the scientific evaluation of ecotoxicological hazards and risks of endocrine-active substances.

    PubMed

    Matthiessen, Peter; Ankley, Gerald T; Biever, Ronald C; Bjerregaard, Poul; Borgert, Christopher; Brugger, Kristin; Blankinship, Amy; Chambers, Janice; Coady, Katherine K; Constantine, Lisa; Dang, Zhichao; Denslow, Nancy D; Dreier, David A; Dungey, Steve; Gray, L Earl; Gross, Melanie; Guiney, Patrick D; Hecker, Markus; Holbech, Henrik; Iguchi, Taisen; Kadlec, Sarah; Karouna-Renier, Natalie K; Katsiadaki, Ioanna; Kawashima, Yukio; Kloas, Werner; Krueger, Henry; Kumar, Anu; Lagadic, Laurent; Leopold, Annegaaike; Levine, Steven L; Maack, Gerd; Marty, Sue; Meador, James; Mihaich, Ellen; Odum, Jenny; Ortego, Lisa; Parrott, Joanne; Pickford, Daniel; Roberts, Mike; Schaefers, Christoph; Schwarz, Tamar; Solomon, Keith; Verslycke, Tim; Weltje, Lennart; Wheeler, James R; Williams, Mike; Wolf, Jeffrey C; Yamazaki, Kunihiko

    2017-03-01

    A SETAC Pellston Workshop(®) "Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Substances (EHRA)" was held in February 2016 in Pensacola, Florida, USA. The primary objective of the workshop was to provide advice, based on current scientific understanding, to regulators and policy makers; the aim being to make considered, informed decisions on whether to select an ecotoxicological hazard- or a risk-based approach for regulating a given endocrine-disrupting substance (EDS) under review. The workshop additionally considered recent developments in the identification of EDS. Case studies were undertaken on 6 endocrine-active substances (EAS-not necessarily proven EDS, but substances known to interact directly with the endocrine system) that are representative of a range of perturbations of the endocrine system and considered to be data rich in relevant information at multiple biological levels of organization for 1 or more ecologically relevant taxa. The substances selected were 17α-ethinylestradiol, perchlorate, propiconazole, 17β-trenbolone, tributyltin, and vinclozolin. The 6 case studies were not comprehensive safety evaluations but provided foundations for clarifying key issues and procedures that should be considered when assessing the ecotoxicological hazards and risks of EAS and EDS. The workshop also highlighted areas of scientific uncertainty, and made specific recommendations for research and methods-development to resolve some of the identified issues. The present paper provides broad guidance for scientists in regulatory authorities, industry, and academia on issues likely to arise during the ecotoxicological hazard and risk assessment of EAS and EDS. The primary conclusion of this paper, and of the SETAC Pellston Workshop on which it is based, is that if data on environmental exposure, effects on sensitive species and life-stages, delayed effects, and effects at low concentrations are robust, initiating environmental risk

  11. The endocrine and reproductive system: adverse effects of hormonally active substances?

    PubMed

    Greim, Helmut A

    2004-04-01

    Chemicals that have the intrinsic property to modulate or even disrupt the endocrine system are present in the human environment. Because it is the potency of such chemicals that determines the toxicologic relevance, assessment of the risk to human health must consider both the endocrine disrupting potential and the potency. Usually in vitro assays are applied to detect the potential of a hormone-like effect, and such data are considered useful to set priorities for additional testing and for mechanistic studies. However, such data allow only determination of relative potency of a chemical as compared with other xenobiotics, natural compounds, or endogenous hormones. Relevant information on the endocrine-disrupting potency can be taken only from in vivo assays, eg, the Hershberger (male reproductive organs) and uterotrophic (female reproductive organs) assays, the updated versions of the 28- and 90-day toxicity studies in rodents, and the 2-generation studies in rodents. With the use of this information and the concentration of these chemicals in humans, the potency of the effect as compared with endogenous hormone activity can be estimated. So far, the relative potencies of chemicals tested in in vitro systems as compared with estradiol are several orders of magnitude smaller, whereas potency of the phytoestrogen, eg, isoflavones such as genistein or daidzein, can even exceed that of estradiol, especially in infants who are fed soy-based formula as a sole source of nutrition. Although there are still open questions regarding in utero or early postnatal exposure, the low potencies and concentrations of manmade chemicals as compared with the endogenous hormones in humans make it unlikely that adverse effects occur at common exposure.

  12. Introduction to the Endocrine System

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... in Balance › Hormones and Health › Journey Through the Endocrine System Journey Through the Endocrine System Endocrine-related Organs ...

  13. ESAM: Endocrine inspired Sensor Activation Mechanism for multi-target tracking in WSNs

    NASA Astrophysics Data System (ADS)

    Adil Mahdi, Omar; Wahab, Ainuddin Wahid Abdul; Idris, Mohd Yamani Idna; Znaid, Ammar Abu; Khan, Suleman; Al-Mayouf, Yusor Rafid Bahar

    2016-10-01

    Target tracking is a significant application of wireless sensor networks (WSNs) in which deployment of self-organizing and energy efficient algorithms is required. The tracking accuracy increases as more sensor nodes are activated around the target but more energy is consumed. Thus, in this study, we focus on limiting the number of sensors by forming an ad-hoc network that operates autonomously. This will reduce the energy consumption and prolong the sensor network lifetime. In this paper, we propose a fully distributed algorithm, an Endocrine inspired Sensor Activation Mechanism for multi target-tracking (ESAM) which reflecting the properties of real life sensor activation system based on the information circulating principle in the endocrine system of the human body. Sensor nodes in our network are secreting different hormones according to certain rules. The hormone level enables the nodes to regulate an efficient sleep and wake up cycle of nodes to reduce the energy consumption. It is evident from the simulation results that the proposed ESAM in autonomous sensor network exhibits a stable performance without the need of commands from a central controller. Moreover, the proposed ESAM generates more efficient and persistent results as compared to other algorithms for tracking an invading object.

  14. Laccase-mediated transformations of endocrine disrupting chemicals abolish binding affinities to estrogen receptors and their estrogenic activity in zebrafish.

    PubMed

    Torres-Duarte, Cristina; Viana, María Teresa; Vazquez-Duhalt, Rafael

    2012-10-01

    Endocrine disrupting chemicals (EDCs) are known to mainly affect aquatic organisms, producing negative effects in aquaculture. Transformation of the estrogenic compounds 17β-estradiol (E2), bisphenol-A (BPA), nonylphenol (NP), and triclosan (TCS) by laccase of Coriolopsis gallica was studied. Laccase is able to efficiently transform them into polymers. The estrogenic activity of the EDCs and their laccase transformation products was evaluated in vitro as their affinity for the human estrogen receptor alpha (hERα) and for the ligand binding domain of zebrafish (Danio rerio) estrogen receptor alpha (zfERαLBD). E2, BPA, NP, and TCS showed higher affinity for the zfERαLBD than for hERα. After laccase treatment, no affinity was found, except a marginal affinity of E2 products for the zfERαLBD. Endocrine disruption studies in vivo on zebrafish were performed using the induction of vitellogenin 1 as a biomarker (VTG1 mRNA levels). The use of enzymatic bioreactors, containing immobilized laccase, efficiently eliminates the endocrine activity of BPA and TCS, and significantly reduces the effects of E2. The potential use of enzymatic reactors to eliminate the endocrine activity of EDCs in supply water for aquaculture is discussed.

  15. Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

    EPA Science Inventory

    In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across organizatio...

  16. Cell density-dependent transcriptional activation of endocrine-related genes in human adipose tissue-derived stem cells.

    PubMed

    Ghosh, Sagar; Dean, Angela; Walter, Marc; Bao, Yongde; Hu, Yanfen; Ruan, Jianhua; Li, Rong

    2010-08-01

    Adipose tissue is recognized as an endocrine organ that plays an important role in human diseases such as type II diabetes and cancer. Human adipose tissue-derived stem cells (ASCs), a distinct cell population in adipose tissue, are capable of differentiating into multiple lineages including adipogenesis. When cultured in vitro under a confluent condition, ASCs reach a commitment stage for adipogenesis, which can be further induced into terminally differentiated adipocytes by a cocktail of adipogenic factors. Here we report that the confluent state of ASCs triggers transcriptional activation cascades for genes that are responsible for the endocrine function of adipose tissue. These include insulin-like growth factor 1 (IGF-1) and aromatase (Cyp19), a key enzyme in estrogen biosynthesis. Despite similar adipogenic potentials, ASCs from different individuals display huge variations in activation of these endocrine-related genes. Bioinformatics and experimental data suggest that transcription factor Foxo1 controls a large number of "early" confluency-response genes, which subsequently induce "late" response genes. Furthermore, siRNA-mediated knockdown of Foxo1 substantially compromises the ability of committed ASCs to stimulate tumor cell migration in vitro. Thus, our work suggests that cell density is an important determinant of the endocrine potential of ASCs.

  17. Biodegradation of endocrine-disrupting compounds and suppression of estrogenic activity by ligninolytic fungi.

    PubMed

    Cajthaml, Tomás; Kresinová, Zdena; Svobodová, Katerina; Möder, Monika

    2009-05-01

    Endocrine-disrupting compounds (EDCs) represent a large group of substances of natural and anthropogenic origin. They are widely distributed in the environment and can pose serious risks to aquatic organisms and to public health. In this study, 4-n-nonylphenol, technical 4-nonylphenol, bisphenol A, 17alpha-ethinylestradiol, and triclosan were biodegraded by eight ligninolytic fungal strains (Irpex lacteus 617/93, Bjerkandera adusta 606/93, Phanerochaete chrysosporium ME 446, Phanerochaete magnoliae CCBAS 134/I, Pleurotus ostreatus 3004 CCBAS 278, Trametes versicolor 167/93, Pycnoporus cinnabarinus CCBAS 595, Dichomitus squalens CCBAS 750). The results show that under the used conditions the fungi were able to degrade the EDCs within 14d of cultivation with exception of B. adusta and P. chrysosporium in the case of triclosane and bisphenol A, respectively. I. lacteus and P. ostreatus were found to be most efficient EDC degraders with their degradation efficiency exceeding 90% or 80%, respectively, in 7d. Both fungi degraded technical 4-nonylphenol, bisphenol-A, and 17alpha-ethinylestradiol below the detection limit within first 3d of cultivation. In general, estrogenic activities assayed with a recombinant yeast test decreased with advanced degradation. However, in case of I. lacteus, P. ostreatus, and P. chrysosporium the yeast assay showed a residual estrogenic activity (28-85% of initial) in 17alpha-ethinylestradiol cultures. Estrogenic activity in B. adusta cultures temporally increased during degradation of technical 4-nonylphenol, suggesting a production of endocrine-active intermediates. Attention was paid also to the effects of EDCs on the ligninolytic enzyme activities of the different fungi strains to evaluate their possible stimulation or suppression of activities during the biodegradation processes.

  18. Distribution of endocrine cells in the digestive tract of Alligator sinensis during the active and hibernating period.

    PubMed

    Wang, Huan; Zhang, Shengzhou; Zhou, Naizhen; Wang, Chaolin; Wu, Xiaobing

    2014-10-01

    The digestive tract is the largest endocrine organ in the body; the distribution pattern of endocrine cells varies with different pathological and physiological states. The aim of the present study was to investigate the distributed density of 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SS) and vasoactive intestinal peptide (VIP) immunoreactive (IR) cells in the digestive tract of Alligator sinensis during the active and hibernating period by immunohistochemical (IHC) method. The results indicated that 5-HT-IR cells were distributed throughout the entire digestive tract, which were most predominant in duodenum and jejunum. The density increased significantly in stomach and duodenum during hibernation. GAS-IR cells were limited in small stomach and small intestine. The density decreased significantly in small stomach during hibernation, while increased in duodenum. What's more, most of the endocrine cells in duodenum were generally spindle shaped with long cytoplasmic processes ending in the lumen during hibernation. SS-IR cells were limited in stomach and small stomach. The density increased in stomach while decreased in small stomach during hibernation, meanwhile, fewer IR cells occurred in small intestine. VIP-IR cells occurred in stomach and small stomach. The density decreased in small stomach, while increased in stomach during hibernation. These results indicated that the endocrine cells in different parts of digestive tract varied differently during hibernation, their changes were adaptive response to the hibernation.

  19. Exposures, Mechanisms, and Impacts of Endocrine-Active Flame Retardants

    PubMed Central

    Dishaw, Laura; Macaulay, Laura; Roberts, Simon C.; Stapleton, Heather M.

    2014-01-01

    This review summarizes the endocrine and neurodevelopmental effects of two current-use additive flame retardants (FRs), tris (1,3-dichloro-isopropyl) phosphate (TDCPP) and Firemaster® 550 (FM 550), and the recently phased-out polybrominated diphenyl ethers (PBDEs), all of which were historically or are currently used in polyurethane foam applications. Use of these chemicals in consumer products has led to widespread exposure in indoor environments. PBDEs and their hydroxylated metabolites appear to primarily target the thyroid system, likely due to their structural similarity to endogenous thyroid hormones. In contrast, much less is known about the toxicity of TDCPP and FM550. However, recent in vitro and in vivo studies suggest that both should be considered endocrine disruptors as studies have linked TDCPP exposure with changes in circulating hormone levels, and FM 550 exposure with changes in adipogenic and osteogenic pathways. PMID:25306433

  20. Exposures, mechanisms, and impacts of endocrine-active flame retardants.

    PubMed

    Dishaw, Laura V; Macaulay, Laura J; Roberts, Simon C; Stapleton, Heather M

    2014-12-01

    This review summarizes the endocrine and neurodevelopmental effects of two current-use additive flame retardants (FRs), tris (1,3-dichloro-isopropyl) phosphate (TDCPP) and Firemaster(®) 550 (FM 550), and the recently phased-out polybrominated diphenyl ethers (PBDEs), all of which were historically or are currently used in polyurethane foam applications. Use of these chemicals in consumer products has led to widespread exposure in indoor environments. PBDEs and their hydroxylated metabolites appear to primarily target the thyroid system, likely due to their structural similarity to endogenous thyroid hormones. In contrast, much less is known about the toxicity of TDCPP and FM 550. However, recent in vitro and in vivo studies suggest that both should be considered endocrine disruptors as studies have linked TDCPP exposure with changes in circulating hormone levels, and FM 550 exposure with changes in adipogenic and osteogenic pathways.

  1. A consolidated method for screening the endocrine activity of drinking water.

    PubMed

    Chevolleau, Sylvie; Debrauwer, Laurent; Stroheker, Thomas; Viglino, Liza; Mourahib, Issam; Meireles, Maria-Helena; Grimaldi, Marina; Balaguer, Patrick; di Gioia, Lodovico

    2016-12-15

    Endocrine activity of drinking water is a matter of growing interest for scientists as well as health authorities. A concentration technique for endocrine activity screening was developed, optimized, and transposed from 200mL to 10L water samples. To avoid any contamination during concentration, the method was developed using exclusively glass, Teflon and stainless steel materials. Any potential losses were tracked using three model radiolabeled molecules, namely BPA, DEHP and 4n-NP. The final method allowed 10L water samples to be concentrated 5000-fold, with good recovery and repeatability. After validation, by concentrating spiked and non-spiked 10L samples of EVIAN natural mineral water, 14 different drinking water samples were concentrated and screened for endocrine disrupting activity using bioluminescent assays. Samples consisting of bottled water, conditioned in various materials (glass, PET) and subjected to different storage conditions, had no hormone-like activities whereas estrogenic activity was found in the filtered tap water.

  2. Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances.

    PubMed

    Coady, Katherine K; Biever, Ronald C; Denslow, Nancy D; Gross, Melanie; Guiney, Patrick D; Holbech, Henrik; Karouna-Renier, Natalie K; Katsiadaki, Ioanna; Krueger, Hank; Levine, Steven L; Maack, Gerd; Williams, Mike; Wolf, Jeffrey C; Ankley, Gerald T

    2017-03-01

    In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid

  3. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    SciTech Connect

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-05-15

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated (/sup 3/H)thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause.

  4. Computational Steroidogenesis Model To Predict Biochemical Responses to Endocrine Active Chemicals: Model Development and Cross Validation

    EPA Science Inventory

    Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

  5. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

    PubMed Central

    Auger, Jacques; Eustache, Florence; Rouiller-Fabre, Virginie; Canivenc-Lavier, Marie Chantal; Livera, Gabriel

    2014-01-01

    In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS) exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA) of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach) for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction. PMID:24369134

  6. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals.

    PubMed

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-03-25

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold² software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed.

  7. A Rat α-Fetoprotein Binding Activity Prediction Model to Facilitate Assessment of the Endocrine Disruption Potential of Environmental Chemicals

    PubMed Central

    Hong, Huixiao; Shen, Jie; Ng, Hui Wen; Sakkiah, Sugunadevi; Ye, Hao; Ge, Weigong; Gong, Ping; Xiao, Wenming; Tong, Weida

    2016-01-01

    Endocrine disruptors such as polychlorinated biphenyls (PCBs), diethylstilbestrol (DES) and dichlorodiphenyltrichloroethane (DDT) are agents that interfere with the endocrine system and cause adverse health effects. Huge public health concern about endocrine disruptors has arisen. One of the mechanisms of endocrine disruption is through binding of endocrine disruptors with the hormone receptors in the target cells. Entrance of endocrine disruptors into target cells is the precondition of endocrine disruption. The binding capability of a chemical with proteins in the blood affects its entrance into the target cells and, thus, is very informative for the assessment of potential endocrine disruption of chemicals. α-fetoprotein is one of the major serum proteins that binds to a variety of chemicals such as estrogens. To better facilitate assessment of endocrine disruption of environmental chemicals, we developed a model for α-fetoprotein binding activity prediction using the novel pattern recognition method (Decision Forest) and the molecular descriptors calculated from two-dimensional structures by Mold2 software. The predictive capability of the model has been evaluated through internal validation using 125 training chemicals (average balanced accuracy of 69%) and external validations using 22 chemicals (balanced accuracy of 71%). Prediction confidence analysis revealed the model performed much better at high prediction confidence. Our results indicate that the model is useful (when predictions are in high confidence) in endocrine disruption risk assessment of environmental chemicals though improvement by increasing number of training chemicals is needed. PMID:27023588

  8. Exploring the Relationship of Autonomic and Endocrine Activity with Social Functioning in Adults with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Smeekens, I.; Didden, R.; Verhoeven, E. W. M.

    2015-01-01

    Several studies indicate that autonomic and endocrine activity may be related to social functioning in individuals with autism spectrum disorder (ASD), although the number of studies in adults is limited. The present study explored the relationship of autonomic and endocrine activity with social functioning in young adult males with ASD compared…

  9. Developing analytical approaches to explore the connectionbetween endocrine-active pharmaceuticals in waterto effects in fish

    EPA Science Inventory

    The emphasis of this research project was to develop, and optimize, a solid-phase extraction (SPE) method and high performance liquid chromatography-electrospray ionization- mass spectrometry (LC-MS/MS) method, such that a linkage between the detection of endocrine active pharma...

  10. Approaches for predicting effects of unintended environmental exposure to an endocrine active pharmaceutical, tamoxifen

    EPA Science Inventory

    Tamoxifen is an endocrine-active pharmaceutical (EAP) that is used world-wide. Because tamoxifen is a ubiquitous pharmaceutical and interacts with estrogen receptors, a case study was conducted with this compound to (1) determine effects on reproductive endpoints in a nontarget s...

  11. In vitro metabolism and bioavailability tests for the predictive toxicology of endocrine active substances

    EPA Science Inventory

    Legislation and prospective legislative proposals internationally (may) require that chemicals are tested for their ability to disrupt the hormonal systems of animals. Chemicals found to test positive in vitro are considered to be endocrine active substances (EAS) and may be puta...

  12. Recommended approaches to the scientific evaluation of environmental hazards and risks of endocrine-active substances

    EPA Science Inventory

    A SETAC Pellston Workshop™ ?‘Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Substances (EHRA)’ was held from 31st January to 5th February 2016 in Pensacola, Florida, USA. The primary aim of the workshop was to provide objective advice, ...

  13. Endocrine disruptors in bottled mineral water: estrogenic activity in the E-Screen.

    PubMed

    Wagner, Martin; Oehlmann, Jörg

    2011-10-01

    Human exposure to endocrine disruptors is well documented by biomonitoring data. However, this information is limited to few chemicals like bisphenol A or phthalate plasticizers. To account for so-far unidentified endocrine disruptors and potential mixture effects we employ bioassays to detect endocrine activity in foodstuff and consequently characterize the integrated exposure to endocrine active compounds. Recently, we reported a broad contamination of commercially available bottled water with estrogenic activity and presented evidence for the plastic packaging being a source of this contamination. In continuation of that work, we here compare different sample preparation methods to extract estrogen-like compounds from bottled water. These data demonstrate that inappropriate extraction methods and sample treatment may lead to false-negative results when testing water extracts in bioassays. Using an optimized sample preparation strategy, we furthermore present data on the estrogenic activity of bottled water from France, Germany, and Italy: eleven of the 18 analyzed water samples (61.1%) induced a significant estrogenic response in a bioassay employing a human carcinoma cell line (MCF7, E-Screen). The relative proliferative effects ranged from 19.8 to 50.2% corresponding to an estrogenic activity of 1.9-12.2 pg estradiol equivalents per liter bottled water. When comparing water of the same spring that is packed in glass or plastic bottles made of polyethylene terephthalate (PET), estrogenic activity is three times higher in water from plastic bottles. These data support the hypothesis that PET packaging materials are a source of estrogen-like compounds. Furthermore, the findings presented here conform to previous studies and indicate that the contamination of bottled water with endocrine disruptors is a transnational phenomenon.

  14. Characterizing field sediments from three European river basins with special emphasis on endocrine effects - A recommendation for Potamopyrgus antipodarum as test organism.

    PubMed

    Schmitt, Claudia; Balaam, Jan; Leonards, Pim; Brix, Rikke; Streck, Georg; Tuikka, Anita; Bervoets, Lieven; Brack, Werner; van Hattum, Bert; Meire, Patrick; de Deckere, Eric

    2010-06-01

    The assessment of endocrine disrupting potentials of field sediments has until now been mostly limited to classical chemical analysis, in vitro assays and in vivo bioassays performed with vertebrates. There is an urgent need for easy, cheap and reproducible invertebrate tests which may be applied in certain monitoring activities. Since the mudsnail Potamopyrgus antipodarum is known to be tolerant to natural stressors, but also sensitive to endocrine disrupting chemicals, it is very likely that this organism could be suitable for the assessment of endocrine effects of e.g. field sediments. Within this study the endocrine potential of sediments in three European river basins was assessed. The yeast estrogen screen (YES) and a sediment contact test with P. antipodarum were performed. Furthermore, analyses of physico-chemical properties and concentrations of heavy metals, PAHs, organotins, natural steroids and alkylphenols were done. In the sediment contact test, the reproduction of the snail was promoted by a part of the sediments. This phenomenon could not be explained by their physico-chemical properties. However, at some of those sites a high estrogenic activity was detected in the YES, leading to the assumption that endocrine disrupting compounds could be responsible for those effects. This assumption could be confirmed to some extent with partially high concentrations of xeno-estrogens (e.g. nonylphenol) at the certain sites. Our study demonstrates the applicability of the test with P. antipodarum for a variety of sediments and once again points out the need of suitable in vivo biotests for the risk assessment of field sediments.

  15. Validation of noninvasive monitoring of adrenocortical endocrine activity in ground-feeding aardwolves (Proteles cristata): exemplifying the influence of consumption of inorganic material for fecal steroid analysis.

    PubMed

    Ganswindt, André; Muilwijk, Charlotte; Engelkes, Monique; Muenscher, Stefanie; Bertschinger, Henk; Paris, Monique; Palme, Rupert; Cameron, Elissa Z; Bennett, Nigel C; Dalerum, Fredrik

    2012-01-01

    Biologically inert material in feces may confound interpretations of noninvasive fecal endocrine data, because it may induce variance related to differences in foraging behavior rather than to differences in endocrine activity. We evaluated two different enzyme immunoassays (EIAs) for the noninvasive evaluation of adrenocortical activity in ground-feeding aardwolves (Proteles cristata) and tested the influence of soil content in aardwolf feces on the interpretation of fecal glucocorticoid metabolite data. Using adrenocorticotropic hormone (ACTH) challenges for validation, we successfully identified a cortisol EIA suitable for assessing adrenocortical activity in aardwolves. An alternatively tested 11-oxoetiocholanolone EIA failed to detect a biologically relevant signal after ACTH administration. Although the proportion of inorganic content in aardwolf feces did not alter qualitative conclusions from the endocrine data, the data related to mass of organic content had a larger amount of variance attributed to relevant biological contrasts and a lower amount of variance attributed to individual variation, compared with data related to total dry mass of extracted material. Compared with data expressed as dry mass of extracted material, data expressed as mass of organic content may provide a more refined and statistically powerful measure of endocrine activity in species that ingest large amounts of indigestible material.

  16. The endocrine activity of beef cattle wastes: do growth-promoting steroids make a difference?

    PubMed

    Sellin, Marlo K; Snow, Daniel D; Gustafson, Sarah T; Erickson, Galen E; Kolok, Alan S

    2009-05-17

    The primary objective of this study was to compare the endocrine activity of wastes from trenbolone acetate:estradiol (TBA:E)-implanted steers to that of wastes from unimplanted steers. To accomplish this, fathead minnows (Pimephales promelas) were exposed to urine or fecal slurry from TBA:E-implanted or unimplanted steers for 7 days. Following exposures, hepatic vitellogenin (vtg) mRNA expression and secondary sexual characteristics were assessed. Among both males and females, there were no differences in vtg mRNA expression between fish exposed to urine from implanted or unimplanted steers at any of the concentrations tested. Furthermore, concentrations of steroid hormones in the urine of implanted and unimplanted steers were similar. These findings indicate a lack of differences in the endocrine activity of urine from TBA:E-implanted and unimplanted steers. With regard to the fecal slurry exposures, there were no significant differences in vtg mRNA expression among females from any of the groups; however, significant differences in male vtg mRNA expression were detected. Specifically, males exposed to 1600 mg dry feces/L from implanted cattle experienced an 840-fold increase in vtg mRNA expression relative to both unexposed males and males exposed to the corresponding fecal concentration from unimplanted steers. These males also appeared to experience a reduction in male secondary sexual characteristics. These findings suggest that steroids associated with the wastes from TBA:E-implanted steers have both feminizing and demasculinizing effects on male fish. Furthermore, these effects are most likely due to the presence of estrogenic compounds, which were detected in the liquid portion of the fecal slurry from TBA:E-implanted steers, but not in that of unimplanted steers. The findings of this study indicate the presence of endocrine-disrupting compounds in the urine and feces of cattle and suggest that the implant history of cattle alters the endocrine activity of

  17. Current limitations and a path forward to improve testing for the environmental assessment of endocrine active substances-presentation

    EPA Science Inventory

    To assess the hazards and risks of possible endocrine active chemicals (EACs), there is a need for robust, validated test methods that detect perturbations of endocrine pathways and provide reliable information for evaluating potential adverse effects on apical endpoints. One iss...

  18. Current limitations and a path forward to improve testing for the environmental assessment of endocrine active substances

    EPA Science Inventory

    To assess the hazards and risks of possible endocrine active chemicals (EACs) there is a need for robust, validated test methods that detect perturbation of endocrine pathways of concern and provide insights reliable information as to assess to potential adverse effects on apical...

  19. Cadmium in vivo exposure alters stress response and endocrine-related genes in the freshwater snail Physa acuta. New biomarker genes in a new model organism.

    PubMed

    Martínez-Paz, Pedro; Morales, Mónica; Sánchez-Argüello, Paloma; Morcillo, Gloria; Martínez-Guitarte, José Luis

    2017-01-01

    The freshwater snail Physa acuta is a sensitive organism to xenobiotics that is appropriate for toxicity testing. Cadmium (Cd) is a heavy metal with known toxic effects on several organisms, which include endocrine disruption and activation of the cellular stress responses. There is scarce genomic information on P. acuta; hence, in this work, we identify several genes related to the hormonal system, the stress response and the detoxification system to evaluate the effects of Cd. The transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), the heat shock proteins genes hsp70 and hsp90 and a metallothionein (MT) gene was analysed in P. acuta exposed to Cd. In addition, the hsp70 and hsp90 genes were also evaluated after heat shock treatment. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that Cd presence induced a significant increase in the mRNA levels of ER, ERR and RXR, suggesting a putative mode of action that could explain the endocrine disruptor activity of this heavy metal at the molecular level on Gastropoda. Moreover, the hsp70 gene was upregulated after 24-h Cd treatment, but the hsp90 gene expression was not affected. In contrast, the hsp70 and hsp90 genes were strongly upregulated during heat shock response. Finally, the MT gene expression showed a non-significant variability after Cd exposure. In conclusion, this study provides, for the first time, information about the effects of Cd on the endocrine system of Gastropoda at the molecular level and offers new putative biomarker genes that could be useful in ecotoxicological studies, risk assessment and bioremediation.

  20. Autoreactive T cells in endocrine/organ-specific autoimmunity: why has progress been so slow?

    PubMed

    Roep, Bart O

    2002-12-01

    It has been generally accepted that T cells play a critical role in endocrine autoimmune diseases. Immunotherapy aimed at T cells usually intervenes in the disease process. Yet, it has proven very difficult to identify the pathogenic T cells. This is partly caused by lack of measures to detect autoreactive T cells in a specific, sensitive and reproducible fashion as is achievable for determination of autoantibodies. There are, however, more explanations for the perhaps disappointing progress in this area: unlike autoantibodies, the relevant (disease-associated) autoreactive T cells act in the tissue lesion, and only circulate in very low precursor frequencies. Moreover, T cell autoreactivity is counteracted by various mechanisms of immune regulation. Candidate target autoantigens of T cells have been identified by autoantibodies, while there is little evidence that these autoantibodies are pathogenic. It is therefore conceivable that additional T cell targets exist. Finally, results from experimental animal models of endocrine autoimmunity have raised false expectations. Nonetheless, significant progress in our understanding of the contribution of (autoreactive) T cells to organ-specific destruction and autoimmune disease has been achieved. Although cross-sectional detection of autoreactive T cells bears little relevance to diagnosis, longitudinal studies have proven useful in determining the fate of islet implantation in type 1 diabetes patients, defined the immunological efficacy of immuno-intervention studies, and have led to definition of relevant target autoantigens and peptides that will help to monitor disease-associated autoimmunity. In conclusion, progress in the area of autoreactive T cells in the pathogenesis of type 1 diabetes may have seemed slow in the eyes of the beholder, but in fact, studies on T cells have contributed significantly to the unravelling of the pathogenic processes leading to the definition of appropriate targets for immuno-intervention.

  1. The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement.

    PubMed

    Toni, Roberto; Casa, Claudia Della; Spaletta, Giulia; Marchetti, Giacomo; Mazzoni, Perseo; Bodria, Monica; Ravera, Simone; Dallatana, Davide; Castorina, Sergio; Riccioli, Vincenzo; Castorina, Emilio Giovanni; Antoci, Salvatore; Campanile, Enrico; Raise, Gabriella; Scalise, Gabriella; Rossi, Raffaella; Rossio, Raffaella; Ugolotti, Giorgio; Ugolottio, Giorgio; Martorella, Andrew; Roti, Elio; Rot, Elio; Sgallari, Fiorella; Pinchera, Aldo

    2007-01-01

    A new concept for ex situ endocrine organ bioengineering is presented, focused on the realization of a human bioartificial thyroid gland. It is based on the theoretical assumption and experimental evidence that symmetries in geometrical coordinates of the thyroid tissue remain invariant with respect to developmental, physiological or pathophysiological transformations occuring in the gland architecture. This topological arrangement is dependent upon physical connections established between cells, cell adhesion molecules and extracellular matrix, leading to the view that the thyroid parenchyma behaves like a deformable "putty", moulded onto an elastic stromal/vascular scaffold (SVS) dictating the final morphology of the gland. In particular, we have raised the idea that the geometry of the SVS per se provides pivotal epigenetic information to address the genetically-programmed, thyrocyte and endothelial/vascular proliferation and differentiation towards a functionally mature gland, making organ form a pre-requirementfor organ function. A number of experimental approaches are explored to obtain a reliable replica of a human thyroid SVS, and an informatic simulation is designed based on fractal growth of the thyroid intraparenchymal arterial tree. Various tissue-compatible and degradable synthetic or biomimetic polymers are discussed to act as a template of the thyroid SVS, onto which to co-seed autologous human thyrocyte (TPC) and endothelial/vascular (EVPC) progenitor cells. Harvest and expansion of both TPC and EVPC in primary culture are considered, with specific attention to the selection of normal thyrocytes growing at a satisfactory rate to colonize the synthetic matrix. In addition, both in vitro and in vivo techniques to authenticate TPC and EVPC lineage differentiation are reviewed, including immunocytochemistry, reverse trascriptase-polymerase chain reaction, flow cytomery and proteomics. Finally, analysis of viability of the thyroid construct following

  2. An assessment of endocrine activity in Australian rivers using chemical and in vitro analyses.

    PubMed

    Scott, Philip D; Bartkow, Michael; Blockwell, Stephen J; Coleman, Heather M; Khan, Stuart J; Lim, Richard; McDonald, James A; Nice, Helen; Nugegoda, Dayanthi; Pettigrove, Vincent; Tremblay, Louis A; Warne, Michael St J; Leusch, Frederic D L

    2014-11-01

    Studies on endocrine disruption in Australia have mainly focused on wastewater effluents. Limited knowledge exists regarding the relative contribution of different potential sources of endocrine active compounds (EACs) to the aquatic environment (e.g., pesticide run-off, animal farming operations, urban stormwater, industrial inputs). In this study, 73 river sites across mainland Australia were sampled quarterly for 1 year. Concentrations of 14 known EACs including natural and synthetic hormones and industrial compounds were quantified by chemical analysis. EACs were detected in 88 % of samples (250 of 285) with limits of quantification (LOQ) ranging from 0.05 to 20 ng/l. Bisphenol A (BPA; LOQ = 20 ng/l) was the most frequently detected EAC (66 %) and its predicted no-effect concentration (PNEC) was exceeded 24 times. The most common hormone was estrone, detected in 28 % of samples (LOQ = 1 ng/l), and the PNEC was also exceeded 24 times. 17α-Ethinylestradiol (LOQ = 0.05 ng/l) was detected in 10 % of samples at concentrations ranging from 0.05 to 0.17 ng/l. It was detected in many samples with no wastewater influence, and the PNEC was exceeded 13 times. In parallel to the chemical analysis, endocrine activity was assessed using a battery of CALUX bioassays. Estrogenic activity was detected in 19 % (53 of 285) of samples (LOQ = 0.1 ng/l 17β-estradiol equivalent; EEQ). Seven samples exhibited estrogenic activity (1-6.5 ng/l EEQ) greater than the PNEC for 17β-estradiol. Anti-progestagenic activity was detected in 16 % of samples (LOQ = 8 ng/l mifepristone equivalents; MifEQ), but the causative compounds are unknown. With several compounds and endocrine activity exceeding PNEC values, there is potential risk to the Australian freshwater ecosystems.

  3. Aqueous leaf extracts display endocrine activities in vitro and disrupt sexual differentiation of male Xenopus laevis tadpoles in vivo.

    PubMed

    Hermelink, Björn; Urbatzka, Ralph; Wiegand, Claudia; Pflugmacher, Stephan; Lutz, Ilka; Kloas, Werner

    2010-09-01

    The occurrence of natural substances acting as endocrine disrupting compounds (EDC) in the environment is to date poorly understood. Therefore, (anti)androgenic and (anti)estrogenic activities of three different aqueous leaf extracts (beech, reed and oak) were analyzed in vitro using yeast androgen and estrogen screen. The most potent extract was selected for in vivo exposure of Xenopus laevis tadpoles to analyze the potential effects on development and reproductive biology of amphibians. Tadpoles were exposed from stage 48 to stage 66 (end of metamorphosis) to aqueous oak leaf extracts covering natural occurring environmental concentrations of dissolved organic carbon. Gene expression analyses of selected genes of the hypothalamus-pituitary-gonad and of the hypothalamus-pituitary-thyroid axis as well as histological investigation of gonads and thyroid glands were used to evaluate endocrine disrupting effects on the reproductive biology and development. Female tadpoles remained unaffected by the exposure whereas males showed severe significant histological alterations of testes at the two highest oak leaf extract concentrations demonstrated by the occurrence of lacunae and oogonia. In addition, a significant elevation of luteinizing hormone beta mRNA expression with increasing extract concentration in male tadpoles indicates an involvement of hypothalamus-pituitary-gonad axis mainly via antiandrogenic activity. These results suggest that antiandrogenic EDC of oak leaf extract are responsible for inducing the observed effects in male tadpoles. The present study demonstrates for the first time that in surface waters, natural occurring oak leaf compounds at environmentally relevant concentrations display antiandrogenic activities and have considerable effects on the endocrine system of anurans affecting sexual differentiation of male tadpoles.

  4. Endocrine glands (image)

    MedlinePlus

    Endocrine glands release hormones (chemical messengers) into the bloodstream to be transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which ...

  5. Multi-tiered Approach to Development of Increased Throughput Assay Models to Assess Endocrine-Disrupting Activity of Chemicals

    EPA Science Inventory

    Screening for endocrine-disrupting chemicals (EDCs) requires sensitive, scalable assays. Current high-throughput screening (HTPS) approaches for estrogenic and androgenic activity yield rapid results, but many are not sensitive to physiological hormone concentrations, suggesting ...

  6. Endocrine activity and developmental toxicity of cosmetic UV filters--an update.

    PubMed

    Schlumpf, Margret; Schmid, Peter; Durrer, Stefan; Conscience, Marianne; Maerkel, Kirsten; Henseler, Manuel; Gruetter, Melanie; Herzog, Ingrid; Reolon, Sasha; Ceccatelli, Raffaella; Faass, Oliver; Stutz, Eva; Jarry, Hubertus; Wuttke, Wolfgang; Lichtensteiger, Walter

    2004-12-01

    UV filters represent a new class of endocrine active chemicals. In vitro, 8/9 chemicals showed estrogenic (MCF-7 cells), and 2/9 antiandrogenic activity (MDA-kb2 cells). Six/nine filters (benzophenone (Bp)-1, Bp-2, Bp-3, 3-benzylidene camphor (3-BC), 4-methylbenzylidene camphor (4-MBC), octyl-methoxycinnamate (OMC)) increased uterine weight in immature rats. 3-Benzylidene camphor and 4-MBC displaced 16alpha125I-estradiol from human estrogen receptor (ER)beta, not ERalpha. Developmental toxicity of 4-MBC (0.7-47 mg/kg body weight/day) and 3-BC (0.24-7 mg/kg), administered in chow was investigated in Long Evans (LE) rats. Weight gain of pregnant rats was reduced only by 3-BC, early postnatal survival rate and thymus weight by both compounds at higher doses. 4-Methylbenzylidene camphor and 3-BC delayed male puberty, and dose-dependently affected reproductive organ weights of adult male and female F1 offspring, with partly different effect patterns. Thyroid weight was increased by higher 4-MBC doses. Tissue-specific changes in mRNA levels of estrogen-regulated genes in prostate, uterus and brain regions, determined by real-time PCR, and in their response to acute estradiol challenge in adult gonadectomized offspring were observed. Lowest effective doses were 0.24 mg/kg/day for 3-BC and 7 mg/kg/day for 4-MBC. Fat tissue levels at 7 mg/kg 4-MBC (GC-MS) approached the range of UV filters in fish (Nagtegaal et al., 1997; Balmer et al., 2004).

  7. Endocrine-Disrupting Activity of Hydraulic Fracturing Chemicals and Adverse Health Outcomes After Prenatal Exposure in Male Mice.

    PubMed

    Kassotis, Christopher D; Klemp, Kara C; Vu, Danh C; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L; Pinatti, Lisa; Zoeller, R Thomas; Drobnis, Erma Z; Balise, Victoria D; Isiguzo, Chiamaka J; Williams, Michelle A; Tillitt, Donald E; Nagel, Susan C

    2015-12-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  8. Endocrine-disrupting activity of hydraulic fracturing chemicals and adverse health outcomes after prenatal exposure in male mice

    USGS Publications Warehouse

    Kassotis, Christopher D.; Klemp, Kara C.; Vu, Danh C.; Lin, Chung-Ho; Meng, Chun-Xia; Besch-Williford, Cynthia L.; Pinatti, Lisa; Zoeller, R. Thomas; Drobnis, Erma Z.; Balise, Victoria D.; Isiguzo, Chiamaka J.; Williams, Michelle A.; Tillitt, Donald E.; Nagel, Susan C.

    2015-01-01

    Oil and natural gas operations have been shown to contaminate surface and ground water with endocrine-disrupting chemicals. In the current study, we fill several gaps in our understanding of the potential environmental impacts related to this process. We measured the endocrine-disrupting activities of 24 chemicals used and/or produced by oil and gas operations for five nuclear receptors using a reporter gene assay in human endometrial cancer cells. We also quantified the concentration of 16 of these chemicals in oil and gas wastewater samples. Finally, we assessed reproductive and developmental outcomes in male C57BL/6J mice after the prenatal exposure to a mixture of these chemicals. We found that 23 commonly used oil and natural gas operation chemicals can activate or inhibit the estrogen, androgen, glucocorticoid, progesterone, and/or thyroid receptors, and mixtures of these chemicals can behave synergistically, additively, or antagonistically in vitro. Prenatal exposure to a mixture of 23 oil and gas operation chemicals at 3, 30, and 300 μg/kg · d caused decreased sperm counts and increased testes, body, heart, and thymus weights and increased serum testosterone in male mice, suggesting multiple organ system impacts. Our results suggest possible adverse developmental and reproductive health outcomes in humans and animals exposed to potential environmentally relevant levels of oil and gas operation chemicals.

  9. The screening of chemicals for juvenoid-related endocrine activity using the water flea Daphnia magna.

    PubMed

    Wang, Helen Ying; Olmstead, Allen W; Li, Hong; Leblanc, Gerald A

    2005-09-10

    U.S. Environmental Protection Agency is charged with developing a screening and testing paradigm for detecting endocrine toxicity of chemicals that are subject to regulation under the Food Quality Protection and the Safe Drinking Water Acts. In this study, we developed and evaluated a screening assay that could be employed to detect juvenoid-related endocrine-modulating activity in an invertebrate species. Juvenoid activity, anti-juvenoid activity, and juvenoid potentiator activity of chemicals was assessed using the water flea Daphnia magna. Male sex determination is under the regulatory control of juvenoid hormone, presumably methyl farnesoate, and this endpoint was used to detect juvenoid modulating activity of chemicals. Eighteen chemicals were evaluated for juvenoid agonist activity. Positive responses were detected with the juvenoid hormones methyl farnesoate and juvenile hormone III along with the insect growth regulating insecticides pyriproxyfen, fenoxycarb, and methoprene. Weak juvenoid activity also was detected with the cyclodiene insecticide dieldrin. Assays performed repetitively with compounds that gave either strong positive, weak positive, or negative response were 100% consistent indicating that the assay is not prone to false positive or negative responses. Five candidate chemicals were evaluated for anti-juvenoid activity and none registered positive. Four chemicals (all trans-retinoic acid, methoprene, kinoprene, bisphenol A) also were evaluated for their ability to potentiate the activity of methyl farnesoate. All registered positive. Results demonstrate that an in vivo assay with a crustacean species customarily employed in toxicity testing can be used to effectively screen chemicals for juvenoid-modulating activity.

  10. Analysis and occurrence of endocrine-disrupting compounds and estrogenic activity in the surface waters of Central Spain.

    PubMed

    Esteban, S; Gorga, M; Petrovic, M; González-Alonso, S; Barceló, D; Valcárcel, Y

    2014-01-01

    Endocrine-disrupting compounds (EDCs) are chemical compounds with the ability to alter the hormonal systems of organisms. Such compounds are used in several industrial and domestic activities and reach the aquatic environment via wastewater discharge. The aim of this study is to assess the occurrence of 30 EDCs and related compounds in the surface waters of central Spain and to determine the overall estrogenic activity of environmental samples. This study analyzed a large number of EDCs and other emergent or suspected compounds with endocrine-disrupting activity. The results have shown the presence of 19 EDCs at concentrations ranging from 2 to 5928 ng L(-1). Organophosphorus-based flame retardants, alkylphenolic compounds and anticorrosives were found at the highest concentrations. Furthermore, although insufficient data are available to calculate an average over time, these preliminary results show the need to monitor the waters in both rivers studied. Alkylphenolic compounds, particularly nonylphenol, were the main contributors to overall estrogenicity. A higher concentration of the compounds studied was detected in the river Jarama, although the estrogenicity expressed as estradiol equivalents (EEQs) was higher in the river Manzanares due to a higher concentration of nonylphenol. However, the total estrogenicity did not exceed 1 ng L(-1) (EEQ), which is the level that may cause estrogenic effects in aquatic organisms, in any of the samples. In conclusion, the potential estrogenic risk in both rivers is low, although organophosphorus-based flame retardants may increase this risk as they were found at high levels in all samples. Unfortunately, these compounds could not be taken into account when calculating the estrogenic activity due to the lack of activity data for them. For future investigations, it will be important to assess the estrogenicity provided by these flame retardants. Due to the significant concentrations of EDCs detected in both rivers, further

  11. Skeletal muscle as an endocrine organ: Role of [Na+]i/[K+]i-mediated excitation-transcription coupling

    PubMed Central

    Kapilevich, Leonid V.; Kironenko, Tatyana A.; Zaharova, Anna N.; Kotelevtsev, Yuri V.; Dulin, Nickolai O.; Orlov, Sergei N.

    2016-01-01

    Summary During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood. It is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Na+ and K+ channels. Recently, we demonstrated that sustained elevation of the [Na+]i/[K+]i ratio triggers expression of dozens ubiquitous genes including several canonical myokines, such as interleukin 6 and cyclooxygenase 2, in the presence of intra- and extracellular Ca2+ chelators. These data allowed us to suggest a novel [Na+]i/[K+]i-sensitive, Ca2+i-independent mechanism of excitation-transcription coupling which triggers myokine production. This pathway exists in parallel with canonical signaling mediated by Ca2+i, AMP-activated protein kinase and hypoxia-inducible factor 1α (HIF-1α). In our mini-review we briefly summarize data supporting this hypothesis as well as unresolved issues aiming to forthcoming studies. PMID:27610402

  12. Bridging epidemiology and model organisms to increase understanding of endocrine disrupting chemicals and human health effects.

    PubMed

    Woodruff, Tracey J

    2011-10-01

    Concerning temporal trends in human reproductive health has prompted concern about the role of environmentally mediated risk factors. The population is exposed to chemicals present in air, water, food and in a variety of consumer and personal care products, subsequently multiple chemicals are found human populations around the globe. Recent reviews find that endocrine disrupting chemicals (EDCs) can adversely affect reproductive and developmental health. However, there are still many knowledge gaps. This paper reviews some of the key scientific concepts relevant to integrating information from human epidemiologic and model organisms to understand the relationship between EDC exposure and adverse human health effects. Additionally, areas of new insights which influence the interpretation of the science are briefly reviewed, including: enhanced understanding of toxicity pathways; importance of timing of exposure; contribution of multiple chemical exposures; and low dose effects. Two cases are presented, thyroid disrupting chemicals and anti-androgens chemicals, which illustrate how our knowledge of the relationship between EDCs and adverse human health effects is strengthened and data gaps reduced when we integrate findings from animal and human studies.

  13. Potential endocrine disrupting organic chemicals in treated municipal wastewater and river water

    USGS Publications Warehouse

    Barber, L.B.; Brown, G.K.; Zaugg, S.D.

    2000-01-01

    Select endocrine disrupting organic chemicals were measured in treated wastewater from Chicago, IL, Minneapolis/St. Paul, MN, Detroit, MI, and Milwaukee, WI, and in the Des Plaines, Illinois, and Minnesota Rivers during the fall of 1997 and the spring of 1998. Emphasis was given to alkylphenolpolyethoxylate (APEO) derived compounds, although 17-??-estradiol, bisphenol A, caffeine, total organic carbon, ethylenediaminetetraacetic acid (EDTA), and other compounds also were measured. Contaminants were isolated by continuous liquid-liquid extraction (CLLE) with methylene chloride and analyzed by gas chromatography/mass spectrometry in full scan and selected ion monitoring modes. The extracts were derivatized to form the methyl esters of alkylphenolethoxycarboxylates (APEC), and EDTA was isolated by evaporation and derivatized to form the tetrapropyl ester. The mass spectra of nonylphenol (NP) and octylphenol (OP) compounds are complex and show variations among the different ethoxylate and carboxylate homologs, reflecting variations in the ethylene oxide chain length. Recoveries for target compounds and surrogate standards ranged from 20-130%, with relative standard deviations of 9.9-53%. Detection limits for the various compounds ranged from 0.06-0.35 ??g/L. Analysis of the wastewater effluents detected a number of compounds including NP, NPEO, OP, OPEO, NPEC, caffeine, and EDTA at concentrations ranging from <1-439 ??g/L, with EDTA and NPEC being most abundant. There was variability in compound distributions and concentrations between the various sewage treatment plants, indicating differences in treatment type and influent composition. Several wastewater-derived compounds were detected in the river samples, with EDTA and NPEC persisting for considerable distance downstream from wastewater discharges, and NP and NPEO being attenuated more rapidly.

  14. Classical Nuclear Hormone Receptor Activity as a Mediator of Complex Concentration Response Relationships for Endocrine Active Compounds

    PubMed Central

    Cookman, Clifford J.; Belcher, Scott M.

    2014-01-01

    Nonmonotonic concentration response relationships are frequently observed for endocrine active ligands that act via nuclear receptors. The curve of best fit for nonmonotonic concentration response relationships are often inverted U-shaped with effects at intermediate concentrations that are different from effects at higher or lower concentrations. Cytotoxicity is a major mode of action responsible for inverted U-shaped concentration response relationships. However, evidence suggests that ligand selectivity, activation of multiple molecular targets, concerted regulation of multiple opposing endpoints, and multiple ligand binding sites within nuclear receptors also contribute to nonmonotonic concentration response relationships of endocrine active ligands. This review reports the current understanding of mechanisms involved in classical nuclear receptor mediated nonmonotonic concentration response relationships with a focus on studies published between 2012 and 2014. PMID:25299165

  15. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity.

    PubMed Central

    Welshons, Wade V; Thayer, Kristina A; Judy, Barbara M; Taylor, Julia A; Curran, Edward M; vom Saal, Frederick S

    2003-01-01

    Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses. These doses are within the range of current exposures to numerous chemicals in wildlife and humans. These problems are exacerbated by the fact that the type of positive and negative controls appropriate to the study of endocrine responses are not part of traditional toxicological testing and are frequently omitted, or when present, have been misinterpreted. PMID:12826473

  16. The Effects of Nanomaterials as Endocrine Disruptors

    PubMed Central

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-01-01

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited. PMID:23949635

  17. QSAR classification models for the screening of the endocrine-disrupting activity of perfluorinated compounds.

    PubMed

    Kovarich, S; Papa, E; Li, J; Gramatica, P

    2012-01-01

    Perfluorinated compounds (PFCs) are a class of emerging pollutants still widely used in different materials as non-adhesives, waterproof fabrics, fire-fighting foams, etc. Their toxic effects include potential for endocrine-disrupting activity, but the amount of experimental data available for these pollutants is limited. The use of predictive strategies such as quantitative structure-activity relationships (QSARs) is recommended under the REACH regulation, to fill data gaps and to screen and prioritize chemicals for further experimentation, with a consequent reduction of costs and number of tested animals. In this study, local classification models for PFCs were developed to predict their T4-TTR (thyroxin-transthyretin) competing potency. The best models were selected by maximizing the sensitivity and external predictive ability. These models, characterized by robustness, good predictive power and a defined applicability domain, were applied to predict the activity of 33 other PFCs of environmental concern. Finally, classification models recently published by our research group for T4-TTR binding of brominated flame retardants and for estrogenic and anti-androgenic activity were applied to the studied perfluorinated chemicals to compare results and to further evaluate the potential for these PFCs to cause endocrine disruption.

  18. Organizing Preservation Activities.

    ERIC Educational Resources Information Center

    Cloonan, Michele

    This resource guide considers issues in the staffing and organization of preservation activities. It provides guidance in implementing a systematic preservation program and evaluates the structures of various types of preservation programs. The following articles complement the discussion of program models and implementation: (1)…

  19. Endocrine system: part 1.

    PubMed

    Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

    2014-05-27

    This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

  20. Persistent Organochlorine Pollutants with Endocrine Activity and Blood Steroid Hormone Levels in Middle-Aged Men

    PubMed Central

    Emeville, Elise; Giton, Frank; Giusti, Arnaud; Oliva, Alejandro; Fiet, Jean; Thomé, Jean-Pierre; Blanchet, Pascal; Multigner, Luc

    2013-01-01

    Background Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. Objective We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. Methods We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. Results DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. Conclusions These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern

  1. Endocrine activity of alternatives to BPA found in thermal paper in Switzerland.

    PubMed

    Goldinger, Daniela M; Demierre, Anne-Laure; Zoller, Otmar; Rupp, Heinz; Reinhard, Hans; Magnin, Roxane; Becker, Thomas W; Bourqui-Pittet, Martine

    2015-04-01

    Alternatives to bisphenol A (BPA) are more and more used in thermal paper receipts. To get an overview of the situation in Switzerland, 124 thermal paper receipts were collected and analyzed. Whereas BPA was detected in most samples (n=100), some alternatives, namely bisphenol S (BPS), Pergafast® 201 and D-8 have been found in 4, 11 and 9 samples respectively. As no or few data on their endocrine activity are available, these chemicals and bisphenol F (BPF) were tested in vitro using the H295R steroidogenesis assay. 17β-Estradiol production was induced by BPA and BPF, whereas free testosterone production was inhibited by BPA and BPS. Both non-bisphenol substances did not show significant effects. The binding affinity to 16 proteins and the toxicological potential (TP) were further calculated in silico using VirtualToxLab™. TP values lay between 0.269 and 0.476 and the main target was the estrogen receptor β (84.4 nM to 1.33 μM). A substitution of BPA by BPF and BPS should be thus considered with caution, since they exhibit almost a similar endocrine activity as BPA. D-8 and Pergafast® 201 could be alternatives to replace BPA, however further analyses are needed to better characterize their effects on the hormonal system.

  2. Endocrine Disruptor Screening Program Reports to Congress

    EPA Pesticide Factsheets

    This page includes EPA reports to congress on pesticide licensing and endocrine disruptor screening activities, Endocrine Disruptor Methods Validation Subcomittee (EDMVS) progress, and Endocrine Disruptor Screening Program (EDSP) implementation progress.

  3. Proteomic Analysis of the Reproductive Organs of the Hermaphroditic Gastropod Lymnaea stagnalis Exposed to Different Endocrine Disrupting Chemicals

    PubMed Central

    Giusti, Arnaud; Leprince, Pierre; Mazzucchelli, Gabriel; Thomé, Jean-Pierre; Lagadic, Laurent; Ducrot, Virginie; Joaquim-Justo, Célia

    2013-01-01

    Many studies have reported perturbations of mollusc reproduction following exposure to low concentrations (ng/L range) of endocrine disrupting chemicals (EDCs). However, the mechanisms of action of these molecules on molluscs are still poorly understood. Investigation of the modifications of protein expression in organisms exposed to chemicals using proteomic methods can provide a broader and more comprehensive understanding of adverse impacts of pollution on organisms than conventional biochemical biomarkers (e.g., heat-shock proteins, metallothioneins, GST, EROD). In this study we have investigated the impacts of four chemicals, which exhibit different endocrine disrupting properties in vertebrates, on the proteome of the hermaphroditic freshwater pulmonate gastropod Lymnaea stagnalis after 21 days of exposure. Testosterone, tributyltin, chlordecone and cyproterone acetate were chosen as tested compounds as they can induce adverse effects on the reproduction of this snail. The 2D-DIGE method was used to identify proteins whose expression was affected by these compounds. In addition to modifying the expression of proteins involved in the structure and function of the cytoskeleton, chemicals had impacts on the expression of proteins involved in the reproduction of L. stagnalis. Exposure to 19.2 µg/L of chlordecone increased the abundance of ovipostatin, a peptide transmitted during mating through seminal fluid, which reduces oviposition in this species. The expression of yolk ferritin, the vitellogenin equivalent in L. stagnalis, was reduced after exposure to 94.2 ng Sn/L of tributyltin. The identification of yolk ferritin and the modification of its expression in snails exposed to chemicals were refined using western blot analysis. Our results showed that the tested compounds influenced the abundance of yolk ferritin in the reproductive organs. Alteration in proteins involved in reproductive pathways (e.g., ovipostatin and yolk ferritin) could constitute relevant

  4. Effects of arsenic supplementation in feed on laying performance, arsenic retention of eggs and organs, biochemical indices and endocrine hormones.

    PubMed

    Zhang, X Y; Zhou, M Y; Li, L L; Jiang, Y J; Zou, X T

    2017-02-01

    1. The primary objective of this experiment was to estimate the toxic effects of arsenic (As) supplementation in feed on laying performance, As retention by eggs and organs, serum biochemical indices and endocrine hormones in laying hens. 2. A total of 320 "Jinghong Number 1" hens, 56-week-old, were randomly allocated into four treatments of four replicates with 20 layers in each. Graded arsenical was added to the basal diet in the experimental diets at As levels of 0, 17, 34 and 51 mg/kg, respectively. The trial lasted for 9 weeks including 1 week for acclimatisation. 3. Supplementation of dietary As for eight weeks had no effect on laying performance. As retention in albumen, yolk, egg, liver and kidney increased as As levels increased The level of serum phosphorus (P) was minimised at the 17 mg As/kg group. The activity of serum glutamic oxaloacetic transaminase (GOT) increased linearly. No differences were observed for levels of serum calcium (Ca), alkaline phosphatase (AKP) and serum glutamic pyruvic transaminase (GPT). Concentrations of estradiol (E2) and progesterone (PG) declined at 34 and 51 mg/kg As levels compared with the control group. As supplementation exerted no influence on levels of serum follicle stimulating hormone (FSH), luteinising hormone (LH), triiodothyronine (T3), thyroxine (T4) and the ratio between T3 and T4. 4. In conclusion, dietary As supplementation accelerated retention in tissues and eggs, and affected the laying rate by diminishing hormone levels of E2 and PG at 51 mg/kg.

  5. Pleiotropic Activities of HGF/c-Met System in Testicular Physiology: Paracrine and Endocrine Implications.

    PubMed

    Ricci, Giulia; Catizone, Angela

    2014-01-01

    In the last decades, a growing body of evidence has been reported concerning the expression and functional role of hepatocyte growth factor (HGF) on different aspects of testicular physiology. This review has the aim to summarize what is currently known regarding this topic. From early embryonic development to adult age, HGF and its receptor c-Met appeared to be clearly detectable in the testis. These molecules acquire different distribution patterns and roles depending on the developmental stage or the post-natal age considered. HGF acts as a paracrine modulator of testicular functions promoting the epithelium-mesenchyme cross-talk as described even in other organs. Interestingly, it has been reported that testicular HGF acts even as an autocrine factor and that its receptor might be modulated by endocrine signals that change at puberty: HGF receptor expressed by Sertoli cells, in fact, is up-regulated by FSH administration. HGF is in turn able to modify endocrine state of the organism being able to increase testosterone secretion of both fetal and adult Leydig cells. Moreover, c-Met is expressed in mitotic and meiotic male germ cells as well as in spermatozoa. The distribution pattern of c-Met on sperm cell membrane changes in the caput and cauda epididymal sperms and HGF is able to maintain epididymal sperm motility in vitro suggesting a physiological role of this growth factor in the acquisition of sperm motility. Noteworthy changes in HGF concentration in seminal plasma have been reported in different andrological diseases. All together these data indicate that HGF has a role in the control of spermatogenesis and sperm quality either directly, acting on male germ cells, or indirectly acting on tubular and interstitial somatic cells of the testis.

  6. Cellular and molecular interactions of thymus with endocrine organs and nervous system.

    PubMed

    Kinoshita, Y; Hato, F

    2001-02-01

    T-cell ontogenesis has been disclosed to depend on the interactions of thymus with endocrine glands and nervous system as follows: i/ Thymic deprivation not only impaired the immunological development but also brought about the dysgenesis of pituitary anterior lobe. Conversely, hypophysectomy resulted in thymus atrophy with the disturbed immune responses. ii/ Binding of pituitary acidophilic cell hormones to their receptors on thymus epithelial cells (TECs) augmented the release of thymic hormonal peptides (THPs) in vitro. iii/ Elevation of blood glucocorticoid level after stress caused atrophy of thymus cortex through double positive thymocyte apoptosis. Morpho-molecular alterations of cytoplasm preceded nuclear damage in the apoptotic thymocytes. iv/ Administration of thymosin to the streptozotocin-induced diabetic mice repressed mononuclear cell infiltration to the pancreatic islets. v/ Autonomic nerve fibers innervate thymic parenchyma. Binding of acetylcholines (Achs) to Ach receptors on TECs enhanced protein synthetic activity which seemed to connect with THP production. vi/ Thymectomy not only depressed the immune responses but also accelerated the reduction of leaming and memory ability with aging. The operation appears to disturb the brain adrenoceptor functions and to suppress the regulatory roles of hypothalamus to other nervous tissues. vii/ Several kinds of THPs, separated from the culture supernatant of TEC line by high performance liquid chromatography, showed a favorable effect on the thymocytes at different stage of differentiation and maturation. viii/ Thymosin, thymulin and THPs were capable of proliferating and differentiating thymocytes in vitro. However, the administration of each thymic product to the thymus-deprived animals could not restore from their "wasting disease". Since TECs are composed of a heterogeneous population, it would be one of essential ways for isolating "true thymus hormone" (TTH) to use the material which consists of

  7. Ecological risk assessment of endocrine disruptors.

    PubMed Central

    Hutchinson, T H; Brown, R; Brugger, K E; Campbell, P M; Holt, M; Länge, R; McCahon, P; Tattersfield, L J; van Egmond, R

    2000-01-01

    The European Centre for Ecotoxicology and Toxicology of Chemicals proposes a tiered approach for the ecological risk assessment of endocrine disruptors, integrating exposure and hazard (effects) characterization. Exposure assessment for endocrine disruptors should direct specific tests for wildlife species, placing hazard data into a risk assessment context. Supplementing the suite of mammalian screens now under Organization for Economic Cooperation and Development (OECD) validation, high priority should be given to developing a fish screening assay for detecting endocrine activity in oviparous species. Taking into account both exposure characterization and alerts from endocrine screening, higher tier tests are also a priority for defining adverse effects. We propose that in vivo mammalian and fish assays provide a comprehensive screening battery for diverse hormonal functions (including androgen, estrogen, and thyroid hormone), whereas Amphibia should be considered at higher tiers if there are exposure concerns. Higher tier endocrine-disruptor testing should include fish development and fish reproduction tests, whereas a full life-cycle test could be subsequently used to refine aquatic risk assessments when necessary. For avian risk assessment, the new OECD Japanese quail reproduction test guideline provides a valuable basis for developing a test to detecting endocrine-mediated reproductive effects; this species could be used, where necessary, for an avian life-cycle test. For aquatic and terrestrial invertebrates, data from existing developmental and reproductive tests remain of high value for ecological risk assessment. High priority should be given to research into comparative endocrine physiology of invertebrates to support data extrapolation to this diverse fauna. PMID:11102288

  8. Endocrine glands

    MedlinePlus Videos and Cool Tools

    ... and nervous systems work very closely together. The brain continuously sends instructions to the endocrine system, and ... master switchboard because it's the part of the brain that controls the endocrine system. The pituitary gland, ...

  9. Associations among central nervous, endocrine, and immune activities when positive emotions are elicited by looking at a favorite person.

    PubMed

    Matsunaga, Masahiro; Isowa, Tokiko; Kimura, Kenta; Miyakoshi, Makoto; Kanayama, Noriaki; Murakami, Hiroki; Sato, Sayaka; Konagaya, Toshihiro; Nogimori, Tsuyoshi; Fukuyama, Seisuke; Shinoda, Jun; Yamada, Jitsuhiro; Ohira, Hideki

    2008-03-01

    Recent studies on psychoneuroimmunology have indicated that positive psychological events are related to immune functions; however, limited information is available regarding associations among the central nervous, endocrine, and immune systems when positive emotions are elicited. In the present study, we demonstrated associations among these systems by simultaneously recording brain, endocrine, and immune activities when positive emotions were evoked in participants as they watched films featuring their favorite persons. Interestingly, the activity of peripheral circulating natural killer cells and the peripheral dopamine level were elevated while participants experienced positive emotions, and these values were positively correlated. The following brain regions were significantly activated in the positive condition relative to the control condition: medial prefrontal cortex, thalamus, hypothalamus, subcallosal gyrus, posterior cingulate cortex, superior temporal gyrus, and cerebellum. Further, covariate analyses indicated that these brain regions were temporally associated with endocrine and immune activities. These results suggest that while an individual experiences positive emotions, the central nervous, endocrine, and immune systems may be interrelated and attraction for favorite persons may be associated with the activation of the innate immune function via the dopaminergic system.

  10. In vitro - in vivo correlations for endocrine activity of a mixture of currently used pesticides

    SciTech Connect

    Taxvig, Camilla; Hadrup, Niels; Boberg, Julie; Axelstad, Marta; Bossi, Rossana; Bonefeld-Jørgensen, Eva Cecilie; Vinggaard, Anne Marie

    2013-11-01

    Two pesticide mixtures were investigated for potential endocrine activity. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included malathion and terbuthylazine in addition to the three pesticides in Mix 3. All five single pesticides and the two mixtures were investigated for their ability to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both mixtures affected steroidogenesis with both mixtures causing increase in progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was seen as well, indicating increased aromatase activity. The two mixtures were also investigated in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. Decreased estradiol and reduced placental testosterone were seen in dams exposed to Mix 5. Also a significant increase in aromatase mRNA-levels in female adrenal glands was found for Mix5. However, either of the two mixtures showed any effects on fetal hormone levels in plasma or testis, or on anogenital distance. Overall, potential aromatase induction was found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to some toxicokinetic issues, as the pesticide levels in the amniotic fluid also were found to be negatively affected by the number of compounds present in the mixtures. Nonetheless, the H295R assay gives hints on conceivable interference with steroidogenesis, thus generating hypotheses on in vivo effects. - Highlights: • The study examines the endocrine disrupting potential of mixtures of pesticides. • All single pesticides and both mixtures affected steroidogenesis in vitro. • Potential aromatase induction was found for Mix 5 both in vitro and in vivo. • The hormonal responses in vitro were only partly reflected in vivo.

  11. COMPUTATIONAL MODELING OF SERUM BINDING PROTEINSAND CLEARANCE IN EXTRAPOLATIONS ACROSS LIFE-STAGES AND SPECIES FOR ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    One measure of the potency of compounds that lead to adverse effects through ligand-dependent gene transcription is the relative affinity for the critical receptor. Endocrine active compounds that are presumed to act principally through binding to the estrogen receptor (e.g. gen...

  12. THE INFLUENCE OF SERUM BINDING PROTEINS AND CLEARANCE ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS

    EPA Science Inventory

    THE INFLUENCE OF SERUM BINDING PROTEINS AND CLEARANCE ON THE COMPARATIVE RECEPTOR BINDING POTENCY OF ENDOCRINE ACTIVE COMPOUNDS. JG Teeguarden1 and HA Barton2. 1ENVIRON International, Ruston LA; 2US EPA, ORD, NHEERL, ETD, Pharmacokinetics Branch, RTP, NC.

    One measure of th...

  13. In vitro metabolism and bioavailability tests for endocrine active substances: What is needed next for regulatory purposes?

    EPA Science Inventory

    Legistation and prospective legislative proposals internationally (may) require that chemicals be tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive in vitro are considered to be endocrine active substances (EAS) and may be puta...

  14. A review of the endocrine activity of parabens and implications for potential risks to human health.

    PubMed

    Golden, Robert; Gandy, Jay; Vollmer, Guenter

    2005-06-01

    Parabens are a group of the alkyl esters of p-hydroxybenzoic acid and typically include methylparaben, ethylparaben, propylparaben, butylparaben, isobutylparaben, isopropylparaben, and benzylparaben. Parabens (or their salts) are widely used as preservatives in cosmetics, toiletries, and pharmaceuticals due to their relatively low toxicity profile and a long history of safe use. Testing of parabens has revealed to varying degrees that individual paraben compounds have weakly estrogenic activity in some in vitro screening tests, such as ligand binding to the estrogen receptor, regulation of CAT gene expression, and proliferation of MCF-7 cells. Reported in vivo effects include increased uterine weight (i.e., butyl-, isobutyl-, and benzylparaben) and male reproductive-tract effects (i.e., butyl- and propylparaben). However, in relation to estrogen as a control during in vivo studies, the parabens with activity are many orders of magnitude less active than estrogen. While exposure to sufficient doses of exogenous estrogen can increase the risk of certain adverse effects, the presumption that similar risks might also result from exposure to endocrine-active chemicals (EACs) with far weaker activity is still speculative. In assessing the likelihood that exposure to weakly active EACs might be etiologically associated with adverse effects due to an endocrine-mediated mode of action, it is paramount to consider both the doses and the potency of such compounds in comparison with estrogen. In this review, a comparative approach involving both dose and potency is used to assess whether in utero or adult exposure to parabens might be associated with adverse effects mediated via an estrogen-modulating mode of action. In utilizing this approach, the paraben doses required to produce estrogenic effects in vivo are compared with the doses of either 17beta-estradiol or diethylstilbestrol (DES) that are well established in their ability to affect endocrine activity. Where possible

  15. [Neurotrophic control in the development and function of two endocrine organs: the ovary and the pancreas].

    PubMed

    Cabrera-Vásquez, Siraam

    2007-01-01

    Neurotrophins (NTs) are important for the survival, differentiation and function of sympathetic and sensorial neurons of central and peripheral nervous system. However, similar functions have been described of NTs in non-neural organs. Nerve Growth factor (NGF) participates in the foliculogenesis and ovulation in the ovary, as well as in the islet morphogenesis and insulin secretion of the pancreatic beta cell. The NTs act by binding to two distinct classes of transmembranal receptors: p75 and Trks. Both receptor types lead to activation of intracellular signaling cascades that end with cell survival or apoptosis. In this review different actions of the NTs in the ovarian and the pancreas are described.

  16. QSAR classification models for the prediction of endocrine disrupting activity of brominated flame retardants.

    PubMed

    Kovarich, Simona; Papa, Ester; Gramatica, Paola

    2011-06-15

    The identification of potential endocrine disrupting (ED) chemicals is an important task for the scientific community due to their diffusion in the environment; the production and use of such compounds will be strictly regulated through the authorization process of the REACH regulation. To overcome the problem of insufficient experimental data, the quantitative structure-activity relationship (QSAR) approach is applied to predict the ED activity of new chemicals. In the present study QSAR classification models are developed, according to the OECD principles, to predict the ED potency for a class of emerging ubiquitary pollutants, viz. brominated flame retardants (BFRs). Different endpoints related to ED activity (i.e. aryl hydrocarbon receptor agonism and antagonism, estrogen receptor agonism and antagonism, androgen and progesterone receptor antagonism, T4-TTR competition, E2SULT inhibition) are modeled using the k-NN classification method. The best models are selected by maximizing the sensitivity and external predictive ability. We propose simple QSARs (based on few descriptors) characterized by internal stability, good predictive power and with a verified applicability domain. These models are simple tools that are applicable to screen BFRs in relation to their ED activity, and also to design safer alternatives, in agreement with the requirements of REACH regulation at the authorization step.

  17. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 2. Model prediction

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) naproxen and carbamazepine and one endocrine disrupting compound (EDC) nonylphenol was studied in pilot-scale granular activated carbon (GAC) adsorbers using post-sedimentation (PS) water from a full-scale drinking water treatment plant. The GAC adsorbents were coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. Acidic naproxen broke through fastest while nonylphenol was removed best, which was consistent with the degree to which fouling affected compound removals. Model predictions and experimental data were generally in good agreement for all three compounds, which demonstrated the effectiveness and robustness of the pore and surface diffusion model (PSDM) used in combination with the time-variable parameter approach for predicting removals at environmentally relevant concentrations (i.e., ng/L range). Sensitivity analyses suggested that accurate determination of film diffusion coefficients was critical for predicting breakthrough for naproxen and carbamazepine, in particular when high removals are targeted. Model simulations demonstrated that GAC carbon usage rates (CURs) for naproxen were substantially influenced by the empty bed contact time (EBCT) at the investigated conditions. Model-based comparisons between GAC CURs and minimum CURs for powdered activated carbon (PAC) applications suggested that PAC would be most appropriate for achieving 90% removal of naproxen, whereas GAC would be more suitable for nonylphenol. 25 refs., 4 figs., 1 tab.

  18. The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

    SciTech Connect

    Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

    2006-01-13

    Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

  19. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound.

    PubMed

    Jorgenson, Z G; Buhl, K; Bartell, S E; Schoenfuss, H L

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption-as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration-than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered Rio

  20. Do laboratory species protect endangered species? Interspecies variation in responses to 17β-estradiol, a model endocrine active compound

    USGS Publications Warehouse

    Jorgenson, Zachary G.; Buhl, Kevin J.; Bartell, Stephen E.; Schoenfuss, Heiko L.

    2015-01-01

    Although the effects of estrogens on model laboratory species are well documented, their utility as surrogates for other species, including those listed as endangered, are less clear. Traditionally, conservation policies are evaluated based on model organism responses but are intended to protect all species in an environment. We tested the hypothesis that the endangered Rio Grande silvery minnow (Hybognathus amarus) is more vulnerable to endocrine disruption—as assessed through its larval predator-escape performance, survival, juvenile sex ratios, and whole-body vitellogenin concentration—than the commonly used toxicological model species fathead minnow (Pimephales promelas) and the bluegill sunfish (Lepomis macrochirus). Fish were exposed concurrently for 21 days to the model endocrine active compound (EAC) 17ß-estradiol (E2) at 10 ng E2/L and 30 ng E2/L in a flow-through system using reconstituted water that simulated the physicochemical conditions of the Middle Rio Grande in New Mexico, USA. No significant differences were observed between the fathead and silvery minnow in larval predator-escape response or juvenile sex ratio. Rio Grande silvery minnow survival decreased significantly at day 14 compared with the other two species; by day 21, both cyprinid species (silvery minnow and fathead minnow) exhibited a significant decrease in survival compared with bluegill sunfish, a member of the family Centrarchidae. Male Rio Grande silvery minnow showed a significant increase in whole-body vitellogenin concentration in the 10 ng/L treatment, whereas fathead minnow and bluegill sunfish showed no significant increases in vitellogenin concentrations across treatments. Our study showed response differences to estrogen exposures between the two cyprinid species and further divergence in responses between the families Cyprinidae and Centrarchidae. These results suggest that commonly used laboratory model organisms may be less sensitive to EACs than the endangered

  1. Genes expressed in the ring gland, the major endocrine organ of Drosophila melanogaster.

    PubMed Central

    Harvie, P D; Filippova, M; Bryant, P J

    1998-01-01

    We have used an enhancer-trap approach to begin characterizing the function of the Drosophila endocrine system during larval development. Five hundred and ten different lethal PZ element insertions were screened to identify those in which a reporter gene within the P element showed strong expression in part or all of the ring gland, the major site of production and release of developmental hormones, and which had a mutant phenotype consistent with an endocrine defect. Nine strong candidate genes were identified in this screen, and eight of these are expressed in the lateral cells of the ring gland that produce ecdysteroid molting hormone (EC). We have confirmed that the genes detected by these enhancer traps are expressed in patterns similar to those detected by the reporter gene. Two of the genes encode proteins, protein kinase A and calmodulin, that have previously been implicated in the signaling pathway leading to EC synthesis and release in other insects. A third gene product, the translational elongation factor EF-1alpha F1, could play a role in the translational regulation of EC production. The screen also identified the genes couch potato and tramtrack, previously known from their roles in peripheral nervous system development, as being expressed in the ring gland. One enhancer trap revealed expression of the gene encoding the C subunit of vacuolar ATPase (V-ATPase) in the medial cells of the ring gland, which produce the juvenile hormone that controls progression through developmental stages. This could reveal a function of V-ATPase in the response of this part of the ring gland to adenotropic neuropeptides. However, the gene identified by this enhancer trap is ubiquitously expressed, suggesting that the enhancer trap is detecting only a subset of its control elements. The results show that the enhancer trap approach can be a productive way of exploring tissue-specific genetic functions in Drosophila. PMID:9584098

  2. Identification of California Condor Estrogen Receptors 1 and 2 and Their Activation by Endocrine Disrupting Chemicals.

    PubMed

    Felton, Rachel G; Steiner, Cynthia C; Durrant, Barbara S; Keisler, Duane H; Milnes, Matthew R; Tubbs, Christopher W

    2015-12-01

    Recently, California condors (Gymnogyps californianus) have been reintroduced to coastal regions of California where they feed on marine mammal carcasses. There is evidence that coastal-dwelling condors experience reproductive issues, such as eggshell thinning, likely resulting from exposure to endocrine-disrupting chemicals (EDCs). To address this problem, we have identified and cloned condor estrogen receptors (ESRs) 1 and 2 and characterized their activation by EDCs present in the coastal habitats where condors reside. Dichlorodiphenyltrichloroethane (DDT) and its metabolites all activated ESR1 and ESR2, although their relative potency differed between the receptors. Bisphenol A, dieldrin, trans-nonachlor, and polychlorinated biphenyl 52 (PCB52) moderately activated both ESRs, whereas PCB138 and PCB153 stimulated little to no activation. Overall, EDC activation of condor ESR2, which is the first ESR2 cloned from a raptor species, was greater than that of ESR1. Significant activation of both condor ESRs by EDCs occurred at high concentrations (≥1μM), which are within the range of plasma levels of certain EDCs (eg, dichlorodiphenyldichloroethylene [p'p-DDE]) in coastal-dwelling condors. Finally, phylogenetic analyses of ESRs of 41 avian species identified a single amino acid position in ESR2 under positive selection. Mutation of this amino acid affected receptor activation by EDCs, suggesting the identity of this amino acid may influence EDC sensitivity of avian species. Together, these findings broaden our understanding of EDC interactions with ESRs in avian species. For condors specifically, these data could be used to evaluate EDC exposure risk at future release sites to identify those least likely to compromise the continued recovery of this species.

  3. [Telomerase reverse transcriptase (TERT) promoter mutations in the tumors of human endocrine organs: Biological and prognostic value].

    PubMed

    Selivanova, L S; Volganova, K S; Abrosimov, A Y U

    2016-01-01

    The analysis of the data available in the literature has shown that telomerase reverse transcriptase TERT promoter may serve as promising markers of malignancy, aggressive disease course, and poor prognosis for malignant tumors of endocrine organs. Considering the established association of mutations with tumors having a poor prognosis (high-grade and anaplastic carcinoma of the thyroid), it is reasonable to perform prognostic-value investigations in a group of low-grade thyroid carcinomas that may occasionally recur and may be resistant to radioactive iodine therapy, i.e. can demonstrate a poor course and prognosis. TERT promoter mutations may be a specific marker of the clinically aggressive forms of adrenocortical carcinoma, but the determination of its diagnostic value calls for additional investigations that will have the larger number cases and establish the association with clinical features and survival rates.

  4. Structural features of endocrine active chemicals--A comparison of in vivo and in vitro data.

    PubMed

    Lewin, Geertje; Escher, Sylvia E; van der Burg, Bart; Simetska, Nelly; Mangelsdorf, Inge

    2015-08-01

    Studies on reproductive toxicity need high numbers of test animals. Therefore, we investigated whether chemical structural features (SF) in combination with in vitro data on specific adverse outcome pathways (AOPs) may be used for predicting reproductive toxicity of untested chemicals. Using the OECD Toolbox and expert judgment, we identified 89 structure groups for 275 chemicals for which the results of prenatal developmental toxicity or multigeneration studies were present in the Fraunhofer database on Fertility and Developmental Toxicity in experimental animals (FeDTex) database. Likewise, we evaluated 220 chemicals which had been tested in reporter gene assays on endocrine ((anti)estrogenic and (anti)androgenic) properties in the CALUX(®) test battery. There was a large spread of effect levels for substances within the chemical structure groups for both, in vivo and in vitro results. The groups of highest concern (diphenyl derivatives, planar conjugated systems with fused rings, phenols and organophosphates) correlated quite well, however, between the in vivo and in vitro data on estrogenic activity. For the 56 chemicals represented in both databases, lowest effect doses in vivo correlated well with the estrogenic activity in vitro. These results suggest that a panel of assays covering relevant AOPs and data on metabolism and toxicokinetics may allow prediction of relative reproductive or development toxicity potency within the identified chemical structure groups.

  5. Measuring Endocrine-active Chemicals at ng/L Concentrations in Water

    EPA Science Inventory

    Analytical chemistry challenges for supporting aquatic toxicity research and risk assessment are many: need for low detection limits, complex sample matrices, small sample size, and equipment limitations to name a few. Certain types of potent endocrine disrupting chemicals (EDCs)...

  6. Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine-related genes in vitro and in vivo.

    PubMed

    Du, Guizhen; Hu, Jialei; Huang, Hongyu; Qin, Yufeng; Han, Xiumei; Wu, Di; Song, Ling; Xia, Yankai; Wang, Xinru

    2013-02-01

    Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. We investigated the endocrine-disrupting effects of PFOS using a combination of in vitro and in vivo assays. Reporter gene assays were used to detect receptor-mediated (anti-)estrogenic, (anti-)androgenic, and (anti-)thyroid hormone activities. The effect of PFOS on steroidogenesis was assessed both at hormone levels in the supernatant and at expression levels of hormone-induced genes in the H295R cell. A zebrafish-based short-term screening method was developed to detect the effect of PFOS on endocrine function in vivo. The results indicate that PFOS can act as an estrogen receptor agonist and thyroid hormone receptor antagonist. Exposure to PFOS decreased supernatant testosterone (T), increased estradiol (E2) concentrations in H295R cell medium and altered the expression of several genes involved in steroidogenesis. In addition, PFOS increased early thyroid development gene (hhex and pax8) expression in a concentration-dependent manner, decreased steroidogenic enzyme gene (CYP17, CYP19a, CYP19b) expression, and changed the expression pattern of estrogen receptor production genes (esr1, esr2b) after 500 µg/L PFOS treatment in zebrafish embryos. These results indicate that PFOS has the ability to act as an endocrine disruptor both in vitro and in vivo by disrupting the function of nuclear hormone receptors, interfering with steroidogenesis, and altering the expression of endocrine-related genes in zebrafish embryo.

  7. Endocrine disorders and medically assisted procreation.

    PubMed

    Luk, J

    2011-04-01

    A normal endocrine environment is imperative to maintain normal reproduction in women. The major endocrine organs that play a part in the reproductive system include hypothalamic pituitary axis, adrenal gland, thyroid gland, and the ovary. Each endocrine organ is in close communication and relationship with one another. Any endocrine disorders that significantly affect any of these organs would disrupt reproduction resulting in infertility. In this review, we will provide an overview of the common endocrine disorders and the available medical management including assisted reproductive technology (ART) and hormonal supplementation to overcome the endocrine disorders in order to achieve fertility for the female patients.

  8. Endocrine Diseases

    MedlinePlus

    ... History Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

  9. Uncertainties in biological responses that influence hazard and risk approaches to the regulation of endocrine active substances.

    PubMed

    Parrott, Joanne L; Bjerregaard, Poul; Brugger, Kristin E; Gray, L Earl; Iguchi, Taisen; Kadlec, Sarah M; Weltje, Lennart; Wheeler, James R

    2017-03-01

    Endocrine-disrupting substances (EDS) may have certain biological effects including delayed effects, multigenerational effects, and may display nonmonotonic dose-response (NMDR) relationships that require careful consideration when determining environmental hazards. Endocrine disrupting substances can have specific and profound effects when exposure occurs during sensitive windows of the life cycle (development, reproduction). This creates the potential for delayed effects that manifest when exposure has ceased, possibly in a different life stage. This potential underscores the need for testing in appropriate (sensitive) life stages and full life cycle designs. Such tests are available in the Organisation for Economic Co-operation and Development (OECD) tool box and should be used to derive endpoints that can be considered protective of all life stages. Similarly, the potential for effects to be manifest in subsequent generations (multigenerational effects) has also been raised as a potential issue in the derivation of appropriate endpoints for EDS. However, multigenerational studies showing increasing sensitivity of successive generations are uncommon. Indeed this is reflected in the design of new higher tier tests to assess endocrine active substances (EAS) that move to extended one-generation designs and away from multi-generational studies. The occurrence of NMDRs is also considered a limiting factor for reliable risk assessment of EDS. Evidence to date indicates NMDRs are more prevalent in in vitro and mechanistic data, not often translating to adverse apical endpoints that would be used in risk assessment. A series of steps to evaluate NMDRs in the context of endocrine hazard and risk assessment procedures is presented. If careful consideration of delayed, multigenerational effects and NMDRs is made, it is feasible to assess environmental endocrine hazards and derive robust apical endpoints for risk assessment procedures ensuring a high level of environmental

  10. Endocrine active contaminants in aquatic systems and intersex in common sport fishes

    USGS Publications Warehouse

    Lee Pow, Crystal S. D.; Law, J. Mac; Kwak, Thomas J.; Cope, W. Gregory; Rice, James A.; Kullman, Seth W.; Aday, D. Derek

    2017-01-01

    Male fish are susceptible to developing intersex, a condition characterized by the presence of testicular oocytes. In the present study, the relationship between intersex and exposure to estrogenic endocrine active contaminants (EACs) was assessed for 2 genera of sport fish, Micropterus and Lepomis, at 20 riverine sites. Seasonal trends and relationships between EACs and intersex (prevalence and severity) were examined at varying putative sources of EACs throughout North Carolina, identified as point sources, nonpoint sources, and reference sites. Intersex was identified in both genera, which was documented for the first time in wild-caught Lepomis. Intersex was more prevalent (59.8%) and more severe (1.6 mean rank) in Micropterus, which was highly correlation to EACs in sediment. In contrast, intersex was less common (9.9%) and less severe (0.2 mean rank) in Lepomis and was highly correlated to EACs in the water column. The authors found that concentrations of polycyclic aromatic hydrocarbons, polychlorinated biphenyls, industrial EACs, and estrogens were highest at point source sites; however, no source type variation was identified in the prevalence or severity of intersex, nor were there seasonal trends in intersex or EAC concentrations. The authors’ results associate genus-specific prevalence of intersex with specific EAC classes in common sport fishes having biological, ecological, and conservation implications.

  11. Endocrine responses to space flights.

    PubMed

    Macho, L; Kvetnansky, R; Fickova, M; Kolena, J; Knopp, J; Tigranian, R A; Popova, I A; Grogoriev, A I

    2001-07-01

    Simultaneously with human space flights several series of observations were performed by using experimental animals--mainly rats--exposed to space flights on board of special satellites BION-COSMOS or in Shuttle Transportation Systems (STS). The aims of these experiments were to study in more details: the mechanisms of the changes in bones and skeletal muscle, the alterations of the function of immune system, the radiation effects on organism, the mechanism of the changes of endocrine functions, the evaluation of the role of hormones in alteration of metabolic processes in organism. The advantages of these animal experiments were the possibilities to analyze not only the plasma samples, but it was possible to obtain samples of organs or tissues: for morphological and biochemical analysis for studies of the changes in enzyme activities and in gene expressions, for measurement of metabolic processes and for investigation of the hormone production in endocrine glands and estimation of the response of tissues to hormones. It was also possible to compare the endocrine response to spaceflight and to other stress stimuli. These animal studies are interesting for verification of some hypothesis in the mechanism of adaptation of human organism to the changes of gravity. The disadvantage was, however, that the animals in almost all experiments could be examined only after space flight. The actual inflight changes were investigated only in two SLS flights. In this short review it is not possible to evaluate all hormonal data available on the response of endocrine system to the conditions of space flights. Therefore we will concentrate on the response of pituitary adrenocortical system, pituitary thyroid and pituitary gonadal functions.

  12. Neonatal Exposure to Endocrine Disrupting Chemicals Impairs Learning Behaviour by Disrupting Hippocampal Organization in Male Swiss Albino Mice.

    PubMed

    Bhaskar, Rakesh; Mishra, Ashish K; Mohanty, Banalata

    2017-02-16

    Hippocampus is highly susceptible to endocrine disrupting chemicals exposure particularly during the critical phase of brain development. In this study, mice offspring were exposed to endocrine disruptors mancozeb (MCZ) and imidacloprid (IMI) individually (40 mg MCZ and 0.65 mg IMI/kg/day) as well as to their equimixture (40 mg MCZ + 0.65 mg IMI/kg/day) through the diet of lactating mothers from post-natal day (PND) 1 to PND 28. Half of the randomly selected male offspring were killed at PND 29, and the rest half were left unexposed and killed at PND 63. Brain weight, histology, plasma hormone profile and working memory performance were the various end-points studied. Brain weight was significantly decreased in the mixture-exposed group at PND 29, which persisted to PND 63. Total thickness of pyramidal cell layers decreased significantly along with misalignment, shrinkage and degeneration of pyramidal neurons in CA1 and CA3 regions of the IMI and mixture-exposed groups. The length and branch points of dendrites of pyramidal neurons were decreased significantly in mixture-exposed group at both PND 29 and PND 63. Dendritic spine density was also reduced in mixture-exposed group offspring. Testosterone level was significantly decreased only at PND 29, but corticosterone level was increased at both PND 29 and PND 63 in mixture-exposed offspring. T-maze task performance revealed significantly increased time duration and reduced path efficiency in mixture-exposed group offspring. The results thus indicate that pesticide mixture exposure could lead to changes in learning behaviour even at doses that individually did not induce any adverse effect on hippocampal organization.

  13. Endocrine Disruptors

    MedlinePlus

    ... and wildlife. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and plasticizers such as bisphenol A. Endocrine disruptors ...

  14. Salmonid sexual development is not consistently altered by embryonic exposure to endocrine-active chemicals.

    PubMed Central

    Carlson, D B; Curtis, L R; Williams, D E

    2000-01-01

    Fish sexual development is sensitive to exogenous hormone manipulation, and salmonids have been used extensively as environmental sentinels and models for biomedical research. We simulated maternal transfer of contaminants by microinjecting rainbow trout (Oncorhynchus mykiss) and chinook salmon (Oncorhynchus tshawytscha) embryos. Fish were reared for 6 months and sexed, and gonads were removed for histology and measurement of in vitro steroid production. Analysis of fat samples showed that dichlorodiphenylethylene (DDE) levels, o, p'M-DDE and p,o, p'-DDE isomers, were elevated 6 months after treatment. A preliminary study showed an increased ratio of males to females after treatment with 80 mg/kg and 160 mg/kg of the xenoestrogen o,o, p'-DDE. One fish treated with 160 mg/kg o,o, p'-DDE had gonads with cells typical of both males and females. A follow-up study, using more fish and excluding the highly toxic 160 mg/kg o,o, p'-DDE dose, showed no effect on sex ratio or gonadal histology. Embryonic exposure of monosex male trout, monosex female trout, and mixed sex salmon to o, o, p'-DDE, p,o, p'-DDE, mixtures of DDE isomers, and octylphenol failed to alter sexual development. We observed no treatment-dependent changes in in vitro gonadal steroid production in any experiments. Trout exposed in ovo and reared to maturity spawned successfully. These results suggest that mortality attributable to the xenoestrogens o,o, p'-DDE, chlordecone, and octylphenol, and the antiandrogen p,o, p'-DDE, is likely to occur before the appearance of subtle changes in sexual development. Because trout appeared to be sensitive to endocrine disruption, we cannot dismiss the threat of heavily contaminated sites or complex mixtures to normal sexual development of salmonids or other aquatic organisms. Images Figure 1 Figure 2 Figure 3 PMID:10706532

  15. In vitro-in vivo correlations for endocrine activity of a mixture of currently used pesticides.

    PubMed

    Taxvig, Camilla; Hadrup, Niels; Boberg, Julie; Axelstad, Marta; Bossi, Rossana; Bonefeld-Jørgensen, Eva Cecilie; Vinggaard, Anne Marie

    2013-11-01

    Two pesticide mixtures were investigated for potential endocrine activity. Mix 3 consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included malathion and terbuthylazine in addition to the three pesticides in Mix 3. All five single pesticides and the two mixtures were investigated for their ability to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both mixtures affected steroidogenesis with both mixtures causing increase in progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was seen as well, indicating increased aromatase activity. The two mixtures were also investigated in pregnant rats dosed from gestational day 7 to 21, followed by examination of dams and fetuses. Decreased estradiol and reduced placental testosterone were seen in dams exposed to Mix 5. Also a significant increase in aromatase mRNA-levels in female adrenal glands was found for Mix5. However, either of the two mixtures showed any effects on fetal hormone levels in plasma or testis, or on anogenital distance. Overall, potential aromatase induction was found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were only partly reflected in vivo, probably due to some toxicokinetic issues, as the pesticide levels in the amniotic fluid also were found to be negatively affected by the number of compounds present in the mixtures. Nonetheless, the H295R assay gives hints on conceivable interference with steroidogenesis, thus generating hypotheses on in vivo effects.

  16. Adsorption characteristics of selected pharmaceuticals and an endocrine disrupting compound-Naproxen, carbamazepine and nonylphenol-on activated carbon.

    PubMed

    Yu, Zirui; Peldszus, Sigrid; Huck, Peter M

    2008-06-01

    The adsorption of two representative pharmaceutically active compounds (PhACs) (naproxen and carbamazepine) and one endocrine disrupting compound (nonylphenol) were evaluated on two types of activated carbon. When determining their isotherms at environmentally relevant concentration levels, it was found that at this low concentration range (10-800 ng/L), removals of the target compounds were contrary to expectations based on their hydrophobicity. Nonylphenol (log K(ow) 5.8) was most poorly adsorbed, whereas carbamazepine (log K(ow) 2.45) was most adsorbable. Nonylphenol Freundlich isotherms at this very low concentration range had a much higher 1/n compared to isotherms at much higher concentrations. This indicates that extrapolation from an isotherm obtained at a high concentration range to predict the adsorption of nonylphenol at a concentration well below the range of the original isotherm, leads to a substantial overestimation of its removals. Comparison of isotherms for the target compounds to those for other conventional micropollutants suggested that naproxen and carbamazepine could be effectively removed by applying the same dosage utilized to remove odorous compounds (geosmin and MIB) at very low concentrations. The impact of competitive adsorption by background natural organic matter (NOM) on the adsorption of the target compounds was quantified by using the ideal adsorbed solution theory (IAST) in combination with the equivalent background compound (EBC) approach. The fulfilment of the requirements for applying the simplified IAST-EBC model, which leads to the conclusion that the percentage removal of the target compounds at a given carbon dosage is independent of the initial contaminant concentration, was confirmed for the situation examined in the paper. On this basis it is suggested that the estimated minimum carbon usage rates (CURs) to achieve 90% removal of these emerging contaminants would be valid at concentrations of less than 500 ng/L in

  17. Endocrine System (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Endocrine System KidsHealth > For Teens > Endocrine System A A A ... is called the endocrine system . What Is the Endocrine System? Although we rarely think about the endocrine system, ...

  18. Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases.

    PubMed

    Fortuño, A; Rodríguez, A; Gómez-Ambrosi, J; Frühbeck, G; Díez, J

    2003-03-01

    Obesity, the most common nutritional disorder in industrial countries, is associated with increased cardiovascular mortality and morbidity. Nevertheless, the molecular basis linking obesity with cardiovascular disturbances have not yet been fully clarified. Recent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ, but also a secretory organ, producing a variety of bioactive substances, including leptin and adiponectin, that may influence the function as well as the structural integrity of the cardiovascular system. Leptin, besides being a satiety signal for the central nervous system and to be related to insulin and glucose metabolism, may also play an important role in regulating vascular tone because of the widespread distribution of functional receptors in the vascular cells. On the other hand, the more recently discovered protein, adiponectin, seems to play a protective role in experimental models of vascular injury, in probable relation to its ability to suppress the attachment of monocytes to endothelial cells, which is an early event in the atherosclerotic process. There is already considerable evidence linking altered production of some adipocyte hormones with the cardiovascular complications of obesity. Therefore, the knowledge of alterations in the endocrine function of adipose tissue may help to further understand the high cardiovascular risk associated with obesity.

  19. Purinergic Signaling Pathways in Endocrine System

    PubMed Central

    Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

    2015-01-01

    Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

  20. Purinergic signaling pathways in endocrine system.

    PubMed

    Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

    2015-09-01

    Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling.

  1. Effects of Neonatal Treatment With 6-Hydroxydopamine and Endocrine Disruptors on Motor Activity and Gene Expression in Rats

    PubMed Central

    Masuo, Yoshinori; Ishido, Masami; Morita, Masatoshi; Oka, Syuichi

    2004-01-01

    To investigate the mechanisms underlying motor hyperactivity, we performed intracisternal injection of 6-hydroxydopamine or endocrine disruptors in rats on postnatal day 5. 6-Hydroxydopamine (100 μg, 488 nmol) caused a significant increase in spontaneous motor activities at 4 weeks of age. Gene-expression profiling using a cDNA membrane array revealed alterations in several classes of gene at 8 weeks of age. In the midbrain, gene expression was enhanced in dopamine transporter 1; a platelet-derived growth factor receptor; dopamine receptor D4; galanin receptor 2; arginine vasopressin receptor 2; neuropeptide Y; tachykinin 2; and fibroblast growth factor 10. Expression was also enhanced in the glutamate/aspartate transporter gene in the striatum. Rats received an endocrine disruptor (87 nmol), such as bisphenol A, nonylphenol, p-octylphenol, or diethylhexylphthalate, which also caused motor hyperactivity at 4 weeks. The effects of bisphenol A on motor activity were dose-dependent from 0.87 to 87 nmol. The phenols caused a deficit in dopamine neurons, similarly to the deficit caused by 6-hydroxydopamine. Gene-expression profiles after treatment with endocrine disruptors showed variation and differed from those of 6- hydroxydopamine. The results suggest that neonatal treatment with environmental chemicals can generate an animal model of attention-deficit hyperactivity disorder, in which clinical symptoms are pervasive. PMID:15303306

  2. PROTEOMICS IN ECOTOXICOLOGY: PROTEIN EXPRESSION PROFILING TO SCREEN CHEMICALS FOR ENDOCRINE ACTIVITY

    EPA Science Inventory

    Abstract for poster.

    Current endocrine testing methods are animal intensive and lack the throughput necessary to screen large numbers of environmental chemicals for adverse effects. In this study, Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry...

  3. STATUS OF ENDOCRINE DISRUPTOR SCREENING AND TESTING ACTIVITIES IN THE US: IMPLEMENTATION OF THE EDSTAC RECOMMENDATIONS

    EPA Science Inventory

    The last two decades have witnessed a growing concern for chemicals that have the potential to adversely affect the normal functioning of the endocrine system. In 1996, the US Congress passed the Food Quality Protection Act (FQPA) that mandated the US Environmental Protection Ag...

  4. The removal of endocrine disrupting compounds, pharmaceutically activated compounds and cyanobacterial toxins during drinking water preparation using activated carbon--a review.

    PubMed

    Delgado, Luis F; Charles, Philippe; Glucina, Karl; Morlay, Catherine

    2012-10-01

    This paper provides a review of recent scientific research on the removal by activated carbon (AC) in drinking water (DW) treatment of 1) two classes of currently unregulated trace level contaminants with potential chronic toxicity-pharmaceutically activate compounds (PhACs) and endocrine disrupting compounds (EDCs); 2) cyanobacterial toxins (CyBTs), which are a group of highly toxic and regulated compounds (as microcystin-LR); and 3) the above mentioned compounds by the hybrid system powdered AC/membrane filtration. The influence of solute and AC properties, as well as the competitive effect from background natural organic matter on the adsorption of such trace contaminants, are also considered. In addition, a number of adsorption isotherm parameters reported for PhACs, EDCs and CyBTs are presented herein. AC adsorption has proven to be an effective removal process for such trace contaminants without generating transformation products. This process appears to be a crucial step in order to minimize PhACs, EDCs and CyBTs in finished DW, hence calling for further studies on AC adsorption removal of these compounds. Finally, a priority chart of PhACs and EDCs warranting further study for the removal by AC adsorption is proposed based on the compounds' structural characteristics and their low removal by AC compared to the other compounds.

  5. Estrogenic and androgenic activity of PCBs, their chlorinated metabolites and other endocrine disruptors estimated with two in vitro yeast assays.

    PubMed

    Svobodová, K; Placková, M; Novotná, V; Cajthaml, T

    2009-11-01

    Investigations of environmental pollution by endocrine-disrupting chemicals are now in progress. Up to now, several in vitro bioassays have been developed for evaluation of the endocrine disruptive activity; however, there is still a lack of comparative studies of their sensitivity. In this work comparison of the estrogen screening assay based on beta-galactosidase expression and a bioluminescent estrogen screen revealed differences in the sensitivity and specificity of the two tests. With the beta-galactosidase screen a slight estrogen-like activity of Delor 103, a commercial mixture of PCB congeners, and a fungicide triclosan was measured whereas no activity was detected using the bioluminescent assay. A bioluminescent androgen test negated previously suggested androgenic potential of triclosan. Further, this work demonstrates the androgenic activity of Delor 103, with an EC(50) value of 2.29 x 10(-2)mg/L. On the other hand, chlorobenzoic acids (CBAs), representing potential PCB degradation metabolites, exhibited no androgenic activity but were slightly estrogenic. Their estrogenicity varied with their chemical structure, with 2,3-CBA, 2,3,6-CBA, 2,4,6-CBA and monochlorinated compounds exhibiting the highest activity. Thus the results indicated possible transitions of the hormonal activity of PCBs during bacterial degradation.

  6. Endocrine Diseases

    MedlinePlus

    ... low, you may have a hormone disorder. Hormone diseases also occur if your body does not respond ... In the United States, the most common endocrine disease is diabetes. There are many others. They are ...

  7. A method for the determination of genetic sex in the fathead minnow, Pimephales promelas, to support testing of endocrine-active chemicals.

    PubMed

    Olmstead, Allen W; Villeneuve, Daniel L; Ankley, Gerald T; Cavallin, Jenna E; Lindberg-Livingston, Annelie; Wehmas, Leah C; Degitz, Sigmund J

    2011-04-01

    Certain endocrine-active toxicants have been reported to completely sex reverse both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species, resulting in a phenotype indistinguishable from unaffected individuals. Detection of low-level sex reversal often requires large numbers of organisms to achieve the necessary statistical power, especially in those species with predominantly genetic sex determination and cryptic/homomorphic sex chromosomes. Here we describe a method for determining the genetic sex in the commonly used ecotoxicological model, the fathead minnow (Pimephales promelas). Analysis of amplified fragment length polymorphisms (AFLP) in a spawn of minnows resulted in detection of 10 sex-linked AFLPs, which were isolated and sequenced. No recombination events were observed with any sex-linked AFLP in the animals examined (n=112). A polymerase chain reaction (PCR) method was then developed that determined the presence of one of these sex-linked polymorphisms for utilization in routine toxicological testing. Analyses of additional spawns from our in-house culture indicate that fathead minnows utilize a XY sex determination strategy and confirm that these markers can be used to genotype sex; however, this method is currently limited to use in laboratory studies in which breeders possess a defined genetic makeup. The genotyping method described herein can be incorporated into endocrine toxicity assays that examine the effects of chemicals on gonad differentiation.

  8. Method of identification and isolation of organs of endocrine secretion in mice

    SciTech Connect

    Kashirina, N.K.

    1987-10-01

    The authors describe a procedure based on electron autoradiography for isolating and determining the morphology of the adrenal, pituitary, and thyroid glands in albino mice, and use the procedure to give a description, in this paper, of the configuration, location, and physiological interaction of these glands relative to the other organs in these laboratory animals. The procedure overcomes the difficulties encountered in such determinations owing to factors such as smallness.

  9. Circumventricular organs: definition and role in the regulation of endocrine and autonomic function.

    PubMed

    Ganong, W F

    2000-01-01

    1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood-brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function. 2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema. 3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain. 4. Feedback control of corticotropin-releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin-releasing hormone secretion. Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.

  10. Effectivity of advanced wastewater treatment: reduction of in vitro endocrine activity and mutagenicity but not of in vivo reproductive toxicity.

    PubMed

    Giebner, Sabrina; Ostermann, Sina; Straskraba, Susanne; Oetken, Matthias; Oehlmann, Jörg; Wagner, Martin

    2016-09-06

    Conventional wastewater treatment plants (WWTPs) have a limited capacity to eliminate micropollutants. One option to improve this is tertiary treatment. Accordingly, the WWTP Eriskirch at the German river Schussen has been upgraded with different combinations of ozonation, sand, and granulated activated carbon filtration. In this study, the removal of endocrine and genotoxic effects in vitro and reproductive toxicity in vivo was assessed in a 2-year long-term monitoring. All experiments were performed with aqueous and solid-phase extracted water samples. Untreated wastewater affected several endocrine endpoints in reporter gene assays. The conventional treatment removed the estrogenic and androgenic activity by 77 and 95 %, respectively. Nevertheless, high anti-estrogenic activities and reproductive toxicity persisted. All advanced treatment technologies further reduced the estrogenic activities by additional 69-86 % compared to conventional treatment, resulting in a complete removal of up to 97 %. In the Ames assay, we detected an ozone-induced mutagenicity, which was removed by subsequent filtration. This demonstrates that a post treatment to ozonation is needed to minimize toxic oxidative transformation products. In the reproduction test with the mudsnail Potamopyrgus antipodarum, a decreased number of embryos was observed for all wastewater samples. This indicates that reproductive toxicants were eliminated by neither the conventional nor the advanced treatment. Furthermore, aqueous samples showed higher anti-estrogenic and reproductive toxicity than extracted samples, indicating that the causative compounds are not extractable or were lost during extraction. This underlines the importance of the adequate handling of wastewater samples. Taken together, this study demonstrates that combinations of multiple advanced technologies reduce endocrine effects in vitro. However, they did not remove in vitro anti-estrogenicity and in vivo reproductive toxicity. This

  11. INCREASED ENDOCRINE ACTIVITY OF XENOBIOTIC CHEMICALS AS MEDIATED BY METABOLIC ACTIVATION

    EPA Science Inventory

    This research is part of an effort to develop in vitro assays and QSARs applicable to untested chemicals on EPA inventories through study of estrogen receptor (ER) binding and estrogen mediated gene expression in fish. The current effort investigates metabolic activation of chemi...

  12. Phytoestrogen signaling and symbiotic gene activation are disrupted by endocrine-disrupting chemicals.

    PubMed Central

    Fox, Jennifer E; Starcevic, Marta; Jones, Phillip E; Burow, Matthew E; McLachlan, John A

    2004-01-01

    Some organochlorine pesticides and other synthetic chemicals mimic hormones in representatives of each vertebrate class, including mammals, reptiles, amphibians, birds, and fish. These compounds are called endocrine-disrupting chemicals (EDCs). Similarly, hormonelike signaling has also been observed when vertebrates are exposed to plant chemicals called phytoestrogens. Previous research has shown the mechanism of action for EDCs and phytoestrogens is as unintended ligands for the estrogen receptor (ER). Although pesticides have been synthesized to deter insects and weeds, plants produce phytoestrogens to deter herbivores, as attractant cues for insects, and as recruitment signals for symbiotic soil bacteria. Our data present the first evidence that some of the same organochlorine pesticides and EDCs known to disrupt endocrine signaling through ERs in exposed wildlife and humans also disrupt the phytoestrogen signaling that leguminous plants use to recruit Sinorhizobium meliloti soil bacteria for symbiotic nitrogen fixation. Here we report that a variety of EDCs and pesticides commonly found in agricultural soils interfere with the symbiotic signaling necessary for nitrogen fixation, suggesting that the principles underlying endocrine disruption may have more widespread biological and ecological importance than had once been thought. PMID:15121509

  13. Screening of endocrine disruption activity in sediments from the Uruguay River.

    PubMed

    Rivas-Rivera, Noelia; Eguren, Gabriela; Carrasco-Letelier, Leonidas; Munkittrick, Kelly R

    2014-08-01

    Sediment constitutes an important sink of endocrine disruptor compounds; however, the potential of sediments to act as a source of endocrine disruptors should be more extensively investigated. The main objective of this study was to determine whether exposure of immature common carp to Uruguay River sediments undergo physiological and endocrine alterations. The lower Uruguay River watershed supports intensive agricultural and forest production, receives municipal sewage discharge and industrial effluent, and a new large pulp mill was constructed in 2006. A 30-day semi-static assay was performed using sediments from four sites along the Uruguay River and compared with an unexposed group in dechlorinated water as a negative control. We focused on two upstream and two downstream sites of a new elemental chlorine free pulp mill. The results showed that plasma vitellogenin levels increased in fish along the river and significant differences were found between the exposed and unexposed groups. Condition factor and gonadosomatic index were not different; however, a significant difference in hepatosomatic index was observed in fish exposed to sediment from an industrial site. A significant reduction in primary spermatocyte accumulation was observed in the exposed group compared with that in the control group, and some individuals exposed to sediments from industrial sites presented with testis-ova. Our results suggest that Uruguay River sediments act as an important source of estrogenic compounds that could be responsible for the alterations observed. Future studies are needed to identify the causal agents and determine exposure routes.

  14. Phytoestrogen signaling and symbiotic gene activation are disrupted by endocrine-disrupting chemicals.

    PubMed

    Fox, Jennifer E; Starcevic, Marta; Jones, Phillip E; Burow, Matthew E; McLachlan, John A

    2004-05-01

    Some organochlorine pesticides and other synthetic chemicals mimic hormones in representatives of each vertebrate class, including mammals, reptiles, amphibians, birds, and fish. These compounds are called endocrine-disrupting chemicals (EDCs). Similarly, hormonelike signaling has also been observed when vertebrates are exposed to plant chemicals called phytoestrogens. Previous research has shown the mechanism of action for EDCs and phytoestrogens is as unintended ligands for the estrogen receptor (ER). Although pesticides have been synthesized to deter insects and weeds, plants produce phytoestrogens to deter herbivores, as attractant cues for insects, and as recruitment signals for symbiotic soil bacteria. Our data present the first evidence that some of the same organochlorine pesticides and EDCs known to disrupt endocrine signaling through ERs in exposed wildlife and humans also disrupt the phytoestrogen signaling that leguminous plants use to recruit Sinorhizobium meliloti soil bacteria for symbiotic nitrogen fixation. Here we report that a variety of EDCs and pesticides commonly found in agricultural soils interfere with the symbiotic signaling necessary for nitrogen fixation, suggesting that the principles underlying endocrine disruption may have more widespread biological and ecological importance than had once been thought.

  15. Activation of PI3K/Akt/mTOR signaling in the tumor stroma drives endocrine therapy-dependent breast tumor regression

    PubMed Central

    Polo, María Laura; Riggio, Marina; May, María; Rodríguez, María Jimena; Perrone, María Cecilia; Stallings-Mann, Melody; Kaen, Diego; Frost, Marlene; Goetz, Matthew; Boughey, Judy; Lanari, Claudia; Radisky, Derek; Novaro, Virginia

    2015-01-01

    Improved efficacy of neoadjuvant endocrine-targeting therapies in luminal breast carcinomas could be achieved with optimal use of pathway targeting agents. In a mouse model of ductal breast carcinoma we identify a tumor regressive stromal reaction that is induced by neoadjuvant endocrine therapy. This reparative reaction is characterized by tumor neovascularization accompanied by infiltration of immune cells and carcinoma-associated fibroblasts that stain for phosphorylated ribosomal protein S6 (pS6), downstream the PI3K/Akt/mTOR pathway. While tumor variants with higher PI3K/Akt/mTOR activity respond well to a combination of endocrine and PI3K/Akt/mTOR inhibitors, tumor variants with lower PI3K/Akt/mTOR activity respond more poorly to the combination therapy than to the endocrine therapy alone, associated with inhibition of stromal pS6 and the reparative reaction. In human breast cancer xenografts we confirm that such differential sensitivity to therapy is primarily determined by the level of PI3K/Akt/mTOR in tumor cells. We further show that the clinical response of breast cancer patients undergoing neoadjuvant endocrine therapy is associated with the reparative stromal reaction. We conclude that tumor level and localization of pS6 are associated with therapeutic response in breast cancer and represent biomarkers to distinguish which tumors will benefit from the incorporation of PI3K/Akt/mTOR inhibitors with neoadjuvant endocrine therapy. PMID:26098779

  16. Performance of calcium peroxide for removal of endocrine-disrupting compounds in waste activated sludge and promotion of sludge solubilization.

    PubMed

    Zhang, Ai; Wang, Jie; Li, Yongmei

    2015-03-15

    Removal of six phenolic endocrine disrupting compounds (EDCs) (estrone, 17β-estradiol, 17α-ethinylestradiol, estriol, bisphenol A, and 4-nonylphenols) from waste activated sludge (WAS) was investigated using calcium peroxide (CaO2) oxidation. Effects of initial pH and CaO2 dosage were investigated. The impacts of CaO2 treatment on sludge solubilization and anaerobic digestion were also evaluated. Specifically, the role of reactive oxygen species (ROS) in EDC degradation during CaO2 oxidation was tested. Effects of 6 metal ions contained in the sludge matrix on EDC degradation were also evaluated. The results showed that CaO2 treatment can be a promising technology for EDC removal and facilitating sludge reuse. The EDC removal efficiencies increased with the increase in CaO2 dosage. At CaO2 doses of more than 0.34 g per gram of total solid (g g(-1) TS), more than 50% of EDCs were removed in a wide pH range of 2-12. Higher removal efficiencies were achieved at initial pH values of 12 and 2. The products of EDCs during CaO2 oxidation had less estrogenic activity than the originals. Under the conditions of neutral pH and CaO2 dosage = 0.34 g g(-1) TS, the sludge solubilization can be improved by increasing the soluble total organic carbon (STOC) and volatile suspended solids (VSS) reduction by 25% and 27% in 7 d, respectively; the volatile fatty acid (VFA) production was enhanced by 96% in the 15 d following anaerobic digestion. The ROS released by CaO2 are the main factors contributing to EDC removal, among which, hydroxyl radicals (OH) play the most important role. Metal ions contained in the sludge matrix also affected EDC removal. For most cases, Fe, Cu, and Zn had positive effects; Mn and Ag had negative effects; and Mg had an insignificant effect on EDC removal.

  17. Endocrine effects of real-life mixtures of persistent organic pollutants (POP) in experimental models and wild fish.

    PubMed

    Berg, Vidar; Kraugerud, Marianne; Nourizadeh-Lillabadi, Rasoul; Olsvik, Pål A; Skåre, Janneche U; Alestrøm, Peter; Ropstad, Erik; Zimmer, Karin Elisabeth; Lyche, Jan L

    2016-01-01

    A series of studies have assessed the occurrence, levels, and potential adverse effects of persistent organic pollutants (POP) in fish from Lake Mjøsa. In this lake, high levels of various POP were detected in biota. Fish from the nearby Lake Losna contain background levels of POP and served as reference (controls) in these studies. Significantly higher prevalence of mycobacteriosis and pathological changes were documented in burbot (Lota lota) from Mjøsa compared to burbot from Losna. Further, transcriptional profiling identified changes in gene expression in burbot from Mjøsa compared to burbot from Losna associated with drug metabolism enzymes and oxidative stress. POP extracted from burbot liver oil from the two lakes was used to expose zebrafish (Danio rerio) during two consecutive generations. During both generations, POP mixtures from both lakes increased the rate of mortality, induced earlier onset of puberty, and skewed sex ratio toward males. However, opposite effects on weight gain were found in exposure groups compared to controls during the two generations. Exposure to POP from both lakes was associated with suppression of ovarian follicle development. Analyses of genome-wide transcription profiling identified functional networks of genes associated with weight homeostasis, steroid hormone functions, and insulin signaling. In human cell studies using adrenocortical H295R and primary porcine theca and granulosa cells, exposure to lake extracts from both populations modulated steroid hormone production with significant difference from controls. The results suggest that POP from both lakes may possess the potential to induce endocrine disruption and may adversely affect health in wild fish.

  18. Endocrine System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Endocrine System KidsHealth > For Parents > Endocrine System A A A ... to help the body function properly. About the Endocrine System The foundations of the endocrine system are the ...

  19. Alkylphenols, Other Endocrine-Active Chemicals, and Fish Responses in Three Streams in Minnesota - Study Design and Data, February-September 2007

    USGS Publications Warehouse

    Lee, Kathy E.; Schoenfuss, Heiko L.; Jahns, Nathan D.; Brown, Greg K.; Barber, Larry B.

    2008-01-01

    This report presents the study design and environmental data for an integrated chemical and biological study of three streams (South Fork Crow River, Redwood River, and Grindstone River) that receive wastewater in Minnesota. The objective of the study was to identify distribution patterns of endocrine-active chemicals and other organic chemicals indicative of wastewater, and to identify fish responses in the same streams. Endocrine-active chemicals are a class of chemicals that interfere with the natural regulation of endocrine systems, and an understanding of their distribution in aquatic systems is important so that aquatic organism exposure can be evaluated. This study was a cooperative effort of the U.S. Geological Survey (USGS), the Minnesota Pollution Control Agency, and St. Cloud State University (St. Cloud, Minn.). The USGS collected and analyzed water and quality-assurance samples and measured streamflow during six sampling events in each of three streams. Water samples were collected upstream from and at two successive points downstream from wastewater-treatment plant (WWTP) effluent discharge and from treated effluent from February through September 2007. Bed-sediment samples were collected during one sampling period at each of the stream locations. Water and bed-sediment samples were analyzed for endocrine-active chemicals including alkylphenols, alkylphenol polyethoxylates, and nonylphenol ethoxycarboxlylates (NPECs). Water samples also were analyzed for major ions, nutrients, and organic carbon. In addition, as part of an intensive time-series investigation, the USGS staff collected daily water samples for 8 weeks from the Redwood River near Marshall, Minn., for analyses of total alkylphenols and atrazine. St. Cloud State University staff collected and analyzed fish to determine male fish responses at all water sampling sites and at an additional site near the discharge of wastewater-treatment plant effluent to these streams. Male fish responses

  20. Occurrence of Endocrine Active Compounds and Biological Responses in the Mississippi River - Study Design and Data, June through August 2006

    USGS Publications Warehouse

    Lee, Kathy E.; Yaeger, Christine S.; Jahns, Nathan D.; Schoenfuss, Heiko L.

    2008-01-01

    Concern that selected chemicals in the environment may act as endocrine active compounds in aquatic ecosystems is widespread; however, few studies have examined the occurrence of endocrine active compounds and identified biological markers of endocrine disruption such as intersex occurrence in fish longitudinally in a river system. This report presents environmental data collected and analyzed by the U.S. Geological Survey, Minnesota Pollution Control Agency and St. Cloud State University as part of an integrated biological and chemical study of endocrine disruption in fish in the Mississippi River. Data were collected from water, bed sediment, and fish at 43 sites along the river from the headwaters at Lake Itasca to 14 miles downstream from Brownsville, Minnesota during June through August 2006. Twenty-four individual compounds were detected in water samples, with cholesterol, atrazine, N,N-diethyl-meta-toluamide, metolachlor, and hexahydrohexamethylcyclopentabenzopyran detected most frequently (in at least 10 percent of the samples). The number of compounds detected in water per site ranged from 0 to 8. Forty individual compounds were detected in bed-sediment samples. The most commonly detected compounds (in at least 50 percent of the samples) were indole, beta-sitosterol, cholesterol, beta-stigmastanol, 3-methyl-1H-indole, p-cresol, pyrene, phenol, fluoranthene, 3-beta coprostanol, benzo[a]pyrene, acetophenone, and 2,6-dimethylnaphthalene. The total number of detections in bed sediment (at a site) ranged from 3 to 31. The compounds NP1EO, NP2EO, and 4-nonylphenol were detected in greater than 10 percent of the samples. Most (80 percent) female fish collected had measurable concentrations of vitellogenin. Vitellogenin also was detected in 62, 63, and 33 percent of male carp, smallmouth bass, and redhorse, respectively. The one male walleye sample plasma sample analyzed had a vitellogenin detection. Vitellogenin concentrations were lower in male fish (not

  1. [Endocrine disruptors are a novel direction of endocrinologic scientific investigation].

    PubMed

    Iaglova, N V; Iaglov, V V

    2012-01-01

    Endocrine disruptors are exogenous anthropogenic chemicals (pesticides, herbicides, polychlorinated biphenyls, bisphenol A, polybrominated diphenyl ethers, phthalates and others), that are able to bind hormonal receptors of endocrine and other cells in vivo and act like hormones. These substances disrupt endocrine regulation of metabolism, reproduction and adaptive reactions of organisms and promote human and animal endocrine disorders.

  2. The Role of Cholesterol Utilization in a Computational Adrenal Steroidogenesis Model to Improve Predictability of Biochemical Responses to Endocrine Active Chemicals

    EPA Science Inventory

    Steroids, which have an important role in a wide range of physiological processes, are synthesized primarily in the gonads and adrenal glands through a series of enzyme-mediated reactions. The activity of steroidogenic enzymes can be altered by a variety of endocrine active chem...

  3. Recognition of familiar food activates feeding via an endocrine serotonin signal in Caenorhabditis elegans.

    PubMed

    Song, Bo-Mi; Faumont, Serge; Lockery, Shawn; Avery, Leon

    2013-02-05

    Familiarity discrimination has a significant impact on the pattern of food intake across species. However, the mechanism by which the recognition memory controls feeding is unclear. Here, we show that the nematode Caenorhabditis elegans forms a memory of particular foods after experience and displays behavioral plasticity, increasing the feeding response when they subsequently recognize the familiar food. We found that recognition of familiar food activates the pair of ADF chemosensory neurons, which subsequently increase serotonin release. The released serotonin activates the feeding response mainly by acting humorally and directly activates SER-7, a type 7 serotonin receptor, in MC motor neurons in the feeding organ. Our data suggest that worms sense the taste and/or smell of novel bacteria, which overrides the stimulatory effect of familiar bacteria on feeding by suppressing the activity of ADF or its upstream neurons. Our study provides insight into the mechanism by which familiarity discrimination alters behavior.DOI:http://dx.doi.org/10.7554/eLife.00329.001.

  4. The Endocrine Machinery.

    ERIC Educational Resources Information Center

    Fillman, David

    1987-01-01

    Promotes a reductionist approach to teaching about the endocrine system in high school biology and anatomy courses. Encourages the study of how hormones travel to the cells and affect them. Provides suggestions for activities and discussion questions, along with sample diagrams and flow charts. (TW)

  5. In vitro characterization of the effectiveness of enhanced sewage treatment processes to eliminate endocrine activity of hospital effluents.

    PubMed

    Maletz, Sibylle; Floehr, Tilman; Beier, Silvio; Klümper, Claudia; Brouwer, Abraham; Behnisch, Peter; Higley, Eric; Giesy, John P; Hecker, Markus; Gebhardt, Wilhelm; Linnemann, Volker; Pinnekamp, Johannes; Hollert, Henner

    2013-03-15

    Occurrence of pharmaceuticals in aquatic ecosystems is related to sewage effluents. Due to the possible adverse effects on wildlife and humans, degradation and removal of pharmaceuticals and their metabolites during wastewater treatment is an increasingly important task. The present study was part of a proof of concept study at a medium sized country hospital in western Germany that investigated efficiency of advanced treatment processes to remove toxic potencies from sewage. Specifically, the efficiency of treatment processes such as a membrane bioreactor (MBR) and ozonation to remove endocrine disruptive potentials was assessed. Estrogenic effects were characterized by use of two receptor-mediated in vitro transactivation assays, the Lyticase Yeast Estrogen Screen (LYES) and the Estrogen Receptor mediated Chemical Activated LUciferase gene eXpression (ER CALUX(®)). In addition, the H295R Steroidogenesis Assay (H295R) was utilized to detect potential disruption of steroidogenesis. Raw sewage contained measurable estrogen receptor (ER)-mediated potency as determined by use of the LYES (28.9 ± 8.6 ng/L, 0.33× concentration), which was reduced after treatment by MBR (2.3 ± 0.3 ng/L) and ozone (1.2 ± 0.4 ng/L). Results were confirmed by use of ER CALUX(®) which measured concentrations of estrogen equivalents (EEQs) of 0.2 ± 0.11 ng/L (MBR) and 0.01 ± 0.02 ng/L (ozonation). In contrast, treatment with ozone resulted in greater production of estradiol and aromatase activity at 3× and greater concentrations in H295R cells. It is hypothesized that this is partly due to formation of active oxidized products during ozonation. Substance-specific analyses demonstrated efficient removal of most of the measured compounds by ozonation. A comparison of the ER-mediated responses measured by use of the LYES and ER CALUX(®) with those from the chemical analysis using a mass-balance approach revealed estrone (E1) to be the main compound that caused the estrogenic effects

  6. Computational modeling of serum-binding proteins and clearance in extrapolations across life stages and species for endocrine active compounds.

    PubMed

    Teeguarden, Justin G; Barton, Hugh A

    2004-06-01

    One measure of the potency of compounds that lead to the effects through ligand-dependent gene transcription is the relative affinity for the critical receptor. Endocrine active compounds that are presumed to act principally through binding to the estrogen receptor (e.g., estradiol, genistein, bisphenol A, and octylphenol) comprise one class of such compounds. For making simple comparisons, receptor-binding affinity has been equated to in vivo potency, which consequently defines the dose-response characteristics for the compound. Direct extrapolation of in vitro estimated affinities to the corresponding in vivo system and to specific species or life stages (e.g., neonatal, pregnancy) can be misleading. Accurate comparison of the potency of endocrine active compounds requires characterization of biochemical and pharmacokinetic factors that affect their free concentration. Quantitative in vitro and in vivo models were developed for integrating pharmacokinetics factors (e.g., serum protein and receptor-binding affinities, clearance) that affect potency. Data for parameterizing these models for several estrogenic compounds were evaluated and the models exercised. While simulations of adult human or rat sera were generally successful, difficulties in describing early life stages were identified. Exogenous compounds were predicted to be largely ineffective at competing estradiol off serum-binding proteins, suggesting this was unlikely to be physiologically significant. Discrepancies were identified between relative potencies based upon modeling in vitro receptor-binding activity versus in vivo activity in the presence of clearance and serum-binding proteins. The examples illustrate the utility of this approach for integrating available experimental data from in vitro and in vivo studies to estimate the relative potency of these compounds.

  7. An evaluation of the endocrine disruptive potential of crude oil water accommodated fractions and crude oil contaminated surface water to freshwater organisms using in vitro and in vivo approaches.

    PubMed

    Truter, J Christoff; van Wyk, Johannes H; Oberholster, Paul J; Botha, Anna-Maria; Mokwena, Lucky M

    2016-10-27

    Knowledge regarding the potential impacts of crude oil on endocrine signaling in freshwater aquatic vertebrates is limited. The expression of selected genes as biomarkers for altered endocrine signaling was studied in African clawed frog, Xenopus laevis, tadpoles and juvenile Mozambique tilapia, Oreochromis mossambicus, exposed to weathered bunker and unweathered refinery crude oil water accommodated fractions (WAFs). In addition, the expression of the aforementioned genes was quantified in X. laevis tadpoles exposed to surface water collected from the proximity of an underground oil bunker. The (anti)estrogenicity and (anti)androgenicity of crude oil, crude oil WAFs, and surface water were furthermore evaluated using recombinant yeast. Thyroid hormone receptor beta expression was significantly down-regulated in X. laevis in response to both oil WAF types, whereas a further thyroid linked gene, type 2 deiodinase, was up-regulated in O. mossambicus exposed to a high concentration of bunker oil WAF. In addition, both WAFs altered the expression of the adipogenesis-linked peroxisome proliferator-activated receptor gamma in X. laevis. The crude oil and WAFs exhibited antiestrogenic and antiandrogenic activity in vitro. However, O. mossambicus androgen receptor 2 was the only gene, representing the reproductive system, significantly affected by WAF exposure. Estrogenicity, antiestrogenicity, and antiandrogenicity were detected in surface water samples; however, no significant changes were observed in the expression of any of the genes evaluated in X. laevis exposed to surface water. The responses varied among the 2 model organisms used, as well as among the 2 types of crude oil. Nonetheless, the data provide evidence that crude oil pollution may lead to adverse health effects in freshwater fish and amphibians as a result of altered endocrine signaling. Environ Toxicol Chem 2016;9999:1-13. © 2016 SETAC.

  8. [Endocrine xenoestrogenics disrupters: molecular mechanisms and detection methods].

    PubMed

    Mnif, Wissem; Pillon, Arnaud; Balaguer, Patrick; Bartegi, Aghleb

    2007-01-01

    The attention paid to endocriniens modulators for purpose micropolluants (endocrine disrupters) has been increasingly studied these last years particularly on animals. The results of this study raised big concerns from Doctors and Biologists on the eventual risks human health can face. Indeed, endocrine systems of the body play an essential and pervasive role in both the short- and long-term regulation of metabolic processes. Nutritional, behavioural, and reproductive processes are intricately regulated by endocrine systems, as are growth (including bone growth/remodelling), gut, cardiovascular, and kidney function and responses to all forms of stress. Disorders of any of the endocrine system, involving both over- and under-active hormone secretion, result inevitably in disease, the effects of which may extend to many different organs and functions and are often debilitating or life-threatening. Viewed from this general perspective, the threat posed from environmental chemicals with endocrine activity (either agonist or antagonistic) is potentially serious. However, the fact that humans and wildlife are exposed to such chemicals does not necessarily mean that clinically manifest disturbance of the relevant endocrine system will result, because much depends on the level and duration of exposure and on the timing of exposure. Indeed, a large numbers of environmental estrogens are suspected of altering human health as well as the marine ecosystem balance. The objective of this review is to study the different molecular mechanisms of these xenoestrogenes micropolluants, in order to emphasize their potential risk and to present some of the different experimental methods for their detection.

  9. Incorporation of endocrine disruption into chemical hazard scoring for pollution prevention and current list of endocrine disrupting chemicals.

    PubMed

    Whaley, D A; Keyes, D; Khorrami, B

    2001-11-01

    Research continues to support the theory of endocrine disruption. Endocrine disruption is defined as the ability of a chemical contaminating the workplace or the environment to interfere with homeostasis, development, reproduction, and/or behavior in a living organism or it's offspring. Certain classes of environmentally persistent chemicals such as polychlorinated biphenyls (PCBs), dioxins, furans, and some pesticides can adversely effect the endocrine systems of aquatic life and terrestrial wildlife. The University of Tennessee, Knoxville (UTN), developed a method for hazard scoring chemicals for the aquatic ecosystem. The Indiana Clean Manufacturing Technology and Safe Materials Institute at Purdue University (CMTI) later expanded the scoring system to include terms for worker hazard as well as terms for contamination of soil and air quality, and for stratospheric ozone depletion. We call the CMTI chemical hazard score the Purdue score. At West Virginia University, two improvements of the Purdue chemical hazard score are developed, a normalizing of the term for soil contamination, and addition of hazard score terms for ecosystem endocrine disruption. The results of incorporating endocrine disruption terms into the hazard scoring equations resulted in increased hazard rankings, often substantially increased, for 26 endocrine disrupting chemicals (EDCs) among 200 Superfund chemicals. Because data suggesting human endocrine disruption from such chemicals is still controversial, no endocrine disruptor term has been added to the human toxicity portions of the chemical hazard scoring system at this time. The third product of this work is assembly of a current consolidated list of (1) established or probable, mostly synthetic, industrial chemical and medication EDCs and (2) suspect (less certain) synthetic and natural (phytoestrogen) possible endocrine disrupting chemicals, with the goal of contributing to future development of quantitative structure activity

  10. Mobilization of endocrine-disrupting chemicals and estrogenic activity in simulated rainfall runoff from land-applied biosolids.

    PubMed

    Giudice, Ben D; Young, Thomas M

    2011-10-01

    Municipal biosolids are commonly applied to land as soil amendment or fertilizer as a form of beneficial reuse of what could otherwise be viewed as waste. Balanced against this benefit are potential risks to groundwater and surface water quality from constituents that may be mobilized during storm events. The objective of the present study was to characterize the mobilization of selected endocrine-disrupting compounds, heavy metals, and total estrogenic activity in rainfall runoff from land-applied biosolids. Rainfall simulations were conducted on soil plots amended with biosolids. Surface runoff and leachate was collected and analyzed for the endocrine-disrupting compounds bisphenol A, 17α-ethynylestradiol, triclocarban, triclosan, octylphenol, and nonylphenol; a suite of 16 metals; and estrogenic activity via the estrogen receptor-mediated chemical activated luciferase gene expression (ER-CALUX) bioassay. Triclocarban (2.3-17.3 ng/L), triclosan (<51-309 ng/L), and octylphenol (<4.9-203 ng/L) were commonly detected. Chromium (2.0-22 µg/L), Co (2.5-10 µg/L), Ni (28-235 µg/L), Cu (14-110 µg/L), As (1.2-2.7 µg/L), and Se (0.29-12 µg/L) were quantifiable over background levels. Triclosan, Ni, and Cu were detected at levels that might pose some risk to aquatic life, though levels of metals in the biosolids were well below the maximum allowable regulatory limits. The ER-CALUX results were mostly explained by background bisphenol A contamination and octylphenol in runoff, although unknown contributors or matrix effects were also found.

  11. Endocrine Effects of Circadian Disruption.

    PubMed

    Bedrosian, Tracy A; Fonken, Laura K; Nelson, Randy J

    2016-01-01

    Disruption of circadian rhythms, provoked by artificial lighting at night, inconsistent sleep-wake schedules, and transmeridian air travel, is increasingly prevalent in modern society. Desynchrony of biological rhythms from environmental light cycles has dramatic consequences for human health. In particular, disrupting homeostatic oscillations in endocrine tissues and the hormones that these tissues regulate can have cascading effects on physiology and behavior. Accumulating evidence suggests that chronic disruption of circadian organization of endocrine function may lead to metabolic, reproductive, sleep, and mood disorders. This review discusses circadian control of endocrine systems and the consequences of distorting rhythmicity of these systems.

  12. [The vitamin D endocrine system].

    PubMed

    Castro, Luiz Claudio Gonçalves de

    2011-11-01

    The vitamin D endocrine system comprises a group of 7-dehydrocholesterol-derived secosteroid molecules, including its active metabolite 1,25-dihydroxy-vitamin D (1,25(OH)(2)D), its precursors and other metabolites, its binding protein (DBP) and nuclear receptor (VDR), as well as cytochrome P450 complex enzymes participating in activation and inactivation pathways of those molecules. The biologic effects of 1,25(OH)(2)D are mediated by VDR, a ligand-activated transcription factor which is a member of the nuclear receptors family, spread in almost all human cells. In addition to its classic role in the regulation of calcium metabolism and bone health, evidence suggests that 1,25(OH)(2)D directly or indirectly modulates about 3% of the human genome, participating in the regulation of chief functions of systemic homeostasis, such as cell growth, differentiation and apoptosis, regulation of immune, cardiovascular and musculoskeletal systems, and insulin metabolism. Given the critical influence of the vitamin D endocrine system in many processes of systemic metabolic equilibrium, the laboratory assays available for the evaluation of this system have to present high accuracy and reproducibility, enabling the establishment of cutoff points that, beyond being consensually accepted, reliably express the vitamin D status of the organism, and the respective clinical-metabolic impacts on the global health of the individual.

  13. [Disperse endocrine system and APUD concept].

    PubMed

    Mil'to, I V; Sukhodolo, I V; Gereng, E A; Shamardina, L A

    2011-01-01

    This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

  14. New aspects of cadmium as endocrine disruptor.

    PubMed

    Takiguchi, Masufumi; Yoshihara, Shin'ichi

    2006-01-01

    Cadmium (Cd) is an industrial and environmental pollutant that exerts adverse effects on a number of organs in humans and animals. Reproductive organs, such as the testis and placenta, are sensitive to the toxic effects of Cd. In animal experiments, high-dose exposure to Cd induced severe testicular interstitial hemorrhage with edema, and increased incidence of fetal death and placental necrosis. Low-dose exposure to Cd affects steroid synthesis in male and female reproductive organs. In 1998, the Ministry of Environment in Japan listed Cd in the strategy plan SPEED98 as one of the chemicals suspected of having possible endocrine disrupting activity. Recently, it has been shown that Cd has potent estrogen- and androgen-like activities in vivo and in vitro, by directly binding to estrogen and androgen receptors. However, the precise mechanisms underlying the effects of Cd as an endocrine disruptor remain to be elucidated. In this review, we will discuss evidence thus far presented concerning the effects of Cd on the endocrine system.

  15. Identification of endocrine disrupting chemicals activating SXR-mediated transactivation of CYP3A and CYP7A1.

    PubMed

    Zhou, Tingting; Cong, Shuyan; Sun, Shiying; Sun, Hongmiao; Zou, Renlong; Wang, Shengli; Wang, Chunyu; Jiao, Jiao; Goto, Kiminobu; Nawata, Hajime; Yanase, Toshihiko; Zhao, Yue

    2013-01-05

    Endocrine disrupting chemicals (EDCs) have emerged as a major public health issue because of their potentially disruptive effects on physiological hormonal actions. SXR (steroid xenobiotic receptor), also known as NR1I2, regulates CYP3A expression in response to exogenous chemicals, such as EDCs, after binding to SXRE (SXR response element). In our study, luciferase assay showed that 14 out of 55 EDCs could enhance SXR-mediated rat or human CYP3A gene transcription nearly evenly, and could also activate rat CYP7A1 gene transcription by cross-interaction of SXR and LXRE (LXRα response element). SXR diffused in the nucleus without ligand, whereas intranuclear foci of liganded SXR were produced. Furthermore, endogenous mRNA expression of CYP3A4 gene was enhanced by the 14 positive EDCs. Our results suggested a probable mechanism of EDCs disrupting the steroid or xenobiotic metabolism homeostasis via SXR.

  16. Modulation of aromatase activity as a mode of action for endocrine disrupting chemicals in a marine fish.

    PubMed

    Mills, Lesley J; Gutjahr-Gobell, Ruth E; Zaroogian, Gerald E; Horowitz, Doranne Borsay; Laws, Susan C

    2014-02-01

    The steroidogenic enzyme aromatase catalyzes the conversion of androgens to estrogens and therefore plays a central role in reproduction. In contrast to most vertebrates, teleost fish have two distinct forms of aromatase. Because brain aromatase activity in fish is up to 1000 times that in mammals, fish may be especially susceptible to negative effects from environmental endocrine-disrupting chemicals (EDCs) that impact aromatase activity. In this study, the effects of estradiol (E2), ethynylestradiol (EE2), octylphenol (OP), and androstatrienedione (ATD) on reproduction and aromatase activity in brains and gonads from the marine fish cunner (Tautogolabrus adspersus) was investigated. The purpose of the study was to explore the relationship between changes in aromatase activity and reproductive output in a marine fish, as well as compare aromatase activity to two commonly used indicators of EDC exposure, plasma vitellogenin (VTG) and gonadosomatic index (GSI). Results with E2, EE2, and ATD indicate that aromatase activity in cunner brain and ovary are affected differently by exposure to these EDCs. In the case of E2 and EE2, male brain aromatase activity was signficantly increased by these treatments, female brain aromatase activity was unaffected, and ovarian aromatase activity was significantly decreased. Treatment with the aromatase inhibitor ATD resulted in significantly decreased aromatase activity in male and female brain, but had no significant impact on ovarian aromatase activity. Regardless of test chemical, a decrease or an increase in male brain aromatase activity relative to controls was associated with decreased egg production in cunner and was also correlated with significant changes in GSI in both sexes. E2 and EE2 significantly elevated plasma VTG in males and females, while ATD had no significant effect. Treatment of cunner with OP had no significant effect on any measured endpoint. Overall, results with these exposures indicate EDCs that impact

  17. Mechanistic Computational Model of Steroidgenesis in H295R Cells: Role of (Oxysterols and Cell Proliferation to Improve Predictability of Biochemical Response to Endocrine Active Chemical-Metyrapone

    EPA Science Inventory

    The human adrenocortical carcinoma cell line H295R is being used as an in vitro steroidogenesis screening assay to assess the impact of endocrine active chemicals (EACs) capable of altering steroid biosynthesis. To enhance the interpretation and quantitative application of measur...

  18. Computational Model of Steroidogenesis in Human H295R Cells to Predict Biochemical Response to Endocrine Active Chemicals: Model Development for Metyrapone

    EPA Science Inventory

    BACKGROUND: An in vitro steroidogenesis assay using the human adrenocortical carcinoma cells H295R is being evaluated as a possible toxicity screening approach to detect and assess the impact of endocrine active chemicals (EAC) capable of altering steroid biosynthesis. Interpreta...

  19. Multi-Criteria Decision Analysis of Test Endpoints for Detecting the Effects of Endocrine Active Substances in Fish Full Life Cycle Tests

    EPA Science Inventory

    Fish full life cycle (FFLC) tests are increasingly required in the ecotoxicological assessment of endocrine active substances. However, FFLC tests have not been internationally standardized or validated, and it is currently unclear how such tests should best be designed to provid...

  20. Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts

    EPA Science Inventory

    Use of an In Vitro, Nuclear Receptor Assay Panel to Characterize the Endocrine-Disrupting Activity Load of Wastewater Treatment Plant Effluent Extracts Katie B. Paul 1.2, Ruth Marfil-Vega 1 Marc A. Mills3, Steve 0. Simmons2, Vickie S. Wilson4, Kevin M. Crofton2 10ak Rid...

  1. ENDOCRINE-DISRUPTING CHEMICALS: PREPUBERTAL EXPOSURES AND EFFECTS ON SEXUAL MATURATION AND THYROID ACTIVITY IN THE FEMALE RAT. A FOCUS ON THE EDSTAC RECOMMENDATIONS

    EPA Science Inventory

    Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid activity in the female rat. A focus on the EDSTAC recommendations.

    Goldman JM, Laws SC, Balchak SK, Cooper RL, Kavlock RJ.

    Reproductive Toxicology Division, National H...

  2. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site.

    PubMed

    Kassotis, Christopher D; Iwanowicz, Luke R; Akob, Denise M; Cozzarelli, Isabelle M; Mumford, Adam C; Orem, William H; Nagel, Susan C

    2016-07-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby.

  3. Endocrine disrupting activities of surface water associated with a West Virginia oil and gas industry wastewater disposal site

    USGS Publications Warehouse

    Kassotis, Christopher D.; Iwanowicz, Luke R.; Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam; Orem, William H.; Nagel, Susan C.

    2016-01-01

    Currently, >95% of end disposal of hydraulic fracturing wastewater from unconventional oil and gas operations in the US occurs via injection wells. Key data gaps exist in understanding the potential impact of underground injection on surface water quality and environmental health. The goal of this study was to assess endocrine disrupting activity in surface water at a West Virginia injection well disposal site. Water samples were collected from a background site in the area and upstream, on, and downstream of the disposal facility. Samples were solid-phase extracted, and extracts assessed for agonist and antagonist hormonal activities for five hormone receptors in mammalian and yeast reporter gene assays. Compared to reference water extracts upstream and distal to the disposal well, samples collected adjacent and downstream exhibited considerably higher antagonist activity for the estrogen, androgen, progesterone, glucocorticoid and thyroid hormone receptors. In contrast, low levels of agonist activity were measured in upstream/distal sites, and were inhibited or absent at downstream sites with significant antagonism. Concurrent analyses by partner laboratories (published separately) describe the analytical and geochemical profiling of the water; elevated conductivity as well as high sodium, chloride, strontium, and barium concentrations indicate impacts due to handling of unconventional oil and gas wastewater. Notably, antagonist activities in downstream samples were at equivalent authentic standard concentrations known to disrupt reproduction and/or development in aquatic animals. Given the widespread use of injection wells for end-disposal of hydraulic fracturing wastewater, these data raise concerns for human and animal health nearby.

  4. Src family kinase activity regulates adhesion, spreading and migration of pancreatic endocrine tumour cells.

    PubMed

    Di Florio, Alessia; Capurso, Gabriele; Milione, Massimo; Panzuto, Francesco; Geremia, Raffaele; Delle Fave, Gianfranco; Sette, Claudio

    2007-03-01

    Pancreatic endocrine tumours (PETs) are rare and 'indolent' neoplasms that usually develop metastatic lesions and exhibit poor response to standard medical treatments. Few studies have investigated pathways responsible for PET cell growth and invasion and no alternative therapeutic strategies have been proposed. In a recent microarray analysis for genes up-regulated in PETs, we have described the up-regulation of soluble Src family tyrosine kinases in this neoplasia, which may represent potentially promising candidates for therapy. Herein, we have investigated the expression and function of Src family kinases in PETS and PET cell lines. Western blot analysis indicated that Src is highly abundant in the PET cell lines CM and QGP-1. Immunohistochemistry and Western blot analyses showed that Src is up-regulated also in human PET lesions. Pharmacological inhibition of Src family kinases by the specific inhibitor PP2 strongly interfered with adhesion, spreading and migration of PET cell lines. Accordingly, the actin cytoskeleton was profoundly altered after inhibition of Src kinases, whereas even prolonged incubation with PP2 exerted no effect on cell cycle progression and/or apoptosis of PET cells. A transient increase in tyrosine phosphorylation of a subset of proteins was observed in QGP-1 cells adhering to the plate, with a peak at 75 min after seeding, when approximately 80% of cells were attached. Inhibition of Src kinases caused a dramatic reduction in the phosphorylation of proteins with different molecular weight that were isolated from the cell extracts by anti-phosphotyrosine immunoprecipitation or pull-down with the SH2 domain of Src. Among them, the docking protein p130Cas interacted with Src and is a major substrate of the Src kinases in QGP-1 cells undergoing adhesion. Our results suggest that Src kinases play a specific role during adhesion, spreading and migration of PET cells and may indicate therapeutical approaches directed to limiting the metastatic

  5. Endocrine disrupting activity in fruits and vegetables evaluated with the E-screen assay in relation to pesticide residues.

    PubMed

    Schilirò, T; Gorrasi, I; Longo, A; Coluccia, S; Gilli, G

    2011-10-01

    Food is likely to be one of the most important routes of human exposure to endocrine disrupting compounds (EDCs). In the present study, we evaluated the total estrogenic activity of fruits and vegetables, which was calculated using the human breast cancer cell line (MCF-7 BUS) proliferation assay (E-screen), in relation to pesticide residues. We analysed 44 food samples, 30 fruits and 14 vegetables. Of these samples, 10 did not contain any pesticide residues. The other 34 samples contained from 1 to 7 pesticide residues in concentrations ranging from 0.03 to 1.91 ppm. Estrogenic activity was detected in the 59% of samples tested. The positive controls used were 17-β-estradiol (E2), the phytoestrogen genistein and the pesticide endosulfan. The average value of estradiol equivalency quantity (EEQ) for all positive samples was 0.15±0.32 μg/100g. A low correlation was found between the concentration of pesticide residues and the EEQ values (Spearman correlation r=0.376 and p=0.012). Using values obtained from the literature, we compared the estrogenic activity of food samples with the intrinsic content of phytoestrogens, but we found no correlations. Our results also suggested that the calculated intake of dietary EDCs might represent a concentration comparable to the normal endogenous estrogen concentration in human blood.

  6. Steroidogenic acute regulatory (StAR) protein and cholesterol side-chain cleavage (P450scc)-regulated steroidogenesis as an organ-specific molecular and cellular target for endocrine disrupting chemicals in fish.

    PubMed

    Arukwe, Augustine

    2008-12-01

    Biologically active steroids are synthesised de novo in specialised cells of several organs, including the adrenal gland, testis, ovary, brain, placenta and adipose tissue. Regardless of organ or tissue, the rate-limiting step in steroid hormone synthesis is the movement of cholesterol across the mitochondrial membrane (i.e. from the outer to the inner membrane) mediated by the steroidogenic acute regulatory (StAR) protein. Subsequent conversion of cholesterol to pregnenolone by cytochrome P450 side-chain cleavage (P450scc) represents the initiation of steroidogenesis. Chemically mediated disruption of StAR and P450scc expression may represent the first step in the sequence of related event cascades underlying xenoestrogen-induced toxicity and transmittable disturbances to the whole organism level. This may include, but is not limited to, alterations in sexual differentiation, growth, reproduction, development and metabolism. Despite the integral role of StAR and P450scc in acute steroidogenesis, and popular demand from regulatory agencies, bioassays for evaluating the effect of endocrine-disrupting chemicals have the potential to overlook chemicals that may modulate estrogenic responses through mechanisms that do not involve direct binding to estrogen receptors (ERs). In addition to their effect as direct ER agonists, the effects of endocrine disruptors may be evaluated and interpreted as interference with steroidogenesis and with the steroidal regulation of the normal development and function of juvenile, male and female individuals. Knowledge of these effects is scarce, indicating that relatively little is known about the mechanisms or mode-of-action of chemical alterations to steroidogenesis and their potential toxicity for wildlife species. In addition, analytical methods for the complete adaptation of these responses as biomarkers of response and effect are yet to be properly validated.

  7. [Xenoestrogens: endocrine disrupting compounds].

    PubMed

    Wozniak, Milena; Murias, Marek

    2008-11-01

    In recent years much attention has been paid to the issues of chemicals that disrupt the normal function of endocrine system, namely xenoestrogens. These chemicals can mimic the activity of endogenous estrogens, antagonize their interaction with estrogen receptors or disrupt the synthesis, metabolism and functions of endogenous female hormones. Due to the fact that they act thanks to many different mechanisms, it is very difficult to estimate their estrogenic activity by means of a simple tests. The important issue remains the fact that xenoestrogens may have a positive or negative influence on the function of the endocrine system. It seems to be very important that there are many sources of xenoestrogens, that is not only vegetables and fruit (phytoestrogens), but also metals (Co, Cu, Ni, Cr, Pb), dental appliances (alkilphenols), food containers or blood containers (PVC--polyvinyl chloride, DEHP--di-(2-ethylhexyl) phthalate), cosmetics (parabens) and pesticides (DDT--dichlor-diphenyl-trichlorethylane, endosulfane).

  8. Endocrine-disrupting chemicals and skin manifestations.

    PubMed

    Ju, Qiang; Zouboulis, Christos C

    2016-09-01

    Endocrine-disrupting chemicals (EDCs) are exogenous compounds that have the ability to disrupt the production and actions of hormones through direct or indirect interaction with hormone receptors, thus acting as agonists or antagonists. Human health is affected after either individual occupation or dietary and environmental exposure to EDCs. On the other hand, skin is one of the largest organs of the body and its main function is protection from noxious substances. EDCs perturb the endocrine system, and they are also carcinogenic, immunotoxic, and hepatotoxic to human skin. In addition, their effects on keratinocytes, melanocytes, sebocytes, inflammatory and immunological cells, and skin stem cells produce inflammatory and allergic skin diseases, chloracne, disorders of skin pigmentation, skin cancer, and skin aging. Mechanisms, which EDCs use to induce these skin disorders are complicated, and involve the interference of endogenous hormones and most importantly the activation of the aryl hydrocarbon receptor signal pathway. Further studies on EDCs and skin diseases are necessary to elucidate these mechanisms.

  9. Endocrine disrupting activities in sewage effluent and river water determined by chemical analysis and in vitro assay in the context of granular activated carbon upgrade.

    PubMed

    Grover, D P; Balaam, J; Pacitto, S; Readman, J W; White, S; Zhou, J L

    2011-09-01

    As part of endocrine disruption in catchments (EDCAT) programme, this work aims to assess the temporal and spatial variations of endocrine disrupting chemicals (EDCs) in River Ray, before and after the commissioning of a full-scale granular activated carbon (GAC) plant at a sewage treatment works (STW). Through spot and passive sampling from effluent and river sites, estrogenic and anti-androgenic activities were determined by chemical analysis and in vitro bio-assay. A correlation was found between chemical analyses of the most potent estrogens (estrone (E1), 17β-estradiol (E2), 17α-ethinylestradiol (EE2)) and yeast estrogen screen (YES) measurement, both showing clearly a reduction in estrogenic activity after the commissioning of the GAC plant at the STW. During the study period, the annual average concentrations of E1, E2 and EE2 had decreased from 3.5 ng L(-1), 3.1 ng L(-1) and 0.5 ng L(-1) to below their limit of detection (LOD), respectively, with a concentration reduction of at least 91%, 81% and 60%. Annual mean estrogenic activity measured by YES of spot samples varied from 1.9 ng L(-1) to 0.4 ng L(-1) E2 equivalent between 2006 and 2008 representing a 79% reduction. Similarly, anti-androgenic activity measured by yeast anti-androgen screen (anti-YAS) of spot samples was reduced from 148.8 to 22.4 μg flutamide L(-1), or by 85%. YES and anti-YAS values were related to each other, suggesting co-existence of both types of activities from chemical mixtures in environmental samples. The findings confirm the effectiveness of a full-scale GAC in removing both estrogenic and anti-androgenic activities from sewage effluent.

  10. Uncertainties in biological responses that influence hazard or risk approaches to the regulation of endocrine active substances

    EPA Science Inventory

    Endocrine Disrupting Chemicals (EDCs) may have delayed or transgenerational effects and display non-monotonic dose response relationships (NMDRs) that require careful consideration when determining environmental hazards. The case studies evaluated for the SETAC Pellston Workshop&...

  11. SETAC Pellston WorkshopTM: Environmental hazard and risk assessment approaches for endocrine-active chemicals (EHRA)

    EPA Science Inventory

    Suspected endocrine disrupting substances (EDS) are now being evaluated by several regulatory authorities. A debate is in progress about whether or not EDS can be adequately assessed by following the standard approach involving identification of intrinsic hazards, prediction of e...

  12. Effect of endocrine disruptor pesticides: a review.

    PubMed

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-06-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  13. Endocrine and metabolic dysfunction in yellow perch, Perca flavescens, exposed to organic contaminants and heavy metals in the St. Lawrence River

    SciTech Connect

    Hontela, A.; Duclos, D.; Fortin, R.; Dumont, P.

    1995-04-01

    The endocrine and biochemical responses to the acute stress of capture and handling were investigated in sexually mature and in immature male and female yellow perch, Perca flavescens, from a site contaminated by organic contaminants (PAHs and PCBs) and heavy metals (Hg, Cd, As, and Zn) and from a reference site in the St. Lawrence River. Following a standardized capture and handling stress, fish from the contaminated site did not exhibit the expected physiological stress response observed in fish from the reference site. Blood cortisol and thyroxine levels were lower, and liver glycogen stores were greater in mature males and females, as well as in the immature fish from the contaminated site, compared to the reference site. Fish from the contaminated site also had smaller gonads and lower condition factor. The impaired ability to elevate blood cortisol in response to an acute stress may be used as a biomarker of toxic stress in health assessment of feral fish from polluted environments.

  14. Endocrine Disruptors

    PubMed Central

    2015-01-01

    Law and science combine in the estimation of risks from endocrine disruptors (EDs) and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change) of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU) has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation and other regulations or directives. The integration of a vast (in kind and in scope) number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices. PMID:26740809

  15. Comparison of UV photolysis, nanofiltration, and their combination to remove hormones from a drinking water source and reduce endocrine disrupting activity.

    PubMed

    Sanches, Sandra; Rodrigues, Alexandre; Cardoso, Vitor V; Benoliel, Maria J; Crespo, João G; Pereira, Vanessa J

    2016-06-01

    A sequential water treatment combining low pressure ultraviolet direct photolysis with nanofiltration was evaluated to remove hormones from water, reduce endocrine disrupting activity, and overcome the drawbacks associated with the individual processes (production of a nanofiltration-concentrated retentate and formation of toxic by-products). 17β-Estradiol, 17α-ethinylestradiol, estrone, estriol, and progesterone were spiked into a real water sample collected after the sedimentation process of a drinking water treatment plant. Even though the nanofiltration process alone showed similar results to the combined treatment in terms of the water quality produced, the combined treatment offered advantage in terms of the load of the retentate and decrease in the endocrine-disrupting activity of the samples. Moreover, the photolysis by-products produced, with higher endocrine disrupting activity than the parent compounds, were effectively retained by the membrane. The combination of direct LP/UV photolysis with nanofiltration is promising for a drinking water utility that needs to cope with sudden punctual discharges or deterioration of the water quality and wants to decrease the levels of chemicals in the nanofiltration retentate.

  16. Canine toys and training devices as sources of exposure to phthalates and bisphenol A: quantitation of chemicals in leachate and in vitro screening for endocrine activity.

    PubMed

    Wooten, Kimberly J; Smith, Philip N

    2013-11-01

    Chewing and mouthing behaviors exhibited by pet dogs are likely to lead to oral exposures to a variety of environmental chemicals. Products intended for chewing and mouthing uses include toys and training devices that are often made of plastics. The goal of the current study was to determine if a subset of phthalates and bisphenol A (BPA), endocrine disrupting chemicals commonly found in plastics, leach out of dog toys and training devices (bumpers) into synthetic canine saliva. In vitro assays were used to screen leachates for endocrine activity. Bumper leachates were dominated by di-2-ethylhexyl phthalate (DEHP) and BPA, with concentrations reaching low μg mL(-1) following short immersions in synthetic saliva. Simulated chewing of bumpers during immersion in synthetic saliva increased concentrations of phthalates and BPA as compared to new bumpers, while outdoor storage had variable effects on concentrations (increased DEHP; decreased BPA). Toys leached substantially lower concentrations of phthalates and BPA, with the exception of one toy which leached considerable amounts of diethyl phthalate. In vitro assays indicated anti-androgenic activity of bumper leachates, and estrogenic activity of both bumper and toy leachates. These results confirm that toys and training devices are potential sources of exposure to endocrine disrupting chemicals in pet dogs.

  17. Separating Tumorigenicity from Bile Acid Regulatory Activity for Endocrine Hormone FGF19.

    PubMed

    Zhou, Mei; Wang, Xueyan; Phung, Van; Lindhout, Darrin A; Mondal, Kalyani; Hsu, Jer-Yuan; Yang, Hong; Humphrey, Mark; Ding, Xunshan; Arora, Taruna; Learned, R Marc; DePaoli, Alex M; Tian, Hui; Ling, Lei

    2014-06-15

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related death, develops from premalignant lesions in chronically damaged livers. Although it is well established that FGF19 acts through the receptor complex FGFR4-β-Klotho (KLB) to regulate bile acid metabolism, FGF19 is also implicated in the development of HCC. In humans, FGF19 is amplified in HCC and its expression is induced in the liver under cholestatic and cirrhotic conditions. In mice, ectopic overexpression of FGF19 drives HCC development in a process that requires FGFR4. In this study, we describe an engineered FGF19 (M70) that fully retains bile acid regulatory activity but does not promote HCC formation, demonstrating that regulating bile acid metabolism is distinct and separable from tumor-promoting activity. Mechanistically, we show that FGF19 stimulates tumor progression by activating the STAT3 pathway, an activity eliminated by M70. Furthermore, M70 inhibits FGF19-dependent tumor growth in a rodent model. Our results suggest that selectively targeting the FGF19-FGFR4 pathway may offer a tractable approach to improve the treatment of chronic liver disease and cancer.

  18. Nanotoxicity: a growing need for study in the endocrine system.

    PubMed

    Lu, Xuefei; Liu, Ying; Kong, Xiangjun; Lobie, Peter E; Chen, Chunying; Zhu, Tao

    2013-05-27

    Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions.

  19. MOBILIZATION OF ENDOCRINE DISRUPTING CHEMICALS AND ESTROGENIC ACTIVITY IN SIMULATED RAINFALL RUNOFF FROM LAND-APPLIED BIOSOLIDS

    PubMed Central

    Giudice, Ben D.; Young, Thomas M.

    2012-01-01

    Municipal biosolids are commonly applied to land as soil amendment or fertilizer as a form of beneficial reuse of what could otherwise be viewed as waste. Balanced against this benefit are potential risks to groundwater and surface water quality from constituents that may be mobilized during storm events. The objective of the present study was to characterize the mobilization of selected endocrine disrupting compounds (EDCs), heavy metals, and total estrogenic activity in rainfall runoff from land-applied biosolids. Rainfall simulations were conducted on soil plots amended with biosolids. Surface runoff and leachate was collected and analyzed for the EDCs bisphenol A, 17α-ethynylestradiol, triclocarban, triclosan, octylphenol, and nonylphenol; a suite of sixteen metals; and estrogenic activity via the ER-CALUX bioassay. Triclocarban (2.3–17.3 ng/L), triclosan (<51–309 ng/L), and octylphenol (<4.9–203 ng/L) were commonly detected. Chromium (2.0–22 µg/L), cobalt (2.5–10 µg/L), nickel (28–235 µg/L), copper (14–110 µg/L), arsenic (1.2–2.7 µg/L), and selenium (0.29–12 µg/L) were quantifiable over background levels. Triclosan, nickel, and copper were detected at levels that might pose some risk to aquatic life, though levels of metals in the biosolids were well below maximum allowable regulatory limits. ER-CALUX results were mostly explained by background bisphenol A contamination and octylphenol in runoff, though unknown contributors and/or matrix effects were also found. PMID:21786314

  20. Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

    EPA Science Inventory

    Endocrine disrupting chemicals (EDCs) are exogenous substances that alter endocrine system function(s) and consequently cause adverse health effects in intact organisms or its progeny. The endocrine system is important for a wide range of biological processes, from normal cell si...

  1. Detection of Bacillus and Stenotrophomonas species growing in an organic acid and endocrine-disrupting chemical-rich environment of distillery spent wash and its phytotoxicity.

    PubMed

    Chandra, Ram; Kumar, Vineet

    2017-01-01

    Sugarcane molasses-based distillery spent wash (DSW) is well known for its toxicity and complex mixture of various recalcitrant organic pollutants with acidic pH, but the chemical nature of these pollutants is unknown. This study revealed the presence of toxic organic acids (butanedioic acid bis(TMS)ester; 2-hydroxysocaproic acid; benzenepropanoic acid, α-[(TMS)oxy], TMS ester; vanillylpropionic acid, bis(TMS)), and other recalcitrant organic pollutants (2-furancarboxylic acid, 5-[[(TMS)oxy] methyl], TMS ester; benzoic acid 3-methoxy-4-[(TMS)oxy], TMS ester; and tricarballylic acid 3TMS), which are listed as endocrine-disrupting chemicals. In addition, several major heavy metals were detected, including Fe (163.947), Mn (4.556), Zn (2.487), and Ni (1.175 mg l(-1)). Bacterial community analysis by restriction fragment length polymorphism revealed that Bacillus and Stenotrophomonas were dominant autochthonous bacterial communities belonging to the phylum Firmicutes and γ-Proteobacteria, respectively. The presence of Bacillus and Stenotrophomonas species in highly acidic environments indicated its broad range adaptation. These findings indicated that these autochthonous bacterial communities were pioneer taxa for in situ remediation of this hazardous waste during ecological succession. Further, phytotoxicity assay of DSW with Phaseolus mungo L. and Triticum aestivum revealed that T. aestivum was more sensitive than P. mungo L. in the seed germination test. The results of this study may be useful for monitoring and toxicity assessment of sugarcane molasses-based distillery waste at disposal sites.

  2. Toxicity on crustaceans and endocrine disrupting activity on Saccharomyces cerevisiae of eight alkylphenols.

    PubMed

    Isidori, Marina; Lavorgna, Margherita; Nardelli, Angela; Parrella, Alfredo

    2006-06-01

    In the last few years many concerns have been raised regarding the environmental safety of alkylphenol polyethoxylate surfactants (APnEOs). They are widely used in detergents, paints, herbicides and many other formulated products. It has been estimated that 60% of APnEOs end up in the aquatic environment; they are biodegradable and transformed into alkylphenols, such as nonylphenol and octylphenol that are hydrophobic and tend to accumulate. In the present study, acute and chronic aquatic toxicity and the estrogenic activity of the following eight alkylphenols were assessed: 4-nonylphenol, 4-octylphenol, 4-nonylphenol-10-ethoxylate, 4-tert-octylphenol, POE (1 to 2)-nonylphenol, POE (6)-nonylphenol, POE (3)-tert-octylphenol and POE (9 to 10)-tert-octylphenol. The toxic potential was measured on the crustaceans Daphnia magna and Ceriodaphnia dubia, while the estrogenic activity was determined by using the YES-test with the strain Saccharomyces cerevisiae RMY326. The results showed that the exposure of crustaceans to the eight xenoestrogens investigated caused both acute and chronic effects. The EC50 values found for C. dubia at 48 h were compared to D. magna at 24h and, gave a first indication about the toxic activity of the compounds investigated, that is better expressed in the long-term. In fact, chronic data showed a strong increase in toxicity with EC50 values one or two orders of magnitude lower than the acute values. The results of the YES-test showed that nonylphenol, octylphenol and 4-tert-octylphenol were the most estrogenic and the bioassay was able to detect their estrogenicity at very low concentrations (ng-microg/l).

  3. Effects of endocrine modulators on sex differentiation in birds.

    PubMed

    Brunström, Björn; Axelsson, Jeanette; Halldin, Krister

    2003-01-01

    This mini-review focuses on sexual differentiation of the reproductive organs and the brain in birds and the effects of endocrine modulators on these processes. Sex determination in birds is genetically controlled, but the genetic events implicated are largely unknown. Female birds have one Z and one W sex chromosome, while males have two Z sex chromosomes. It is not clear whether it is the presence of the W chromosome in females, the double dose of the Z chromosome in males vis-à-vis females, or both of these characteristics that are crucial for the determination of sex in birds. Oestradiol directs sexual differentiation in birds during critical periods of development. Consequently, exogenous compounds that interfere with the endogenous oestrogen balance can disrupt sexual differentiation of the reproductive organs and the brain. Therefore, sexual differentiation in birds provides a good model for studying the effects of endocrine modulators at various biological levels from gene expression to behaviour. Some compounds known to be present in the environment can alter endocrine function and have adverse effects when administered during development, resulting in alterations in gonads, accessory sexual organs, and behaviour. Data reviewed in this paper are mostly from laboratory studies on endocrine modulators with oestrogenic activity, whereas evidence for adverse effects of pollutants on sexual differentiation in avian wildlife is scarce.

  4. Comparison of activation media and pyrolysis temperature for activated carbons development by pyrolysis of potato peels for effective adsorption of endocrine disruptor bisphenol-A.

    PubMed

    Arampatzidou, Anastasia C; Deliyanni, Eleni A

    2016-03-15

    Activated carbon prepared from potato peels, a solid waste by product has been studied for the adsorption of an endocrine disruptor, Bisphenol-A, from aqueous solutions. The potato peels biomass was activated with H3PO4, KOH and ZnCl2 in order the effect of the activation agent to be evaluated. The activated biomass was carbonized at 400, 600 and/or 800 °C in order the effect of carbonization temperature on the texture, surface chemistry and adsorption properties to be found. The activated carbons prepared were characterized by nitrogen adsorption, Scanning Electron Microscope, thermal analysis and Fourier Transform Infrared Spectroscopy. Equilibrium adsorption data followed both Langmuir and Freundlich isotherms. Adsorption followed second order rate kinetics. The adsorption capacity calculated from the Langmuir isotherm was found 454.62 mg g(-1) at an initial pH 3 at 25 °C for the phosphoric acid activated carbon carbonized at 400 °C that proved to be the best adsorbent.

  5. Exploring the role of physician communication about adjuvant endocrine therapy among breast cancer patients on active treatment: a qualitative analysis

    PubMed Central

    Farias, Albert J.; Ornelas, India J.; Hohl, Sarah D.; Zeliadt, Steven B.; Hansen, Ryan N.; Li, Christopher I.; Thompson, Beti

    2016-01-01

    Purpose To better understand how physicians communicate with breast cancer patients about adjuvant endocrine therapy (AET), we explored, from the breast cancer patient’s perspective, dimensions of the patient-provider communication among women who were on active AET treatment. Methods Qualitative methods using semi-structured in-depth interviews were conducted with breast cancer patients (n = 22) who filled a prescription for AET in the previous 12 months. Interview questions aimed to elicit experiences with AET. We reviewed and coded interview transcripts using qualitative principles of inductive reasoning to identify concepts and themes from interview data. Results We grouped emergent themes into four major functions of physician-patient communication: (1) information exchange, (2) decision-making to take and continue AET, (3) enabling patient self-management and monitoring potential side effects, and (4) emotional support. Physicians exchanged information with patients in a way that they understood and enhanced patient’s health literacy regarding the benefits and knowledge of AET. Physicians empowered patients to make decisions about their care. Patients expressed trust and confidence in their physician which helped them seek care when needed. Patients reported a high degree of self-efficacy to self-manage AET and were continuing treatment despite potential side effects. Conclusions The results from our study suggest that women’s interactions and communication with their physician may be an important factor that contributes to the continued use of AET. Physicians who can communicate information about AET treatment benefits, purpose, and expectations in a way that patients can understand is a critical aspect of care that needs to be further studied. PMID:27557832

  6. Developing analytical approaches to explore the connection between endocrine-active pharmaceuticals in water to effects in fish

    USGS Publications Warehouse

    Jones-Lepp, Tammy L.; Taniguchi-Fu, Randi L.; Morgan, Jade; Nance Jr., Trevor; Ward, Matthew; Alvarez, David A.; Mills, Lesley

    2015-01-01

    The emphasis of this research project was to develop and optimize a solid-phase extraction method and highperformance liquid chromatography-electrospray ionizationmass spectrometry method, such that a linkage between the detection of endocrine-active pharmaceuticals (EAPs) in the aquatic environment and subsequent effects on fish populations could eventually be studied. Four EAPs were studied: tamoxifen (TAM), exemestane (EXE), letrozole (LET), anastrozole (ANA); and three TAM metabolites: 4- hydroxytamoxifen, e/z endoxifen, and n-desmethyl tamoxifen. In aqueous matrices, the use of isotopically labeled standards for the EAPs allowed for the generation of good recoveries, greater than 80 %, and low relative standard deviations (% RSDs) (3 to 27 %). TAM metabolites had lower recoveries in the spiked water matrices: 35 to 93 % in waste/source water compared to 58 to 110 % in DI water. The precision in DI water was acceptable ranging from 8 to 38 % RSD. However, the precision in real environmental wastewaters could be poor, ranging from 15 to 120 % RSD, dependent upon unique matrix effects. In plasma, the overall recoveries of the EAPs were acceptable: 88 to 110 %, with %RSDs of 6 to 18 % (Table 3). The spiked recoveries of the TAM metabolites from plasma were good, ranging from 77 to 120 %, with %RSDs ranging from 27 to 32 %. Two of the TAM metabolites, 4- hydroxytamoxifen and n-desmethyl tamoxifen, were confirmed in most of the environmental aqueous samples. The discovery of TAM metabolites demonstrates that the source of the TAM metabolites, TAM, is constant, introducing a pseudo-persistence of this chemical into the environment.

  7. Organic active materials for batteries

    SciTech Connect

    Abouimrane, Ali; Weng, Wei; Amine, Khalil

    2016-08-16

    A rechargeable battery includes a compound having at least two active sites, R.sup.1 and R.sup.2; wherein the at least two active sites are interconnected by one or more conjugated moieties; each active site is coordinated to one or more metal ions M.sup.a+ or each active site is configured to coordinate to one or more metal ions; and "a" is 1, 2, or 3.

  8. Magnetic recovery of modified activated carbon powder used for removal of endocrine disruptors present in water.

    PubMed

    Borghi, Chiara Caterina; Fabbri, Massimo

    2014-01-01

    This paper was aimed at studying sustainable solutions for the treatment of water polluted by octylphenols and nonylphenols that are xenoextrogen compounds affecting human health and dangerous for the aquatic environment. We studied the removal of 4-octylphenol and 4-n-nonylphenol with concentrations of the order of 5-10 mg/l on a laboratory scale. A mixing time of 10 min with 0.1 g/l of magnetic-activated carbons (MACs) was enough to obtain 95 +/- 5% adsorption of both 4-octylphenol and 4-n-nonylphenol. The adsorption of the surfactants IGEPAL CO-630 and TRITON X-100, which are precursors of branched 4-nonylphenol and the carcinogenic 4-tert-octylphenol, respectively, was also studied using the same technique. For concentrations between 2 and 10mg/l of these alkylphenols ethoxylated, after 10min mixing with 0.5 g/l of MACs, a 95 +/- 5% adsorption was obtained. A 97 +/- 1% removal of MACs was achieved after 10min of continuous-flow magnetic filtration (14.5 l/min). The filter used was made of SUS440C magnetic steel spheres. Srm-Co permanent magnets provided a uniform flux density field of about 500 mT.

  9. Promoting Business Education through Student Organization Activities.

    ERIC Educational Resources Information Center

    Yelverton, Sandra

    1983-01-01

    Discusses the promotion of business education through the activities of student organizations. Describes specific programs, projects, and leadership development activities and their effectiveness in publicizing business education programs. (JOW)

  10. Chronobiology in the endocrine system.

    PubMed

    Haus, Erhard

    2007-08-31

    Biological signaling occurs in a complex web with participation and interaction of the central nervous system, the autonomous nervous system, the endocrine glands, peripheral endocrine tissues including the intestinal tract and adipose tissue, and the immune system. All of these show an intricate time structure with rhythms and pulsatile variations in multiple frequencies. Circadian (about 24-hour) and circannual (about 1-year) rhythms are kept in step with the cyclic environmental surrounding by the timing and length of the daily light span. Rhythmicity of many endocrine variables is essential for their efficacy and, even in some instances, for the qualitative nature of their effects. Indeed, the continuous administration of certain hormones and their synthetic analogues may show substantially different effects than expected. In the design of drug-delivery systems and treatment schedules involving directly or indirectly the endocrine system, consideration of the human time organization is essential. A large amount of information on the endocrine time structure has accumulated, some of which is discussed in this review.

  11. Endocrine controls of keratin expression.

    PubMed

    Ramot, Yuval; Paus, Ralf; Tiede, Stephan; Zlotogorski, Abraham

    2009-04-01

    Keratins are a family of intermediate filaments that serve various crucial roles in skin physiology. For mammalian skin to function properly, and to produce epidermal and hair keratins that are optimally adapted for their environment, it is critical that keratin gene and protein expression are stringently controlled. Given that the skin is not only targeted by multiple hormones, but also constitutes a veritable peripheral endocrine organ, it is not surprizing that intracutaneous keratin expression is underlined by tight endocrine controls. These controls encompass thyroid hormones, steroid hormones such as glucocorticoids (GCs), retinoic acid (RA) and vitamin D, and several neuroendocrine mediators. Here, we review why a better understanding of the endocrine controls of keratin expression is not only required for an improved insight into normal human skin and hair function, but may also open new therapeutic avenues in a wide range of skin and hair diseases.

  12. The significance of Ciona intestinalis as a stem organism in integrative studies of functional evolution of the chordate endocrine, neuroendocrine, and nervous systems.

    PubMed

    Matsubara, Shin; Kawada, Tsuyoshi; Sakai, Tsubasa; Aoyama, Masato; Osugi, Tomohiro; Shiraishi, Akira; Satake, Honoo

    2016-02-01

    Ascidians are the closest phylogenetic neighbors to vertebrates and are believed to conserve the evolutionary origin in chordates of the endocrine, neuroendocrine, and nervous systems involving neuropeptides and peptide hormones. Ciona intestinalis harbors various homologs or prototypes of vertebrate neuropeptides and peptide hormones including gonadotropin-releasing hormones (GnRHs), tachykinins (TKs), and calcitonin, as well as Ciona-specific neuropeptides such as Ciona vasopressin, LF, and YFV/L peptides. Moreover, molecular and functional studies on Ciona tachykinin (Ci-TK) have revealed the novel molecular mechanism of inducing oocyte growth via up-regulation of vitellogenesis-associated protease activity, which is expected to be conserved in vertebrates. Furthermore, a series of studies on Ciona GnRH receptor paralogs have verified the species-specific regulation of GnRHergic signaling including unique signaling control via heterodimerization among multiple GnRH receptors. These findings confirm the remarkable significance of ascidians in investigations of the evolutionary processes of the peptidergic systems in chordates, leading to the promising advance in the research on Ciona peptides in the next stage based on the recent development of emerging technologies including genome-editing techniques, peptidomics-based multi-color staining, machine-learning prediction, and next-generation sequencing. These technologies and bioinformatic integration of the resultant "multi-omics" data will provide unprecedented insights into the comprehensive understanding of molecular and functional regulatory mechanisms of the Ciona peptides, and will eventually enable the exploration of both conserved and diversified endocrine, neuroendocrine, and nervous systems in the evolutionary lineage of chordates.

  13. Effects of un-ionized ammonia on histological, endocrine, and whole organism endpoints in slimy sculpin (Cottus cognatus).

    PubMed

    Spencer, P; Pollock, R; Dubé, M

    2008-12-11

    mine effluents hold potential to affect the health of slimy sculpin including acute, chronic, histological and endocrine endpoints.

  14. Endocrine system and obesity.

    PubMed

    Ashburn, Doyle D; Reed, Mary Jane

    2010-10-01

    Obesity is associated with significant alterations in endocrine function. An association with type 2 diabetes mellitus and dyslipidemia has been well documented. This article highlights the complexities of treating endocrine system disorders in obese patients.

  15. Risk assessment of 'endocrine substances': guidance on identifying endocrine disruptors.

    PubMed

    Lewis, Richard W

    2013-12-16

    The European regulation on plant protection products (1107/2009) and other related legislation only support the marketing and use of chemical products on the basis that they do not induce endocrine disruption in humans or wildlife species. This legislation would appear to make the assumption that endocrine active chemicals should be managed differently from other chemicals presumably due to an assumed lack of a threshold for adverse effects. In the absence of agreed scientific criteria and guidance on how to identify and evaluate endocrine activity and disruption within these pieces of legislation, a European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to provide scientific criteria that may be used within the context of these three legislative documents. The first ECETOC technical report and associated workshop, held in 2009, presented a science-based concept on how to identify endocrine activity and disrupting properties of chemicals for both human health and the environment. Specific scientific criteria for the determination of endocrine activity and disrupting properties that integrate information from both regulatory toxicity studies and mechanistic/screening studies were proposed. These criteria combined the nature of the adverse effects detected in studies which give concern for endocrine toxicity with an understanding of the mode of action of toxicity so that adverse effects can be explained scientifically. A key element in the data evaluation is the consideration of all available information in a weight-of-evidence approach. Both sets of data (evidence of the adverse effect in apical studies and conclusive mode of action knowledge) are essential in order to correctly identify endocrine disruption according to accepted definitions. As the legislation seeks to regulate chemicals on a mode of action rather than the more traditional approach of adverse endpoints, then conclusive evidence of the mode of action of concern

  16. Endocrine disruption: fact or urban legend?

    PubMed

    Nohynek, Gerhard J; Borgert, Christopher J; Dietrich, Daniel; Rozman, Karl K

    2013-12-16

    Endocrine disruptors (EDs) are substances that cause adverse health effects via endocrine-mediated mechanisms in an intact organism or its progeny or (sub) populations. Purported EDCs in personal care products include 4-MBC (UV filter) or parabens that showed oestrogenic activity in screening tests, although regulatory toxicity studies showed no adverse effects on reproductive endpoints. Hormonal potency is the key issue of the safety of EDCs. Oestrogen-based drugs, e.g. the contraceptive pill or the synthetic oestrogen DES, possess potencies up to 7 orders of magnitude higher than those of PCP ingredients; yet, in utero exposure to these drugs did not adversely affect fertility or sexual organ development of offspring unless exposed to extreme doses. Additive effects of EDs are unlikely due to the multitude of mechanisms how substances may produce a hormone-like activity; even after uptake of different substances with a similar mode of action, the possibility of additive effects is reduced by different absorption, metabolism and kinetics. This is supported by a number of studies on mixtures of chemical EDCs. Overall, despite of 20 years of research a human health risk from exposure to low concentrations of exogenous chemical substances with weak hormone-like activities remains an unproven and unlikely hypothesis.

  17. Designing Endocrine Disruption Out of the Next Generation of Chemicals

    PubMed Central

    Schug, T.T; Abagyan, R.; Blumberg, B.; Collins, T.J.; Crews, D.; DeFur, P.L.; Dickerson, S.M.; Edwards, T.M.; Gore, A.C.; Guillette, L.J.; Hayes, T.; Heindel, J.J.; Moores, A.; Patisaul, H.B.; Tal, T.L.; Thayer, K.A.; Vandenberg, L.N.; Warner, J.; Watson, C.S.; Saal, F.S. vom; Zoeller, R.T.; O’Brien, K.P.; Myers, J.P.

    2013-01-01

    A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical’s potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at “the drawing board.” It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a ‘proof-of-principle’ test, we ran 6 endocrine disrupting chemicals (EDCs) that act

  18. Designing Endocrine Disruption Out of the Next Generation of Chemicals.

    PubMed

    Schug, T T; Abagyan, R; Blumberg, B; Collins, T J; Crews, D; DeFur, P L; Dickerson, S M; Edwards, T M; Gore, A C; Guillette, L J; Hayes, T; Heindel, J J; Moores, A; Patisaul, H B; Tal, T L; Thayer, K A; Vandenberg, L N; Warner, J; Watson, C S; Saal, F S Vom; Zoeller, R T; O'Brien, K P; Myers, J P

    2013-01-01

    A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at "the drawing board." It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a 'proof-of-principle' test, we ran 6 endocrine disrupting chemicals (EDCs) that act via

  19. Genetic testing by cancer site: endocrine system.

    PubMed

    Pilarski, Robert; Nagy, Rebecca

    2012-01-01

    Numerous hereditary syndromes, caused by mutations in multiple tumor suppressor genes and oncogenes, can cause tumors in organs of the endocrine system. The primary syndromes (and genes) addressed here include multiple endocrine neoplasia types 1 and 2 (MEN1 and RET genes), Cowden syndrome (PTEN), hereditary pheochromocytoma/paraganglioma syndromes (multiple genes), and von Hippel-Lindau disease (VHL). Clinical genetic testing is available for each of these syndromes and is generally directed to individuals with endocrine or other tumors and additional features suggestive of a hereditary syndrome. However, for some endocrine tumors, the proportion because of heredity is so high that genetic testing may be appropriate for all affected individuals. Management for hereditary cases typically involves aggressive screening and/or surgical protocols, starting at young ages to minimize morbidity and mortality. Endocrine tumors can be less commonly seen in a number of other hereditary syndromes (eg, neurofibromatosis), which are not reviewed in this section.

  20. 78 FR 57859 - Draft Guidance for Industry on Endocrine Disruption Potential of Drugs: Nonclinical Evaluation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... determine the potential for a drug to disrupt the endocrine system. This draft guidance also discusses... compounds that have the potential to interfere with some aspect of the endocrine system of an organism or its progeny. Any component of the endocrine system can be a target of endocrine disruptors,...

  1. [Regeneration of endocrine gastroenteropancreatic system in experimental and clinical pathology: concept development and current problems].

    PubMed

    Ivanova, V F

    2013-01-01

    Literature review contains the literature data and the results of author's own investigations describing the coming into being and the development of the concepts on the regeneration of endocrine gastroenteropancreatic (GEP) system under the conditions of norm, experimental and clinical pathology. Data analysis permitted to reveal the similarities and differences in the course of this process in various organs of the digestive system. Endocrine GEP system renewal occurs at different levels of its organization. At the tissue level, the endocrine cells renewal occurs via the transformation of exocrine cells into the endocrine ones and as a result of differentiation from stem cells via the "agranular" cell stage which are precursors of the endocrine cells. This pathway of regeneration is the major one after the damage. Regeneration at cellular level occurs through mitotic division of the differentiated endocrine cells (early stage of regeneration) and as a result of the formation granules with different hormonal profile in D-cells. At the intracellular level, the regeneration is realized through the intracellular structure restoration after their damage induced by the increase of cell functional activity accompanied by degranulation and dystrophic changes development

  2. Endocrine dysfunction in sepsis: a beneficial or deleterious host response?

    PubMed

    Gheorghiţă, Valeriu; Barbu, Alina Elena; Gheorghiu, Monica Livia; Căruntu, Florin Alexandru

    2015-03-01

    Sepsis is a systemic, deleterious inflammatory host response triggered by an infective agent leading to severe sepsis, septic shock and multi-organ failure. The host response to infection involves a complex, organized and coherent interaction between immune, autonomic, neuroendocrine and behavioral systems. Recent data have confirmed that disturbances of the autonomic nervous and neuroendocrine systems could contribute to sepsis-induced organ dysfunction. Through this review, we aimed to summarize the current knowledge about the endocrine dysfunction as response to sepsis, specifically addressed to vasopressin, copeptin, cortisol, insulin and leptin. We searched the following readily accessible, clinically relevant databases: PubMed, UpToDate, BioMed Central. The immune system could be regarded as a "diffuse sensory organ" that signals the presence of pathogens to the brain through different pathways, such as the vagus nerve, endothelial activation/dysfunction, cytokines and neurotoxic mediators and the circumventricular organs, especially the neurohypophysis. The hormonal profile changes substantially as a consequence of inflammatory mediators and microorganism products leading to inappropriately low levels of vasopressin, sick euthyroid syndrome, reduced adrenal responsiveness to ACTH, insulin resistance, hyperglycemia as well as hyperleptinemia. In conclusion, clinical diagnosis of this "pan-endocrine illness" is frequently challenging due to the many limiting factors. The most important benefits of endocrine markers in the management of sepsis may be reflected by their potential to be used as biomarkers in different scoring systems to estimate the severity of the disease and the risk of death.

  3. Evaluation of endocrine disrupting activity of plasticizers in polyvinyl chloride tubes by estrogen receptor alpha binding assay.

    PubMed

    Ohashi, Atsushi; Kotera, Hirohisa; Hori, Hideo; Hibiya, Makoto; Watanabe, Koji; Murakami, Kazutaka; Hasegawa, Midori; Tomita, Makoto; Hiki, Yoshinobu; Sugiyama, Satoshi

    2005-01-01

    Polyvinyl chloride (PVC) tubing is an indispensable medical material for extracorporeal circulation therapy. However, di(2-ethylhexyl)phthalate (DEHP), a suspected endocrine disruptor, can be eluted from PVC, suggesting that an alternative material that does not contain DEHP is needed for clinical applications. First, we evaluated the endocrine disrupting risks of the plasticizers contained in PVC tubes by investigating their binding affinities for the human estrogen receptor alpha (ERalpha). Our results revealed that, while DEHP has some binding affinity for ERalpha, neither epoxidized soybean oil nor tris(2-ethylhexyl)trimellitate (an alternative to DEHP) has any affinity for ERalpha. Second, we evaluated the endocrine disrupting risks of a tube made of newly developed plasticizer-free (PF) materials. We confirmed the presence of DEHP and detected several unidentified substances in plasma stored within the PVC tube. This plasma's competitive binding affinity for ERalpha was significantly higher than that of control plasma (P < 0.01). In contrast, the profile of plasma stored in the PF tube was similar to that of the control, both in terms of high-performance liquid chromatography chromatograms and competitive binding capacity for ERalpha, suggesting that the PF tube is biocompatible and is useful for reducing the elution of substances capable of binding to ERalpha.

  4. D-Amino Acids in the Nervous and Endocrine Systems

    PubMed Central

    Kiriyama, Yoshimitsu

    2016-01-01

    Amino acids are important components for peptides and proteins and act as signal transmitters. Only L-amino acids have been considered necessary in mammals, including humans. However, diverse D-amino acids, such as D-serine, D-aspartate, D-alanine, and D-cysteine, are found in mammals. Physiological roles of these D-amino acids not only in the nervous system but also in the endocrine system are being gradually revealed. N-Methyl-D-aspartate (NMDA) receptors are associated with learning and memory. D-Serine, D-aspartate, and D-alanine can all bind to NMDA receptors. H2S generated from D-cysteine reduces disulfide bonds in receptors and potentiates their activity. Aberrant receptor activity is related to diseases of the central nervous system (CNS), such as Alzheimer's disease, amyotrophic lateral sclerosis, and schizophrenia. Furthermore, D-amino acids are detected in parts of the endocrine system, such as the pineal gland, hypothalamus, pituitary gland, pancreas, adrenal gland, and testis. D-Aspartate is being investigated for the regulation of hormone release from various endocrine organs. Here we focused on recent findings regarding the synthesis and physiological functions of D-amino acids in the nervous and endocrine systems. PMID:28053803

  5. How Somatic Adult Tissues Develop Organizer Activity.

    PubMed

    Vogg, Matthias C; Wenger, Yvan; Galliot, Brigitte

    2016-01-01

    The growth and patterning of anatomical structures from specific cellular fields in developing organisms relies on organizing centers that instruct surrounding cells to modify their behavior, namely migration, proliferation, and differentiation. We discuss here how organizers can form in adult organisms, a process of utmost interest for regenerative medicine. Animals like Hydra and planarians, which maintain their shape and fitness thanks to a highly dynamic homeostasis, offer a useful paradigm to study adult organizers in steady-state conditions. Beside the homeostatic context, these model systems also offer the possibility to study how organizers form de novo from somatic adult tissues. Both extracellular matrix remodeling and caspase activation play a key role in this transition, acting as promoters of organizer formation in the vicinity of the wound. Their respective roles and the crosstalk between them just start to be deciphered.

  6. Fish endocrine disruption responses to a major wastewater treatment facility upgrade.

    PubMed

    Barber, Larry B; Vajda, Alan M; Douville, Chris; Norris, David O; Writer, Jeffery H

    2012-02-21

    The urban-water cycle modifies natural stream hydrology, and domestic and commercial activities increase the burden of endocrine-disrupting chemicals, such as steroidal hormones and 4-nonylphenol, that can disrupt endocrine system function in aquatic organisms. This paper presents a series of integrated chemical and biological investigations into the occurrence, fate, and effects of endocrine-disrupting chemicals in the City of Boulder Colorado's WWTF and Boulder Creek, the receiving stream. Results are presented showing the effects of a full-scale upgrade of the WWTF (that treats 0.6 m(3) s(-1) of sewage) from a trickling filter/solids contact process to an activated sludge process on the removal of endocrine-disrupting compounds and other contaminants (including nutrients, boron, bismuth, gadolinium, and ethylenediaminetetraacetic acid) through each major treatment unit. Corresponding impacts of pre- and postupgrade effluent chemistry on fish reproductive end points were evaluated using on-site, continuous-flow experiments, in which male fathead minnows (Pimephales promelas) were exposed for 28 days to upstream Boulder Creek water and WWTF effluent under controlled conditions. The upgrade of the WWTF resulted in improved removal efficiency for many endocrine-disrupting chemicals, particularly 17β-estradiol and estrone, and fish exposed to the postupgrade effluent indicated reduction in endocrine disruption relative to preupgrade conditions.

  7. Tracking multiple modes of endocrine activity in Australia's largest inland sewage treatment plant and effluent- receiving environment using a panel of in vitro bioassays.

    PubMed

    Roberts, Jenna; Bain, Peter A; Kumar, Anupama; Hepplewhite, Christopher; Ellis, David J; Christy, Andrew G; Beavis, Sara G

    2015-10-01

    Estrogenicity of sewage effluents, and related ecotoxicological effects in effluent-receiving environments, have been widely reported over the last 2 decades. However, relatively little attention has been given to other endocrine pathways that may be similarly disrupted by a growing list of contaminants of concern. Furthermore, the Australian evidence base is limited compared with those of Europe and North America. During a low dilution period in summer, the authors investigated multiple endocrine potencies in Australia's largest inland sewage treatment plant (STP) and the Lower Molonglo/Upper Murrumbidgee effluent-receiving environment. This STP receives 900 L/s of mostly domestic wastewater from a population of 350 000, and contributes a high proportion of total flow in the lower catchment during dry periods. A panel of in vitro receptor-driven transactivation assays were used to detect (anti)estrogenic, (anti) androgenic, (anti)progestagenic, glucocorticoid, and peroxisome-proliferator activity at various stages of the sewage treatment process. Total estrogenic and (anti)androgenic potency was removed after primary and/or secondary treatment; however, total removal efficiency for glucocorticoid potency was poorer (53-66%), and progestagenic potency was found to increase along the treatment train. Estrogenicity was detected in surface waters and bed sediments upstream and downstream of the effluent outfall, at maximum levels 10 times lower than low-hazard thresholds. Glucocorticoid and progestagenic activity were found to persist to 4 km downstream of the effluent outfall, suggesting that future research is needed on these endocrine-disrupting chemical categories in effluent-receiving systems.

  8. Endocrine FGFs: Evolution, Physiology, Pathophysiology, and Pharmacotherapy

    PubMed Central

    Itoh, Nobuyuki; Ohta, Hiroya; Konishi, Morichika

    2015-01-01

    The human fibroblast growth factor (FGF) family comprises 22 structurally related polypeptides that play crucial roles in neuronal functions, development, and metabolism. FGFs are classified as intracrine, paracrine, and endocrine FGFs based on their action mechanisms. Paracrine and endocrine FGFs are secreted signaling molecules by acting via cell-surface FGF receptors (FGFRs). Paracrine FGFs require heparan sulfate as a cofactor for FGFRs. In contrast, endocrine FGFs, comprising FGF19, FGF21, and FGF23, require α-Klotho or β-Klotho as a cofactor for FGFRs. Endocrine FGFs, which are specific to vertebrates, lost heparan sulfate-binding affinity and acquired a systemic signaling system with α-Klotho or β-Klotho during early vertebrate evolution. The phenotypes of endocrine FGF knockout mice indicate that they play roles in metabolism including bile acid, energy, and phosphate/active vitamin D metabolism. Accumulated evidence for the involvement of endocrine FGFs in human genetic and metabolic diseases also indicates their pathophysiological roles in metabolic diseases, potential risk factors for metabolic diseases, and useful biomarkers for metabolic diseases. The therapeutic utility of endocrine FGFs is currently being developed. These findings provide new insights into the physiological and pathophysiological roles of endocrine FGFs and potential diagnostic and therapeutic strategies for metabolic diseases. PMID:26483756

  9. GATA factors in endocrine neoplasia

    PubMed Central

    Pihlajoki, Marjut; Färkkilä, Anniina; Soini, Tea; Heikinheimo, Markku; Wilson, David B.

    2015-01-01

    GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted. PMID:26027919

  10. Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation

    PubMed Central

    Fanning, Sean W; Mayne, Christopher G; Dharmarajan, Venkatasubramanian; Carlson, Kathryn E; Martin, Teresa A; Novick, Scott J; Toy, Weiyi; Green, Bradley; Panchamukhi, Srinivas; Katzenellenbogen, Benita S; Tajkhorshid, Emad; Griffin, Patrick R; Shen, Yang; Chandarlapaty, Sarat; Katzenellenbogen, John A; Greene, Geoffrey L

    2016-01-01

    Somatic mutations in the estrogen receptor alpha (ERα) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERα constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy resistance. Here, we integrate biophysical and structural biology data to reveal how these mutations lead to a constitutively active and antiestrogen-resistant ERα. We show that these mutant ERs recruit coactivator in the absence of hormone while their affinities for estrogen agonist (estradiol) and antagonist (4-hydroxytamoxifen) are reduced. Further, they confer antiestrogen resistance by altering the conformational dynamics of the loop connecting Helix 11 and Helix 12 in the ligand-binding domain of ERα, which leads to a stabilized agonist state and an altered antagonist state that resists inhibition. DOI: http://dx.doi.org/10.7554/eLife.12792.001 PMID:26836308

  11. Steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota—Study design, methods, and data, 2009–10

    USGS Publications Warehouse

    Erickson, Melinda L.

    2012-01-01

    The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of steroidal hormones and other endocrine active compounds in shallow groundwater in nonagricultural areas of Minnesota during 2009–10. This report describes the study design and methods, and presents the data collected on steroidal hormones and other related compounds. Environmental and quality-control samples were collected from 40 wells as part of this study. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 16 steroidal hormones and 4 other related compounds, of which all but 2 compounds are endocrine active compounds. Most of the water samples did not contain detectable concentrations of any of the 20 compounds analyzed. Water samples from three wells had detectable concentrations of one or more compounds. Bisphenol A was detected in samples from three wells, and trans-diethylstilbestrol was detected in one of the samples in which bisphenol A also was detected.

  12. A mutation in the RET proto-oncogene in Hirschsprung's disease affects the tyrosine kinase activity associated with multiple endocrine neoplasia type 2A and 2B.

    PubMed Central

    Cosma, M P; Panariello, L; Quadro, L; Dathan, N A; Fattoruso, O; Colantuoni, V

    1996-01-01

    We demonstrate that a Hirschsprung (HSCR) mutation in the tyrosine kinase domain of the RET proto-oncogene abolishes in cis the tyrosine-phosphorylation associated with the activating mutation in multiple endocrine neoplasia type 2A (MEN2A) in transiently transfected Cos cells. Yet the double mutant RET2AHS retains the ability to form stable dimers, thus dissociating the dimerization from the phosphorylation potential. Co-transfection experiments with single and double mutants carrying plasmids RET2A and RET2AHS in different ratios drastically reduced the phosphorylation levels of the RET2A protein, suggesting a dominant-negative effect of the HSCR mutation. Also, the phosphorylation associated with the multiple endocrine neoplasia type 2B (MEN2B) allele was affected in experiments with single and double mutants carrying plasmids co-transfected under the same conditions. Finally, analysis of the enzymic activity of MEN2A and MEN2B tumours confirmed the relative levels of tyrosine phosphorylation observed in Cos cells, indicating that this condition, in vivo, may account for the RET transforming potential. PMID:8670046

  13. Adrenocortical endocrine disruption.

    PubMed

    Harvey, Philip W

    2016-01-01

    The adrenal has been neglected in endocrine disruption regulatory testing strategy. The adrenal is a vital organ, adrenocortical insufficiency is recognised in life threatening "adrenal crises" and Addison's disease, and the consequences of off-target toxicological inhibition of adrenocortical steroidogenesis is well recognised in clinical medicine, where drugs such as aminoglutethimide and etomidate killed patients via unrecognised inhibition of adrenocortical steroidogenic enzymes (e.g. CYP11B1) along the cortisol and aldosterone pathways. The consequences of adrenocortical dysfunction during early development are also recognised in the congenital salt wasting and adrenogenital syndromes presenting neonatally, yet despite a remit to focus on developmental and reproductive toxicity mechanisms of endocrine disruption by many regulatory agencies (USEPA EDSTAC; REACH) the assessment of adrenocortical function has largely been ignored. Further, every step in the adrenocortical steroidogenic pathway (ACTH receptor, StAR, CYP's 11A1, 17, 21, 11B1, 11B2, and 3-hydroxysteroid dehydrogenase Δ4,5 isomerase) is known to be a potential target with multiple examples of chemicals inhibiting these targets. Many of these chemicals have been detected in human and wildlife tissues. This raises the question of whether exposure to low level environmental chemicals may be affecting adrenocortical function. This review examines the omission of adrenocortical testing in the current regulatory frameworks; the characteristics that make the adrenal cortex particularly vulnerable to toxic insult; chemicals and their toxicological targets within the adrenocortical steroidogenic pathways; the typical manifestations of adrenocortical toxicity (e.g. human iatrogenically induced pharmacotoxicological adrenal insufficiency, manifestations in typical mammalian regulatory general toxicology studies, manifestations in wildlife) and models of adrenocortical functional assessment. The utility of the

  14. Identification of triclosan intermediates produced by oxidative degradation using TiO2 in pure water and their endocrine disrupting activities.

    PubMed

    Sankoda, K; Matsuo, H; Ito, M; Nomiyama, K; Arizono, K; Shinohara, R

    2011-05-01

    The photodegradation pathways of 2-(2,4-dichlorophenoxy)-5-chlorophenol (triclosan) in water were studied. The main purposes were to identify structures of intermediates derived by radical reaction using TiO(2) advanced oxidation processes and to evaluate the endocrine disrupting activities in treated triclosan during oxidative reactions. Intermediates such as dichlorophenols, 2,8-dibenzo-p-dioxin, tetrachlorinated diphenyl ether (tetraclosan) and hydroxylated triclosan were produced by photoreaction. The estrogen, thyroid hormone and retinoid X receptor activities of the treated triclosan were measured with the yeast two-hybrid assay. It was found that tetraclosan and 2,4-dichlorophenol have stronger thyroid hormone activities than triclosan in the presence of S9.

  15. [Postpartum endocrine syndrome].

    PubMed

    Ducarme, G; Châtel, P; Luton, D

    2008-05-01

    Postpartum endocrine syndromes occur in the year after delivery. They are due to immunologic and vascular modifications during pregnancy. The Sheehan syndrome is the first described postpartum endocrine syndrome and consists on a hypophyse necrosis in relation with a hypovolemic shock during delivery. The immunologic consequences of the pregnancy are the most frequent, sometimes discrete and transitory. The physiological evolution of the endocrine glands during pregnancy and the most frequent post-partum endocrine syndromes are discussed: postpartum lymphocytic hypophysitis, thyroiditis and Sheehan' syndrome.

  16. Performance of metal-organic framework MIL-101 after surfactant modification in the extraction of endocrine disrupting chemicals from environmental water samples.

    PubMed

    Huang, Zhenzhen; Lee, Hian Kee

    2015-10-01

    The research presented in this paper explored the modification and application of a metal-organic framework, MIL-101, with nonionic surfactant-Triton X-114 in dispersive solid-phase extraction for the preconcentration of four endocrine disrupting chemicals (estrone, 17α-ethynylestradiol, estriol and diethylstilbestrol) from environmental water samples. Triton X-114 molecules could be adsorbed by the hydrophobic surface of the MIL-101 crystals, and thus improved the dispersibility of MIL-101 in aqueous solution by serving as a hydrophilic coating. Cloud point phase separation from Triton X-114 accelerated the separation of extracts from the aqueous matrix. The proposed method combines the favorable attributes of strong adsorption capacity resulting from the porous structure of MIL-101 and self-assembly of Triton X-114 molecules. Post-extraction derivatization using N-methyl-N-(trimethylsilyl)trifluoroacetamide was employed to facilitate the quantitative determination of the extracts by gas chromatography-mass spectrometry. The main factors affecting the preparation of modified MIL-101, and extraction of the analytes, such as the amount of surfactant, the ultrasonic and vortex durations, solution pH and desorption conditions, were investigated in detail. Under the optimized conditions, the present method yielded low limits of detection (0.006-0.023 ng/mL), good linearity from 0.09 to 45 ng/mL (coefficients of determination higher than 0.9980) and acceptable precision (relative standard deviations of 2.2-13%). The surface modified MIL-101 was demonstrated to be effective for the extraction of the selected estrogens from aqueous samples, giving rise to markedly improved extraction performance compared to the unmodified MIL-101.

  17. Adrenomedullin and endocrine disorders.

    PubMed

    Letizia, C; Rossi, G; Cerci, S

    2003-12-01

    Adrenomedullin (AM) is a recently discovered potent vasodilatory peptide, originally isolated in extracts of human pheochromocytoma, with activities including maintenance of cardiovascular and renal homeostasis through vasodilatation, diuresis and natriuresis. Human AM consists of 52 amino acids with a 6-member ring structure linked by a disulfide bond and amidated COOH terminal, which belongs to calcitonin gene-related peptide (CGRP) and amylin. The main sites of AM production are the lungs, vascular tissues (both endothelial and smooth muscle cells), heart, kidney, adrenal glands, pancreatic islets, placenta, anterior pituitary gland and gastrointestinal neuroendocrine system. Intravenous injection of AM increases blood flow predominantly in the tissues with the highest AM expression, suggesting that AM functions primarily as a paracrine/autocrine hormone, but it is also important as circulating hormone. The objective of this review is to analyze the evidence that AM may play a role in some endocrine disorders.

  18. [Acne vulgaris: endocrine aspects].

    PubMed

    Dekkers, O M; Thio, B H; Romijn, J A; Smit, J W A

    2006-06-10

    Androgens play an important part in the development of acne vulgaris. Androgen levels in patients with acne are higher than those in controls and people with the androgen insensitivity syndrome do not develop acne. Local factors other than androgen plasma levels, also play a part in the development of acne. The skin contains enzymes that convert precursor hormones to the more potent androgens such as testosterone and dihydrotestosterone. Androgen synthesis can therefore be regulated locally. The effects of androgens on the skin are the result of circulating androgens and enzyme activity in local tissues and androgen receptors. Acne is a clinical manifestation of some endocrine diseases. The polycystic ovary syndrome has the highest prevalence. In women with acne that persists after puberty, in 10-200% of cases polycystic ovary syndrome is later diagnosed. The mechanism of hormonal anti-acne therapy may work by blocking the androgen-production (oestrogens) or by blocking the androgen receptor (cyproterone, spironolactone).

  19. Sleep and the endocrine system.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2015-07-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  20. Sleep and the Endocrine System.

    PubMed

    Morgan, Dionne; Tsai, Sheila C

    2016-03-01

    In this article, the effect of sleep and sleep disorders on endocrine function and the influence of endocrine abnormalities on sleep are discussed. Sleep disruption and its associated endocrine consequences in the critically ill patient are also reviewed.

  1. ENDOCRINE DISRUPTORS IN THE ENVIRONMENT

    EPA Science Inventory

    The endocrine system produces hormones which are powerful natural chemicals that regulate important life processes. Endocrine disruptors are human-made chemicals distributed globally which have the potential to interfere with the endocrine system and produce serious biological e...

  2. Associations among Endocrine, Inflammatory, and Bone Markers, Body Composition and Physical Activity to Weight Loss Induced Bone Loss

    PubMed Central

    Labouesse, Marie A.; Gertz, Erik R.; Piccolo, Brian D.; Souza, Elaine C.; Schuster, Gertrud U.; Witbracht, Megan G.; Woodhouse, Leslie R.; Adams, Sean H.; Keim, Nancy L.; Van Loan, Marta D.

    2015-01-01

    INTRODUCTION Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE Our aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; 3) model the contribution of these variables to post weight-loss BMD and BMC METHODS Overweight/obese women (BMI: 28–37 kg/m2) were enrolled in an energy reduced (−500 kcal/d; −2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n=25, 32.2 ± 8.8y) or low dairy (LD: ≤ 1 serving/d; n=26, 31.7 ± 8.4 y). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS Following weight loss, AD intake resulted in significantly greater (p= 0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post- body fat were negatively associated with hip and lumbar spine BMC (r= −0.28, p=0.04 to −0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = −0.29 (p=0.04) to r = −0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss Factors. Pre-weight loss Factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss Factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the Factors contributed to the variance in lumbar spine BMD. CONCLUSION AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD

  3. Phosphofructokinase Activities in Photosynthetic Organisms 1

    PubMed Central

    Carnal, Nancy Wieland; Black, Clanton C.

    1983-01-01

    A pyrophosphate-dependent phosphofructokinase (PPi-PFK) activity is detectable in extracts of a wide variety of primitive and advanced plants, the Charalean algae, and in the photosynthetic bacterium, Rhodospirillum rubrum. Angiosperms with extractable PPi-PFK activities 4- to 70-fold higher than the respective ATP-PFK activities tend to be succulent and to exhibit CAM. Even though PPi-PFK activity is not detected in crude extracts of some well known CAM plants, e.g. plants in the Crassulaceae, gel filtration of the extract and/or inclusion of the PPi-PFK activator, fructose 2,6-bisphosphate, in the assay reveals that a PPi-PFK activity is present in these species. Fructose 2,6-bisphosphate likewise activates PPi-PFK activities in extracts of C3 and C4 plants. C3 and C4 plant PPi-PFK activities are roughly equivalent to ATP-PFK activities in the same species. PPi-PFK activity is also detected in some bryophytes, lower vascular plants, ferns, and gymnosperms. The Charophytes, advanced algae presumed to be similar to species ancestral to vascular plants, exhibit at least 4-fold higher PPi-PFK than ATP-PFK activities. R. rubrum also exhibits a much higher PPi-PFK activity than ATP-PFK activity. These data indicate that PPi-PFK may serve as an alternate enzyme to ATP-PFK in glycolysis in a wide range of photosynthetic organisms. PMID:16662776

  4. Circadian clock control of endocrine factors.

    PubMed

    Gamble, Karen L; Berry, Ryan; Frank, Stuart J; Young, Martin E

    2014-08-01

    Organisms experience dramatic fluctuations in demands and stresses over the course of the day. In order to maintain biological processes within physiological boundaries, mechanisms have evolved for anticipation of, and adaptation to, these daily fluctuations. Endocrine factors have an integral role in homeostasis. Not only do circulating levels of various endocrine factors oscillate over the 24 h period, but so too does responsiveness of target tissues to these signals or stimuli. Emerging evidence suggests that these daily endocrine oscillations do not occur solely in response to behavioural fluctuations associated with sleep-wake and feeding-fasting cycles, but are orchestrated by an intrinsic timekeeping mechanism known as the circadian clock. Disruption of circadian clocks by genetic and/or environmental factors seems to precipitate numerous common disorders, including the metabolic syndrome and cancer. Collectively, these observations suggest that strategies designed to realign normal circadian rhythmicities hold potential for the treatment of various endocrine-related disorders.

  5. The endocrine quiz.

    PubMed

    Kalra, Sanjay; Baruah, Manash P; Nagesh, V Sri

    2014-05-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject.

  6. The endocrine quiz

    PubMed Central

    Kalra, Sanjay; Baruah, Manash P.; Nagesh, V. Sri

    2014-01-01

    With the recent explosion in endocrine conferences, audience fatigue has set in and conference planners are now looking at newer pedagogic methods to revive the interest of audiences in these conferences. The endocrine quiz has finally come of vogue and is increasingly becoming one of the most popular attractions of any ranking endocrine conference. The endocrine quiz has a large and varied palette and draws questions from religious scriptures, history, literature, current affairs, sports, movies and basic and paramedical sciences. The more we delve into the quizzable aspects of endocrinology, the more we realize that endocrinology is ubiquitous and there is no sphere in human life untouched by endocrine disorders. Be it epic characters like Kumbhakarna and Bheema, fiction characters like Tintin or Orphan Annie, sportspersons like Gail Devers or heads of state like George Bush Sr and Boris Yeltsin, all have contributed to the melting pot of endocrine quizzing. Adding further grist to the endocrine mill are the Nobel prizes, with their attendant anecdotes and controversies. Step into this world of endocrine quizzing to have an up close and personal look at the diverse facets of this subject. PMID:24944922

  7. Endocrine disorders & female infertility.

    PubMed

    Unuane, David; Tournaye, Herman; Velkeniers, Brigitte; Poppe, Kris

    2011-12-01

    Female infertility occurs in about 37% of all infertile couples and ovulatory disorders account for more than half of these. The ovaries are in continuous interaction with the other endocrine organs. The interplay may account for infertility occurring at different levels and may render the diagnosis of infertility a difficult exercise for the involved physician. A hypothalamic cause of female infertility should be considered in an appropriate clinical context, with tests pointing to a hypogonadotropic hypogonadism. It can be functional, physiological or related to organic causes. Hyperprolactinemia has well characterized effects on the normal gonadal function and treatment is well established. Acromegaly and Cushing's disease may impair fertility at different levels, mechanisms involved however remain ill defined. Thyroid disorders, both hyperthyroidism and hypothyroidism, can interact with the ovaries, through a direct effect on ovarian function, but autoimmunity may be involved, as well as alterations of the sex hormone binding protein levels. Primary ovarian disorders, such as the polycystic ovary syndrome and primary ovarian insufficiency are frequent diseases, for which novel treatments are currently being developed and discussed. We will propose an algorithm for the diagnosis and approach of the female patient presenting with infertility on the basis of the available evidence in literature.

  8. Human biological monitoring of suspected endocrine-disrupting compounds

    PubMed Central

    Faniband, Moosa; Lindh, Christian H; Jönsson, Bo AG

    2014-01-01

    Endocrine-disrupting compounds are exogenous agents that interfere with the natural hormones of the body. Human biological monitoring is a powerful method for monitoring exposure to endocrine disrupting compounds. In this review, we describe human biological monitoring systems for different groups of endocrine disrupting compounds, polychlorinated biphenyls, brominated flame retardants, phthalates, alkylphenols, pesticides, metals, perfluronated compounds, parabens, ultraviolet filters, and organic solvents. The aspects discussed are origin to exposure, metabolism, matrices to analyse, analytical determination methods, determinants, and time trends. PMID:24369128

  9. Critical analysis of endocrine disruptive activity of triclosan and its relevance to human exposure through the use of personal care products.

    PubMed

    Witorsch, Raphael J

    2014-07-01

    This review examines the mammalian and human literature pertaining to the potential endocrine disruptive effects of triclosan (TCS). Dietary exposure to TCS consistently produces a dose-dependent decrease in serum thyroxine (T4) in rats without any consistent change in TSH or triiodothyronine (T3). Human studies reveal no evidence that the TCS exposure through personal care product use affects the thyroid system. TCS binds to both androgen and estrogen receptors in vitro with low affinity and evokes diverse responses (e.g., agonist, antagonist, or none) in steroid receptor transfected cell-based reporter assays. Two of three studies in rats have failed to show that TCS exposure suppresses male reproductive function in vivo. Three of four studies have failed to show that TCS possesses estrogenic (or uterotrophic) activity in rats. However, two studies reported that, while TCS lacks estrogenic activity, it can amplify the action of estrogen in vivo. The in vitro, in vivo, and epidemiologic studies reviewed herein show little evidence that TCS adversely affects gestation or postpartum development of offspring. Furthermore, previously reported toxicity testing in a variety of mammalian species shows little evidence that TCS adversely affects thyroid function, male and female reproductive function, gestation, or postpartum development of offspring. Finally, doses of TCS reported to produce hypothyroxinemia, and occasional effects on male and female reproduction, gestation, and offspring in animal studies are several orders of magnitude greater than the estimated exposure levels of TCS in humans. Overall, little evidence exists that TCS exposure through personal care product use presents a risk of endocrine disruptive adverse health effects in humans.

  10. Mitochondria and endocrine function of adipose tissue.

    PubMed

    Medina-Gómez, Gema

    2012-12-01

    Excess of adipose tissue is accompanied by an increase in the risk of developing insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless, total or partial absence of fat or its accumulation in other tissues (lipotoxicity) is also associated to these complications. White adipose tissue (WAT) was traditionally considered a metabolically active storage tissue for lipids while brown adipose tissue (BAT) was considered as a thermogenic adipose tissue with higher oxidative capacity. Nowadays, WAT is also considered an endocrine organ that contributes to energy homeostasis. Experimental evidence tends to link the malfunction of adipose mitochondria with the development of obesity and T2D. This review discusses the importance of mitochondrial function in adipocyte biology and the increased evidences of mitochondria dysfunction in these epidemics. New strategies targeting adipocyte mitochondria from WAT and BAT are also discussed as therapies against obesity and its complications in the near future.

  11. Criteria for malignancy in gastrointestinal endocrine tumors.

    PubMed

    Bordi, Cesare; D'Adda, Tiziana; Azzoni, Cinzia; Pizzi, Silvia; Bottarelli, Lorena; Mormandi, Francesca; Antonetti, Tommaso; Luong, Tu Vinh; Rindi, Guido

    2006-01-01

    In contrast with the large amount of data generated from endocrine tumors of the pancreas, sparse and mostly unconfirmed data are available on the criteria for the assessment of malignancy risk and patient outcome in endocrine tumors of the gastrointestinal tract. In these conditions the 2000 WHO classification with its standardized scheme of pathologic report constitutes a framework facilitating the assessment of tumor malignancy and has been regarded as useful for clinical purposes, providing the basis for proper management of the patients and for the design of treatment protocols. The classification is based on a combination of pathological and clinical features with parameters specific for each organ in which the endocrine tumors originate. Three main categories, one further subdivided into two subgroups, are considered: (1) well-differentiated endocrine tumors, further subdivided into tumors with benign and with uncertain behavior; (2) well-differentiated endocrine carcinomas, low grade; and (3) poorly differentiated endocrine carcinomas, high grade. In this review the differential tumor characteristics between the different categories are summarized. Moreover, the relevance of additional features with respect to tumor prognostication, chiefly the Ki-67 proliferation index and malignancy-associated genetic changes, is discussed with emphasis on the discrepancies emerging between tumors of foregut and of midgut origin.

  12. Pharmaceutical chemicals and endocrine disrupters in municipal wastewater in Tokyo and their removal during activated sludge treatment.

    PubMed

    Nakada, Norihide; Tanishima, Toshikatsu; Shinohara, Hiroyuki; Kiri, Kentaro; Takada, Hideshige

    2006-10-01

    We measured six acidic analgesics or anti-inflammatories (aspirin, ibuprofen, naproxen, ketoprofen, fenoprofen, mefenamic acid), two phenolic antiseptics (thymol, triclosan), four amide pharmaceuticals (propyphenazone, crotamiton, carbamazepine, diethyltoluamide), three phenolic endocrine disrupting chemicals (nonylphenol, octylphenol, bisphenol A), and three natural estrogens (17beta-estradiol, estrone, estriol) in 24-h composite samples of influents and secondary effluents collected seasonally from five municipal sewage treatment plants in Tokyo. Aspirin was most abundant in the influent, with an average concentration of 7300 ng/L (n = 16), followed by crotamiton (921 ng/L), ibuprofen (669 ng/L), triclosan (511 ng/L), and diethyltoluamide (503 ng/L). These concentrations were 1 order of magnitude lower than those reported in the USA and Europe. This can be ascribed to lower consumption of the pharmaceuticals in Japan. Aspirin, ibuprofen, and thymol were removed efficiently during primary + secondary treatment (> 90% efficiency). On the other hand, amide-type pharmaceuticals, ketoprofen, and naproxen showed poor removal (< 50% efficiency), which is probably due to their lower hydrophobicity (logKow < 3). Because of the persistence of crotamiton during secondary treatment, crotamiton was most abundant among the target pharmaceuticals in the effluent. This is the first paper to report ubiquitous occurrence of crotamiton, a scabicide, in sewage. Because crotamiton is used worldwide and it is persistent during secondary treatment, it is a promising molecular marker of sewage and secondary effluent.

  13. Polycyclodextrin and Carbon Nanotubes as Composite for Tyrosinase Immobilization and Its Superior Electrocatalytic Activity Towards Butylparaben an Endocrine Disruptor.

    PubMed

    Rather, Jahangir Ahmad; Pilehvar, Sanaz; De Wael, Karolien

    2015-05-01

    We developed a protocol for the immobilization of tyrosinase (Tyr) on the composite of polycyclodextrin polymer (CDP) and carbon nanotubes for the detection of an endocrine disruptor, i.e., butylparaben (BP). The formation of the CDP polymer was characterized by UV-Vis spectrophotometry. The conducting film of cross-linked CDP and carbon nanotubes, displays excellent matrix capabilities for Tyr immobilization. The host-guest chemical reaction ability of CD and the π-π stacking interaction assure the bioactivity of Tyr towards butylparaben. The developed biosensor was characterized electrochemically by electrochemical impedance spectroscopy. The enzyme-substrate kinetic parameters such as the apparent Michaelis-Menten constant (K(M)(app)) was measured under saturated substrate concentration. The determination of butylparaben was carried out by using square wave voltammetry over the concentration range of 2.1 to 35.4 μM with a detection limit of 0.1 μM. The fabricated biosensor was successfully applied in real-life cosmetic samples with good recovery ranging from 98.5 to 102.8%.

  14. Syndromes that Link the Endocrine System and Genitourinary Tract.

    PubMed

    Özlük, Yasemin; Kılıçaslan, Işın

    2015-01-01

    The endocrine system and genitourinary tract unite in various syndromes. Genitourinary malignancies may cause paraneoplastic endocrine syndromes by secreting hormonal substances. These entities include Cushing`s syndrome, hypercalcemia, hyperglycemia, polycythemia, hypertension, and inappropriate ADH or HCG production. The most important syndromic scenarios that links these two systems are hereditary renal cancer syndromes with specific genotype/phenotype correlation. There are also some very rare entities in which endocrine and genitourinary systems are involved such as Carney complex, congenital adrenal hyperplasia and Beckwith-Wiedemann syndrome. We will review all the syndromes regarding manifestations present in endocrine and genitourinary organs.

  15. Research on Endocrine Disruptors

    EPA Pesticide Factsheets

    EPA researchers are developing innovative approaches, tools, models and data to improve the understanding of potential risks to human health and wildlife from chemicals that could disrupt the endocrine system.

  16. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... Endocrine Neoplasia Syndromes By Patricia A. Daly, MD, University of Virginia;Front Royal Internal Medicine, VA ; Lewis Landsberg, MD, Northwestern University NOTE: This is the Consumer Version. DOCTORS: Click ...

  17. Endocrine Drugs in Aircrew

    DTIC Science & Technology

    2001-06-01

    stresses. common endocrine diseases are diabetes mellitus, thyrotoxicosis, hypothyroidism, nodular goiter , The human adrenal consists of an outer cortex...about 40% goiter or thyroid carcinoma. of patients with primary hypothyroidism. Insulin requirements in diabetics are frequently increased in

  18. Endocrine Disrupting Chemicals (EDCs)

    MedlinePlus

    ... your body handles stress and responds to the environment. Results of animal and human scientific studies support a link between EDCs and ... to cause endocrine, reproductive, or neurological problems in humans. ... environmental contamination. For example, in 1976 an industrial accident ...

  19. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

    PubMed Central

    Diamanti-Kandarakis, Evanthia; Bourguignon, Jean-Pierre; Giudice, Linda C.; Hauser, Russ; Prins, Gail S.; Soto, Ana M.; Zoeller, R. Thomas; Gore, Andrea C.

    2009-01-01

    There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness. PMID:19502515

  20. Endocrine system: part 2.

    PubMed

    Hendry, Charles; Farley, Alistair; McLafferty, Ella; Johnstone, Carolyn

    2014-06-03

    This article, the last in the life sciences series, is the second of two articles on the endocrine system. It discusses human growth hormone, the pancreas and adrenal glands. The relationships between hormones and their unique functions are also explored. It is important that nurses understand how the endocrine system works and its role in maintaining health to provide effective care to patients. Several disorders caused by human growth hormone or that affect the pancreas and adrenal glands are examined.

  1. U.S. BURNING PLASMA ORGANIZATION ACTIVITIES

    SciTech Connect

    Raymond J. Fonck

    2009-08-11

    The national U.S. Burning Plasma Organization (USBPO) was formed to provide an umbrella structure in the U.S. fusion science research community. Its main purpose is the coordination of research activities in the U.S. program relevant to burning plasma science and preparations for participation in the international ITER experiment. This grant provided support for the continuing development and operations of the USBPO in its first years of existence. A central feature of the USBPO is the requirement for broad community participation in and governance of this effort. We concentrated on five central areas of activity of the USBPO during this grant period. These included: 1) activities of the Director and support staff in continuing management and development of the USBPO activity; 2) activation of the advisory Council; 3) formation and initial research activities of the research community Topical Groups; 4) formation of Task Groups to perform specific burning plasma related research and development activities; 5) integration of the USBPO community with the ITER Project Office as needed to support ITER development in the U.S.

  2. Short-Term Unilateral Resistance Training Results in Cross Education of Strength Without Changes in Muscle Size, Activation, or Endocrine Response.

    PubMed

    Beyer, Kyle S; Fukuda, David H; Boone, Carleigh H; Wells, Adam J; Townsend, Jeremy R; Jajtner, Adam R; Gonzalez, Adam M; Fragala, Maren S; Hoffman, Jay R; Stout, Jeffrey R

    2016-05-01

    Short-term unilateral resistance training results in cross education of strength without changes in muscle size, activation, or endocrine response. J Strength Cond Res 30(5): 1213-1223, 2016-The purpose of this study was to assess the cross education of strength and changes in the underlying mechanisms (muscle size, activation, and hormonal response) after a 4-week unilateral resistance training (URT) program. A group of 9 untrained men completed a 4-week URT program on the dominant leg (DOM), whereas cross education was measured in the nondominant leg (NON); and were compared with a control group (n = 8, CON). Unilateral isometric force (PKF), leg press (LP) and leg extension (LE) strength, muscle size (by ultrasonography) and activation (by electromyography) of the rectus femoris and vastus lateralis, and the hormonal response (testosterone, growth hormone, insulin, and insulin-like growth factor-1) were tested pretraining and posttraining. Group × time interactions were present for PKF, LP, LE, and muscle size in DOM and for LP in NON. In all interactions, the URT group improved significantly better than CON. There was a significant acute hormonal response to URT, but no chronic adaptation after the 4-week training program. Four weeks of URT resulted in an increase in strength and size of the trained musculature, and cross education of strength in the untrained musculature, which may occur without detectable changes in muscle size, activation, or the acute hormonal response.

  3. Voltage-activated Ca2+ channels and their role in the endocrine function of the pituitary gland in newborn and adult mice

    PubMed Central

    Sedej, Simon; Tsujimoto, Tetsuhiro; Zorec, Robert; Rupnik, Marjan

    2004-01-01

    We have prepared fresh pituitary gland slices from adult and, for the first time, from newborn mice to assess modulation of secretory activity via voltage-activated Ca2+ channels (VACCs). Currents through VACCs and membrane capacitance have been measured with the whole-cell patch-clamp technique. Melanotrophs in newborns were significantly larger than in adults. In both newborn and adult melanotrophs activation of VACCs triggered exocytosis. All pharmacologically isolated VACC types contributed equally to the secretory activity. However, the relative proportion of VACCs differed between newborns and adults. In newborn cells L-type channels dominated and, in addition, an exclusive expression of a toxin-resistant R-type-like current was found. The expression of L-type VACCs was up-regulated by the increased oestrogen levels observed in females, and was even more emphasized in the cells of pregnant females and oestrogen-treated adult male mice. We suggest a general mechanism modulating endocrine secretion in the presence of oestrogen and particularly higher sensitivity to treatments with L-type channel blockers during high oestrogen physiological states. PMID:14724188

  4. Endocrine Disrupting Contaminants—Beyond the Dogma

    PubMed Central

    Guillette, Louis J.

    2006-01-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p′-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms. PMID:16818240

  5. Endocrine disrupting contaminants--beyond the dogma.

    PubMed

    Guillette, Louis J

    2006-04-01

    Descriptions of endocrine disruption have largely been associated with wildlife and driven by observations documenting estrogenic, androgenic, antiandrogenic, and antithyroid actions. These actions, in response to exposure to ecologically relevant concentrations of various environmental contaminants, have now been established in numerous vertebrate species. However, many potential mechanisms and endocrine actions have not been studied. For example, the DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] metabolite, p,p -DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] is known to disrupt prostaglandin synthesis in the uterus of birds, providing part of the explanation for DDT-induced egg shell thinning. Few studies have examined prostaglandin synthesis as a target for endocrine disruption, yet these hormones are active in reproduction, immune responses, and cardiovascular physiology. Future studies must broaden the basic science approach to endocrine disruption, thereby expanding the mechanisms and endocrine end points examined. This goal should be accomplished even if the primary influence and funding continue to emphasize a narrower approach based on regulatory needs. Without this broader approach, research into endocrine disruption will become dominated by a narrow dogma, focusing on a few end points and mechanisms.

  6. Adsorption of selected pharmaceuticals and an endocrine disrupting compound by granular activated carbon. 1. Adsorption capacity and kinetics

    SciTech Connect

    Yu, Z.; Peldszus, S.; Huck, P.M.

    2009-03-01

    The adsorption of two representative PhACs (naproxen and carbamazepine) and one EDC (nonylphenol) were evaluated on two granular activated carbons (GAC) namely coal-based Calgon Filtrasorb 400 and coconut shell-based PICA CTIF TE. The primary objective was to investigate preloading effects by natural organic matter (NOM) on adsorption capacity and kinetics under conditions and concentrations (i.e., ng/L) relevant for drinking water treatment. Isotherms demonstrated that all compounds were significantly negatively impacted by NOM fouling. Adsorption capacity reduction was most severe for the acidic naproxen, followed by the neutral carbamazepine and then the more hydrophobic nonylphenol. The GAC with the wider pore size distribution had considerably greater NOM loading, resulting in lower adsorption capacity. Different patterns for the change in Freundlich KF and 1/n with time revealed different competitive mechanisms for the different compounds. Mass transport coefficients determined by short fixed-bed (SFB) tests with virgin and preloaded GAC demonstrated that film diffusion primarily controls mass transfer on virgin and preloaded carbon. Naproxen suffered the greatest deteriorative effect on kinetic parameters due to preloading, followed by carbamazepine, and then nonylphenol. A type of surface NOM/biofilm, which appeared to add an additional mass transfer resistance layer and thus reduce film diffusion, was observed. In addition, electrostatic interactions between NOM/biofilm and the investigated compounds are proposed to contribute to the reduction of film diffusion. A companion paper building on this work describes treatability studies in pilot-scale GAC adsorbers and the effectiveness of a selected fixed-bed model. 32 refs., 3 figs., 2 tabs.

  7. THE USE OF STRUCTURE-ACTIVITY RELATIONSHIPS IN INTEGRATING THE CHEMISTRY AND TOXICOLOGY OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Structure activity relationships (SARs) are based on the principle that structurally similar chemicals should have similar biological activity. SARs relate specifically-defined toxicological activity of chemicals to their molecular structure and physico-chemical properties. To de...

  8. Long non-coding RNAs as regulators of the endocrine system.

    PubMed

    Knoll, Marko; Lodish, Harvey F; Sun, Lei

    2015-03-01

    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

  9. Long non-coding RNAs as regulators of the endocrine system

    PubMed Central

    Knoll, Marko; Lodish, Harvey F.; Sun, Lei

    2015-01-01

    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers. PMID:25560704

  10. Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes

    USGS Publications Warehouse

    Writer, J.H.; Barber, L.B.; Brown, G.K.; Taylor, H.E.; Kiesling, R.L.; Ferrey, M.L.; Jahns, N.D.; Bartell, S.E.; Schoenfuss, H.L.

    2010-01-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17??-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use. ?? 2010.

  11. Anthropogenic tracers, endocrine disrupting chemicals, and endocrine disruption in Minnesota lakes.

    PubMed

    Writer, Jeffrey H; Barber, Larry B; Brown, Greg K; Taylor, Howard E; Kiesling, Richard L; Ferrey, Mark L; Jahns, Nathan D; Bartell, Steve E; Schoenfuss, Heiko L

    2010-12-01

    Concentrations of endocrine disrupting chemicals and endocrine disruption in fish were determined in 11 lakes across Minnesota that represent a range of trophic conditions and land uses (urban, agricultural, residential, and forested) and in which wastewater treatment plant discharges were absent. Water, sediment, and passive polar organic integrative samplers (POCIS) were analyzed for steroidal hormones, alkylphenols, bisphenol A, and other organic and inorganic molecular tracers to evaluate potential non-point source inputs into the lakes. Resident fish from the lakes were collected, and caged male fathead minnows were deployed to evaluate endocrine disruption, as indicated by the biological endpoints of plasma vitellogenin and gonadal histology. Endocrine disrupting chemicals, including bisphenol A, 17β-estradiol, estrone, and 4-nonylphenol were detected in 90% of the lakes at part per trillion concentrations. Endocrine disruption was observed in caged fathead minnows and resident fish in 90% of the lakes. The widespread but variable occurrence of anthropogenic chemicals in the lakes and endocrine disruption in fish indicates that potential sources are diverse, not limited to wastewater treatment plant discharges, and not entirely predictable based on trophic status and land use.

  12. Hormones and endocrine disruptors in human seminal plasma.

    PubMed

    Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

    2013-07-01

    Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

  13. Glucuronidation and sulfonation, in vitro, of the major endocrine-active metabolites of methoxychlor in the channel catfish, Ictalurus punctatus, and induction following treatment with 3-methylcholanthrene

    PubMed Central

    James, Margaret O.; Stuchal, Leah D.; Nyagode, Beatrice A.

    2008-01-01

    of the conjugation pathways with those published for the demethylation of MXC showed that formation of the endocrine-active metabolites was more efficient than either conjugation pathway. Residues of OH-MXC and HPTE were detected in extracts of liver microsomes from MXC-treated fish. This work showed that although OH-MXC and HPTE could be eliminated by glucuronidation and sulfonation, the phase II pathways were less efficient than the phase I pathway leading to formation of these endocrine-active metabolites. PMID:18078677

  14. Metabolism of UV-filter benzophenone-3 by rat and human liver microsomes and its effect on endocrine-disrupting activity

    SciTech Connect

    Watanabe, Yoko; Kojima, Hiroyuki; Takeuchi, Shinji; Uramaru, Naoto; Sanoh, Seigo; Sugihara, Kazumi; Kitamura, Shigeyuki; Ohta, Shigeru

    2015-01-15

    Benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) is widely used as sunscreen for protection of human skin and hair from damage by ultraviolet (UV) radiation. In this study, we examined the metabolism of BP-3 by rat and human liver microsomes, and the estrogenic and anti-androgenic activities of the metabolites. When BP-3 was incubated with rat liver microsomes in the presence of NADPH, 2,4,5-trihydroxybenzophenone (2,4,5-triOH BP) and 3-hydroxylated BP-3 (3-OH BP-3) were newly identified as metabolites, together with previously detected metabolites 5-hydroxylated BP-3 (5-OH BP-3), a 4-desmethylated metabolite (2,4-diOH BP) and 2,3,4-trihydroxybenzophenone (2,3,4-triOH BP). In studies with recombinant rat cytochrome P450, 3-OH BP-3 and 2,4,5-triOH BP were mainly formed by CYP1A1. BP-3 was also metabolized by human liver microsomes and CYP isoforms. In estrogen reporter (ER) assays using estrogen-responsive CHO cells, 2,4-diOH BP exhibited stronger estrogenic activity, 2,3,4-triOH BP exhibited similar activity, and 5-OH BP-3, 2,4,5-triOH BP and 3-OH BP-3 showed lower activity as compared to BP-3. Structural requirements for activity were investigated in a series of 14 BP-3 derivatives. When BP-3 was incubated with liver microsomes from untreated rats or phenobarbital-, 3-methylcholanthrene-, or acetone-treated rats in the presence of NADPH, estrogenic activity was increased. However, liver microsomes from dexamethasone-treated rats showed decreased estrogenic activity due to formation of inactive 5-OH BP-3 and reduced formation of active 2,4-diOH BP. Anti-androgenic activity of BP-3 was decreased after incubation with liver microsomes. - Highlights: • Metabolic modification of the endocrine-disrupting activity of BP-3 was examined. • 2,4,5-TriOH BP and 3-OH BP-3 were identified as new BP-3 metabolites. • 2,4-DiOH BP and 2,3,4-triOH BP exhibited high or similar estrogenic activities. • Estrogenic activity of BP-3 was enhanced by incubation with rat liver

  15. Glucose sensing by gut endocrine cells and activation of the vagal afferent pathway is impaired in a rodent model of type 2 diabetes mellitus.

    PubMed

    Lee, Jennifer; Cummings, Bethany P; Martin, Elizabeth; Sharp, James W; Graham, James L; Stanhope, Kimber L; Havel, Peter J; Raybould, Helen E

    2012-03-15

    Glucose in the gut lumen activates gut endocrine cells to release 5-HT, glucagon-like peptide 1/2 (GLP-1/2), and glucose-dependent insulinotropic polypeptide (GIP), which act to change gastrointestinal function and regulate postprandial plasma glucose. There is evidence that both release and action of incretin hormones is reduced in type 2 diabetes (T2D). We measured cellular activation of enteroendocrine and enterochromaffin cells, enteric neurons, and vagal afferent neurons in response to intestinal glucose in a model of type 2 diabetes mellitus, the UCD-T2DM rat. Prediabetic (PD), recent-diabetic (RD, 2 wk postonset), and 3-mo diabetic (3MD) fasted UCD-T2DM rats were given an orogastric gavage of vehicle (water, 0.5 ml /100 g body wt) or glucose (330 μmol/100 g body wt); after 6 min tissue was removed and cellular activation was determined by immunohistochemistry for phosphorylated calcium calmodulin-dependent kinase II (pCaMKII). In PD rats, pCaMKII immunoreactivity was increased in duodenal 5-HT (P < 0.001), K (P < 0.01) and L (P < 0.01) cells in response to glucose; glucose-induced activation of all three cell types was significantly reduced in RD and 3MD compared with PD rats. Immunoreactivity for GLP-1, but not GIP, was significantly reduced in RD and 3MD compared with PD rats (P < 0.01). Administration of glucose significantly increased pCaMKII in enteric and vagal afferent neurons in PD rats; glucose-induced pCaMKII immunoreactivity was attenuated in enteric and vagal afferent neurons (P < 0.01, P < 0.001, respectively) in RD and 3MD. These data suggest that glucose sensing in enteroendocrine and enterochromaffin cells and activation of neural pathways is markedly impaired in UCD-T2DM rats.

  16. Effects of Alcohol on the Endocrine System

    PubMed Central

    Rachdaoui, Nadia; Sarkar, Dipak K.

    2013-01-01

    Synopsis The endocrine system ensures a proper communication between various organs of the body to maintain a constant internal environment. The endocrine system also plays an essential role in enabling the body to respond and appropriately cope with changes in the internal or external environments, such as respond to stress and injury. These functions of the endocrine system to maintain body homeostasis are aided by its communication with the nervous system, immune system and body’s circadian mechanism. Chronic consumption of a large amount of alcohol disrupts the communication between nervous, endocrine and immune system and causes hormonal disturbances that lead to profound and serious consequences at physiological and behavioral levels. These alcohol-induced hormonal dysregulations affect the entire body and can result in various disorders such as stress abnormalities, reproductive deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone disease and psychological and behavioral disorders. This review summarizes the findings from human and animal studies that provide consistent evidence on the various effects of alcohol abuse on the endocrine system. PMID:24011889

  17. Oxidative stress and the ageing endocrine system.

    PubMed

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

    Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

  18. Genetics Home Reference: multiple endocrine neoplasia

    MedlinePlus

    ... Multiple endocrine neoplasia, type 4 Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 1 Genomics Education Programme (UK): Multiple Endocrine Neoplasia type 2A MalaCards: multiple endocrine ...

  19. Multiple Endocrine Neoplasia Syndromes

    PubMed Central

    Pont, Allan

    1980-01-01

    The multiple endocrine neoplasia (MEN) syndromes consist of three distinct disease entities. They have in common adenomatous, carcinomatous or hyperplastic involvement of a variety of endocrine glands, and an autosomal dominant inheritance. MEN I includes hyperparathyroidism, islet cell and pituitary tumors. The components of MEN IIa are hyperparathyroidism, medullary thyroid carcinoma and pheochromocytoma. MEN IIb includes multiple neuromas, medullary thyroid carcinoma and pheochromocytoma. Effective tests are available for the early detection of components of the syndromes in potentially affected patients. Screening can lead to therapeutic intervention before clinical sequelae ensue. PMID:6247851

  20. Endocrine disruption by dietary phyto-oestrogens: impact on dimorphic sexual systems and behaviours.

    PubMed

    Patisaul, Heather B

    2016-07-08

    A wide range of health benefits have been ascribed to soya intake including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. Because it is a hormonally active diet, however, soya can also be endocrine disrupting, suggesting that intake has the potential to cause adverse health effects in certain circumstances, particularly when exposure occurs during development. Consequently, the question of whether or not soya phyto-oestrogens are beneficial or harmful to human health is neither straightforward nor universally applicable to all groups. Possible benefits and risks depend on age, health status, and even the presence or absence of specific gut microflora. As global consumption increases, greater awareness and consideration of the endocrine-disrupting properties of soya by nutrition specialists and other health practitioners is needed. Consumption by infants and small children is of particular concern because their hormone-sensitive organs, including the brain and reproductive system, are still undergoing sexual differentiation and maturation. Thus, their susceptibility to the endocrine-disrupting activities of soya phyto-oestrogens may be especially high. As oestrogen receptor partial agonists with molecular and cellular properties similar to anthropogenic endocrine disruptors such as bisphenol A, the soya phyto-oestrogens provide an interesting model for how attitudes about what is 'synthetic' v. what is 'natural,' shapes understanding and perception of what it means for a compound to be endocrine disrupting and/or potentially harmful. This review describes the endocrine-disrupting properties of soya phyto-oestrogens with a focus on neuroendocrine development and behaviour.

  1. Your Endocrine System (For Kids)

    MedlinePlus

    ... Dictionary of Medical Words En Español What Other Kids Are Reading Taking Care of Your Ears Taking ... an X-ray Your Endocrine System KidsHealth > For Kids > Your Endocrine System Print A A A en ...

  2. HIF2 and endocrine neoplasia: an evolving story.

    PubMed

    Maher, Eamonn R

    2013-06-01

    In this issue of Endocrine-Related Cancer, Toledo et al. report the identification of activating mutations in the HIF2 (EPAS1) transcription factor in a subset of sporadic pheochromocytomas and paragangliomas. These findings add significantly to an evolving and complex story of the role of hypoxic gene response pathways in human endocrine neoplasia.

  3. Occurrence and distribution of pharmaceutically active and endocrine disrupting compounds in Singapore's marine environment: influence of hydrodynamics and physical-chemical properties.

    PubMed

    Bayen, Stéphane; Zhang, Hui; Desai, Malan Manish; Ooi, Seng Keat; Kelly, Barry C

    2013-11-01

    The fate and exposure risks of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs) in marine environments are not well-understood. In this study we developed a multi-residue analytical method for quantifying concentrations of forty target compounds in seawater from Singapore. Analyses of samples (n = 24) from eight sites showed the occurrence of several compounds, including gemfibrozil (<0.09-19.8 ng/L), triclosan (<0.55-10.5 ng/L), carbamazepine (<0.28-10.9 ng/L) and ibuprofen (<2.2-9.1 ng/L). A 3D hydrodynamic model for Singapore was used to predict residence time (tR). Principal Components Analysis revealed a strong relationship between tR and contaminant concentrations. While source emissions are undoubtedly important, proximate distance to a wastewater treatment plant had little influence on concentrations. The site with the greatest tR, which exhibited the highest concentrations, is adjacent to Singapore's largest protected wetland reserve. The results highlight an important linkage between hydrodynamic behavior and contaminant exposure risks in complex coastal marine ecosystems.

  4. Self-Organization Activities of College Students: Challenges and Opportunities

    ERIC Educational Resources Information Center

    Shmurygina, Natalia; Bazhenova, Natalia; Bazhenov, Ruslan; Nikolaeva, Natalia; Tcytcarev, Andrey

    2016-01-01

    The article provides the analysis of self-organization activities of college students related to their participation in youth associations activities. The purpose of research is to disclose a degree of students' activities demonstration based on self-organization processes, assessment of existing self-organization practices of the youth,…

  5. Ecotoxicological assessment of cimetidine and determination of its potential for endocrine disruption using three test organisms: Daphnia magna, Moina macrocopa, and Danio rerio.

    PubMed

    Lee, Saeram; Jung, Dawoon; Kho, Younglim; Ji, Kyunghee; Kim, Pilje; Ahn, Byeongwoo; Choi, Kyungho

    2015-09-01

    Cimetidine is a histamine H2-receptor antagonist used for treatment of gastrointestinal disorders. It is often detected in aquatic environments, but its ecotoxicological effects have not been well studied. Thus, ecotoxicity of cimetidine was evaluated using Daphnia magna and Moina macrocopa, and zebrafish (Danio rerio), and a predicted no effect concentration (PNEC) was derived. In D. magna, 48 h immobilization EC50 was determined at 394.9 mg L(-1). However, reproduction damages in D. magna were not found even at the maximum exposure level (30 mg L(-1)). For M. macrocopa, 48 h EC50 was found at 175.8 mg L(-1) and the 7 d reproduction no observed effect concentration (NOEC) was 1.1 mg L(-1). For D. rerio, 40 d growth NOEC was determined at 100 mg L(-1), the highest experimental concentration. The PNEC of cimetidine was estimated at 0.1 mg L(-1) based on M. macrocopa 7d reproduction NOEC. In 14 d adult zebrafish exposure, endocrine disruption potentials of cimetidine were observed. In male, decrease in plasma 17β-estradiol and testosterone levels, up-regulation of gonadal cyp17, and down-regulation of hepatic erα were observed at 300 mg L(-1). In female, increase in plasma E2 level and down-regulation of hepatic cyp1a were noted at 3 mg L(-1). Endocrine disruption effects were also observed in early life stage exposure. Up-regulation of erβ at 17d, and cyp19a and vtg at 40 d post fertilization were detected at 100 mg L(-1), and co-occurrence of ovary and putative testis was observed at as low as 1.1 mg L(-1). The results indicate that there is little evidence for cimetidine to cause direct ecological impact at the current ambient levels in the aquatic environment. However potential consequences of endocrine disruption following long-term exposure in aquatic environment deserves further investigation.

  6. Your Endocrine System (For Kids)

    MedlinePlus

    ... Room? What Happens in the Operating Room? Your Endocrine System KidsHealth > For Kids > Your Endocrine System A A A en español Tu sistema endocrino ... a pea, is the "master gland" of the endocrine system. It makes and releases a bunch of hormones ...

  7. Computational Model of the Hypothalamic-pituitary-gonadal Axis to Predict Biochemical Adaptive Response to Endocrine Disrupting Fungicide Prochloraz

    EPA Science Inventory

    There is increasing evidence that exposure to endocrine disrupting chemicals can induce adverse effects on reproduction and development in both humans and wildlife. Recent studies report adaptive changes within exposed organisms in response to endocrine disrupting chemicals, and ...

  8. ENDOCRINE DISRUPTORS: LESSONS LEARNED

    EPA Science Inventory

    For more than ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; its occurrence in the real world; and in developing tools for screening and prediction of risk. Mu...

  9. Assessment of the pesticides atrazine, endosulfan sulphate and chlorpyrifos for juvenoid-related endocrine activity using Daphnia magna.

    PubMed

    Palma, P; Palma, V L; Matos, C; Fernandes, R M; Bohn, A; Soares, A M V M; Barbosa, I R

    2009-07-01

    The water flea Daphnia magna belongs to the cyclical parthenogenic species, which can reproduce by either parthenogenesis or sexual reproduction. Recent studies have reported the involvement of the methylfarnesoate hormone, in male sex determination of D. magna. The aim of this study was to evaluate the juvenoid and anti-juvenoid activity of atrazine, endosulfan sulphate, and chlorpyrifos. To assess the juvenoid activity we exposed maternal daphnids to several concentrations of the respective pesticides, using the percentage of male production as endpoint. Fenoxycarb (1microgL(-1)) was used as a positive control. The anti-juvenoid activity was assessed using a similar bioassay after the addition of fenoxycarb (1microgL(-1)) to all test solutions. Fenoxycarb is an insect growth regulator that mimics the action of methylfarnesoate, and promoted the production of 95% of male offspring at the given concentration. Weak juvenoid-agonist activity was detected for endosulfan sulphate, with a significant increase of the percentage of male daphnids detected through logistic regression. In addition, atrazine and endosulfan sulphate antagonized the juvenoid activity of fenoxycarb. These results also corroborate the hypothesis that weak juvenoid agonists can simultaneously act as juvenoid antagonists as it has been observed in other hormonal systems.

  10. Biochemical, endocrine, and hematological factors in human oxygen tolerance extension: Predictive studies 6

    NASA Technical Reports Server (NTRS)

    Lambertsen, C. J.; Clark, J. M.

    1992-01-01

    The Predictive Studies VI (Biochemical, endocrine, and hematological factors in human oxygen tolerance extension) Program consisted of two related areas of research activity, integrated in design and performance, that were each based on an ongoing analysis of human organ oxygen tolerance data obtained for the continuous oxygen exposures of the prior Predictive Studies V Program. The two research areas effectively blended broad investigation of systematically varied intermittent exposure patterns in animals with very selective evaluation of specific exposure patterns in man.

  11. AroER tri-screen is a biologically relevant assay for endocrine disrupting chemicals modulating the activity of aromatase and/or the estrogen receptor.

    PubMed

    Chen, Shiuan; Zhou, Dujin; Hsin, Li-Yu; Kanaya, Noriko; Wong, Cynthie; Yip, Richard; Sakamuru, Srilatha; Xia, Menghang; Yuan, Yate-Ching; Witt, Kristine; Teng, Christina

    2014-05-01

    Endocrine disrupting chemicals (EDCs) interfere with the biosynthesis, metabolism, and functions of steroid hormones, including estrogens and androgens. Aromatase enzyme converts androgen to estrogen. Thus, EDCs against aromatase significantly impact estrogen- and/or androgen-dependent functions, including the development of breast cancer. The current study aimed to develop a biologically relevant cell-based high-throughput screening assay to identify EDCs that act as aromatase inhibitors (AIs), estrogen receptor (ER) agonists, and/or ER antagonists. The AroER tri-screen assay was developed by stable transfection of ER-positive, aromatase-expressing MCF-7 breast cancer cells with an estrogen responsive element (ERE) driven luciferase reporter plasmid. The AroER tri-screen can identify: estrogenic EDCs, which increase luciferase signal without 17β-estradiol (E2); anti-estrogenic EDCs, which inhibit the E2-induced luciferase signal; and AI-like EDCs, which suppress a testosterone-induced luciferase signal. The assay was first optimized in a 96-well plate format and then miniaturized into a 1536-well plate format. The AroER tri-screen was demonstrated to be suitable for high-throughput screening in the 1536-well plate format, with a 6.9-fold signal-to-background ratio, a 5.4% coefficient of variation, and a screening window coefficient (Z-factor) of 0.78. The assay suggested that bisphenol A (BPA) functions mainly as an ER agonist. Results from screening the 446 drugs in the National Institutes of Health Clinical Collection revealed 106 compounds that modulated ER and/or aromatase activities. Among these, two AIs (bifonazole and oxiconazole) and one ER agonist (paroxetine) were confirmed through alternative aromatase and ER activity assays. These findings indicate that AroER tri-screen is a useful high-throughput screening system for identifying ER ligands and aromatase-inhibiting chemicals.

  12. Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate

    PubMed Central

    Gomez, Danielle L.; O’Driscoll, Marci; Sheets, Timothy P.; Hruban, Ralph H.; Oberholzer, Jose; McGarrigle, James J.; Shamblott, Michael J.

    2015-01-01

    Neurogenin 3 (NGN3) is necessary and sufficient for endocrine differentiation during pancreatic development and is expressed by a population of progenitor cells that give rise exclusively to hormone-secreting cells within islets. NGN3 protein can be detected in the adult rodent pancreas only following certain types of injury, when it is transiently expressed by exocrine cells undergoing reprogramming to an endocrine cell fate. Here, NGN3 protein can be detected in 2% of acinar and duct cells in living biopsies of histologically normal adult human pancreata and 10% in cadaveric biopsies of organ donor pancreata. The percentage and total number of NGN3+ cells increase during culture without evidence of proliferation or selective cell death. Isolation of highly purified and viable NGN3+ cell populations can be achieved based on coexpression of the cell surface glycoprotein CD133. Transcriptome and targeted expression analyses of isolated CD133+ / NGN3+ cells indicate that they are distinct from surrounding exocrine tissue with respect to expression phenotype and Notch signaling activity, but retain high level mRNA expression of genes indicative of acinar and duct cell function. NGN3+ cells have an mRNA expression profile that resembles that of mouse early endocrine progenitor cells. During in vitro differentiation, NGN3+ cells express genes in a pattern characteristic of endocrine development and result in cells that resemble beta cells on the basis of coexpression of insulin C-peptide, chromogranin A and pancreatic and duodenal homeobox 1. NGN3 expression in the adult human exocrine pancreas marks a dedifferentiating cell population with the capacity to take on an endocrine cell fate. These cells represent a potential source for the treatment of diabetes either through ex vivo manipulation, or in vivo by targeting mechanisms controlling their population size and endocrine cell fate commitment. PMID:26288179

  13. ERR Gamma: Does an Orphan Nuclear Receptor Link Steroid Hormone Biogenesis to Endocrine Resistance?

    DTIC Science & Technology

    2007-09-01

    pair of breast cancer cell lines – one sensitive to endocrine therapy (SUM44) and the other resistant to endocrine therapy (LCCTam, TAM). We found...expression and/or activity regulates the level of cholesterol in a pair of breast cancer cell lines – one sensitive to endocrine therapy (SUM44) and...endocrine therapies . 1.1.2. Selective estrogen receptor downregulators (SERDs) The pure ER antagonist ICI 182,780 (hereafter called fulvestrant ) binds

  14. Pharmaceutically active compounds and endocrine disrupting chemicals in water, sediments and mollusks in mangrove ecosystems from Singapore.

    PubMed

    Bayen, Stéphane; Estrada, Elvagris Segovia; Juhel, Guillaume; Kit, Lee Wei; Kelly, Barry C

    2016-08-30

    This study investigated the occurrence of bisphenol A (BPA), atrazine and selected pharmaceutically active compounds (PhACs) in mangrove habitats in Singapore in 2012-2013, using multiple tools (sediment sampling, POCIS and filter feeder molluscs). Using POCIS, the same suite of contaminants (atrazine, BPA and eleven PhACs) was detected in mangrove waters in 28-days deployments in both 2012 and 2013. POCIS concentrations ranged from pg/L to μg/L. Caffeine, BPA, carbamazepine, E1, triclosan, sulfamerazine, sulfamethazine, and lincomycin were also detected in mangrove sediments from the low pg/g dw (e.g. carbamazepine) to ng/g dw (e.g. BPA). The detection of caffeine, carbamazepine, BPA, sulfamethoxazole or lincomycin in bivalve tissues also showed that these chemicals are bioavailable in the mangrove habitat. Since there are some indications that some pharmaceutically active substances may be biologically active in the low ppb range in marine species, further assessment should be completed based on ecotoxicological data specific to mangrove species.

  15. Environmental endocrine disruption: an effects assessment and analysis.

    PubMed

    Crisp, T M; Clegg, E D; Cooper, R L; Wood, W P; Anderson, D G; Baetcke, K P; Hoffmann, J L; Morrow, M S; Rodier, D J; Schaeffer, J E; Touart, L W; Zeeman, M G; Patel, Y M

    1998-02-01

    This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter.

  16. Environmental endocrine disruption: an effects assessment and analysis.

    PubMed Central

    Crisp, T M; Clegg, E D; Cooper, R L; Wood, W P; Anderson, D G; Baetcke, K P; Hoffmann, J L; Morrow, M S; Rodier, D J; Schaeffer, J E; Touart, L W; Zeeman, M G; Patel, Y M

    1998-01-01

    This report is an overview of the current state of the science relative to environmental endocrine disruption in humans, laboratory testing, and wildlife species. Background information is presented on the field of endocrinology, the nature of hormones, and potential sites for endocrine disruption, with specific examples of chemicals affecting these sites. An attempt is made to present objectively the issue of endocrine disruption, consider working hypotheses, offer opposing viewpoints, analyze the available information, and provide a reasonable assessment of the problem. Emphasis is placed on disruption of central nervous system--pituitary integration of hormonal and sexual behavioral activity, female and male reproductive system development and function, and thyroid function. In addition, the potential role of environmental endocrine disruption in the induction of breast, testicular, and prostate cancers, as well as endometriosis, is evaluated. The interrelationship of the endocrine and immune system is documented. With respect to endocrine-related ecological effects, specific case examples from the peer-reviewed literature of marine invertebrates and representatives of the five classes of vertebrates are presented and discussed. The report identifies some data gaps in our understanding of the environmental endocrine disruption issue and recommends a few research needs. Finally, the report states the U.S. Environmental Protection Agency Science Policy Council's interim position on endocrine disruption and lists some of the ongoing activities to deal with this matter. PMID:9539004

  17. 42 CFR 423.162 - Quality improvement organization activities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Quality improvement organization activities. 423... Cost Control and Quality Improvement Requirements § 423.162 Quality improvement organization activities. (a) General rule. Quality improvement organizations (QIOs) are required to offer...

  18. Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells.

    PubMed

    Hiscox, Stephen; Barnfather, Peter; Hayes, Edd; Bramble, Pamela; Christensen, James; Nicholson, Robert I; Barrett-Lee, Peter

    2011-02-01

    Acquired resistance to endocrine therapy in breast cancer is a major clinical problem. Previous reports have demonstrated that cell models of acquired endocrine resistance have altered cell-matrix adhesion and a highly migratory phenotype, features which may impact on tumour spread in vivo. Focal adhesion kinase (FAK) is an intracellular kinase that regulates signalling pathways central to cell adhesion, migration and survival and its expression is frequently deregulated in breast cancer. In this study, we have used the novel FAK inhibitor PF573228 to address the role of FAK in the development of endocrine resistance. Whilst total-FAK expression was similar between endocrine-sensitive and endocrine-resistant MCF7 cells, FAK phosphorylation status (Y397 or Y861) was altered in resistance. PF573228 promoted a dose-dependent inhibition of FAK phosphorylation at Y397 but did not affect other FAK activation sites (pY407, pY576 and pY861). Endocrine-resistant cells were more sensitive to these inhibitory effects versus MCF7 (mean IC(50) for FAK pY397 inhibition: 0.43 μM, 0.05 μM and 0.13 μM for MCF7, TamR and FasR cells, respectively). Inhibition of FAK pY397 was associated with a reduction in TamR and FasR adhesion to, and migration over, matrix components. PF573228 as a single agent (0-1 μM) did not affect the growth of MCF7 cells or their endocrine-resistant counterparts. However, treatment of endocrine-sensitive cells with PF573228 and tamoxifen combined resulted in greater suppression of proliferation versus single agent treatment. Together these data suggest the importance of FAK in the process of endocrine resistance, particularly in the development of an aggressive, migratory cell phenotype and demonstrate the potential to improve endocrine response through combination treatment.

  19. An in vitro/in vivo screening assay as a sensitive tool to assess endocrine disruptive activity in surface water.

    PubMed

    Bogers, Rinus; De Vries-Buitenweg, Selinda; Geuijen, Ine; van de Waart, Beppy; Kuiper, Raoul; Van Der Linden, Sander; Puijker, Leo; Murk, Albertinka; Van Der Burg, Bart; Legler, Juliette

    2007-04-01

    Adult male fathead minnow were exposed for 14 or 28-days under flow-through conditions to undiluted filtered water samples from the rivers Meuse and Rhine in the Netherlands. The experiment included two vessels per treatment each containing 10 fish and samples of five fish were taken after 14 and 28 days. Additional groups were exposed to 17alpha-ethinylestradiol (EE2) as a reference and untreated drinking water as a negative control. Major endpoints examined included induction of vitellogenin (VTG) synthesis, VTG mRNA activity, hepato- and gonadosomatic indices (HSI and GSI) and gonadal histology. No significant difference was recorded in body weight or mean GSI values between the various treatments. Only exposure to Meuse water resulted in significantly higher HSI means after 14 days. Histological examination showed no apparent effects on gonadal tissue except for eosinophilic blood plasma in fish exposed to Meuse water or EE2. After 14 and 28 days, elevated VTG and VTG mRNA levels were measured in most livers of the fish exposed to Meuse water, but not in the fish exposed to Rhine water. This was confirmed by measuring estrogenic responses in the in vitro ER CALUX assay. Induction of VTG synthesis proved to be the most sensitive endpoint in the Non Spawning Male Fish Assay for in vivo detection of bio-available estrogenic activity supplementary to a sensitive in vitro assay. The other endpoints examined varied too much and required a higher number of fish or replicates to achieve sufficient power for statistical testing making them less animal friendly.

  20. Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down.

    PubMed

    Hogg, K; Robinson, W P; Beristain, A G

    2014-07-01

    Increasingly, placental DNA methylation is assessed as a factor in pregnancy-related complications, yet the transcriptional impact of such findings is not always clear. Using a proliferative in vitro placental model, the effect of DNA methylation loss on gene activation was evaluated at a number of genes selected for being differentially methylated in pre-eclampsia-associated placentae in vivo. We aimed to determine whether reduced DNA methylation at specific loci was associated with transcriptional changes at the corresponding gene, thus providing mechanistic underpinnings for previous clinical findings and to assess the degree of transcriptional response amongst our candidate genes. BeWo and JEG3 choriocarcinoma cells were exposed to 1 μM 5-Aza-2'-deoxycytidine (5-Aza-CdR) or vehicle control for 48 h, and re-plated and cultured for a further 72 h in normal media before cells were harvested for RNA and DNA. Bisulphite pyrosequencing confirmed that DNA methylation was reduced by ∼30-50% points at the selected loci studied in both cell lines. Gene activation, measured by qRT-PCR, was highly variable and transcript specific, indicating differential sensitivity to DNA methylation. Most notably, loss of DNA methylation at the leptin (LEP) promoter corresponded to a 200-fold and 40-fold increase in LEP expression in BeWo and JEG3 cells, respectively (P < 0.01). Transcripts of steroidogenic pathway enzymes CYP11A1 and HSD3B1 were up-regulated ∼40-fold in response to 5-Aza-CdR exposure in BeWo cells (P < 0.01). Other transcripts, including aromatase (CYP19), HSD11B2, inhibin (INHBA) and glucocorticoid receptor (NR3C1) were more moderately, although significantly, affected by loss of associated DNA methylation. These data present a mixed effect of DNA methylation changes at selected loci supporting cautionary interpretation of DNA methylation results in the absence of functional data.

  1. Cofactor-embedded nanoporous activated carbon matrices for the immobilization of intracellular enzymes and degradation of endocrine disruptor.

    PubMed

    Paranji, Saranya; Ganesan, Sekaran

    2016-03-14

    The mixed intracellular enzyme (MICE) from Citrobacter freundii, capable of degrading o-phenylene diamine (OPD), was extracted and characterized. Cofactors such as zinc and copper ions enhanced the MICE activity. The functionalized nanoporous-activated carbon (FNAC) matrix, zinc-impregnated FNAC matrix (Zn(2+) -FNAC), copper-impregnated FNAC matrix (Cu(2+) -FNAC), and zinc- and copper-impregnated FNAC matrix (Zn(2+) -Cu(2+) -FNAC) were prepared and characterized to immobilize MICE. The parameters such as time (0-240 Min), pH (1-10), temperature (20-50 ºC), amount of MICE (1-5 mg), particle size of carbon (100-600 μm), and mass of carbon (0.5-2.5 g) were optimized for immobilization of MICE on different FNAC matrices. The carrier matrices in the free and MICE immobilized form were characterized using SEM, FT-IR, XPS, XRD, thermogravimetric analysis (TGA), and DSC analyses. The kinetic and adsorption models for the immobilization of MICE on FNAC matrices were studied. The parameters such as time, pH, temperature, concentration of OPD, and agitation speed were optimized for the degradation of OPD using FNAC-MICE and MICE-immobilized metal-impregnated FNAC matrices. The maximum amount of pyruvic acid formed was found to be 133 μg/mg of OPD using Zn(2+) -Cu(2+) -FNAC-MICE matrix. The kinetic models were studied for the formation of pyruvic acid on OPD degradation and confirmed using FT-IR spectroscopy.

  2. Raw and biologically treated paper mill wastewater effluents and the recipient surface waters: Cytotoxic and genotoxic activity and the presence of endocrine disrupting compounds.

    PubMed

    Balabanič, Damjan; Filipič, Metka; Krivograd Klemenčič, Aleksandra; Žegura, Bojana

    2017-01-01

    Paper mill effluents are complex mixtures containing different toxic compounds including endocrine-disrupting (EDCs) and genotoxic compounds. In the present study non-concentrated raw and biologically treated wastewaters from two paper mill plants with different paper production technologies i) Paper mill A uses virgin fibres, and ii) Paper mill B uses recycled fibres for paper production and the corresponding receiving surface waters, were assessed for their cytotoxic/genotoxic activity with SOS/umuC, Ames MPF 98/100 Aqua, and comet assay with human hepatoma HepG2 cells. In addition the levels of seven selected EDCs were quantified in wastewater samples and receiving surface waters. All investigated EDCs were confirmed in raw and biologically treated effluents from both paper mills with concentrations being markedly higher in Paper mill B effluents. In the receiving surface waters three of the studied EDCs were determined downstream of both paper mills effluent discharge. The wastewater samples and the recipient surface water samples from Paper mill A were not mutagenic for bacteria and did not induce DNA damage in HepG2 cells. On the contrary, half of the raw wastewater samples from Paper mill B were mutagenic whereas biologically treated wastewater and the recipient surface water samples were negative. In HepG2 cells most of the raw and biologically treated wastewater samples from Paper mill B as well as surface water samples collected downstream of Paper mill B effluent discharge induced DNA damage. The results confirmed that genotoxic contaminants were present only in wastewaters from Paper mill B that uses recycled fibres for paper production, and that the combined aerobic and anaerobic wastewater treatment procedure efficiently reduced contaminants that are bacterial mutagens, but not those that induce DNA damage in HepG2 cells. This study highlights that in addition to chemical analyses bioassays are needed for a comprehensive toxicological evaluation of

  3. The Herbicide Atrazine Activates Endocrine Gene Networks via Non-Steroidal NR5A Nuclear Receptors in Fish and Mammalian Cells

    PubMed Central

    Suzawa, Miyuki; Ingraham, Holly A.

    2008-01-01

    Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite the fact that this s-chlorotriazine has been linked to reproductive abnormalities in fish and amphibians. Here, using zebrafish we report that environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 µg/L), and increased the ratio of female to male fish (22 µg/L). ATR selectively increased zcyp19a1, a known gene target of the nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained unchanged. Remarkably, in mammalian cells ATR functions in a cell-specific manner to upregulate SF-1 targets and other genes critical for steroid synthesis and reproduction, including Cyp19A1, StAR, Cyp11A1, hCG, FSTL3, LHß, INHα, αGSU, and 11ß-HSD2. Our data appear to eliminate the possibility that ATR directly affects SF-1 DNA- or ligand-binding. Instead, we suggest that the stimulatory effects of ATR on the NR5A receptor subfamily (SF-1, LRH-1, and zff1d) are likely mediated by receptor phosphorylation, amplification of cAMP and PI3K signaling, and possibly an increase in the cAMP-responsive cellular kinase SGK-1, which is known to be upregulated in infertile women. Taken together, we propose that this pervasive and persistent environmental chemical alters hormone networks via convergence of NR5A activity and cAMP signaling, to potentially disrupt normal endocrine development and function in lower and higher vertebrates. PMID:18461179

  4. The herbicide atrazine activates endocrine gene networks via non-steroidal NR5A nuclear receptors in fish and mammalian cells.

    PubMed

    Suzawa, Miyuki; Ingraham, Holly A

    2008-05-07

    Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite the fact that this s-chlorotriazine has been linked to reproductive abnormalities in fish and amphibians. Here, using zebrafish we report that environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 microg/L), and increased the ratio of female to male fish (22 microg/L). ATR selectively increased zcyp19a1, a known gene target of the nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained unchanged. Remarkably, in mammalian cells ATR functions in a cell-specific manner to upregulate SF-1 targets and other genes critical for steroid synthesis and reproduction, including Cyp19A1, StAR, Cyp11A1, hCG, FSTL3, LHss, INHalpha, alphaGSU, and 11ss-HSD2. Our data appear to eliminate the possibility that ATR directly affects SF-1 DNA- or ligand-binding. Instead, we suggest that the stimulatory effects of ATR on the NR5A receptor subfamily (SF-1, LRH-1, and zff1d) are likely mediated by receptor phosphorylation, amplification of cAMP and PI3K signaling, and possibly an increase in the cAMP-responsive cellular kinase SGK-1, which is known to be upregulated in infertile women. Taken together, we propose that this pervasive and persistent environmental chemical alters hormone networks via convergence of NR5A activity and cAMP signaling, to potentially disrupt normal endocrine development and function in lower and higher vertebrates.

  5. The role of activated carbon and disinfection on the removal of endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs from wastewater.

    PubMed

    Noutsopoulos, Constantinos; Mamais, Daniel; Mpouras, Thanasis; Kokkinidou, Despina; Samaras, Vasilios; Antoniou, Korina; Gioldasi, Marianna

    2014-01-01

    Endocrine disrupting chemicals and non-steroidal anti-inflammatory drugs are two important groups of emerging pollutants due to their toxicological and chemical characteristics and their persistent detection in the aquatic environment. Wastewater treatment plants are a significant pathway for their transfer to the water courses. It is well evidenced that these chemicals are only partially removed through biological treatment of wastewater and therefore being detected in secondary effluents. This work focuses on the evaluation of the efficiency of two well-established disinfection technologies (chlorination and UV irradiation) along with UV/H2O2 and powdered activated carbon (PAC) to remove these chemicals from biologically treated wastewater. Based on the results it is shown that appreciable removal efficiencies due to chlorination should be expected for most of the target compounds, whereas this was not the case for ibuprofen and ketoprofen. With the exemption of diclofenac and ketoprofen direct UV irradiation did not efficiently removed target compounds for UV doses usually applied for disinfection purposes. The application of advanced UV treatment through the addition of H2O2 although resulted in increased removal of the target compounds is not sufficient at moderate UV and H2O2 doses to achieve satisfactory removal efficiencies. PAC use resulted in sufficient removal of target compounds although high PAC doses were required for some chemicals. Comparison of Freundlich isotherms of this study with those of other studies, derived employing water samples, suggested that the water matrix along with the target compounds concentration range can significantly affect the outcome of the experiments.

  6. [Endocrine disease symptoms].

    PubMed

    Reincke, M

    2013-10-01

    Diseases of the endocrine system can be classified according to the prevalence into two categories: very frequent endocrinopathies, which affect a population of several millions in Germany and include diabetes mellitus, endemic goiter, osteoporosis and obesity. On the other hand there are a large number of rare endocrine diseases which share the paradox of other rare diseases: they are also often falsely suspected in patients who are not affected but at the same time there are sometimes long delays in diagnosis in those who do have the disease. In cases of adrenal insufficiency, absolute glucocorticoid deficiency can progress to an adrenal crisis which is fatal if not treated. Patients with de Quervain thyroiditis often suffer from prolonged episodes of fever with tender, diffuse goiter and neck pain. Pheochromocytomas should be recognized early in the course of disease because of life-threatening cardiovascular complications. This article highlights the essential characteristics in order to increase awareness.

  7. Endocrine disrupters as obesogens

    PubMed Central

    Grün, Felix; Blumberg, Bruce

    2009-01-01

    The recent dramatic rise in obesity rates is an alarming global health trend that consumes an ever increasing portion of health care budgets in Western countries. The root cause of obesity is thought to be a prolonged positive energy balance. Hence, the major focus of preventative programs for obesity has been to target overeating and inadequate physical exercise. Recent research implicates environmental risk factors, including nutrient quality, stress, fetal environment and pharmaceutical or chemical exposure as relevant contributing influences. Evidence points to endocrine disrupting chemicals that interfere with the body's adipose tissue biology, endocrine hormone systems or central hypothalamic-pituitary-adrenal axis as suspects in derailing the homeostatic mechanisms important to weight control. This review highlights recent advances in our understanding of the molecular targets and mechanisms of action for these compounds and areas of future research needed to evaluate the significance of their contribution to obesity. PMID:19433244

  8. Opioids and endocrine dysfunction

    PubMed Central

    Hester, Joan

    2012-01-01

    The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized. The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable. If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist. PMID:26516462

  9. Endocrine oncology in pregnancy.

    PubMed

    Lansdown, A; Rees, D A

    2011-12-01

    Endocrine tumours occur rarely in pregnant women but present clinicians with unique challenges. A high index of suspicion is often required to make a diagnosis since the symptoms and signs associated with many of these tumours, including insulinoma, adrenocortical carcinoma and phaeochromocytoma, mimic those of normal pregnancy or its complications, such as pre-eclampsia. The evidence base which informs management is very limited hence decisions on investigation and therapy must be individualised and undertaken jointly by the multidisciplinary medical team and the patient. The optimal strategy will depend on the nature and stage of the endocrine tumour, gestational stage, treatments available and patient wishes. Thus, surgical intervention, appropriately timed, may be considered in pregnancy for resectable adrenocortical carcinoma or phaeochromocytoma, but delayed until the postpartum period for well-differentiated thyroid cancer. Medical therapy may be required to reduce the drive to tumour growth, control symptoms of hormone excess and to minimise the risks of surgery, anaesthesia or labour.

  10. Bromocriptine and endocrine disorders.

    PubMed

    Spark, R F; Dickstein, G

    1979-06-01

    Bromocriptine, a dopaminergic agonist, has been used to treat many endocrine disorders. In hyperprolactinemia associated with galactorrhea, amenorrhea, oligospermia, and impotence, bromocriptine reduces prolactin levels to normal and allows for satisfactory return of sexual and reproductive function in 90% of patients. In acromegaly, bromocriptine brings about subjective improvement in 75% of patients with reduction in growth-hormone levels to normal in 22% of patients. Bromocriptine has been used in premenstrual tension, functional infertility, Nelson's syndrome, and Cushing's disease with variable benefit. In low doses, side-effects are minimal. In higher doses, digital vasospasm and gastrointestinal bleeding have occurred. Although bromocriptine has been used in a wide variety of endocrine disorders, it appears to be most useful in treatment of male and female infertility associated with hyperprolactinemia.

  11. Automated image analysis of intra-tumoral and peripheral endocrine organ vascular bed regression using 'Fibrelength' as a novel structural biomarker.

    PubMed

    Hargreaves, Adam; Bigley, Alison; Price, Shirley; Kendrew, Jane; Barry, Simon T

    2017-02-10

    The study of vascular modulation has received a great deal of attention in recent years as knowledge has increased around the role of angiogenesis within disease contexts such as cancer. Despite rapidly expanding insights into the molecular processes involved and the concomitant generation of a number of anticancer vascular modulating chemotherapeutics, techniques used in the measurement of structural vascular change have advanced more modestly, particularly with regard to the preclinical quantification of off-target vascular regression within systemic, notably endocrine, blood vessels. Such changes translate into a number of major clinical side effects and there remains a need for improved preclinical screening and analysis. Here we present the generation of a novel structural biomarker, which can be incorporated into a number of contemporary image analysis platforms and used to compare tumour versus systemic host tissue vascularity. By contrasting the measurements obtained, the preclinical efficacy of vascular modulating chemotherapies can be evaluated in light of the predicted therapeutic window. Copyright © 2017 John Wiley & Sons, Ltd.

  12. The acute salinity changes activate the dual pathways of endocrine responses in the brain and pituitary of tilapia.

    PubMed

    Aruna, Adimoolam; Nagarajan, Ganesan; Chang, Ching-Fong

    2015-01-15

    To analyze and compare the stress and osmoregulatory hormones and receptors in pituitary during acute salinity changes, the expression patterns of corticotropin releasing hormone (crh) in hypothalamus, prolactin (prl) releasing peptide (pRrp) in telencephalon and diencephalon, glucocorticoid receptors 2 (gr2), and mineralocorticoid receptor (mr), crh-r, pro-opiomelanocorticotropin (pomc), pRrp, prl, dopamine 2 receptor (d2-r), growth hormone (gh), gh-receptor (gh-r) and insulin-like growth hormone (igf-1) transcripts in pituitary were characterized in euryhaline tilapia. The results indicate that the crh transcripts increased in the hypothalamus and rostral pars distalis of the pituitary after the transfer of fish to SW. Similarly, the pRrp transcripts were more abundant in SW acclimated tilapia forebrain and hypothalamus. The crh-r, gr2 and mr transcripts were more expressed in rostral pars distalis and pars intermedia of pituitary at SW than FW tilapia. The data indicate that the SW acclimation stimulates these transcripts in the specific regions of the brain and pituitary which may be related to the activation of the hypothalamic-pituitary-interrenal (HPI)-axis. The results of dual in situ hybridization reveal that the transcripts of crh-r, gr2 and mr with pomc are highly co-localized in corticotrophs of pituitary. Furthermore, we demonstrate high expression of pRrp in the brain and low expression of pRrp and prl transcripts in the pituitary of SW fish. No crh-r and corticosteroid receptors were co-localized with prl transcripts in the pituitary. The gh-r and igf-1 mRNA levels were significantly increased in SW acclimated tilapia pituitary whereas there was no difference in the gh mRNA levels. The data suggest that the locally produced pRrp and d2-r may control and regulate the expression of prl mRNA in pituitary. Therefore, the dual roles of pRrp are involved in the stress (via brain-pituitary) and osmoregulatory (via pituitary) pathways in tilapia exposed to

  13. A Method for the Determination of Genetic Sex in the Fathead Minnow, Pimephales promelas, to Support Testing of Endocrine-active Chemicals

    EPA Science Inventory

    Fathead minnows are used as a model fish species for the characterization of the endocrine-disrupting potential of environmental contaminants. This research describes the development of a PCR method that can determine the genetic sex in this species. This method, when incorpora...

  14. The changing role of ER in endocrine resistance.

    PubMed

    Nardone, Agostina; De Angelis, Carmine; Trivedi, Meghana V; Osborne, C Kent; Schiff, Rachel

    2015-11-01

    Estrogen receptor (ER) is expressed in approximately 70% of newly diagnosed breast tumors. Although endocrine therapy targeting ER is highly effective, intrinsic or acquired resistance is common, significantly jeopardizing treatment outcomes and minimizing overall survival. Even in the presence of endocrine resistance, a continued role of ER signaling is suggested by several lines of clinical and preclinical evidence. Indeed, inhibition or down-regulation of ER reduces tumor growth in preclinical models of acquired endocrine resistance, and many patients with recurrent ER+ breast tumors progressing on one type of ER-targeted treatment still benefit from sequential endocrine treatments that target ER by a different mechanism. New insights into the nature and biology of ER have revealed several mechanisms sustaining altered ER signaling in endocrine-resistant tumors, including deregulated growth factor receptor signaling that results in ligand-independent ER activation, unbalanced ER co-regulator activity, and genomic alterations involving the ER gene ESR1. Therefore, biopsies of recurrent lesions are needed to assess the changes in epi/genomics and signaling landscape of ER and associated pathways in order to tailor therapies to effectively overcome endocrine resistance. In addition, more completely abolishing the levels and activity of ER and its co-activators, in combination with selected signal transduction inhibitors or agents blocking the upstream or downstream targets of the ER pathway, may provide a better therapeutic strategy in combating endocrine resistance.

  15. Toxicogenomics to Evaluate Endocrine Disrupting Effects of Environmental Chemicals Using the Zebrafish Model.

    PubMed

    Caballero-Gallardo, Karina; Olivero-Verbel, Jesus; Freeman, Jennifer L

    2016-12-01

    The extent of our knowledge on the number of chemical compounds related to anthropogenic activities that can cause damage to the environment and to organisms is increasing. Endocrine disrupting chemicals (EDCs) are one group of potentially hazardous substances that include natural and synthetic chemicals and have the ability to mimic endogenous hormones, interfering with their biosynthesis, metabolism, and normal functions. Adverse effects associated with EDC exposure have been documented in aquatic biota and there is widespread interest in the characterization and understanding of their modes of action. Fish are considered one of the primary risk organisms for EDCs. Zebrafish (Danio rerio) are increasingly used as an animal model to study the effects of endocrine disruptors, due to their advantages compared to other model organisms. One approach to assess the toxicity of a compound is to identify those patterns of gene expression found in a tissue or organ exposed to particular classes of chemicals, through new technologies in genomics (toxicogenomics), such as microarrays or whole-genome sequencing. Application of these technologies permit the quantitative analysis of thousands of gene expression changes simultaneously in a single experiment and offer the opportunity to use transcript profiling as a tool to predict toxic outcomes of exposure to particular compounds. The application of toxicogenomic tools for identification of chemicals with endocrine disrupting capacity using the zebrafish model system is reviewed.

  16. Evaluating the effects of endocrine disruptors on endocrine function during development.

    PubMed Central

    Bigsby, R; Chapin, R E; Daston, G P; Davis, B J; Gorski, J; Gray, L E; Howdeshell, K L; Zoeller, R T; vom Saal, F S

    1999-01-01

    The major concerns with endocrine disruptors in the environment are based mostly on effects that have been observed on the developing embryo and fetus. The focus of the present manuscript is on disruption of three hormonal systems: estrogens, androgens, and thyroid hormones. These three hormonal systems have been well characterized with regard to their roles in normal development, and their actions during development are known to be perturbed by endocrine-disrupting chemicals. During development, organs are especially sensitive to low concentrations of the sex steroids and thyroid hormones. Changes induced by exposure to these hormones during development are often irreversible, in contrast with the reversible changes induced by transient hormone exposure in the adult. Although it is known that there are differences in embryonic/fetal/neonatal versus adult endocrine responses, minimal experimental information is available to aid in characterizing the risk of endocrine disruptors with regard to a number of issues. Issues discussed here include the hypothesis of greater sensitivity of embryos/fetuses to endocrine disruptors, irreversible consequences of exposure before maturation of homeostatic systems and during periods of genetic imprinting, and quantitative information related to the shape of the dose-response curve for specific developmental phenomena. PMID:10421771

  17. Executive Summary to EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

    PubMed Central

    Chappell, V. A.; Fenton, S. E.; Flaws, J. A.; Nadal, A.; Prins, G. S.; Toppari, J.; Zoeller, R. T.

    2015-01-01

    This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health. PMID:26414233

  18. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

    PubMed Central

    Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

    2015-01-01

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  19. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition.

    PubMed

    Pierre, Joseph F; Neuman, Joshua C; Brill, Allison L; Brar, Harpreet K; Thompson, Mary F; Cadena, Mark T; Connors, Kelsey M; Busch, Rebecca A; Heneghan, Aaron F; Cham, Candace M; Jones, Elaina K; Kibbe, Carly R; Davis, Dawn B; Groblewski, Guy E; Kudsk, Kenneth A; Kimple, Michelle E

    2015-09-15

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.

  20. ENDOCRINE DISRUPTING CONTAMINANTS AND ALLIGATOR EMBRYOS: A LESSON FROM WILDLIFE?

    EPA Science Inventory

    Many xenobiotic compounds introduced into the environment by human activity adversely affect wildlife. A number of these contaminants have been hypothesized to induce non lethal, multigenerational effects by acting as endocrine disrupting agents. One case is that of the alligator...

  1. Endocrine active chemicals, pharmaceuticals, and other chemicals of concern in surface water, wastewater-treatment plant effluent, and bed sediment, and biological characteristics in selected streams, Minnesota-design, methods, and data, 2009

    USGS Publications Warehouse

    Lee, Kathy E.; Langer, Susan K.; Barber, Larry B.; Writer, Jeff H.; Ferrey, Mark L.; Schoenfuss, Heiko L.; Furlong, Edward T.; Foreman, William T.; Gray, James L.; ReVello, Rhiannon C.; Martinovic, Dalma; Woodruff, Olivia R.; Keefe, Steffanie H.; Brown, Greg K.; Taylor, Howard E.; Ferrer, Imma; Thurman, E. Michael

    2011-01-01

    This report presents the study design, environmental data, and quality-assurance data for an integrated chemical and biological study of selected streams or lakes that receive wastewater-treatment plant effluent in Minnesota. This study was a cooperative effort of the U.S. Geological Survey, the Minnesota Pollution Control Agency, St. Cloud State University, the University of St. Thomas, and the University of Colorado. The objective of the study was to identify distribution patterns of endocrine active chemicals, pharmaceuticals, and other organic and inorganic chemicals of concern indicative of wastewater effluent, and to identify biological characteristics of estrogenicity and fish responses in the same streams. The U.S. Geological Survey collected and analyzed water, bed-sediment, and quality-assurance samples, and measured or recorded streamflow once at each sampling location from September through November 2009. Sampling locations included surface water and wastewater-treatment plant effluent. Twenty-five wastewater-treatment plants were selected to include continuous flow and periodic release facilities with differing processing steps (activated sludge or trickling filters) and plant design flows ranging from 0.002 to 10.9 cubic meters per second (0.04 to 251 million gallons per day) throughout Minnesota in varying land-use settings. Water samples were collected from the treated effluent of the 25 wastewater-treatment plants and at one point upstream from and one point downstream from wastewater-treatment plant effluent discharges. Bed-sediment samples also were collected at each of the stream or lake locations. Water samples were analyzed for major ions, nutrients, trace elements, pharmaceuticals, phytoestrogens and pharmaceuticals, alkylphenols and other neutral organic chemicals, carboxylic acids, and steroidal hormones. A subset (25 samples) of the bed-sediment samples were analyzed for carbon, wastewater-indicator chemicals, and steroidal hormones; the

  2. [Hypotension from endocrine origin].

    PubMed

    Vantyghem, Marie-Christine; Douillard, Claire; Balavoine, Anne-Sophie

    2012-11-01

    Hypotension is defined by a low blood pressure either permanently or only in upright posture (orthostatic hypotension). In contrast to hypertension, there is no threshold defining hypotension. The occurrence of symptoms for systolic and diastolic measurements respectively below 90 and 60 mm Hg establishes the diagnosis. Every acute hypotensive event should suggest shock, adrenal failure or an iatrogenic cause. Chronic hypotension from endocrine origin may be linked to adrenal failure from adrenal or central origin, isolated hypoaldosteronism, pseudohypoaldosteronism, pheochromocytoma, neuro-endocrine tumors (carcinoïd syndrome) or diabetic dysautonomia. Hypotension related to hypoaldosteronism associates low blood sodium and above all high blood potassium levels. They are generally classified according to their primary (hyperreninism) or secondary (hyporeninism) adrenal origin. Isolated primary hypoaldosteronisms are rare in adults (intensive care unit, selective injury of the glomerulosa area) and in children (aldosterone synthase deficiency). Isolated secondary hypoaldosteronism is related to mellitus diabetes complicated with dysautonomia, kidney failure, age, iatrogenic factors, and HIV infections. In both cases, they can be associated to glucocorticoid insufficiency from primary adrenal origin (adrenal failure of various origins with hyperreninism, among which congenital 21 hydroxylase deficiency with salt loss) or from central origin (hypopituitarism with hypo-reninism). Pseudohypoaldosteronisms are linked to congenital (type 1 pseudohypoaldosteronism) or acquired states of resistance to aldosterone. Acquired salt losses from enteric (total colectomy with ileostomy) or renal (interstitial nephropathy, Bartter and Gitelman syndromes…) origin might be responsible for hypotension and are associated with hyperreninism-hyperaldosteronism. Hypotension is a rare manifestation of pheochromocytomas, especially during surgical removal when the patient has not been

  3. Endocrine disrupting chemicals and disease susceptibility.

    PubMed

    Schug, Thaddeus T; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J

    2011-11-01

    Environmental chemicals have significant impacts on biological systems. Chemical exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurological, cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products--including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints associated with endocrine disruption.

  4. Canonical nucleosome organization at promoters forms during genome activation.

    PubMed

    Zhang, Yong; Vastenhouw, Nadine L; Feng, Jianxing; Fu, Kai; Wang, Chenfei; Ge, Ying; Pauli, Andrea; van Hummelen, Paul; Schier, Alexander F; Liu, X Shirley

    2014-02-01

    The organization of nucleosomes influences transcriptional activity by controlling accessibility of DNA binding proteins to the genome. Genome-wide nucleosome binding profiles have identified a canonical nucleosome organization at gene promoters, where arrays of well-positioned nucleosomes emanate from nucleosome-depleted regions. The mechanisms of formation and the function of canonical promoter nucleosome organization remain unclear. Here we analyze the genome-wide location of nucleosomes during zebrafish embryogenesis and show that well-positioned nucleosome arrays appear on thousands of promoters during the activation of the zygotic genome. The formation of canonical promoter nucleosome organization is independent of DNA sequence preference, transcriptional elongation, and robust RNA polymerase II (Pol II) binding. Instead, canonical promoter nucleosome organization correlates with the presence of histone H3 lysine 4 trimethylation (H3K4me3) and affects future transcriptional activation. These findings reveal that genome activation is central to the organization of nucleosome arrays during early embryogenesis.

  5. Designing Culturally Responsive Organized After-School Activities

    ERIC Educational Resources Information Center

    Simpkins, Sandra D.; Riggs, Nathaniel R.; Ngo, Bic; Vest Ettekal, Andrea; Okamoto, Dina

    2017-01-01

    Organized after-school activities promote positive youth development across a range of outcomes. To be most effective, organized activities need to meet high-quality standards. The eight features of quality developed by the National Research Council's Committee on Community-Level Programs for Youth have helped guide the field in this regard.…

  6. Predicting chemical impacts on vertebrate endocrine systems.

    PubMed

    Nichols, John W; Breen, Miyuki; Denver, Robert J; Distefano, Joseph J; Edwards, Jeremy S; Hoke, Robert A; Volz, David C; Zhang, Xiaowei

    2011-01-01

    Animals have evolved diverse protective mechanisms for responding to toxic chemicals of both natural and anthropogenic origin. From a governmental regulatory perspective, these protective responses complicate efforts to establish acceptable levels of chemical exposure. To explore this issue, we considered vertebrate endocrine systems as potential targets for environmental contaminants. Using the hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-gonad (HPG), and hypothalamic-pituitary-adrenal (HPA) axes as case examples, we identified features of these systems that allow them to accommodate and recover from chemical insults. In doing so, a distinction was made between effects on adults and those on developing organisms. This distinction was required because endocrine system disruption in early life stages may alter development of organs and organ systems, resulting in permanent changes in phenotypic expression later in life. Risk assessments of chemicals that impact highly regulated systems must consider the dynamics of these systems in relation to complex environmental exposures. A largely unanswered question is whether successful accommodation to a toxic insult exerts a fitness cost on individual animals, resulting in adverse consequences for populations. Mechanistically based mathematical models of endocrine systems provide a means for better understanding accommodation and recovery. In the short term, these models can be used to design experiments and interpret study findings. Over the long term, a set of validated models could be used to extrapolate limited in vitro and in vivo testing data to a broader range of untested chemicals, species, and exposure scenarios. With appropriate modification, Tier 2 assays developed in support of the U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program could be used to assess the potential for accommodation and recovery and inform the development of mechanistically based models.

  7. Sun lotion chemicals as endocrine disruptors.

    PubMed

    Maipas, Sotirios; Nicolopoulou-Stamati, Polyxeni

    2015-01-01

    Ultraviolet solar radiation is a well-known environmental health risk factor and the use of sun lotions is encouraged to achieve protection mainly from skin cancer. Sun lotions are cosmetic commercial products that combine active and inactive ingredients and many of these are associated with health problems, including allergic reactions and endocrine disorders. This review focuses on their ability to cause endocrine and reproductive impairments, with emphasis laid on the active ingredients (common and less common UV filters). In vitro and in vivo studies have demonstrated their ability to show oestrogenic/anti-oestrogenic and androgenic/anti-androgenic activity. Many ingredients affect the oestrous cycle, spermatogenesis, sexual behaviour, fertility and other reproductive parameters in experimental animals. Their presence in aquatic environments may reveal a new emerging environmental hazard.

  8. [Organisms producing hypolipidemic compounds with antioxidant activity].

    PubMed

    Puzhevskaia, T O; Grammatikova, N E; Bibikova, M V; Katlinskiĭ, A V

    2009-01-01

    Complex compounds produced by fungal cultures of Lecanicilium and Beauveria with both high hypolipidemic and antioxydant activities were screened. Two fractions of the hypolipipidemic compounds with antioxidant activity of 95 and 75% in a dose of 25 mcg/ml were isolated.

  9. Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation.

    PubMed

    Vos, J G; Dybing, E; Greim, H A; Ladefoged, O; Lambré, C; Tarazona, J V; Brandt, I; Vethaak, A D

    2000-01-01

    Many wildlife species may be exposed to biologically active concentrations of endocrine-disrupting chemicals. There is strong evidence obtained from laboratory studies showing the potential of several environmental chemicals to cause endocrine disruption at environmentally realistic exposure levels. In wildlife populations, associations have been reported between reproductive and developmental effects and endocrine-disrupting chemicals. In the aquatic environment, effects have been observed in mammals, birds, reptiles, fish, and mollusks from Europe, North America, and other areas. The observed abnormalities vary from subtle changes to permanent alterations, including disturbed sex differentiation with feminized or masculinized sex organs, changed sexual behavior, and altered immune function. For most reported effects in wildlife, however, the evidence for a causal link with endocrine disruption is weak or nonexisting. Crucial in establishing causal evidence for chemical-induced wildlife effects appeared semifield or laboratory studies using the wildlife species of concern. Impaired reproduction and development causally linked to endocrine-disrupting chemicals are well documented in a number of species and have resulted in local or regional population changes. These include: Masculinization (imposex) in female marine snails by tributyltin, a biocide used in antifouling paints, is probably the clearest case of endocrine disruption caused by an environmental chemical. The dogwhelk is particularly sensitive, and imposex has resulted in decline or extinction of local populations worldwide, including coastal areas all over Europe and the open North Sea. DDE-induced egg-shell thinning in birds has caused severe population declines in a number of raptor species in Europe and North America. Endocrine-disrupting chemicals have adversely affected a variety of fish species. In the vicinity of certain sources (e.g., effluents of water treatment plants) and in the most

  10. World Trade Organization activity for health services.

    PubMed

    Gros, Clémence

    2012-01-01

    Since the establishment of a multilateral trading system and the increasing mobility of professionals and consumers of health services, it seems strongly necessary that the World Trade Organization (WTO) undertakes negotiations within the General Agreement on Trade in Services (GATS), and that WTO's members attempt to reach commitments for health-related trade in services. How important is the GATS for health policy and how does the GATS refer to health services? What are the current negotiations and member's commitments?

  11. Trauma and the endocrine system.

    PubMed

    Mesquita, Joana; Varela, Ana; Medina, José Luís

    2010-12-01

    The endocrine system may be the target of different types of trauma with varied consequences. The present article discusses trauma of the hypothalamic-pituitary axes, adrenal glands, gonads, and pancreas. In addition to changes in circulating hormone levels due to direct injury to these structures, there may be an endocrine response in the context of the stress caused by the trauma.

  12. Active Pharmaceutical Ingredients and Aquatic Organisms

    EPA Science Inventory

    The presence of active pharmaceuticals ingredients (APIs) in aquatic systems in recent years has led to a burgeoning literature examining environmental occurrence, fate, effects, risk assessment, and treatability of these compounds. Although APIs have received much attention as ...

  13. Nonoxidative removal of organics in the activated sludge process

    PubMed Central

    Modin, Oskar; Persson, Frank; Wilén, Britt-Marie; Hermansson, Malte

    2016-01-01

    ABSTRACT The activated sludge process is commonly used to treat wastewater by aerobic oxidation of organic pollutants into carbon dioxide and water. However, several nonoxidative mechanisms can also contribute to removal of organics. Sorption onto activated sludge can remove a large fraction of the colloidal and particulate wastewater organics. Intracellular storage of, e.g., polyhydroxyalkanoates (PHA), triacylglycerides (TAG), or wax esters can convert wastewater organics into precursors for high-value products. Recently, several environmental, economic, and technological drivers have stimulated research on nonoxidative removal of organics for wastewater treatment. In this paper, we review these nonoxidative removal mechanisms as well as the existing and emerging process configurations that make use of them for wastewater treatment. Better utilization of nonoxidative processes in activated sludge could reduce the wasteful aerobic oxidation of organic compounds and lead to more resource-efficient wastewater treatment plants. PMID:27453679

  14. Structural complexities in the active layers of organic electronics.

    PubMed

    Lee, Stephanie S; Loo, Yueh-Lin

    2010-01-01

    The field of organic electronics has progressed rapidly in recent years. However, understanding the direct structure-function relationships between the morphology in electrically active layers and the performance of devices composed of these materials has proven difficult. The morphology of active layers in organic electronics is inherently complex, with heterogeneities existing across multiple length scales, from subnanometer to micron and millimeter range. A major challenge still facing the organic electronics community is understanding how the morphology across all of the length scales in active layers collectively determines the device performance of organic electronics. In this review we highlight experiments that have contributed to the elucidation of structure-function relationships in organic electronics and also point to areas in which knowledge of such relationships is still lacking. Such knowledge will lead to the ability to select active materials on the basis of their inherent properties for the fabrication of devices with prespecified characteristics.

  15. FOXO factors and breast cancer: outfoxing endocrine resistance.

    PubMed

    Bullock, M

    2016-02-01

    The majority of metastatic breast cancers cannot be cured and present a major public health problem worldwide. Approximately 70% of breast cancers express the estrogen receptor, and endocrine-based therapies have significantly improved patient outcomes. However, the development of endocrine resistance is extremely common. Understanding the molecular pathways that regulate the hormone sensitivity of breast cancer cells is important to improving the efficacy of endocrine therapy. It is becoming clearer that the PI3K-AKT-forkhead box O (FOXO) signaling axis is a key player in the hormone-independent growth of many breast cancers. Constitutive PI3K-AKT pathway activation, a driver of breast cancer growth, causes down-regulation of FOXO tumor suppressor functions. This review will summarize what is currently known about the role of FOXOs in endocrine-resistance mechanisms. It will also suggest potential therapeutic strategies for the restoration of normal FOXO transcriptional activity.

  16. Endocrine effects of the herbicide linuron on the American Goldfinch (Carduelis tristis)

    USGS Publications Warehouse

    Sughrue, K.M.; Brittingham, M.C.; French, J.B.

    2008-01-01

    Certain contaminants alter normal physiological function, morphology, and behavior of exposed organisms through an endocrine mechanism. We evaluated how the herbicide linuron, an endocrine-active compound, affects physiological parameters and secondary sex characteristics of the American Goldfinch (Carduelis tristis). When administered at relatively low doses (control, 1.0, 4.0, and 16.0 mu g linuron per gram of body mass per day), linuron delayed prealternate molt progression in a dose-dependent manner. At the high dose level, linuron exposure lowered hematocrit and female plasma thyroxine concentrations and increased body mass. Neither plasma testosterone concentrations nor the color of plumage or integument of birds in the treatment groups were different from those of the control group. Overall, the physiological effects that were measured suggested disruption of thyroid function. These results highlight the importance of continual monitoring of avian populations for potential effects of exposure to pesticides and other chemicals at sublethal concentrations.

  17. t4 workshop report--lessons learned, challenges, and opportunities: the U.S. Endocrine Disruptor Screening Program.

    PubMed

    Juberg, Daland R; Borghoff, Susan J; Becker, Richard A; Casey, Warren; Hartung, Thomas; Holsapple, Michael P; Marty, M Sue; Mihaich, Ellen M; Van Der Kraak, Glen; Wade, Michael G; Willett, Catherine E; Andersen, Melvin E; Borgert, Christopher J; Coady, Katherine K; Dourson, Michael L; Fowle, John R; Gray, L Earl; Lamb, James C; Ortego, Lisa S; Schug, Thaddeus T; Toole, Colleen M; Zorrilla, Leah M; Kroner, Oliver L; Patterson, Jacqueline; Rinckel, Lori A; Jones, Brett R

    2014-01-01

    In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the Safe Drinking Water Act (SDWA) requiring the U.S. Environmental Protection Agency (EPA) to implement a screening program to investigate the potential of pesticide chemicals and drinking water contaminants to adversely affect endocrine pathways. Consequently, the EPA launched the Endocrine Disruptor Screening Program (EDSP) to develop and validate estrogen, androgen, and thyroid (EAT) pathway screening assays and to produce standardized and harmonized test guidelines for regulatory application. In 2009, the EPA issued the first set of test orders for EDSP screening and a total of 50 pesticide actives and 2 inert ingredients have been evaluated using the battery of EDSP Tier 1 screening assays (i.e., five in vitro assays and six in vivo assays). To provide a framework for retrospective analysis of the data generated and to collect the insight of multiple stakeholders involved in the testing, more than 240 scientists from government, industry, academia, and non-profit organizations recently participated in a workshop titled "Lessons Learned, Challenges, and Opportunities: The U.S. Endocrine Disruptor Screening Program." The workshop focused on the science and experience to date and was organized into three focal sessions: (a) Performance of the EDSP Tier 1 Screening Assays for Estrogen, Androgen, and Thyroid Pathways; (b) Practical Applications of Tier 1 Data; and (c) Indications and Opportunities for Future Endocrine Testing. A number of key learnings and recommendations related to future EDSP evaluations emanated from the collective sessions.

  18. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals.

    PubMed

    Sanderson, J Thomas

    2006-11-01

    Various chemicals found in the human and wildlife environments have the potential to disrupt endocrine functions in exposed organisms. Increasingly, the enzymes involved in the steroid biosynthesis pathway are being recognized as important targets for the actions of various endocrine-disrupting chemicals. Interferences with steroid biosynthesis may result in impaired reproduction, alterations in (sexual) differentiation, growth, and development and the development of certain cancers. Steroid hormone synthesis is controlled by the activity of several highly substrate-selective cytochrome P450 enzymes and a number of steroid dehydrogenases and reductases. Particularly aromatase (CYP19), the enzyme that converts androgens to estrogens, has been the subject of studies into the mechanisms by which chemicals interfere with sex steroid hormone homeostasis and function, often related to (de)feminization and (de)masculinazation processes. Studies in vivo and in vitro have focussed on ovarian and testicular function, with less attention given to other steroidogenic organs, such as the adrenal cortex. This review aims to provide a comprehensive overview of the state of knowledge regarding the mechanisms by which chemicals interfere with the function of steroidogenic enzymes in various tissues and organisms. The endocrine toxicities and mechanisms of action related to steroidogenesis of a number of classes of drugs and environmental contaminants are discussed. In addition, several potential in vitro bioassays are reviewed for their usefulness as screening tools for the detection of chemicals that can interfere with steroidogenesis. Analysis of the currently scattered state of knowledge indicates that still relatively little is known about the underlying mechanisms of interference of chemicals with steroidogenesis and their potential toxicity in steroidogenic tissues, neither in humans nor in wildlife. Considerably more detailed and systematic research in this area of

  19. [Effects of different fertilizer application on soil active organic carbon].

    PubMed

    Zhang, Rui; Zhang, Gui-Long; Ji, Yan-Yan; Li, Gang; Chang, Hong; Yang, Dian-Lin

    2013-01-01

    The variation characteristics of the content and components of soil active organic carbon under different fertilizer application were investigated in samples of calcareous fluvo-aquic soil from a field experiment growing winter wheat and summer maize in rotation in the North China Plain. The results showed that RF (recommended fertilization), CF (conventional fertilization) and NPK (mineral fertilizer alone) significantly increased the content of soil dissolved organic carbon and easily oxidized organic carbon by 24.92-38.63 mg x kg(-1) and 0.94-0.58 mg x kg(-1) respectively compared to CK (unfertilized control). The soil dissolved organic carbon content under OM (organic manure) increased greater than those under NPK and single fertilization, soil easily oxidized organic carbon content under OM and NPK increased greater than that under single chemical fertilization. OM and NPK showed no significant role in promoting the soil microbial biomass carbon, but combined application of OM and NPK significantly increased the soil microbial biomass carbon content by 36.06% and 20.69%, respectively. Soil easily oxidized organic carbon, dissolved organic carbon and microbial biomass carbon accounted for 8.41% - 14.83%, 0.47% - 0.70% and 0.89% - 1.20% of the total organic carbon (TOC), respectively. According to the results, the fertilizer application significantly increased the proportion of soil dissolved organic carbon and easily oxidized organic carbon, but there was no significant difference in the increasing extent of dissolved organic carbon. The RF and CF increased the proportion of soil easily oxidized organic carbon greater than OM or NPK, and significantly increased the proportion of microbial biomass carbon. OM or RF had no significant effect on the proportion of microbial biomass carbon. Therefore, in the field experiment, appropriate application of organic manure and chemical fertilizers played an important role for the increase of soil active organic carbon

  20. Pulp and paper mill effluent treatments have differential endocrine-disrupting effects on rainbow trout.

    PubMed

    Orrego, Rodrigo; Guchardi, John; Hernandez, Victor; Krause, Rachelle; Roti, Lucia; Armour, Jeffrey; Ganeshakumar, Mathumai; Holdway, Douglas

    2009-01-01

    Endocrine disruption (ED) effects due to pulp and paper mill effluents extracts involving different industrial procedures and effluent treatments (nontreated, primary, and secondary treated) were evaluated using immature triploid rainbow trout in a pulse-exposure toxicity experiment. The protocol involved the use of intraperitoneal injection of mill extracts (solid-phase extraction [SPE]) corrected for individual fish weight and included several laboratory standards (steroidal hormones and phytosterols). Biological endpoints at two different levels of biological organization were analyzed (molecular and individual organism). Results indicated that nonsignificant changes were observed in the individual physiological indices represented by condition factor, liver somatic index, and gonad somatic index during the experiment. Significant induction of liver ethoxyresorufin-O-deethylase activity was observed between different effluent treatments and experimental controls. Significant endocrine-disrupting effects at the reproductive level were observed in all effluent treatments involving significant increments in plasma vitellogenin (VTG) levels. Fish exposed to untreated effluent extracts had significantly higher VTG levels compared to fish exposed to primary and secondary treatment effluent extracts, indicating a decrease of the estrogenic effect due to the effluent treatment. The present study has shown that for the Chilean pulp and paper mill SPE extracts evaluated, an endocrine disruption effect was induced in immature triploid rainbow, reaffirming the significant estrogenic effects demonstrated previously in laboratory and field experiments.

  1. Alliance Affiliate Activities: Non-Governmental Organizations in Environmental Education.

    ERIC Educational Resources Information Center

    Disinger, John F., Comp.

    Short descriptions of organizational structure and goals and descriptions of environmental education interests, activities, and priorities are presented for 32 nongovernmental organizations affiliated with the Alliance for Environmental Education. The organizations included are listed in the table of contents. The groups included represent a…

  2. Cancer and developmental exposure to endocrine disruptors.

    PubMed Central

    Birnbaum, Linda S; Fenton, Suzanne E

    2003-01-01

    Developing organisms have increased susceptibility to cancer if they are exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and there is suggestive evidence that brain tumors and leukemia are associated with parental exposures to chemicals. Animal experiments have demonstrated increased tumor formation induced by prenatal or neonatal exposure to a variety of chemicals, including direct-acting carcinogens and drugs. Recently, natural estrogens have been classified as known human carcinogens. Prenatal exposure to natural and synthetic estrogens is associated with increases in breast and vaginal tumors in humans as well as uterine tumors in animals. Synthetic halogenated chemicals increase liver tumors after early life-stage exposure. Recently, a prototypical endocrine-disrupting compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin, has been shown to be a developmental toxicant of the mammary gland in rodents. Dioxin alters multiple endocrine systems, and its effects on the developing breast involve delayed proliferation and differentiation of the mammary gland, as well as an elongation of the window of sensitivity to potential carcinogens. Implications of these new findings suggest that causes of endocrine-related cancers or susceptibility to cancer may be a result of developmental exposures rather than exposures existing at or near the time of tumor detection. PMID:12676588

  3. Cancer and developmental exposure to endocrine disruptors.

    PubMed

    Birnbaum, Linda S; Fenton, Suzanne E

    2003-04-01

    Developing organisms have increased susceptibility to cancer if they are exposed to environmental toxicants during rapid growth and differentiation. Human studies have demonstrated clear increases in cancer after prenatal exposure to ionizing radiation, and there is suggestive evidence that brain tumors and leukemia are associated with parental exposures to chemicals. Animal experiments have demonstrated increased tumor formation induced by prenatal or neonatal exposure to a variety of chemicals, including direct-acting carcinogens and drugs. Recently, natural estrogens have been classified as known human carcinogens. Prenatal exposure to natural and synthetic estrogens is associated with increases in breast and vaginal tumors in humans as well as uterine tumors in animals. Synthetic halogenated chemicals increase liver tumors after early life-stage exposure. Recently, a prototypical endocrine-disrupting compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin, has been shown to be a developmental toxicant of the mammary gland in rodents. Dioxin alters multiple endocrine systems, and its effects on the developing breast involve delayed proliferation and differentiation of the mammary gland, as well as an elongation of the window of sensitivity to potential carcinogens. Implications of these new findings suggest that causes of endocrine-related cancers or susceptibility to cancer may be a result of developmental exposures rather than exposures existing at or near the time of tumor detection.

  4. Feedback control of growth, differentiation, and morphogenesis of pancreatic endocrine progenitors in an epithelial plexus niche

    PubMed Central

    Bankaitis, Eric D.; Bechard, Matthew E.; Wright, Christopher V.E.

    2015-01-01

    In the mammalian pancreas, endocrine cells undergo lineage allocation upon emergence from a bipotent duct/endocrine progenitor pool, which resides in the “trunk epithelium.” Major questions remain regarding how niche environments are organized within this epithelium to coordinate endocrine differentiation with programs of epithelial growth, maturation, and morphogenesis. We used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. The bulk of endocrine progenitors is maintained in an epithelial “plexus state,” which is a transient intermediate during epithelial maturation within which endocrine cell differentiation is continually robust and surprisingly long-lived. Within the plexus, local feedback effects derived from the differentiating and delaminating endocrine cells nonautonomously regulate the flux of endocrine cell birth as well as proliferative growth of the bipotent cell population using Notch-dependent and Notch-independent influences, respectively. These feedback effects in turn maintain the plexus state to ensure prolonged allocation of endocrine cells late into gestation. These findings begin to define a niche-like environment guiding the genesis of the endocrine pancreas and advance current models for how differentiation is coordinated with the growth and morphogenesis of the developing pancreatic epithelium. PMID:26494792

  5. Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases

    PubMed Central

    Erdöl, Şahin; Sağlam, Halil

    2016-01-01

    Objective: Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Methods: Data were obtained retrospectively from the medical reports of patients with IMDs who were followed by the division of pediatric metabolism and nutrition between June 2011 and November 2013. Results: In total, 260 patients [139 males (53%) and 121 females (47%)] with an IMD diagnosis were included in the study. The mean age of the patients was 5.94 (range; 0.08 to 49) years and 95.8% (249 of 260 patients) were in the pediatric age group. Growth status was evaluated in 258 patients and of them, 27 (10.5%) had growth failure, all cases of which were attributed to non-endocrine reasons. There was a significant correlation between growth failure and serum albumin levels below 3.5 g/dL (p=0.002). Only three of 260 (1.1%) patients had endocrine dysfunction. Of these, one with lecithin-cholesterol acyltransferase deficiency and another with Kearns-Sayre syndrome had diabetes, and one with glycerol kinase deficiency had glucocorticoid deficiency. Conclusion: Endocrine dysfunction in patients with IMDs is relatively rare. For this reason, there is no need to conduct routine endocrine evaluations in most patients with IMDs unless a careful and detailed history and a physical examination point to an endocrine dysfunction. PMID:27086477

  6. Computational model of the fathead minnow hypothalamic-pituitary-gonadal axis: Incorporating protein synthesis in improving predictability of responses to endocrine active chemicals.

    PubMed

    Breen, Miyuki; Villeneuve, Daniel L; Ankley, Gerald T; Bencic, David; Breen, Michael S; Watanabe, Karen H; Lloyd, Alun L; Conolly, Rory B

    2016-01-01

    There is international concern about chemicals that alter endocrine system function in humans and/or wildlife and subsequently cause adverse effects. We previously developed a mechanistic computational model of the hypothalamic-pituitary-gonadal (HPG) axis in female fathead minnows exposed to a model aromatase inhibitor, fadrozole (FAD), to predict dose-response and time-course behaviors for apical reproductive endpoints. Initial efforts to develop a computational model describing adaptive responses to endocrine stress providing good fits to empirical plasma 17β-estradiol (E2) data in exposed fish were only partially successful, which suggests that additional regulatory biology processes need to be considered. In this study, we addressed short-comings of the previous model by incorporating additional details concerning CYP19A (aromatase) protein synthesis. Predictions based on the revised model were evaluated using plasma E2 concentrations and ovarian cytochrome P450 (CYP) 19A aromatase mRNA data from two fathead minnow time-course experiments with FAD, as well as from a third 4-day study. The extended model provides better fits to measured E2 time-course concentrations, and the model accurately predicts CYP19A mRNA fold changes and plasma E2 dose-response from the 4-d concentration-response study. This study suggests that aromatase protein synthesis is an important process in the biological system to model the effects of FAD exposure.

  7. Short-term fish reproduction assays with methyl tertiary butyl ether with zebrafish and fathead minnow: Implications for evaluation of potential for endocrine activity.

    PubMed

    Mihaich, Ellen; Erler, Steffen; Le Blanc, Gerald; Gallagher, Sean

    2015-09-01

    The authors report on short-term fish reproduction assays in zebrafish and fathead minnow conducted to examine the potential for methyl tertiary butyl ether (MTBE) to cause effects on the endocrine system. Both studies were performed under good laboratory practice and in accordance with Organisation for Economic Co-operation and Development and US Environmental Protection Agency test guidelines. The results of the first study demonstrated that exposure to a high test concentration (147 mg/L) of MTBE impaired reproductive output of female zebrafish, evident by a reduction in fecundity. Based on the endpoints evaluated in the present study however, there was no supporting evidence to indicate that this effect was caused by disruption of or interaction with the endocrine system. In the second study, fathead minnows exposed to a wider but lower range of test concentrations showed no effects on any reproductive parameter of male or female fish, at the maximum recommended testing concentration of 100 mg/L (62 mg/L measured). The results of these 2 guideline studies indicate that MTBE does not interact with the hypothalamic-pituitary-gonadal axis of zebrafish or fathead minnow.

  8. Endocrine disruptors and thyroid hormone physiology.

    PubMed

    Jugan, Mary-Line; Levi, Yves; Blondeau, Jean-Paul

    2010-04-01

    Endocrine disruptors are man-made chemicals that can disrupt the synthesis, circulating levels, and peripheral action of hormones. The disruption of sex hormones was subject of intensive research, but thyroid hormone synthesis and signaling are now also recognized as important targets of endocrine disruptors. The neurological development of mammals is largely dependent on normal thyroid hormone homeostasis, and it is likely to be particularly sensitive to disruption of the thyroid axis. Here, we survey the main thyroid-disrupting chemicals, such as polychlorinated biphenyls, perchlorates, and brominated flame-retardants, that are characteristic disruptors of thyroid hormone homeostasis, and look at their suspected relationships to impaired development of the human central nervous system. The review then focuses on disrupting mechanisms known to be directly or indirectly related to the transcriptional activity of the thyroid hormone receptors.

  9. Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

    PubMed Central

    De Coster, Sam; van Larebeke, Nicolas

    2012-01-01

    The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand. PMID:22991565

  10. Comparative assessment of endocrine modulators with oestrogenic activity: I. Definition of a hygiene-based margin of safety (HBMOS) for xeno-oestrogens against the background of European developments.

    PubMed

    Bolt, H M; Janning, P; Michna, H; Degen, G H

    2001-01-01

    A novel concept - the hygiene-based margin of safety (HBMOS) - is suggested for the assessment of the impact of potential endocrine modulators. It integrates exposure scenarios and potency data for industrial chemicals and naturally occurring dietary compounds with oestrogenic activity. An HBMOS is defined as a quotient of estimated daily intakes weighted by the relative in vivo potencies of these compounds. The Existing Chemicals Programme of the European Union provides Human and Environmental Risk Assessments of Existing Chemicals which include human exposure scenarios. Such exposure scenarios, along with potency estimates for endocrine activities, may provide a basis for a quantitative comparison of the potential endocrine-modulating effects of industrial chemicals with endocrine modulators as natural constituents of human diet. Natural phyto-oestrogens exhibit oestrogenic activity in vitro and in vivo. Important phyto-oestrogens for humans are isoflavones (daidzein, genistein) and lignans, with the highest quantities found in soybeans and flaxseed, respectively. Daily isoflavone exposures calculated for infants on soy-based formulae were in the ranges of 4.5-8 mg/kg body wt.; estimates for adults range up to 1 mg/kg body wt. The Senate Commission on the Evaluation of Food Safety (SKLM) of the Deutsche Forschungsgemeinschaft has also indicated a wide range of dietary exposures. For matters of risk assessment, the SKLM has based recommendations on dietary exposure scenarios, implying a daily intake of phyto-oestrogens in the order of 1 mg/kg body wt. On the basis of information compiled within the Existing Chemicals Programme of the EU, it appears that a daily human exposure to nonylphenol of 2 microg/kg body wt. may be a worst-case assumption, but which is based on valid scenarios. The intake of octylphenol is much lower, due to a different use pattern and applications, and may be neglected. Data from migration studies led to estimations of the daily human

  11. Cloud condensation nuclei activation of limited solubility organic aerosol

    NASA Astrophysics Data System (ADS)

    Huff Hartz, Kara E.; Tischuk, Joshua E.; Chan, Man Nin; Chan, Chak K.; Donahue, Neil M.; Pandis, Spyros N.

    The cloud condensation nuclei (CCN) activation of 19 organic species with water solubilities ( Csat) ranging from 10 -4 to 10 2 g solute 100 g -1 H 2O was measured. The organic particles were generated by nebulization of an aqueous or an alcohol solution. Use of alcohols as solvents enables the measurement of low solubility, non-volatile organic CCN activity and reduces the likelihood of residual water in the aerosol. The activation diameter of organic species with very low solubility in water ( Csat<0.3 g 100 g -1 H 2O) is in agreement with Köhler theory using the bulk solubility (limited solubility case) of the organic in water. Many species, including 2-acetylbenzoic acid, aspartic acid, azelaic acid, glutamic acid, homophthalic acid, phthalic acid, cis-pinonic acid, and salicylic acid are highly CCN active in spite of their low solubility (0.3 g 100 g -1 H 2O< Csat<1 g 100 g -1 H 2O), and activate almost as if completely water soluble. The CCN activity of most species is reduced, if the particles are produced using non-aqueous solvents. The existence of the particles in a metastable state at low RH can explain the observed enhancement in CCN activity beyond the levels suggested by their solubility.

  12. Developmental effects of endocrine-disrupting chemicals in wildlife and humans.

    PubMed Central

    Colborn, T; vom Saal, F S; Soto, A M

    1993-01-01

    Large numbers and large quantities of endocrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, transgenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistence of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans. PMID:8080506

  13. Photocatalytic activity of ZnO doped with Ag on the degradation of endocrine disrupting under UV irradiation and the investigation of its antibacterial activity

    NASA Astrophysics Data System (ADS)

    Bechambi, Olfa; Chalbi, Manel; Najjar, Wahiba; Sayadi, Sami

    2015-08-01

    Ag-doped ZnO photocatalysts with different Ag molar content (0.0, 0.5, 1.0, 2.0 and 4.0%) were prepared via hydrothermal method. The X-ray diffraction (XRD), Nitrogen physisorption at 77 K, Fourier transformed infrared spectroscopy (FTIR), UV--Visible spectroscopy, Photoluminescence spectra (PL) and Raman spectroscopy were used to characterize the structural, textural and optical properties of the samples. The results showed that Ag-doping does not change the average crystallite size with the Ag low content (≤1.0%) but slightly decreases with Ag high content (>1.0%). The specific surface area (SBET) increases with the increase of the Ag content. The band gap values of ZnO are decreased with the increase of the Ag doping level. The results of the photocatalytic degradation of bisphenol A (BPA) and nonylphenol (NP) in aqueous solutions under UV irradiation and in the presence of hydrogen peroxide (H2O2) showed that silver ions doping greatly improved the photocatalytic efficiency of ZnO. The TOC conversion BPA and NP are 72.1% and 81.08% respectively obtained using 1% Ag-doped ZnO. The enhancement of photocatalytic activity is ascribed to the fact that the modification of ZnO with an appropriate amount of Ag can increase the separation efficiency of the photogenerated electrons-holes in ZnO. The antibacterial activity of the catalysts which uses Escherichia coli as a model for Gram-negative bacteria confirmed that Ag-doped ZnO possessed more antibacterial activity than the pure ZnO.

  14. Two-Dimensional Perovskite Activation with an Organic Luminophore.

    PubMed

    Jemli, Khaoula; Audebert, Pierre; Galmiche, Laurent; Trippé-Allard, Gaelle; Garrot, Damien; Lauret, Jean-Sébastien; Deleporte, Emmanuelle

    2015-10-07

    A great advantage of the hybrid organic-inorganic perovskites is the chemical flexibility and the possibility of a molecular engineering of each part of the material (the inorganic part and the organic part respectively) in order to improve or add some functionalities. An adequately chosen organic luminophore has been introduced inside a lead bromide type organic-inorganic perovskite, while respecting the two-dimensional perovskite structure. A substantial increase of the brilliance of the perovskite is obtained. This activation of the perovskite luminescence by the adequate engineering of the organic part is an original approach, and is particularly interesting in the framework of the light-emitting devices such as organic light-emitting diodes (OLEDs) or lasers.

  15. Recent Advances on Endocrine Disrupting Effects of UV Filters

    PubMed Central

    Wang, Jiaying; Pan, Liumeng; Wu, Shenggan; Lu, Liping; Xu, Yiwen; Zhu, Yanye; Guo, Ming; Zhuang, Shulin

    2016-01-01

    Ultraviolet (UV) filters are used widely in cosmetics, plastics, adhesives and other industrial products to protect human skin or products against direct exposure to deleterious UV radiation. With growing usage and mis-disposition of UV filters, they currently represent a new class of contaminants of emerging concern with increasingly reported adverse effects to humans and other organisms. Exposure to UV filters induce various endocrine disrupting effects, as revealed by increasing number of toxicological studies performed in recent years. It is necessary to compile a systematic review on the current research status on endocrine disrupting effects of UV filters toward different organisms. We therefore summarized the recent advances on the evaluation of the potential endocrine disruptors and the mechanism of toxicity for many kinds of UV filters such as benzophenones, camphor derivatives and cinnamate derivatives. PMID:27527194

  16. Hormones in the city: endocrine ecology of urban birds.

    PubMed

    Bonier, Frances

    2012-05-01

    Urbanization dramatically changes the landscape, presenting organisms with novel challenges and often leading to reduced species diversity. Urban ecologists have documented numerous biotic and abiotic consequences of urbanization, such as altered climate, species interactions, and community composition, but we lack an understanding of the mechanisms underlying organisms' responses to urbanization. Here, I review findings from the nascent field of study of the endocrine ecology of urban birds. Thus far, no clear or consistent patterns have been revealed, but we do have evidence that urban habitat can shape endocrine traits, and that those traits might contribute to adaptation to the urban environment. I suggest strong approaches for future work addressing exciting questions about the role of endocrine traits in mediating responses to urbanization within species across the globe.

  17. Activism or "Slacktivism?": Digital Media and Organizing for Social Change

    ERIC Educational Resources Information Center

    Glenn, Cerise L.

    2015-01-01

    The influence of social media and technological developments has changed how groups and organizations advocating for social change generate awareness and participation in their causes. In this single class activity students will (a) analyze notions of activism and "slacktivism" from scholarly and popular sources to apply these concepts…

  18. Enzyme activities by indicator of quality in organic soil

    NASA Astrophysics Data System (ADS)

    Raigon Jiménez, Mo; Fita, Ana Delores; Rodriguez Burruezo, Adrián

    2016-04-01

    The analytical determination of biochemical parameters, as soil enzyme activities and those related to the microbial biomass is growing importance by biological indicator in soil science studies. The metabolic activity in soil is responsible of important processes such as mineralization and humification of organic matter. These biological reactions will affect other key processes involved with elements like carbon, nitrogen and phosphorus , and all transformations related in soil microbial biomass. The determination of biochemical parameters is useful in studies carried out on organic soil where microbial processes that are key to their conservation can be analyzed through parameters of the metabolic activity of these soils. The main objective of this work is to apply analytical methodologies of enzyme activities in soil collections of different physicochemical characteristics. There have been selective sampling of natural soils, organic farming soils, conventional farming soils and urban soils. The soils have been properly identified conserved at 4 ° C until analysis. The enzyme activities determinations have been: catalase, urease, cellulase, dehydrogenase and alkaline phosphatase, which bring together a representative group of biological transformations that occur in the soil environment. The results indicate that for natural and agronomic soil collections, the values of the enzymatic activities are within the ranges established for forestry and agricultural soils. Organic soils are generally higher level of enzymatic, regardless activity of the enzyme involved. Soil near an urban area, levels of activities have been significantly reduced. The vegetation cover applied to organic soils, results in greater enzymatic activity. So the quality of these soils, defined as the ability to maintain their biological productivity is increased with the use of cover crops, whether or spontaneous species. The practice of cover based on legumes could be used as an ideal choice

  19. Weight control, endocrine hormones and cancer prevention.

    PubMed

    King, Brenee; Jiang, Yu; Su, Xiaoyu; Xu, Jianteng; Xie, Linglin; Standard, Joseph; Wang, Weiqun

    2013-05-01

    The prevalence of obesity is increasing which becomes worrisome due to its association with several diseases and certain types of cancers. While weight control through dietary caloric restriction and/or physical activity protects against cancer in animal models, the underlying mechanisms are not fully defined. Weight loss due to negative energy balance is associated with alterations of multiple growth factors and endocrine hormones. The altered hormones and hormone-related functions appear to be responsible for anti-cancer mechanisms. In this review, we summarize the recent studies related to weight loss and the altered endocrine hormones, focusing on the reduced levels of the mitogenic insulin-like growth factor 1 (IGF-1) and adipokine leptin as well as the raised levels of adiponectin and glucocorticoids. The potential molecular targets of these hormone-dependent signalling pathways are also discussed. Considering the increasing trends of obesity throughout the world, a better understanding of the underlying mechanisms between body weight, endocrine hormones and cancer risk may lead to novel approaches to cancer prevention and treatment.

  20. Non-invasive endocrine monitoring of ovarian and adrenal activity in chinchilla (Chinchilla lanigera) females during pregnancy, parturition and early post-partum period.

    PubMed

    Mastromonaco, Gabriela F; Cantarelli, Verónica I; Galeano, María G; Bourguignon, Nadia S; Gilman, Christine; Ponzio, Marina F

    2015-03-01

    The chinchilla is a rodent that bears one of the finest and most valuable pelts in the world. The wild counterpart is, however, almost extinct because of a drastic past and ongoing population decline. The present work was developed to increase our knowledge of the reproductive physiology of pregnancy and post-partum estrus in the chinchilla, characterizing the endocrine patterns of urinary progesterone, estradiol, LH and cortisol metabolites throughout gestation and post-partum estrus and estimating the ovulation timing at post-partum estrus. Longitudinal urine samples were collected once per week throughout pregnancy and analyzed for creatinine, cortisol, LH, estrogen and progesterone metabolite concentrations. To indirectly determine the ovulation timing at post-partum estrus, a second experiment was performed using pregnant females subjected to a post-partum in vivo fertilization scheme. Urinary progestagen metabolites increased above baseline levels in early pregnancy between weeks-8 and -11 respectively to parturition, and slightly declined at parturition time. Urinary estrogens showed rising levels throughout mid- and late pregnancy (weeks-9 to -6 and a further increase at week-5 to parturition) and decreased in a stepwise manner after parturition, returning to baseline levels two weeks thereafter. Cortisol metabolite levels were relatively constant throughout pregnancy with a tendency for higher levels in the last third of gestation and after the pups' birth. Parturition was associated with dramatic reductions in urinary concentrations of sex steroids (especially progestagens). Observations in breeding farms indicated that the females that resulted in a second pregnancy after mating, did so on the second day after parturition. These data were in agreement with an LH peak detected 24h after parturition. Urinary steroid hormone patterns of estrogen and progestagen metabolites provided valuable information on endocrine events during pregnancy and after

  1. Health Disparities in Endocrine Disorders: Biological, Clinical, and Nonclinical Factors—An Endocrine Society Scientific Statement

    PubMed Central

    Brown, Arleen; Cauley, Jane A.; Chin, Marshall H.; Gary-Webb, Tiffany L.; Kim, Catherine; Sosa, Julie Ann; Sumner, Anne E.; Anton, Blair

    2012-01-01

    Objective: The aim was to provide a scholarly review of the published literature on biological, clinical, and nonclinical contributors to race/ethnic and sex disparities in endocrine disorders and to identify current gaps in knowledge as a focus for future research needs. Participants in Development of Scientific Statement: The Endocrine Society's Scientific Statement Task Force (SSTF) selected the leader of the statement development group (S.H.G.). She selected an eight-member writing group with expertise in endocrinology and health disparities, which was approved by the Society. All discussions regarding the scientific statement content occurred via teleconference or written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: The primary sources of data on global disease prevalence are from the World Health Organization. A comprehensive literature search of PubMed identified U.S. population-based studies. Search strategies combining Medical Subject Headings terms and keyword terms and phrases defined two concepts: 1) racial, ethnic, and sex differences including specific populations; and 2) the specific endocrine disorder or condition. The search identified systematic reviews, meta-analyses, large cohort and population-based studies, and original studies focusing on the prevalence and determinants of disparities in endocrine disorders. Consensus Process: The writing group focused on population differences in the highly prevalent endocrine diseases of type 2 diabetes mellitus and related conditions (prediabetes and diabetic complications), gestational diabetes, metabolic syndrome with a focus on obesity and dyslipidemia, thyroid disorders, osteoporosis, and vitamin D deficiency. Authors reviewed and synthesized evidence in their areas of expertise. The final statement incorporated responses to several levels of review: 1) comments of the SSTF and the

  2. Telomerase and the endocrine system.

    PubMed

    Pacini, Furio; Cantara, Silvia; Capezzone, Marco; Marchisotta, Stefania

    2011-03-29

    Telomeres are nucleoprotein complexes located at the ends of chromosomes that have a critical role in the maintenance of chromosomal integrity. This involvement is based on complex secondary and tertiary structures that rely on DNA-DNA, DNA-protein and protein-protein interactions. De novo synthesis and maintenance of telomere repeats is controlled by telomerase, a specialized complex that consists of a telomerase RNA component and a protein component--telomerase reverse transcriptase. When telomerase is silent (its default state in differentiated somatic cells), chromosomes shorten with every cell division, thus limiting the lifespan of the cells (the process of senescence) and preventing unlimited cell proliferation, which might eventually lead to the development of cancer. During this process, occasionally, a cell can activate telomerase, which stabilizes short telomeres and enables immortalization-a process essential for malignant transformation. Thus, although telomere erosion is a barrier to malignant progression, paradoxically, in certain circumstances it might also trigger tumorigenesis. A number of studies have demonstrated unequivocally that reactivation of telomerase in the presence of short telomeres is one of the most common features of human cancers, including those of the endocrine system.

  3. Endocrine remodelling of the adult intestine sustains reproduction in Drosophila

    PubMed Central

    Reiff, Tobias; Jacobson, Jake; Cognigni, Paola; Antonello, Zeus; Ballesta, Esther; Tan, Kah Junn; Yew, Joanne Y; Dominguez, Maria; Miguel-Aliaga, Irene

    2015-01-01

    The production of offspring is energetically costly and relies on incompletely understood mechanisms that generate a positive energy balance. In mothers of many species, changes in key energy-associated internal organs are common yet poorly characterised functionally and mechanistically. In this study, we show that, in adult Drosophila females, the midgut is dramatically remodelled to enhance reproductive output. In contrast to extant models, organ remodelling does not occur in response to increased nutrient intake and/or offspring demands, but rather precedes them. With spatially and temporally directed manipulations, we identify juvenile hormone (JH) as an anticipatory endocrine signal released after mating. Acting through intestinal bHLH-PAS domain proteins Methoprene-tolerant (Met) and Germ cell-expressed (Gce), JH signals directly to intestinal progenitors to yield a larger organ, and adjusts gene expression and sterol regulatory element-binding protein (SREBP) activity in enterocytes to support increased lipid metabolism. Our findings identify a metabolically significant paradigm of adult somatic organ remodelling linking hormonal signals, epithelial plasticity, and reproductive output. DOI: http://dx.doi.org/10.7554/eLife.06930.001 PMID:26216039

  4. In vivo recordings of brain activity using organic transistors

    PubMed Central

    Khodagholy, Dion; Doublet, Thomas; Quilichini, Pascale; Gurfinkel, Moshe; Leleux, Pierre; Ghestem, Antoine; Ismailova, Esma; Hervé, Thierry; Sanaur, Sébastien; Bernard, Christophe; Malliaras, George G.

    2013-01-01

    In vivo electrophysiological recordings of neuronal circuits are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. Here we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device, tested in vivo on epileptiform discharges, displayed superior signal-to-noise ratio due to local amplification compared with surface electrodes. The organic transistor was able to record on the surface low-amplitude brain activities, which were poorly resolved with surface electrodes. This study introduces a new class of biocompatible, highly flexible devices for recording brain activity with superior signal-to-noise ratio that hold great promise for medical applications. PMID:23481383

  5. Drug Trafficking Organizations and Local Economic Activity in Mexico

    PubMed Central

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000–2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations. PMID:26348041

  6. Drug Trafficking Organizations and Local Economic Activity in Mexico.

    PubMed

    González, Felipe

    2015-01-01

    Little is known about the relationship between illegal firms and local economic activity. In this paper I study changes in satellite night lights across Mexican municipalities after the arrival of large drug trafficking organizations in the period 2000-2010. After accounting for state trends and differences in political regimes, results indicate no significant change in night lights after the arrival of these illegal firms. Estimated coefficients are precise, robust, and similar across different drug trafficking organizations.

  7. Controlling epileptiform activity with organic electronic ion pumps.

    PubMed

    Williamson, Adam; Rivnay, Jonathan; Kergoat, Loïg; Jonsson, Amanda; Inal, Sahika; Uguz, Ilke; Ferro, Marc; Ivanov, Anton; Sjöström, Theresia Arbring; Simon, Daniel T; Berggren, Magnus; Malliaras, George G; Bernard, Christophe

    2015-05-27

    In treating epilepsy, the ideal solution is to act at a seizure's onset, but only in the affected regions of the brain. Here, an organic electronic ion pump is demonstrated, which directly delivers on-demand pure molecules to specific brain regions. State-of-the-art organic devices and classical pharmacology are combined to control pathological activity in vitro, and the results are verified with electrophysiological recordings.

  8. Endocrine disorders and the neurologic manifestations

    PubMed Central

    2014-01-01

    The nervous system and the endocrine system are closely interrelated and both involved intimately in maintaining homeostasis. Endocrine dysfunctions may lead to various neurologic manifestations such as headache, myopathy, and acute encephalopathy including coma. It is important to recognize the neurologic signs and symptoms caused by the endocrine disorders while managing endocrine disorders. This article provides an overview of the neurologic manifestations found in various endocrine disorders that affect pediatric patients. It is valuable to think about 'endocrine disorder' as a cause of the neurologic manifestations. Early diagnosis and treatment of hormonal imbalance can rapidly relieve the neurologic symptoms. Better understanding of the interaction between the endocrine system and the nervous system, combined with the knowledge about the pathophysiology of the neurologic manifestations presented in the endocrine disorders might allow earlier diagnosis and better treatment of the endocrine disorders. PMID:25654063

  9. Selenium and endocrine systems.

    PubMed

    Beckett, Geoffrey J; Arthur, John R

    2005-03-01

    The trace element selenium (Se) is capable of exerting multiple actions on endocrine systems by modifying the expression of at least 30 selenoproteins, many of which have clearly defined functions. Well-characterized selenoenzymes are the families of glutathione peroxidases (GPXs), thioredoxin reductases (TRs) and iodothyronine deiodinases (Ds). These selenoenzymes are capable of modifying cell function by acting as antioxidants and modifying redox status and thyroid hormone metabolism. Se is also involved in cell growth, apoptosis and modifying the action of cell signalling systems and transcription factors. During thyroid hormone synthesis GPX1, GPX3 and TR1 are up-regulated, providing the thyrocytes with considerable protection from peroxidative damage. Thyroidal D1 in rats and both D1 and D2 in humans are also up-regulated to increase the production of bioactive 3,5,3'-tri-iodothyronine (T3). In the basal state, GPX3 is secreted into the follicular lumen where it may down-regulate thyroid hormone synthesis by decreasing hydrogen peroxide concentrations. The deiodinases are present in most tissues and provide a mechanism whereby individual tissues may control their exposure to T3. Se is also able to modify the immune response in patients with autoimmune thyroiditis. Low sperm production and poor sperm quality are consistent features of Se-deficient animals. The pivotal link between Se, sperm quality and male fertility is GPX4 since the enzyme is essential to allow the production of the correct architecture of the midpiece of spermatozoa. Se also has insulin-mimetic properties, an effect that is probably brought about by stimulating the tyrosine kinases involved in the insulin signalling cascade. Furthermore, in the diabetic rat, Se not only restores glycaemic control but it also prevents or alleviates the adverse effects that diabetes has on cardiac, renal and platelet function.

  10. Are endocrine disrupting compounds a health risk in drinking water?

    PubMed

    Falconer, Ian R

    2006-06-01

    There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North America, which have been attributed to estrogenic compounds in the effluent. The anatomical and physiological changes in the fauna are illustrated by feminization of male gonads. The compounds of greatest hormonal activity in sewage effluent are the natural estrogens 17Beta-estradiol, estrone, estriol and the synthetic estrogen ethinylestradiol. Androgens are also widely present in wastewaters. Investigations of anthropogenic chemical contaminants in freshwaters and wastewaters have shown a wide variety of organic compounds, many of which have low levels of estrogenic activity. In many highly populated countries the drinking water is sourced from the same rivers and lakes that are the recipients of sewage and industrial discharge. The River Thames which flows through London, England, has overall passed through drinking water and sewage discharge 5 times from source to mouth of the river. Under these types of circumstance, any accumulation of endocrine disrupting compounds from sewage or industry potentially affects the quality of drinking water. Neither basic wastewater treatment nor basic drinking water treatment will eliminate the estrogens, androgens or detergent breakdown products from water, due to the chemical stability of the structures. Hence a potential risk to health exists; however present data indicate that estrogenic contamination of drinking water is very unlikely to result in physiologically detectable effects in consumers. Pesticide, detergent and industrial contamination remain issues of concern. As a result of this concern, increased attention is being given to enhanced wastewater treatment in locations where the effluent is directly or indirectly in use for drinking water

  11. Are Endocrine Disrupting Compounds a Health Risk in Drinking Water?

    PubMed Central

    Falconer, Ian R.

    2006-01-01

    There has been a great deal of international discussion on the nature and relevance of endocrine disrupting compounds in the environment. Changes in reproductive organs of fish and mollusks have been demonstrated in rivers downstream of sewage discharges in Europe and in North America, which have been attributed to estrogenic compounds in the effluent. The anatomical and physiological changes in the fauna are illustrated by feminization of male gonads. The compounds of greatest hormonal activity in sewage effluent are the natural estrogens 17β-estradiol, estrone, estriol and the synthetic estrogen ethinylestradiol. Androgens are also widely present in wastewaters. Investigations of anthropogenic chemical contaminants in freshwaters and wastewaters have shown a wide variety of organic compounds, many of which have low levels of estrogenic activity. In many highly populated countries the drinking water is sourced from the same rivers and lakes that are the recipients of sewage and industrial discharge. The River Thames which flows through London, England, has overall passed through drinking water and sewage discharge 5 times from source to mouth of the river. Under these types of circumstance, any accumulation of endocrine disrupting compounds from sewage or industry potentially affects the quality of drinking water. Neither basic wastewater treatment nor basic drinking water treatment will eliminate the estrogens, androgens or detergent breakdown products from water, due to the chemical stability of the structures. Hence a potential risk to health exists; however present data indicate that estrogenic contamination of drinking water is very unlikely to result in physiologically detectable effects in consumers. Pesticide, detergent and industrial contamination remain issues of concern. As a result of this concern, increased attention is being given to enhanced wastewater treatment in locations where the effluent is directly or indirectly in use for drinking water. In

  12. Levels and distributions of organic pollutants in subtidal sediments from the Loire estuary: Are there any relationships with TTR-binding activity?

    NASA Astrophysics Data System (ADS)

    Couderc, M.; Gandolfi, F.; Zalouk-Vergnoux, A.; Beyeler, N.; Malleret, L.; Ambidina, I.; Kamari, A.; Blanchet-Letrouvé, I.; Mouneyrac, C.; Hamers, T.; Poirier, L.

    2016-12-01

    The Loire estuary runs through important urban sites with shipping, industrial and agricultural activities, being the receptacle of diffusive pollutants comprising, a mixture of contaminants such as persistent organic pollutants (POPs). This work was set out to evaluate the occurrence of thyroid endocrine disruptors in sediments of this estuary. Sediments were collected in September 2012 and April 2013, in subtidal zones along the estuary. Targeted chemical analyses of five classes of pollutants, i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), alkylphenols (APs), and bisphenol A (BPA) were performed in sediment extracts. Extracts were further tested for their thyroid hormone (TH) disrupting potency to compete with TH for binding to its transporter protein transthyretin (TTR). The Haute-Indre site was characterized by a significant PAH contamination whereas Saint-Nazaire, Bellevue and Rezé would be particularly contaminated by PCBs. These observations could be linked to the different type of anthropogenic activities taking place close to these sites. Donges, Mindin and Paimboeuf were the sampling sites displaying the lowest contamination in PAHs, APs, PCBs and PBDEs. No inter-site difference could be observed for TTR-binding activity, which should be attributed to different compounds than the chemically analyzed compounds, as confirmed by PCA analyses. Furthermore, the TTR-binding potencies of the extracts were relatively low compared to data from literature. More investigations on the quantification of PCB and PBDE hydroxylated metabolites and other known endocrine disruptors such as pesticides or perfluorinated compounds could be considered, as well as bioassays highlighting other endocrine disrupting effects.

  13. Effects of Common Pesticides on Prostaglandin D2 (PGD2) Inhibition in SC5 Mouse Sertoli Cells, Evidence of Binding at the COX-2 Active Site, and Implications for Endocrine Disruption

    PubMed Central

    Kugathas, Subramaniam; Audouze, Karine; Ermler, Sibylle; Orton, Frances; Rosivatz, Erika; Scholze, Martin; Kortenkamp, Andreas

    2015-01-01

    Background: There are concerns that diminished prostaglandin action in fetal life could increase the risk of congenital malformations. Many endocrine-disrupting chemicals have been found to suppress prostaglandin synthesis, but to our knowledge, pesticides have never been tested for these effects. Objectives: We assessed the ability of pesticides that are commonly used in the European Union to suppress prostaglandin D2 (PGD2) synthesis. Methods: Changes in PGD2 secretion in juvenile mouse Sertoli cells (SC5 cells) were measured using an ELISA. Coincubation with arachidonic acid (AA) was conducted to determine the site of action in the PGD2 synthetic pathway. Molecular modeling studies were performed to assess whether pesticides identified as PGD2-active could serve as ligands of the cyclooxygenase-2 (COX-2) binding pocket. Results: The pesticides boscalid, chlorpropham, cypermethrin, cyprodinil, fenhexamid, fludioxonil, imazalil (enilconazole), imidacloprid, iprodione, linuron, methiocarb, o-phenylphenol, pirimiphos-methyl, pyrimethanil, and tebuconazole suppressed PGD2 production. Strikingly, some of these substances—o-phenylphenol, cypermethrin, cyprodinil, linuron, and imazalil (enilconazole)—showed potencies (IC50) in the range between 175 and 1,500 nM, similar to those of analgesics intended to block COX enzymes. Supplementation with AA failed to reverse this effect, suggesting that the sites of action of these pesticides are COX enzymes. The molecular modeling studies revealed that the COX-2 binding pocket can accommodate most of the pesticides shown to suppress PGD2 synthesis. Some of these pesticides are also capable of antagonizing the androgen receptor. Conclusions: Chemicals with structural features more varied than previously thought can suppress PGD2 synthesis. Our findings signal a need for in vivo studies to establish the extent of endocrine-disrupting effects that might arise from simultaneous interference with PGD2 signaling and androgen action

  14. Endocrine causes of secondary hypertension.

    PubMed

    Sica, Domenic A

    2008-07-01

    Secondary hypertension is common in clinical practice if a broad definition is applied. Various patterns of hypertension exist in the patient with an endocrine source of their disease, including new-onset hypertension in a previously normotensive individual, a loss of blood pressure control in a patient with previously well-controlled blood pressure, and/or labile blood pressure in the setting of either of these 2 patterns. A thorough history and physical exam, which can rule out concomitant medications, alcohol intake, and over-the-counter medication use, is an important prerequisite to the workup for endocrine causes of hypertension. Endocrine forms of secondary hypertension, such as pheochromocytoma and Cushing's disease, are extremely uncommon. Conversely, primary aldosteronism now occurs with sufficient frequency so as to be considered "top of the list" for secondary endocrine causes in otherwise difficult-to-treat or resistant hypertension. Primary aldosteronism can be insidious in its presentation since a supposed hallmark finding, hypokalemia, may be variable in its presentation. It is important to identify secondary causes of hypertension that are endocrine in nature because surgical intervention may result in correction or substantial improvement of the hypertension.

  15. Hybrid energy storage systems utilizing redox active organic compounds

    SciTech Connect

    Wang, Wei; Xu, Wu; Li, Liyu; Yang, Zhenguo

    2015-09-08

    Redox flow batteries (RFB) have attracted considerable interest due to their ability to store large amounts of power and energy. Non-aqueous energy storage systems that utilize at least some aspects of RFB systems are attractive because they can offer an expansion of the operating potential window, which can improve on the system energy and power densities. One example of such systems has a separator separating first and second electrodes. The first electrode includes a first current collector and volume containing a first active material. The second electrode includes a second current collector and volume containing a second active material. During operation, the first source provides a flow of first active material to the first volume. The first active material includes a redox active organic compound dissolved in a non-aqueous, liquid electrolyte and the second active material includes a redox active metal.

  16. Self-Organized Transition to Coherent Activity in Disordered Media

    NASA Astrophysics Data System (ADS)

    Singh, Rajeev; Xu, Jinshan; Garnier, Nicolas G.; Pumir, Alain; Sinha, Sitabhra

    2012-02-01

    Synchronized oscillations are of critical functional importance in many biological systems. We show that such oscillations can arise without centralized coordination in a disordered system of electrically coupled excitable and passive cells. Increasing the coupling strength results in waves that lead to coherent periodic activity, exhibiting cluster, local and global synchronization under different conditions. Our results may explain the self-organized transition in a pregnant uterus from transient, localized activity initially to system-wide coherent excitations just before delivery.

  17. ALTERATIONS IN DEVELOPMENT OF REPRODUCTIVE AND ENDOCRINE SYSTEMS OF WILDLIFE POPULATIONS EXPOSED TO ENDOCRINE-DISRUPTING CONTAMINANTS.

    EPA Science Inventory

    Wildlife and human populations are affected by contaminants in natural settings. This problem has been a growing concern over the last decade with the realization that various environmental chemicals can alter the development and functioning of endocrine organs, cells and target ...

  18. Endocrine abnormalities in anorexia nervosa.

    PubMed

    Lawson, Elizabeth A; Klibanski, Anne

    2008-07-01

    Anorexia nervosa (AN) is a psychiatric disease associated with notable medical complications and increased mortality. Endocrine abnormalities, including hypogonadotropic hypogonadism, hypercortisolemia, growth hormone resistance and sick euthyroid syndrome, mediate the clinical manifestations of this disease. Alterations in anorexigenic and orexigenic appetite-regulating pathways have also been described. Decreases in fat mass result in adipokine abnormalities. Although most of the endocrine changes that occur in AN represent physiologic adaptation to starvation, some persist after recovery and might contribute to susceptibility to AN recurrence. In this Review, we summarize key endocrine alterations in AN, with a particular focus on the profound bone loss that can occur in this disease. Although AN is increasingly prevalent among boys and men, the disorder predominantly affects girls and women who are, therefore, the focus of this Review.

  19. Endocrine disrupters and menopausal health.

    PubMed

    Holmes, Philip; Rumsby, Paul; Harrison, Paul T C

    2004-06-01

    Chemicals known to disrupt the endocrine system of animal models are assessed for their potential impact on the health of menopausal and postmenopausal women. These "endocrine disrupters" consist of two groups of compounds - man-made and naturally occurring. There is some evidence to suggest that the naturally occurring phytoestrogens, derived from plant material, may have some beneficial effects on menopausal symptoms and the risk of breast cancer, cardiovascular disease and osteoporosis. Further studies are required to confirm these possibilities. Some man-made environmental pollutants appear to increase the risk of breast cancer, although again the evidence is inconclusive. Mechanistic experiments indicate that these chemicals interact with oestrogen receptors and alter metabolism in a number of different ways, some of which may be important in postmenopausal women. Further investigation of the differences in mode of action between the man-made and the natural endocrine disrupters may lead to important insights into their effects on women's health.

  20. A review: Potential and challenges of biologically activated carbon to remove natural organic matter in drinking water purification process.

    PubMed

    Korotta-Gamage, Shashika Madushi; Sathasivan, Arumugam

    2017-01-01

    The use of biologically activated carbon (BAC) in drinking water purification is reviewed. In the past BAC is seen mostly as a polishing treatment. However, BAC has the potential to provide solution to recent challenges faced by water utilities arising from change in natural organic matter (NOM) composition in drinking water sources - increased NOM concentration with a larger fraction of hydrophilic compounds and ever increasing trace level organic pollutants. Hydrophilic NOM is not removed by traditional coagulation process and causes bacterial regrowth and increases disinfection by-products (DBPs) formation during disinfection. BAC can offer many advantages by removing hydrophilic fraction and many toxic and endocrine compounds which are not otherwise removed. BAC can also aid the other downstream processes if used as a pre-treatment. Major drawback of BAC was longer empty bed contact time (EBCT) required for an effective NOM removal. This critical review analyses the strategies that have been adopted to enhance the biological activity of the carbon by operational means and summarises the surface modification methods. To maximize the benefit of the BAC, a rethink of current treatment plant configuration is proposed. If the process can be expedited and adopted appropriately, BAC can solve many of the current problems.

  1. Removal of Biologically Active Organic Contaminants using Atomic Oxygen

    NASA Technical Reports Server (NTRS)

    Banks, Bruce A. (Inventor); Banks, Michael A. (Inventor); Banks, Eric B. (Inventor)

    2003-01-01

    Biomedical devices that are to come into contact with living tissue, such as prosthetic and other implants for the human body and the containers used to store and transport them, are together cleaned of non-living, but biologically active organic materials, including endotoxins such as lipopolysaccharides, and assembled into a hermetically sealed package without recontamination. This is achieved by cleaning both the device and package components together in an apparatus, which includes a hermetically sealed chamber, in which they are contacted with atomic oxygen which biocleans them, by oxidizing the biologically active organic materials. The apparatus also includes means for manipulating the device and container and hermetically sealing the cleaned device into the cleaned container to form the package. A calibrated witness coupon visually indicates whether or not the device and container have received enough exposure to the atomic oxygen to have removed the organic materials from their surfaces. Gamma radiation is then used to sterilize the device in the sealed container.

  2. Effects of organic dairy manure amendment on soil phosphatase activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Organic dairy production is increasing in the U.S. due to concerns over environmental, human, and animal health. It is well known that the application of livestock manure to soil can influence enzyme activities involved in nutrient cycling and soil fertility, such as soil phosphatases; however, orga...

  3. Prospective Relations between Organized Activity Participation and Psychopathology during Adolescence

    ERIC Educational Resources Information Center

    Bohnert, Amy M.; Garber, Judy

    2007-01-01

    This longitudinal study examined psychopathology as a predictor and outcome of organized activity involvement during high school among 198 adolescents who varied in risk for psychopathology as a function of their mother's depression history. Higher levels of internalizing and externalizing symptoms in eighth grade significantly predicted lower…

  4. The Reciprocal Organization of Constructive Activity in Drug Addiction

    ERIC Educational Resources Information Center

    Akhmetzyanova, Anna I.; Nikishina, Vera B.; Klyueva, Nadezhda V.; Petrash, Ekaterina A.

    2016-01-01

    The urgency of the problem stated in the article is caused by the fact that modern scientific studies show that sustainable neuro-associative connections with the object of addiction arise at chemical addiction. The aim of this study is to examine the features of the reciprocal organization of constructive activities in drug addiction. Study of…

  5. Magneto-optical activity in organic thin film materials

    NASA Astrophysics Data System (ADS)

    Vleugels, Rick; de Vega, Laura; Brullot, Ward; Verbiest, Thierry; Gómez-Lor, Berta; Gutierrez-Puebla, Enrique; Hennrich, Gunther

    2016-12-01

    A series of CF3-capped phenylacetylenes with varying symmetry is obtained by a conventional palladium-catalyzed cross-coupling protocol. The phenylacetylene targets form thin films both, liquid crystalline (LC) and crystalline in nature depending on their molecular structure. The magneto-optical activity of the resulting organic material is extraordinarily high as proved by Faraday rotation spectroscopy on thin film devices.

  6. Multiple endocrine neoplasia type 1

    PubMed Central

    Marini, Francesca; Falchetti, Alberto; Monte, Francesca Del; Sala, Silvia Carbonell; Gozzini, Alessia; Luzi, Ettore; Brandi, Maria Luisa

    2006-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. PMID:17014705

  7. Dramatic enhancement of enzymatic activity in organic solvents by lyoprotectants

    SciTech Connect

    Dabulis, K.; Klibanov, A.M. )

    1993-03-05

    When seven different hydrolytic enzymes (four proteases and three lipases) were lyophilized from aqueous solution containing a ligand, N-Ac-L-Phe-NH[sub 2], their catalytic activity in anhydrous solvents was far greater (one to two orders of magnitude) than that of the enzymes lyophilized without the ligand. This ligand-induced activation was expressed regardless of whether the substrate employed in organic solvents structurally resembled the ligand. Furthermore, nonligand lyoprotectants [sorbitol, other sugars, and poly(ethylene glycol)] also dramatically enhanced enzymatic activity in anhydrous solvents when present in enzyme aqueous solution prior to lyophilization. The effects of the ligand and of the lyoprotectants were nonadditive, suggesting the same mechanism of action. Excipient-activated and nonactivated enzymes exhibited identical activities in water. Also, addition of the excipients directly to suspensions of nonactivated enzymes in organic solvents had no appreciable effect on catalytic activity. These observations indicate that the mechanism of the excipient-induced activation is based on the ability of the excipients to alleviate reversible denaturation of enzymes upon lyophilization. Activity enhancement induced by the excipients is displayed even after their removal by washing enzymes with anhydrous solvents. Subtilisin Carlsberg, lyophilized with sorbitol, was found to be a much more efficient practical catalyst than its regular' counterpart.

  8. Single-cell approaches for molecular classification of endocrine tumors

    PubMed Central

    Koh, James; Allbritton, Nancy L.; Sosa, Julie A.

    2015-01-01

    Purpose of review In this review, we summarize recent developments in single-cell technologies that can be employed for the functional and molecular classification of endocrine cells in normal and neoplastic tissue. Recent findings The emergence of new platforms for the isolation, analysis, and dynamic assessment of individual cell identity and reactive behavior enables experimental deconstruction of intratumoral heterogeneity and other contexts, where variability in cell signaling and biochemical responsiveness inform biological function and clinical presentation. These tools are particularly appropriate for examining and classifying endocrine neoplasias, as the clinical sequelae of these tumors are often driven by disrupted hormonal responsiveness secondary to compromised cell signaling. Single-cell methods allow for multidimensional experimental designs incorporating both spatial and temporal parameters with the capacity to probe dynamic cell signaling behaviors and kinetic response patterns dependent upon sequential agonist challenge. Summary Intratumoral heterogeneity in the provenance, composition, and biological activity of different forms of endocrine neoplasia presents a significant challenge for prognostic assessment. Single-cell technologies provide an array of powerful new approaches uniquely well suited for dissecting complex endocrine tumors. Studies examining the relationship between clinical behavior and tumor compositional variations in cellular activity are now possible, providing new opportunities to deconstruct the underlying mechanisms of endocrine neoplasia. PMID:26632769

  9. Influence of Slightly Soluble Organics on Aerosol Activation

    SciTech Connect

    Abdul-Razzak, Hayder; Ghan, Steven J.

    2005-03-22

    This paper examines the effects of slightly soluble organics on aerosol activation in a parcel of air rising adiabatically. Slightly soluble organics can affect aerosol activation by three mechanisms: lowering surface tension, altering the bulk hygroscopicity, and delaying the growth of particles due to their lower solubilities. Here, we address the third mechanism by simulating the activation process of aerosol particles modeled using a single lognormal size distribution and consisting of an internal uniform chemical mixture of adipic acid (representing slightly soluble organics having extremely low solubility) and ammonium sulfate. The simulations were carried out using measured solubility of adipic acid spanning a wide range of physical and dynamical parameters. The same conditions were re-simulated but assuming fully soluble aerosols. Results of the simulations show that although that the low solubility of the adipic acid alters Köhler curves and increases critical supersaturation of the smaller particles (Köhler curves of the larger particles are not effected since these particles are completely dissolved at the initial supersaturation of zero), it has minimal to no effect on the parcel’s supersaturation except for particles consisting of more than 95% adipic acid. Accordingly, since aerosols in realistic atmospheric conditions do not contain more than 90% organics, we conclude that it is not necessary to retune the parameterization of aerosol activation previously developed and modified to address the other two mechanisms. The slightly soluble organics can thus be assumed to be fully soluble for the purpose of predicting the fraction of activation and the maximum supersaturation with negligible error.

  10. Environmental Endocrine Disruptors: Effects on the human male reproductive system

    PubMed Central

    Sweeney, M.F.; Hasan, N.; Soto, A.M.; Sonnenschein, C.

    2016-01-01

    Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically “endocrine disruptors,” that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward. PMID:26847433

  11. Environmental endocrine disruptors: Effects on the human male reproductive system.

    PubMed

    Sweeney, M F; Hasan, N; Soto, A M; Sonnenschein, C

    2015-12-01

    Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

  12. ENVIRONMENTAL ENGINEERING AND ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Endocrine disruptors are a class of chemicals of growing interest to the environmental community. USEPA's Risk Assessment Forum defined an endocrine disrupting chemical (EDC) as "an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or elim...

  13. ANALYTICAL CHALLENGES OF ENVIRONMENTAL ENDOCRINE DISRUPTOR MONITORING

    EPA Science Inventory

    Reported increases in the incidence of endocrine-related conditions have led to speculation about environmental causes. Environmental scientists are focusing increased research effort into understanding the mechanisms by which endocrine disruptors affect human and ecological h...

  14. Bariatric Surgery and the Endocrine System

    MedlinePlus

    ... Bariatric Surgery and the Endocrine System Fact Sheet Bariatric Surgery and the Endocrine System February, 2012 Download PDFs ... John Morton, MD Marzieh Salehi, MD What is bariatric surgery? Bariatric surgery helps people who are very obese ...

  15. "Braking" the Cycle of Resistance in Endocrine Therapy for Breast Cancer.

    PubMed

    DeMichele, Angela; Chodosh, Lewis A

    2015-11-15

    Endocrine resistance leads to recurrence and death from breast cancer. Animal models of endocrine resistance enable preclinical identification of efficacious therapeutic combinations and further our understanding of resistance. This strategy provides new insights into optimally targeting interactions between estrogen receptor (ESR-1) activity and the cell cycle by CDK4/6 inhibitors. See related article by Wardell et al., p. 5121.

  16. DETERMINING INDICATORS OF EXPOSURE AND EFFECTS FOR ENDOCRINE DISRUPTING CHEMICALS (EDCS): AN OVERVIEW.

    EPA Science Inventory

    Endocrine disruptors are characterized by their influence on animal endocrine systems resulting in reproductive, developmental, neurological, and immune dysfunction. The purpose of this overview is to provide the reader with a sense of the activities within the U.S. Environmental...

  17. RELATIVE BINDING AFFINITY OF ENDOCRINE DISRUPTING CHEMICALS TO ESTROGEN RECEPTOR IN TWO SPECIES OF FRESHWATER FISH

    EPA Science Inventory

    The US EPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. To evaluate the potential for chemicals to cause endocrine disruption in fish we have previously measured the affinity of a number of chemicals for the rainbow trout estr...

  18. PROGRESS IN THE OECD WORK ON ENDOCRINE DISRUPTORS TESTING AND ASSESSMENT FOR ENVIRONMENTAL SPECIES

    EPA Science Inventory

    The OECD Special Activity on endocrine disruptors testing and assessment (EDTA) started in 1996 at the request of member countries and industry with the objective to develop test methods for the detection and characterization of endocrine disrupting chemicals. The purpose of the ...

  19. Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

    PubMed

    Bechard, Matthew E; Bankaitis, Eric D; Hipkens, Susan B; Ustione, Alessandro; Piston, David W; Yang, Yu-Ping; Magnuson, Mark A; Wright, Christopher V E

    2016-08-15

    The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3(TA.LO) cell population, defined as Neurog3 transcriptionally active and Sox9(+) and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9(+) Neurog3(TA.LO) progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3(HI) cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9(+) Neurog3(TA.LO) progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9(+) Neurog3(TA.LO) endocrine-biased progenitors feed production of Neurog3(HI) endocrine-committed cells during pancreas organogenesis.

  20. Finite-element model of the active organ of Corti

    PubMed Central

    Elliott, Stephen J.; Baumgart, Johannes

    2016-01-01

    The cochlear amplifier that provides our hearing with its extraordinary sensitivity and selectivity is thought to be the result of an active biomechanical process within the sensory auditory organ, the organ of Corti. Although imaging techniques are developing rapidly, it is not currently possible, in a fully active cochlea, to obtain detailed measurements of the motion of individual elements within a cross section of the organ of Corti. This motion is predicted using a two-dimensional finite-element model. The various solid components are modelled using elastic elements, the outer hair cells (OHCs) as piezoelectric elements and the perilymph and endolymph as viscous and nearly incompressible fluid elements. The model is validated by comparison with existing measurements of the motions within the passive organ of Corti, calculated when it is driven either acoustically, by the fluid pressure or electrically, by excitation of the OHCs. The transverse basilar membrane (BM) motion and the shearing motion between the tectorial membrane and the reticular lamina are calculated for these two excitation modes. The fully active response of the BM to acoustic excitation is predicted using a linear superposition of the calculated responses and an assumed frequency response for the OHC feedback. PMID:26888950

  1. Refractory Organic Compounds in Enceladus' Ice Grains and Hydrothermal Activity

    NASA Astrophysics Data System (ADS)

    Postberg, F.; Khawaja, N.; Hsu, H. W.; Sekine, Y.; Shibuya, T.

    2015-12-01

    Cassini's Cosmic Dust Analyzer (CDA) generates time-of-flight mass spectra of individual grains impinging on the instruments target-plate. Following the analysis of salt rich ice grains emitted by Enceladus that indicated a salt-water ocean in contact with the moon's rocky core [1,2] a recent CDA analysis of nano-phase silica particles pointed at hydrothermal activity at the moon's rock/water interface [3]. The results imply temperatures above 80 - 90°C and alkaline pH values around 10 reminiscent of alkaline hydrothermal vents on Earth like the Lost City Hydrothermal Field. In this context the compositional analysis of organic components in CDA mass spectra of the ejected ice grains is of particular relevance. A multitude of volatile organic species has already been identified in the gas component of the plume [4]. As expected, we find more complex organic molecules in ice grains than in the gas indicating aromatic species, amines, and carbonyl group species. The composition of organic-bearing ice grains displays a great diversity indicating a variety of different organic species in varying concentrations. Recent spatially resolved CDA in situ measurements inside Enceladus' plume indicate that these organic compounds are especially frequent in 'young' ice grains that have just been ejected by high velocity jets. We investigate the implications of our findings with respect to ice grain formation at the water surface and inside the icy vents. We constrain the generation of organic compounds at the rock/water interface in the light of hydrothermal activity and the potential for the formation of life precursor molecules in Enceladus' ocean. Ref:[1] Postberg et al., Nature 459, 1098-1101 (2009). [2] Postberg et al., Nature 474, 620-622 (2011). [3]. Hsu, Postberg, Sekine et al., Nature, 519, 207-210 (2015). [4] Waite et al., Nature 460, 487-490 (2009).

  2. Female sexual behavior, estrous cycle and gene expression in sexually dimorphic brain regions after pre- and postnatal exposure to endocrine active UV filters.

    PubMed

    Faass, Oliver; Schlumpf, Margret; Reolon, Sasha; Henseler, Manuel; Maerkel, Kirsten; Durrer, Stefan; Lichtensteiger, Walter

    2009-03-01

    The developing female brain represents a potential target for estrogenic environmental chemicals because it depends on estrogen but is exposed to low endogenous estrogen levels, thus facilitating competition by exogenous estrogen receptor (ER) agonists. We investigated effects of two estrogenic UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC). 4-MBC has been detected in human milk, indicating potential exposure of fetus and infant. The two chemicals were administered in chow to rats of the parent generation before mating, during pregnancy and lactation, and to their offspring until adulthood. Female sexual behavior was recorded on videotape in adult female offspring on proestrus evening at the beginning of the dark phase. 4-MBC (7 and 24mg/kg bw/day) and 3-BC (2.4 and 7mg/kg bw/day) reduced proceptive behavior (jump and ear wiggling) and receptive behavior (lordosis quotient), and increased rejection behavior towards the male. Estrous cycles were not affected by 4-MBC but disturbed by 3-BC. mRNAs encoding for genes involved in female sexual behavior, ERalpha, ERbeta, progesterone receptor (PR) and steroid receptor coactivator-1 (SRC-1), were measured by real-time RT-PCR in ventromedial hypothalamic nucleus (VMH) and medial preoptic area of adult male and female offspring (studied in diestrus) after pre- and postnatal exposure to 3-BC (0.24, 0.7, 2.4 and 7mg/kg bw/day). Gene expression was affected in a sex- and region-specific manner. PR mRNA in female VMH was reduced to male levels at dose levels of 2.4 and 7mg/kg bw/day 3-BC. Our data demonstrate that female sexual behavior represents a sensitive target of endocrine disrupters and point to an involvement of PR in VMH.

  3. Endocrine Responses to Resistance Exercise,

    DTIC Science & Technology

    1987-08-30

    jo- Rfe 681 ENDOCRINE RESPONSES TO RESISTANCE EXERCISE(U) RIRMY RESERRCH INST OF ENYIRWUIENTAL MEDICINE NATICK M N J KRRENER 30 RUG 87 USARIEN-R59-B...factors have been shown to influence GH release including gonadal. thyroid and adrenal hormones (32). Whether it is via a direct or indirect mechanism

  4. The Vitamin D Endocrine System.

    ERIC Educational Resources Information Center

    Norman, Anthony W.

    1985-01-01

    Discusses the physiology and biochemistry of the vitamin D endocrine system, including role of biological calcium and phosphorus, vitamin D metabolism, and related diseases. A 10-item, multiple-choice test which can be used to obtain continuing medical education credit is included. (JN)

  5. CURRENT CHALLENGES ON ENDOCRINE DISRUPTORS

    EPA Science Inventory

    For over ten years, major international efforts have been aimed at understanding the mechanism and extent of endocrine disruption in experimental models, wildlife, and people; the occurrence of this in the real world and in developing tools for screening and prediction of risk. ...

  6. Environmental exposures that affect the endocrine system: public health implications.

    PubMed

    DeRosa, C; Richter, P; Pohl, H; Jones, D E

    1998-01-01

    In recent years much attention has been focused on the potential for a wide range of xenobiotic chemicals to interact with and disrupt the endocrine systems of animal and human populations. An overview of the chemicals that have been implicated as endocrine disruptors is presented. The ubiquity in the environment and associated body burdens of these chemicals in human populations are described. Potential mechanisms of action are reviewed, including the role of specific intracellular receptors and their interactions with endogenous and exogenous materials. The subsequent upregulation or downregulation of physiological processes at critical stages of development is discussed. The potential for joint toxic action and interaction of chemical mixtures is also discussed. The acknowledged role of wildlife populations as sentinels of potential human health effects is reviewed, and the weight of evidence for the role and impact of endocrine disruptors is presented. The implications of exposure to endocrine-disrupting chemicals for human health are reviewed, with special emphasis on the potential for transgenerational effects in at-risk populations. Recommendations for future research include the development of (1) structural activity and in vivo and in vitro functional toxicology methods to screen chemicals for their endocrine-disrupting ability, (2) biomarkers of exposure and effect, and (3) in situ sentinel systems.

  7. The osteocyte: an endocrine cell ... and more.

    PubMed

    Dallas, Sarah L; Prideaux, Matthew; Bonewald, Lynda F

    2013-10-01

    Few investigators think of bone as an endocrine gland, even after the discovery that osteocytes produce circulating fibroblast growth factor 23 that targets the kidney and potentially other organs. In fact, until the last few years, osteocytes were perceived by many as passive, metabolically inactive cells. However, exciting recent discoveries have shown that osteocytes encased within mineralized bone matrix are actually multifunctional cells with many key regulatory roles in bone and mineral homeostasis. In addition to serving as endocrine cells and regulators of phosphate homeostasis, these cells control bone remodeling through regulation of both osteoclasts and osteoblasts, are mechanosensory cells that coordinate adaptive responses of the skeleton to mechanical loading, and also serve as a manager of the bone's reservoir of calcium. Osteocytes must survive for decades within the bone matrix, making them one of the longest lived cells in the body. Viability and survival are therefore extremely important to ensure optimal function of the osteocyte network. As we continue to search for new therapeutics, in addition to the osteoclast and the osteoblast, the osteocyte should be considered in new strategies to prevent and treat bone disease.

  8. Ultraviolet filters differentially impact the expression of key endocrine and stress genes in embryos and larvae of Chironomus riparius.

    PubMed

    Ozáez, Irene; Morcillo, Gloria; Martínez-Guitarte, José-Luis

    2016-07-01

    Several organic UV filters have hormonal activity in vertebrates, as demonstrated in fishes, rodents and human cells. Despite the accumulation of filter contaminants in aquatic systems, research on their effects on the endocrine systems of freshwaters invertebrates is scarce. In this work, the effects of five frequently used UV filters were investigated in embryos and larvae of Chironomus riparius, which is a reference organism in ecotoxicology. LC50 values for larvae as well as the percentage of eclosion of eggs were determined following exposures to: octyl-p-methoxycinnamate (OMC) also known as 2-ethylhexyl-4-methoxycinnamate (EHMC); 4-methylbenzylidene camphor (4MBC); 4-hydroxybenzophenone (4HB); octocrylene (OC); and octyldimethyl-p-aminobenzoate (OD-PABA). To assess sublethal effects, expression levels of the genes coding for the ecdysone receptor (EcR) and heat shock protein HSP70 were investigated as biomarkers for endocrine and stress effects at the cellular level. Life-stage-dependent sensitivity was found. In embryos, all of the UV filters provoked a significant overexpression of EcR at 24h after exposure. OC, 4MBC and OD-PABA also triggered transcriptional activation of the hsp70 stress gene in embryos. In contrast, in larvae, only 4MBC and OMC/EHMC increased EcR and hsp70 mRNA levels and OD-PABA upregulated only the EcR gene. These results revealed that embryos are particularly sensitive to UV filters, which affect endocrine regulation during development. Most UV filters also triggered the cellular stress response, and thus exhibit proteotoxic effects. The differences observed between embryos and larvae and the higher sensitivity of embryos highlight the importance of considering different life stages when evaluating the environmental risks of pollutants, particularly when analyzing endocrine effects.

  9. Worldwide overview of critical care nursing organizations and their activities.

    PubMed

    Williams, G; Chaboyer, W; Thornsteindóttir, R; Fulbrook, P; Shelton, C; Wojner, A; Chan, D

    2001-12-01

    While critical care has been a specialty within nursing for almost 50 years, with many countries having professional organizations representing these nurses, it is only recently that the formation of an international society has been considered. A three-phased study was planned: the aim of the first phase was to identify critical care organizations worldwide; the aim of the second was to describe the characteristics of these organizations, including their issues and activities; and the aim of the third was to plan for an international society, if international support was evident. In the first phase, contacts in 44 countries were identified using a number of strategies. In the second phase, 24 (55%) countries responded to a survey about their organizations. Common issues for critical care nurses were identified, including concerns over staffing levels, working conditions, educational programme standards and wages. Critical care nursing organizations were generally favourable towards the notion of establishing a World Federation of their respective societies. Some of the important issues that will need to be addressed in the lead up to the formation of such a federation are now being considered.

  10. Self-organization via active exploration in robotic applications

    NASA Technical Reports Server (NTRS)

    Ogmen, H.; Prakash, R. V.

    1992-01-01

    We describe a neural network based robotic system. Unlike traditional robotic systems, our approach focussed on non-stationary problems. We indicate that self-organization capability is necessary for any system to operate successfully in a non-stationary environment. We suggest that self-organization should be based on an active exploration process. We investigated neural architectures having novelty sensitivity, selective attention, reinforcement learning, habit formation, flexible criteria categorization properties and analyzed the resulting behavior (consisting of an intelligent initiation of exploration) by computer simulations. While various computer vision researchers acknowledged recently the importance of active processes (Swain and Stricker, 1991), the proposed approaches within the new framework still suffer from a lack of self-organization (Aloimonos and Bandyopadhyay, 1987; Bajcsy, 1988). A self-organizing, neural network based robot (MAVIN) has been recently proposed (Baloch and Waxman, 1991). This robot has the capability of position, size rotation invariant pattern categorization, recognition and pavlovian conditioning. Our robot does not have initially invariant processing properties. The reason for this is the emphasis we put on active exploration. We maintain the point of view that such invariant properties emerge from an internalization of exploratory sensory-motor activity. Rather than coding the equilibria of such mental capabilities, we are seeking to capture its dynamics to understand on the one hand how the emergence of such invariances is possible and on the other hand the dynamics that lead to these invariances. The second point is crucial for an adaptive robot to acquire new invariances in non-stationary environments, as demonstrated by the inverting glass experiments of Helmholtz. We will introduce Pavlovian conditioning circuits in our future work for the precise objective of achieving the generation, coordination, and internalization

  11. Opinion and evidence for treatments in endocrine disorders.

    PubMed

    2002-01-01

    New treatments and treatment protocols for endocrine disorders are evolving rapidly, and research and development activity in the endocrinology field is high. Optimal therapy remains contentious in some areas. To help you keep up-to-date with the latest advances worldwide on all aspects of drug therapy and management of endocrine disorders, this section of the journal brings you information selected from the rapid drug news alerting service Inpharma Weekly. Each issue contains easy-to-read summaries of the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse drug reaction news, and expert opinion pieces published in the world's top endocrinology journals.

  12. Opinion and evidence for treatments in endocrine disorders.

    PubMed

    2003-01-01

    New treatments and treatment protocols for endocrine disorders are evolving rapidly, and research and development activity in the endocrinology field is high. Optimal therapy remains contentious in some areas. To help you keep up-to-date with the latest advances worldwide on all aspects of drug therapy and management of endocrine disorders, this section of the journal brings you information selected from the rapid drug news alerting service Inpharma Weekly. Each issue contains easy-to-read summaries of the most important research and development news, clinical studies, treatment guidelines, pharmacoeconomic and adverse drug reaction news, and expert opinion pieces published in the world's top endocrinology journals.

  13. The endocrine system and sarcopenia: potential therapeutic benefits.

    PubMed

    McIntire, Kevin L; Hoffman, Andrew R

    2011-12-01

    Age related muscle loss, known as sarcopenia, is a major factor in disability, loss of mobility and quality of life in the elderly. There are many proposed mechanisms of age-related muscle loss that include the endocrine system. A variety of hormones regulate growth, development and metabolism throughout the lifespan. Hormone activity may change with age as a result of reduced hormone secretion or decreased tissue responsiveness. This review will focus on the complex interplay between the endocrine system, aging and skeletal muscle and will present possible benefits of therapeutic interventions for sarcopenia.

  14. Endocrine modulation of the adolescent brain: a review.

    PubMed

    Vigil, Pilar; Orellana, Renán F; Cortés, Manuel E; Molina, Carmen T; Switzer, Barbara E; Klaus, Hanna

    2011-12-01

    Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones.

  15. Enhanced activities of organically bound tritium in biota samples.

    PubMed

    Svetlik, I; Fejgl, M; Malátová, I; Tomaskova, L

    2014-11-01

    A pilot study aimed on possible occurrence of elevated activity of non-exchangable organically bound tritium (NE-OBT) in biota was performed. The first results showed a significant surplus of NE-OBT activity in biota of the valley of Mohelno reservoir and Jihlava river. The liquid releases of HTO from the nuclear power plant Dukovany is the source of tritium in this area. This area can be a source of various types of natural samples for future studies of tritium pathways.

  16. Developmental effects of endocrine-disrupting chemicals in wildlife and humans

    SciTech Connect

    Colborn, T. ); vom Saal, F.S. ); Soto, A.M. )

    1993-10-01

    Large numbers and large quantities of endoncrine-disrupting chemicals have been released into the environment since World War II. Many of these chemicals can disturb development of the endocrine system and of the organs that respond to endocrine signals in organisms indirectly exposed during prenatal and/or early postnatal life; effects of exposure during development are permanent and irreversible. The risk to the developing organism can also stem from direct exposure of the offspring after birth or hatching. In addition, trangenerational exposure can result from the exposure of the mother to a chemical at any time throughout her life before producing offspring due to persistent of endocrine-disrupting chemicals in body fat, which is mobilized during egg laying or pregnancy and lactation. Mechanisms underlying the disruption of the development of vital systems, such as the endocrine, reproductive, and immune systems, are discussed with reference to wildlife, laboratory animals, and humans.

  17. Impact of endocrine disrupting chemicals on onset and development of female reproductive disorders and hormone-related cancer.

    PubMed

    Scsukova, Sona; Rollerova, Eva; Bujnakova Mlynarcikova, Alzbeta

    2016-12-01

    A growing body of evidence suggests that exposure to chemical substances designated as endocrine disrupting chemicals (EDCs) due to their ability to disturb endocrine (hormonal) activity in humans and animals, may contribute to problems with fertility, pregnancy, and other aspects of reproduction. The presence of EDCs has already been associated with reproductive malfunction in wildlife species, but it remains difficult to prove causal relationships between the presence of EDCs and specific reproductive problems in vivo, especially in females. On the other hand, the increasing number of experiments with laboratory animals and in vitro research indicate the ability of different EDCs to influence the normal function of female reproductive system, and even their association with cancer development or progression. Research shows that EDCs may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are forming. In this review article, we aim to point out a possible contribution of EDCs to the onset and development of female reproductive disorders and endocrine-related cancers with regard to the period of exposure to EDCs and affected endpoints (organs or processes).

  18. Antimicrobial activity of organically modified nano-clays.

    PubMed

    Hong, Seek-In; Rhim, Jong-Whan

    2008-11-01

    Antimicrobial activity of three kinds of commercially available montmorillonite nano-clays including a naturally occurring one (Cloisite Na+) and two organically modified ones (Cloisite 20A and Cloisite 30B) against four representative pathogenic bacteria (two Gram-positive ones such as Staphylococcus aureus and Listeria monocytogenes, and two Gram-negative ones such as Salmonella typhimurium and E. coli O157:H7) was investigated. Antimicrobial activity was found to be dependent on the type of nano-clay and microorganisms tested. Among the nano-clays tested, Cloisite 30B showed the highest antibacterial activity followed by Cloisite 20A, however, the unmodified montmorillonite (Cloisite Na+) did not show any antibacterial activity. Especially, Cloisite 30B inactivated Gram-positive bacteria completely within an hour of incubation and inactivated Gram-negative bacteria by more than 2-3 log cycles after 8 hours incubation. SEM and TEM images of cell structure indicated that the organically modified nano-clay caused rupture of cell membrane and inactivation of the bacteria. This finding of antimicrobial activity of the organo-clay would open a new opportunity to develop polymer nanocomposites with additional functionality, i.e., antimicrobial function.

  19. Effects of organic carbon sequestration strategies on soil enzymatic activities

    NASA Astrophysics Data System (ADS)

    Puglisi, E.; Suciu, N.; Botteri, L.; Ferrari, T.; Coppolecchia, D.; Trevisan, M.; Piccolo, A.

    2009-04-01

    Greenhouse gases emissions can be counterbalanced with proper agronomical strategies aimed at sequestering carbon in soils. These strategies must be tested not only for their ability in reducing carbon dioxide emissions, but also for their impact on soil quality: enzymatic activities are related to main soil ecological quality, and can be used as early and sensitive indicators of alteration events. Three different strategies for soil carbon sequestration were studied: minimum tillage, protection of biodegradable organic fraction by compost amendment and oxidative polimerization of soil organic matter catalyzed by biometic porfirins. All strategies were compared with a traditional agricultural management based on tillage and mineral fertilization. Experiments were carried out in three Italian soils from different pedo-climatic regions located respectively in Piacenza, Turin and Naples and cultivated with maize or wheat. Soil samples were taken for three consecutive years after harvest and analyzed for their content in phosphates, ß-glucosidase, urease and invertase. An alteration index based on these enzymatic activities levels was applied as well. The biomimetic porfirin application didn't cause changes in enzymatic activities compared to the control at any treatment or location. Enzymatic activities were generally higher in the minimum tillage and compost treatment, while differences between location and date of samplings were limited. Application of the soil alteration index based on enzymatic activities showed that soils treated with compost or subjected to minimum tillage generally have a higher biological quality. The work confirms the environmental sustainability of the carbon sequestering agronomical practices studied.

  20. Purely Organic Thermally Activated Delayed Fluorescence Materials for Organic Light-Emitting Diodes.

    PubMed

    Wong, Michael Y; Zysman-Colman, Eli

    2017-03-03

    The design of thermally activated delayed fluorescence (TADF) materials both as emitters and as hosts is an exploding area of research. The replacement of phosphorescent metal complexes with inexpensive organic compounds in electroluminescent (EL) devices that demonstrate comparable performance metrics is paradigm shifting, as these new materials offer the possibility of developing low-cost lighting and displays. Here, a comprehensive review of TADF materials is presented, with a focus on linking their optoelectronic behavior with the performance of the organic light-emitting diode (OLED) and related EL devices. TADF emitters are cross-compared within specific color ranges, with a focus on blue, green-yellow, orange-red, and white OLEDs. Organic small-molecule, dendrimer, polymer, and exciplex emitters are all discussed within this review, as is their use as host materials. Correlations are provided between the structure of the TADF materials and their optoelectronic properties. The success of TADF materials has ushered in the next generation of OLEDs.

  1. Water Activity Limits the Hygroscopic Growth Factor of Organic Aerosols

    NASA Astrophysics Data System (ADS)

    Rodriguez, L. I.; Cabrera, J. A.; Golden, D.; Tabazadeh, A.

    2007-12-01

    In this work we study the hygroscopic behavior of organic aerosols, which has important implications for Earth's climate. The hygroscopic growth factor (HGF) is defined as the ratio of the diameter of a spherical particle when it is exposed to dry conditions to that at humid conditions. We present a new formulation to express the HGF of an aerosol particle as a function of water activity (aw) in the aqueous phase. This new formulation matches reported HGFs for common inorganic salts and water-miscible organic particles that are known to deliquesce into aqueous drops at high relative humidities (RH). Many studies use tandem differential mobility analyzers (TDMA) to determine the HGF of organic aerosols. For example, Brooks et al. used a TDMA to measure a HGF of 1.2 for 2 μm phthalic acid (PA) particles at 90% RH (aw= 0.9). However, water activity limits the growth of a particle that can be attributed to water uptake. We have assembled a vapor pressure apparatus to measure aw of aqueous solutions at room temperature. Measured water activities for PA, used in our growth formulation, yield a HGF of ~ 1.0005 for 2 μm PA particles at 90% RH. Comparing our results against Brooks et al. suggests that TDMA experiments may grossly overestimate the HGF of PA particles since water activity limits this growth to below 1.0005. Alternatively, we suggest that the adsorption of a negligible mass of water by a highly porous PA particle can lead to an apparent growth in particle size by changing its morphology. Other studies also use TDMAs to measure HGFs of secondary organic aerosols (SOAs). HGFs reported for SOAs are very similar to PA, suggesting that the observed growth may be due to morphological changes in particle size rather than water uptake as commonly assumed. We built a smog chamber where an organic precursor, such as d-limonene, reacts with nitrogen oxides under UV radiation to produce SOAs. We compare the HGFs for SOAs obtained with our method to those obtained with

  2. Cloud condensation nuclei activity of isoprene secondary organic aerosol

    NASA Astrophysics Data System (ADS)

    Engelhart, Gabriella J.; Moore, Richard H.; Nenes, Athanasios; Pandis, Spyros N.

    2011-01-01

    This work explores the cloud condensation nuclei (CCN) activity of isoprene secondary organic aerosol (SOA), likely a significant source of global organic particulate matter and CCN, produced from the oxidation with OH from HONO/HOOH photolysis in a temperature-controlled SOA chamber. CCN concentrations, activation diameter, and droplet growth kinetic information were monitored as a function of supersaturation (from 0.3% to 1.5%) for several hours using a cylindrical continuous-flow streamwise thermal gradient CCN counter connected to a scanning mobility particle sizer. The initial SOA concentrations ranged from 2 to 30 μg m-3 and presented CCN activity similar to monoterpene SOA with an activation diameter of 35 nm for 1.5% supersaturation and 72 nm for 0.6% supersaturation. The CCN activity improved slightly in some experiments as the SOA aged chemically and did not depend significantly on the level of NOx during the SOA production. The measured activation diameters correspond to a hygroscopicity parameter κ value of 0.12, similar to κ values of 0.1 ± 0.04 reported for monoterpene SOA. Analysis of the water-soluble carbon extracted from filter samples of the SOA suggest that it has a κ of 0.2-0.3 implying an average molar mass between 90 and 150 g mol-1 (assuming a zero and 5% surface tension reduction with respect to water, respectively). These findings are consistent with known oxidation products of isoprene. Using threshold droplet growth analysis, the CCN activation kinetics of isoprene SOA was determined to be similar to pure ammonium sulfate aerosol.

  3. Challenges in assigning endocrine-specific modes of action: Recommendations for researchers and regulators.

    PubMed

    Mihaich, Ellen M; Schäfers, Christoph; Dreier, David A; Hecker, Markus; Ortego, Lisa; Kawashima, Yukio; Dang, Zhi-Chao; Solomon, Keith

    2017-03-01

    As regulatory programs evaluate substances for their endocrine-disrupting properties, careful study design and data interpretation are needed to distinguish between responses that are truly endocrine specific and those that are not. This is particularly important in regulatory environments where criteria are under development to identify endocrine-disrupting properties to enable hazard-based regulation. Irrespective of these processes, most jurisdictions use the World Health Organization/International Programme on Chemical Safety definition of an endocrine disruptor, requiring that a substance is demonstrated to cause a change in endocrine function that consequently leads to an adverse effect in an intact organism. Such a definition is broad, and at its most cautious might capture many general mechanisms that would not specifically denote an endocrine disruptor. In addition, endocrine responses may be adaptive in nature, designed to maintain homeostasis rather than induce an irreversible adverse effect. The likelihood of indirect effects is increased in (eco)toxicological studies that require the use of maximum tolerated concentrations or doses, which must produce some adverse effect. The misidentification of indirect effects as truly endocrine mediated has serious consequences for prompting animal- and resource-intensive testing and regulatory consequences. To minimize the risk for misidentification, an objective and transparent weight-of-evidence procedure based on biological plausibility, essentiality, and empirical evidence of key events in an adverse outcome pathway is recommended to describe the modes of action that may be involved in toxic responses in nontarget organisms. Confounding factors such as systemic toxicity, general stress, and infection can add complexity to such an evaluation and should be considered in the weight of evidence. A recommended set of questions is proffered to help guide researchers and regulators in discerning endocrine and

  4. SEQUESTERING AGENTS FOR ACTIVE CAPS - REMEDIATION OF METALS AND ORGANICS

    SciTech Connect

    Knox, A; Michael Paller, M; Danny D. Reible, D; Xingmao Ma, X; Ioana G. Petrisor, I

    2007-05-10

    This research evaluated organoclays, zeolites, phosphates, and a biopolymer as sequestering agents for inorganic and organic contaminants. Batch experiments were conducted to identify amendments and mixtures of amendments for metal and organic contaminants removal and retention. Contaminant removal was evaluated by calculating partitioning coefficients. Metal retention was evaluated by desorption studies in which residue from the removal studies was extracted with 1 M MgCl{sub 2} solution. The results indicated that phosphate amendments, some organoclays, and the biopolymer, chitosan, were very effective sequestering agents for metals in fresh and salt water. Organoclays were very effective sorbents for phenanthrene, pyrene, and benzo(a)pyrene. Partitioning coefficients for the organoclays were 3000-3500 ml g{sup -1} for benzo(a)pyrene, 400-450 ml g{sup -1} for pyrene, and 50-70 ml g{sup -1} for phenanthrene. Remediation of sites with a mixture of contaminants is more difficult than sites with a single contaminant because metals and organic contaminants have different fate and transport mechanisms in sediment and water. Mixtures of amendments (e.g., organoclay and rock phosphate) have high potential for remediating both organic and inorganic contaminants under a broad range of environmental conditions, and have promise as components in active caps for sediment remediation.

  5. Optogenetically enhanced pituitary corticotroph cell activity post-stress onset causes rapid organizing effects on behaviour

    PubMed Central

    De Marco, Rodrigo J.; Thiemann, Theresa; Groneberg, Antonia H.; Herget, Ulrich; Ryu, Soojin

    2016-01-01

    The anterior pituitary is the major link between nervous and hormonal systems, which allow the brain to generate adequate and flexible behaviour. Here, we address its role in mediating behavioural adjustments that aid in coping with acutely threatening environments. For this we combine optogenetic manipulation of pituitary corticotroph cells in larval zebrafish with newly developed assays for measuring goal-directed actions in very short timescales. Our results reveal modulatory actions of corticotroph cell activity on locomotion, avoidance behaviours and stimulus responsiveness directly after the onset of stress. Altogether, the findings uncover the significance of endocrine pituitary cells for rapidly optimizing behaviour in local antagonistic environments. PMID:27646867

  6. Male reprotoxicity and endocrine disruption

    PubMed Central

    Campion, Sarah; Catlin, Natasha; Heger, Nicholas; McDonnell, Elizabeth V.; Pacheco, Sara E.; Saffarini, Camelia; Sandrof, Moses A.; Boekelheide, Kim

    2013-01-01

    Mammalian reproductive tract development is a tightly regulated process that can be disrupted following exposure to drugs, toxicants, endocrine disrupting chemicals or other compounds via alterations to gene and protein expression or epigenetic regulation. Indeed, the impacts of developmental exposure to certain toxicants may not be fully realized until puberty or adulthood when the reproductive tract becomes sexually mature and altered functionality is manifested. Exposures that occur later in life, once development is complete, can also disrupt the intricate hormonal and paracrine interactions responsible for adult functions, such as spermatogenesis. In this chapter, the biology and toxicology of the male reproductive tract is explored, proceeding through the various life stages including in utero development, puberty, adulthood and senescence. Special attention is given to the discussion of endocrine disrupting chemicals, chemical mixtures, low dose effects, transgenerational effects, and potential exposure-related causes of male reproductive tract cancers. PMID:22945574

  7. Endocrine therapy of breast cancer

    SciTech Connect

    Cavalli, F.

    1986-01-01

    This book results from a meeting of the ESO (European School of Oncology) Task Force on endocrine aspects of breast cancer. The contributions stem from some of the most outstanding researchers in Europe and highlight mainly methodological issues and new avenues for future research. The chapters on basic research deal primarily with experimental strategies for studying the relationship between steroid hormones, growth factors, and oncongenes. The clinically oriented chapters treat the methodology of clinical trials. Provocative questions are raised, such as: What are the pitfalls in endocrine trials. What does statistical proof mean. How can we consider a quality of life endpoint in the adjuvant setting. Two special reports deal with the controversial issues of chemoprevention in high-risk normal women and the optimization of the hormonal contribution to the adjuvant therapy of breast cancer. Topics considered included oncogenic transformations, radiotherapy, steroid hormones, cell proliferation, tamoxifen, and preventive medicine.

  8. Multiple endocrine neoplasia type 2.

    PubMed

    Lodish, Maya

    2013-01-01

    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter.

  9. Ferrocene Functionalized Endocrine Modulators as Anticancer Agents

    NASA Astrophysics Data System (ADS)

    Hillard, Elizabeth A.; Vessières, Anne; Jaouen, Gerard

    We present here some of our studies on the synthesis and behaviour of ferrocenyl selective endocrine receptor modulators against cancer cells, particularly breast and prostate cancers. The proliferative/anti-proliferative effects of compounds based on steroidal and non-steroidal endocrine modulators have been extensively explored in vitro. Structure-activity relationship studies of such molecules, particularly the hydroxyferrocifens and ferrocene phenols, have shown the effect of (1) the presence and the length of the N,N-dimethylamino side chain, (2) the presence and position of the phenol group, (3) the role of the ferrocenyl moiety, (4) that of conjugation, (5) phenyl functionalisation and (6) the placement of the phenyl group. Compounds possessing a ferrocene moiety linked to a p-phenol by a conjugated π-system are among the most potent of the series, with IC50 values ranging from 0.090 to 0.6µM on hormone independent breast cancer cells. Based on the SAR data and electrochemical studies, we have proposed an original mechanism to explain the unusual behaviour of these bioorganometallic species and coin the term "kronatropic" to qualify this effect, involving ROS production and bio-oxidation. In addition, the importance of formulation is underlined. We also discuss the behaviour of ferrocenyl androgens and anti-androgens for possible use against prostate cancers. In sum, ferrocene has proven to be a fascinating substituent due to its vast potential for oncology.

  10. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2005-06-01

    breast cancers is whether an aromatase inhibitor, e.g., letrozole (LET) or TAM should be given as first line endocrine therapy . Unfortunately...response rates are lower, and response durations are shorter, on crossover than when these agents are given as first line therapies , e.g., -40% of tumors...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  11. Endocrine Therapy of Breast Cancer

    DTIC Science & Technology

    2006-06-01

    or TAM should be given as first line endocrine therapy . Unfortunately, response rates are lower, and response durations are shorter, on crossover than...when these agents are given as first line therapies , e.g., ~40% of tumors show cross resistance to TAM or an aromatase inhibitor on crossover. Only...effective treatment for hormone receptor positive invasive breast cancer. Such therapy includes antiestrogens (tamoxifen, fulvestrant ) and aromatase

  12. Self-organizing model of motor cortical activities during drawing

    NASA Astrophysics Data System (ADS)

    Lin, Siming H.; Si, Jennie; Schwartz, Andrew B.

    1996-05-01

    The population vector algorithm has been developed to combine the simultaneous direction- related activities of a population of motor cortical neurons to predict the trajectory of the arm movement. In our study, we consider a self-organizing model of a neural representation of the arm trajectory based on neuronal discharge rates. Self-organizing feature mapping (SOFM) is used to select the optimal set of weights in the model to determine the contribution of individual neuron to the overall movement. The correspondence between the movement directions and the discharge patterns of the motor cortical neurons is established in the output map. The topology preserving property of the SOFM is used to analyze real recorded data of a behavior monkey. The data used in this analysis were taken while the monkey was drawing spirals and doing the center out movement. Using such a statistical model, the monkey's arm moving directions could be well predicted based on the motor cortex neuronal firing information.

  13. Calibration and field test of the Polar Organic Chemical Integrative Samplers for the determination of 15 endocrine disrupting compounds in wastewater and river water with special focus on performance reference compounds (PRC).

    PubMed

    Vallejo, A; Prieto, A; Moeder, M; Usobiaga, A; Zuloaga, O; Etxebarria, N; Paschke, A

    2013-05-15

    In this work, home-made Polar Organic Chemical Integrative Samplers (POCIS) were studied for passive sampling of 15 endocrine disrupting compounds (4 alkylphenols and steroid hormones) in influent and effluent samples of wastewater treatment plants (WWTPs) as well as up- and downstream of the receiving river water. POCIS calibration at laboratory conditions was carried out using a continuous-flow calibration system. The influence of the exposure position of the POCIS within the calibration device, horizontal or vertical, to the water flow direction was evaluated. While the sampling rates of most of the target substances were not affected by the sampler position, for cis-ADT, E1, E2 and E3, the vertical position provided the highest analyte accumulation. Hence, the POCIS samplers were preferably exposed vertical to the water flow in overall experiments. Using the continuous-flow calibration device, lab-based sampling rates were determined for all the target compounds (RSBPA = 0.0326 L/d; RScisADT = 0.0800 L/d, RSE1 = 0.0398 L/d, RSEQ = 0.0516 L/d, RSTT = 0.0745 L/d, RSE2 = 0.0585 L/d, RSEE2 = 0.0406 L/d, RSNT = 0.0846 L/d, RSPG = 0.0478 L/d and RSE3 = 0.1468 L/d), except for DES, MeEE2, 4tOP, 4OP, 4NPs, where the uptake after 14 days POCIS exposure was found to be insignificant or indicated a no linear behaviour. Recoveries from POCIS extractions were in the range between 71 and 152% for most of the target analytes except for DES and E3 with around 59%. Good precision of the sampling procedure up till 20% was observed and limits of detection were at ng/L level. Two deuterated compounds ([(2)H3]-E2 and [(2)H4]-EQ) were successfully tested as performance reference compounds (PRC, [Formula: see text] = 0.0507 L/d and [Formula: see text] = 0.0543 L/d)). Finally, the POCIS samplers were tested for monitoring EDCs at two wastewater treatment plants, in Halle and Leipzig (Germany). BPA, E1, EQ, E2, MeEE2, NT, EE2, PG and E3 were quantified and their time-weighted average

  14. [Contamination, endocrine disruptors and cancer].

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-03-01

    Since the mid-twentieth century, many species, very different from each other and located in all areas and comers of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called "endocrine disrupting chemicals". When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations.

  15. Respiratory manifestations in endocrine diseases

    PubMed Central

    LENCU, CODRUŢA; ALEXESCU, TEODORA; PETRULEA, MIRELA; LENCU, MONICA

    2016-01-01

    The control mechanisms of respiration as a vital function are complex: voluntary – cortical, and involuntary – metabolic, neural, emotional and endocrine. Hormones and hypothalamic neuropeptides (that act as neurotrasmitters and neuromodulators in the central nervous system) play a role in the regulation of respiration and in bronchopulmonary morphology. This article presents respiratory manifestations in adult endocrine diseases that evolve with hormone deficit or hypersecretion. In hyperthyroidism, patients develop ventilation disorders, obstructive and central sleep apnea, and pleural collection. The respiratory abnormalities in hyperthyroidism as a result of the hypermetabolic action of thyroid hormones are hyperventilation, myopathy and cardiovascular involvement; recent studies have reported pulmonary arterial hypertension in Graves’ disease, as a result of the association of several mechanisms. Thyroid hypertrophy can induce through compression of the upper airways dyspnea, stridor, wheezing and cough. The respiratory disorders in acromegaly are ventilatory dysfunction and sleep apnea, which contribute to an unfavorable evolution of the disease. Respiratory changes in parathyroid, adrenal and reproductive system diseases have been described. Respiratory disorders should be recognized, investigated and monitored by medical practitioners of various specialties (family physicians, internists, endocrinologists, pneumologists, cardiologists). They are frequently severe, causing an unfavorable evolution of the associated endocrine and respiratory disease. PMID:27857512

  16. Endocrine manifestations in celiac disease

    PubMed Central

    Freeman, Hugh James

    2016-01-01

    Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison’s disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet. PMID:27784959

  17. Spectrum of Endocrine Disorders in Central Ghana

    PubMed Central

    Sarfo, Fred Stephen; Ansah, Eunice Oparebea; Kyei, Ishmael

    2017-01-01

    Background. Although an increasing burden of endocrine disorders is recorded worldwide, the greatest increase is occurring in developing countries. However, the spectrum of these disorders is not well described in most developing countries. Objective. The objective of this study was to profile the frequency of endocrine disorders and their basic demographic characteristics in an endocrine outpatient clinic in Kumasi, central Ghana. Methods. A retrospective review was conducted on endocrine disorders seen over a five-year period between January 2011 and December 2015 at the outpatient endocrine clinic of Komfo Anokye Teaching Hospital. All medical records of patients seen at the endocrine clinic were reviewed by endocrinologists and all endocrinological diagnoses were classified according to ICD-10. Results. 3070 adults enrolled for care in the endocrine outpatient service between 2011 and 2015. This comprised 2056 females and 1014 males (female : male ratio of 2.0 : 1.0) with an overall median age of 54 (IQR, 41–64) years. The commonest primary endocrine disorders seen were diabetes, thyroid, and adrenal disorders at frequencies of 79.1%, 13.1%, and 2.2%, respectively. Conclusions. Type 2 diabetes and thyroid disorders represent by far the two commonest disorders seen at the endocrine clinic. The increased frequency and wide spectrum of endocrine disorders suggest the need for well-trained endocrinologists to improve the health of the population. PMID:28326101

  18. The restless brain: how intrinsic activity organizes brain function.

    PubMed

    Raichle, Marcus E

    2015-05-19

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.

  19. The restless brain: how intrinsic activity organizes brain function

    PubMed Central

    Raichle, Marcus E.

    2015-01-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  20. Genotoxic activity of organic chemicals in drinking water.

    PubMed

    Meier, J R

    1988-11-01

    The information summarized in this review provides substantial evidence for the widespread presence of genotoxins in drinking water. In many, if not most cases, the genotoxic activity can be directly attributed to the chlorination stage of drinking water treatment. The genotoxic activity appears to originate primarily from reactions of chlorine with humic substances in the source waters. Genotoxic activity in drinking water concentrates has been most frequently demonstrated using bacterial mutagenicity tests but results with mammalian cell assay systems are generally consistent with the findings from the bacterial assays. There is currently no evidence for genotoxic damage following in vivo exposures to animals. In some locations genotoxic contaminants of probable industrial and/or agricultural origin occur in the source waters and contribute substantially to the genotoxic activity of finished drinking waters. The method used for sample concentration can have an important bearing on study results. In particular, organic acids account for most of the mutagenicity of chlorinated drinking water, and their recovery from water requires a sample acidification step prior to extraction or XAD resin adsorption. Considerable work has been done to determine the identity of the compounds responsible for the mutagenicity of organic concentrates of drinking water. Recently, one class of acidic compounds, the chlorinated hydroxyfuranones, has been shown to be responsible for a major part of the mutagenic activity. Strategies for drinking water treatment that have been evaluated with respect to reduction of genotoxins in drinking water include granular activated carbon (GAC) filtration, chemical destruction, and the use of alternative means of treatment (i.e., ozone, chlorine dioxide, and monochloramine). GAC treatment has been found to be effective for removal of mutagens from drinking water even after the GAC is beyond its normal use for organic carbon removal. All disinfectant

  1. The eye as a window to rare endocrine disorders

    PubMed Central

    Chopra, Rupali; Chander, Ashish; Jacob, Jubbin J.

    2012-01-01

    The human eye, as an organ, can offer critical clues to the diagnosis of various systemic illnesses. Ocular changes are common in various endocrine disorders such as diabetes mellitus and Graves’ disease. However there exist a large number of lesser known endocrine disorders where ocular involvement is significant. Awareness of these associations is the first step in the diagnosis and management of these complex patients. The rare syndromes involving the pituitary hypothalamic axis with significant ocular involvement include Septo-optic dysplasia, Kallman's syndrome, and Empty Sella syndrome all affecting the optic nerve at the optic chiasa. The syndromes involving the thyroid and parathyroid glands that have ocular manifestations and are rare include Mc Cune Albright syndrome wherein optic nerve decompression may occur due to fibrous dysplasia, primary hyperparathyroidism that may present as red eye due to scleritis and Ascher syndrome wherein ptosis occurs. Allgrove's syndrome, Cushing's disease, and Addison's disease are the rare endocrine syndromes discussed involving the adrenals and eye. Ocular involvement is also seen in gonadal syndromes such as Bardet Biedl, Turner's, Rothmund's, and Klinefelter's syndrome. This review also highlights the ocular manifestation of miscellaneous syndromes such as Werner's, Cockayne's, Wolfram's, Kearns Sayre's, and Autoimmune polyendocrine syndrome. The knowledge of these relatively uncommon endocrine disorders and their ocular manifestations will help an endocrinologist reach a diagnosis and will alert an ophthalmologist to seek specialty consultation of an endocrinologist when encountered with such cases. PMID:22629495

  2. Endocrine Aspects of Environmental “Obesogen” Pollutants

    PubMed Central

    Nappi, Francesca; Barrea, Luigi; Di Somma, Carolina; Savanelli, Maria Cristina; Muscogiuri, Giovanna; Orio, Francesco; Savastano, Silvia

    2016-01-01

    Growing evidence suggests the causal link between the endocrine-disrupting chemicals (EDCs) and the global obesity epidemics, in the context in the so-called “obesogenic environment”. Dietary intake of contaminated foods and water, especially in association with unhealthy eating pattern, and inhalation of airborne pollutants represent the major sources of human exposure to EDCs. This is of particular concern in view of the potential impact of obesity on chronic non-transmissible diseases, such as type 2 diabetes, cardiovascular disease, and hormone-sensitive cancers. The key concept is the identification of adipose tissue not only as a preferential site of storage of EDCs, but also as an endocrine organ and, as such, susceptible to endocrine disruption. The timing of exposure to EDCs is critical to the outcome of that exposure, with early lifetime exposures (e.g., fetal or early postnatal) particularly detrimental because of their permanent effects on obesity later in life. Despite that the mechanisms operating in EDCs effects might vary enormously, this minireview is aimed to provide a general overview on the possible association between the pandemics of obesity and EDCs, briefly describing the endocrine mechanisms linking EDCs exposure and latent onset of obesity. PMID:27483295

  3. Exposure to Environmental Endocrine Disruptors and Child Development

    PubMed Central

    Meeker, John D.

    2013-01-01

    Exposure to exogenous chemicals can impact endocrine function at multiple sites and through numerous specific modes of action, which may have far-reaching impacts on human health and development. Widespread human exposure to numerous known or suspected endocrine disrupting chemicals (EDCs) has been documented in the US and worldwide, as have trends for increased rates of endocrine-related diseases and disorders among children. While human epidemiology studies of exposure to EDCs and children’s health remain extremely limited, there is a growing body of evidence showing that exposure to a number of chemicals commonly found in consumer goods, personal care products, food, drinking water, and other sources may adversely impact child development through altered endocrine function. This narrative review provides a brief introduction to several common EDCs (with a specific focus on persistent organic pollutants, phthalates, bisphenol A, and contemporary use pesticides, which only represents a small number of all known or suspected EDCs), an overview of the state of the human evidence for adverse impacts of EDCs on child development (fetal growth, early reproductive tract development, pubertal development, neurodevelopment, and obesity), guidance for health care providers based on current knowledge, and recommendations for future research. PMID:22664748

  4. Application of ecotoxicogenomics for studying endocrine disruption in vertebrates and invertebrates.

    PubMed

    Iguchi, Taisen; Watanabe, Hajime; Katsu, Yoshinao

    2006-04-01

    Chemicals released into the environment potentially disrupt the endocrine system in wild animals and humans. Developing organisms are particularly sensitive to estrogenic chemicals. Exposure to estrogens or estrogenic chemicals during critical periods of development induces persistent changes in both reproductive and nonreproductive organs, including persistent molecular alterations. Estrogen-responsive genes and critical developmental windows of various animal species, therefore, need to be identified for investigators to understand the molecular basis of estrogenic activity during embryonic development. For investigators to understand molecular mechanisms of toxicity in various species, toxicogenomics/ecotoxicogenomics, defined as the integration of genomics (transcriptomics, proteomics, metabolomics) into toxicology and ecotoxicology, need to be established as powerful tools for research. As the initial step toward using genomics to examine endocrine-disrupting chemicals, estrogen receptors and other steroid hormone receptors have been cloned in various species, including reptiles, amphibians, and fish, and alterations in the expression of these genes in response to chemicals were investigated. We are identifying estrogen-responsive genes in mouse reproductive tracts using cDNA microarrays and trying to establish microarray systems in the American alligator, roach, medaka, and water fleas (Daphnia magna). It is too early to define common estrogen-responsive genes in various animal species; however, toxicogenomics and ectotoxicogenomics provide powerful tools to help us understand the molecular mechanism of chemical toxicities in various animal species.

  5. The effects of the endocrine disruptors dithiocarbamates on the mammalian ovary with particular regard to mancozeb.

    PubMed

    Cecconi, Sandra; Paro, Rita; Rossi, Gianna; Macchiarelli, Guido

    2007-01-01

    Many human-made chemicals are called endocrine disruptors (EDs) because they have the potential to disrupt endocrine functions in exposed organisms. Many EDs can disrupt hormonal homeostasis by interfering with hormone receptor recognition, binding and activation, while others act by still unknown mechanisms. Among the EDs specifically affecting the female reproductive system, those with steroidogenic/antisteroidogenic effects have been extensively studied and the mechanisms of toxicity clarified also at molecular level. For many others, information is restricted to few epidemiological data and in vivo/in vitro experiments with animal models. This is the case of the dithiocarbamates, and in particular of the fungicide mancozeb, an ethylenedithiocarbamate widely used to protect fruit and vegetables, ginseng included, because of its low acute toxicity in humans. Although the mechanism(s) by which mancozeb may specifically act on female reproductive organs are largely unknown, data on experimental animals in vivo have demonstrated that the fungicide can induce several disturbances on estrus cycle. When used in vitro at concentrations considered too low to cause human health injuries, the fungicide impairs mouse embryo development and meiotic spindle assembly. The possibility that the female germ cell (the oocyte) could be a specific target of mancozeb suggests a role for this fungicide as probable inductor of infertility also in exposed human populations.

  6. Active gels: dynamics of patterning and self-organization

    NASA Astrophysics Data System (ADS)

    Backouche, F.; Haviv, L.; Groswasser, D.; Bernheim-Groswasser, A.

    2006-12-01

    The actin cytoskeleton is an active gel which constantly remodels during cellular processes such as motility and division. Myosin II molecular motors are involved in this active remodeling process and therefore control the dynamic self-organization of cytoskeletal structures. Due to the complexity of in vivo systems, it is hard to investigate the role of myosin II in the reorganization process which determines the resulting cytoskeletal structures. Here we use an in vitro model system to show that myosin II actively reorganizes actin into a variety of mesoscopic patterns, but only in the presence of bundling proteins. We find that the nature of the reorganization process is complex, exhibiting patterns and dynamical phenomena not predicted by current theoretical models and not observed in corresponding passive systems (excluding motors). This system generates active networks, asters and even rings depending on motor and bundling protein concentrations. Furthermore, the motors generate the formation of the patterns, but above a critical concentration they can also disassemble them and even totally prevent the polymerization and bundling of actin filaments. These results may suggest that tuning the assembly and disassembly of cytoskeletal structures can be obtained by tuning the local myosin II concentration/activity.

  7. Cosmetics as endocrine disruptors: are they a health risk?

    PubMed

    Nicolopoulou-Stamati, Polyxeni; Hens, Luc; Sasco, Annie J

    2015-12-01

    Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

  8. New Space Weather Activities in the World Meteorological Organization

    NASA Astrophysics Data System (ADS)

    Bogdan, Thomas J.; Onsager, Terrance G.

    2010-10-01

    A new era of enhanced international cooperation in space weather operations has begun with the recent initiation of space weather activities within the World Meteorological Organization (WMO), an agency of the United Nations (U.N.) with a membership of 189 states and territories. These activities aim to standardize and enhance space weather observations and data exchange, coordinate end products and services, and foster dialogue between the research and operational communities. The WMO's role is to foster collaboration among the meteorological and hydrological (and now space weather) service providers and to promote the establishment of networks for making and exchanging geophysical observations and the standardization of data and metadata. It also contributes to policy making and has a lead role in efforts to monitor and protect the environment.

  9. Scientific and Regulatory Policy Committee (SRPC) Points to Consider*: Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors

    PubMed Central

    Keane, Kevin A.; Parker, George A.; Regan, Karen S.; Picut, Catherine; Dixon, Darlene; Creasy, Dianne; Giri, Dipak; Hukkanen, Renee R.

    2015-01-01

    The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a multitiered approach to determine the potential for environmental chemicals to alter the endocrine system. The Pubertal Development and Thyroid Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450, 890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream mechanistic pathways along with downstream morphological end points including histological evaluation of the kidneys, thyroid, and select male/female reproductive tissues (ovaries, uterus, testes, and epididymides). These assays are part of a battery of in vivo and in vitro screens used for initial detection of test article endocrine activity. In this Points to Consider article, we describe tissue processing, evaluation, and nomenclature to aid in standardization of assay results across laboratories. Pubertal assay end points addressed include organ weights, estrous cyclicity, clinical pathology, hormonal assays, and histological evaluation. Potential treatment-related findings that may indicate endocrine disruption are reviewed. Additional tissues that may be useful in assessment of endocrine disruption (vagina, mammary glands, and liver) are discussed. This Points to Consider article is intended to provide information for evaluating peripubertal tissues within the context of individual assay end points, the overall pubertal assay, and tier I assays of the EDSP program. PMID:25948506

  10. A flexible organic active matrix circuit fabricated using novel organic thin film transistors and organic light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Gutiérrez-Heredia, G.; González, L. A.; Alshareef, H. N.; Gnade, B. E.; Quevedo-López, M.

    2010-11-01

    We present an active matrix circuit fabricated on plastic (polyethylene naphthalene, PEN) and glass substrates using organic thin film transistors and organic capacitors to control organic light-emitting diodes (OLEDs). The basic circuit is fabricated using two pentacene-based transistors and a capacitor using a novel aluminum oxide/parylene stack (Al2O3/parylene) as the dielectric for both the transistor and the capacitor. We report that our circuit can deliver up to 15 µA to each OLED pixel. To achieve 200 cd m-2 of brightness a 10 µA current is needed; therefore, our approach can initially deliver 1.5× the required current to drive a single pixel. In contrast to parylene-only devices, the Al2O3/parylene stack does not fail after stressing at a field of 1.7 MV cm-1 for >10 000 s, whereas 'parylene only' devices show breakdown at approximately 1000 s. Details of the integration scheme are presented.

  11. REMOVAL OF ORGANIC POLLUTANTS FROM SUBCRITICAL WATER WITH ACTIVATED CARBON

    SciTech Connect

    Steven B. Hawthorne; Arnaud J. Lagadec

    1999-08-01

    The Energy & Environmental Research Center (EERC) has demonstrated that controlling the temperature (and to a lesser extent, the pressure) of water can dramatically change its ability to extract organics and inorganics from matrices ranging from soils and sediments to waste sludges and coal. The dielectric constant of water can be changed from about 80 (a very polar solvent) to <5 (similar to a nonpolar organic solvent) by controlling the temperature (from ambient to about 400 C) and pressure (from about 5 to 350 bar). The EERC has shown that hazardous organic pollutants such as pesticides, PACS (polycyclic aromatic hydrocarbons), and PCBs (polychlorinated biphenyls) can be completely removed from soils, sludges, and sediments at temperatures (250 C) and pressures (<50 atm) that are much milder than typically used for supercritical water processes (temperature >374 C, pressure >221 atm). In addition, the process has been demonstrated to be particularly effective for samples containing very high levels of contaminants (e.g., part per thousand). Current projects include demonstrating the subcritical water remediation process at the pilot scale using an 8-liter system constructed under separate funding during 1997. To date, subcritical water has been shown to be an effective extraction fluid for removing a variety of organic pollutants from soils and sludges contaminated with fossil fuel products and waste products, including PACS from soil (e.g., town gas sites), refining catalysts, and petroleum tank bottom sludges; PCBs from soil and sediments; toxic gasoline components (e.g., benzene) from soil and waste sludge; and phenols from petroleum refinery sludges. The obvious need to clean the wastewater from subcritical water processes led to preliminary experiments with activated carbon placed in line after the extractor. Initial experiments were performed before and after cooling the extractant water (e.g., with water at 200 C and with water cooled to 25 C

  12. Oncogenic programmes and Notch activity: an 'organized crime'?

    PubMed

    Dominguez, Maria

    2014-04-01

    The inappropriate Notch signalling can influence virtually all aspect of cancer, including tumour-cell growth, survival, apoptosis, angiogenesis, invasion and metastasis, although it does not do this alone. Hence, elucidating the partners of Notch that are active in cancer is now the focus of much intense research activity. The genetic toolkits available, coupled to the small size and short life of the fruit fly Drosophila melanogaster, makes this an inexpensive and effective animal model, suited to large-scale cancer gene discovery studies. The fly eye is not only a non-vital organ but its stereotyped size and disposition also means it is easy to screen for mutations that cause tumours and metastases and provides ample opportunities to test cancer theories and to unravel unanticipated nexus between Notch and other cancer genes, or to discover unforeseen Notch's partners in cancer. These studies suggest that Notch's oncogenic capacity is brought about not simply by increasing signal strength but through partnerships, whereby oncogenes gain more by cooperating than acting individually, as in a ring 'organized crime'.

  13. USE OF THE LABORATORY RAT AS A MODEL IN ENDOCRINE DISRUPTOR SCREENING AND TESTING

    EPA Science Inventory

    The screening and testing program the US Environmental Protection Agency is currently developing to detect endocrine-disrupting chemicals (EDCs) is described. EDCs have been shown to alter the following activities: hypothalamic-pituitary-gonadal [HPG] function; estrogen, androge...

  14. Pancreatic endocrine neoplasms: Epidemiology and prognosis of pancreatic endocrine tumors

    PubMed Central

    Halfdanarson, Thorvardur R.; Rubin, Joseph; Farnell, Michael B.; Grant, Clive S.; Petersen, Gloria M.

    2009-01-01

    Pancreatic endocrine neoplasms (PETs) are uncommon tumors with an annual incidence less than 1 per 100,000 persons per year in the general population. PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are nonfunctional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis and established and novel prognostic markers of PETs are reviewed. PMID:18508996

  15. Anatomical and functional imaging in endocrine hypertension

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2012-01-01

    In endocrine hypertension, hormonal excess results in clinically significant hypertension. The functional imaging (such as radionuclide imaging) complements anatomy-based imaging (such as ultrasound, computed tomography, and magnetic resonance imaging) to facilitate diagnostic localization of a lesion causing endocrine hypertension. The aim of this review article is to familiarize general radiologists, endocrinologists, and clinicians with various anatomical and functional imaging techniques used in patients with endocrine hypertension. PMID:23087854

  16. Bovine dentine organic matrix down-regulates osteoclast activity.

    PubMed

    Sriarj, Wantida; Aoki, Kazuhiro; Ohya, Keiichi; Takagi, Yuzo; Shimokawa, Hitoyata

    2009-01-01

    Physiological root resorption is a phenomenon that normally takes place in deciduous teeth; root resorption of permanent teeth occurs only under pathological conditions. The molecular mechanisms underlying these processes are still unclear. Our previous study showed that osteoclasts cultured on deciduous dentine exhibited a higher degree of resorption and higher levels of cathepsin K and MMP-9 mRNA than osteoclasts cultured on permanent dentine. These results could be because of different susceptibilities to acid and the different organic matrices between deciduous and permanent dentine. Thus, the purpose of this study was to investigate the effect of dentine extracts from bovine deciduous and permanent dentine on osteoclast activity. Osteoclasts, obtained from mouse bone marrow cells co-cultured with an osteoblast-rich fraction in the presence of 1,25-(OH)(2)-vitamin D3 and PGE2, were incubated with or without 0.6 M HCl extracts from bovine deciduous or permanent dentine for 48 h. TRAP positive cell number, TRAP activity, the areas of resorption pits, and mRNA levels of TRAP, v-ATPase, calcitonin receptor, cathepsin K, and MMP-9 were examined. The results illustrated that TRAP activity, the resorbed area, and the mRNA levels of osteoclast marker genes seemed to be suppressed by both deciduous and permanent dentine extracts. These findings indicate that some factors that suppress osteoclast activity are contained in both deciduous and permanent dentine extracts. Although there was no significant difference in osteoclast activity between deciduous and permanent dentine extracts, osteoclasts incubated with permanent dentine extracts tend to exhibit less resorption activity than those incubated with deciduous dentine extracts. However, we could not clearly explain the causes of this.

  17. Altered mental status and endocrine diseases.

    PubMed

    Park, Elizabeth; Abraham, Michael K

    2014-05-01

    Although the altered mental status is a common presentation in the emergency department, altered mental status caused by endocrine emergencies is rare. The altered patient could have an endocrine cause that can quickly improve with appropriate diagnosis and interventions. When dealing with limited information and an obtunded patient, it is important to have a broad differential diagnosis, pick up on the physical examination findings, and evaluate laboratory abnormalities that could suggest an underlying endocrine emergency. This article outlines the findings and provides a description of altered patients with endocrine emergencies to facilitate the diagnosis and treatment in the emergency department.

  18. Active Matrix Driving Organic Light-Emitting Diode Panel Using Organic Thin-Film Transistors

    NASA Astrophysics Data System (ADS)

    Ohta, Satoru; Chuman, Takashi; Miyaguchi, Satoshi; Satoh, Hideo; Tanabe, Takahisa; Okuda, Yoshiyuki; Tsuchida, Masami

    2005-06-01

    We developed an active matrix driving organic light-emitting diode (OLED) panel on a glass substrate using two organic thin-film transistors (OTFTs) per pixel, a switching OTFT and a driving OTFT. The OTFTs are bottom contact structures with the high-dielectric constant gate insulator tantalum oxide (Ta2O5, relative dielectric constant of 23) produced by anodization in ammonium adipate solution and with pentacene as the active layer. The W/L (where W and L are the OTFTs channel width and length, respectively) was 400 μm/10 μm for the switching OTFTs and 680 μm/10 μm for the driving OTFTs. The characteristics of the OTFTs were improved by treating the Ta2O5 surface with hexamethyldisilazane (HMDS), so that the field-effect mobility was 2.0× 10-1 cm2 V-1 s-1 and the current on/off ratio was 105. A green phosphorescent dopant, tris(2-phenylpyridine)iridium [Ir(ppy)3], was used for the OLED layer. The panel had 8× 8 pixels and the aperture ratio was 27%. We confirmed a 16-gray-scale representation and a luminance of 400 cd/m2.

  19. Summary of the National Toxicology Program's report of the endocrine disruptors low-dose peer review.

    PubMed Central

    Melnick, Ronald; Lucier, George; Wolfe, Mary; Hall, Roxanne; Stancel, George; Prins, Gail; Gallo, Michael; Reuhl, Kenneth; Ho, Shuk-Mei; Brown, Terry; Moore, John; Leakey, Julian; Haseman, Joseph; Kohn, Michael

    2002-01-01

    At the request of the U.S. Environmental Protection Agency (U.S. EPA), the National Toxicology Program organized an independent and open peer review to evaluate the scientific evidence on low-dose effects and nonmonotonic dose-response relationships for endocrine-disrupting chemicals in mammalian species. For this peer review, "low-dose effects" referred to biologic changes that occur in the range of human exposures or at doses lower than those typically used in the standard testing paradigm of the U.S. EPA for evaluating reproductive and developmental toxicity. The demonstration that an effect is adverse was not required because in many cases the long-term health consequences of altered endocrine function during development have not been fully characterized. A unique aspect of this peer review was the willing submission of individual animal data by principal investigators of primary research groups active in this field and the independent statistical reanalyses of selected parameters prior to the peer review meeting by a subpanel of statisticians. The expert peer-review panel (the panel) also considered mechanistic data that might influence the plausibility of low-dose effects and identified study design issues or other biologic factors that might account for differences in reported outcomes among studies. The panel found that low-dose effects, as defined for this review, have been demonstrated in laboratory animals exposed to certain endocrine-active agents. In some cases where low-dose effects have been reported, the findings have not been replicated. The shape of the dose-response curves for reported effects varied with the end point and dosing regimen and were low-dose linear, threshold-appearing, or nonmonotonic. The findings of the panel indicate that the current testing paradigm used for assessments of reproductive and developmental toxicity should be revisited to see whether changes are needed regarding dose selection, animal-model selection, age when

  20. Is nitrate an ecologically relevant endocrine disruptor in vertebrates?

    PubMed

    Guillette, Louis J; Edwards, Thea M

    2005-01-01

    The last three decades have brought clear recognition that many populations of animals are experiencing severe declines or local and global extinctions. Many examples have become common knowledge to the general public, such as worldwide declines in amphibian populations and extensive loss of coral reefs. The mechanisms underlying these and other changes are poorly understood. However, a growing literature indicates that a wide array of chemical contaminants have the potential to disrupt normal cell-to-cell signaling mechanisms. A global pollutant of most aquatic systems, nitrate has the potential to be an endocrine disrupting contaminant. This paper reviews studies performed on vertebrates demonstrating that nitrate and/or nitrite have the potential to alter endocrine function. Further, a retrospective study of our work on alligators from various lakes in Florida suggests that nitrate could contribute to some of the altered endocrine parameters previously reported in juvenile animals. We propose hypotheses suggesting that nitrate could alter steroidogenesis by 1) conversion to nitrite and nitric oxide in the mitochondria, the site of initial steroid synthesis, 2) altering Cl(-) ion concentrations in the cell by substituting for Cl(-) in the membrane transport pump or 3) binding to the heme region of various P450 enzymes associated with steroidogenesis and altering enzymatic action. Future studies are needed to examine the endocrine disruptive action of this ubiquitous pollutant. A growing literature indicates that all biologists studying natural systems, whether they choose to or not, must now consider contaminant exposure as a direct influence on their studies. That is, ubiquitous global contamination has the potential to alter the endocrine, nervous and immune systems of all organisms with resulting changes in gene expression and phenotypes.

  1. Toxicogenomics and ecotoxicogenomics for studying endocrine disruption and basic biology.

    PubMed

    Iguchi, Taisen; Watanabe, Hajime; Katsu, Yoshinao

    2007-01-01

    Chemicals released into the environment have the potential to disrupt the endocrine system in wild animals, mouse, and humans. To understand molecular mechanisms of chemical toxicity in various species, toxicogenomics/ecotoxicogenomics, describing the integration of genomics (trascriptomics, proteomics and metabolomics) into toxicology/ecotoxicology, needs to be established as a powerful tool for research. Ecotoxicogenomics is defined as the study of gene and protein expression in non-target organisms that is important in responses to environmental toxicant exposures. Estrogen-responsive genes and estrogen response element(s) in genes have been identified in the mouse reproductive tract by application of cDNA microarray technology. Additionally, functional mechanisms of tributyltin action via nuclear receptors such as retinoid X receptor alpha and peroxisome proliferator activated receptor gamma also have been identified using cDNA microarray. A microarray system has been established for Daphnia magna. Toxicogenomics/ecotoxicogenomics provide powerful tools to help us understand not only molecular mechanisms of chemical toxicity but also the basic biology of various animal species.

  2. Organized Activity Involvement among Rural Youth: Gender Differences in Associations between Activity Type and Developmental Outcomes

    ERIC Educational Resources Information Center

    Ferris, Kaitlyn A.; Oosterhoff, Benjamin; Metzger, Aaron

    2013-01-01

    The current study examined associations between organized activity involvement, academic achievement, and problem behavior in a sample of youth from a non-agricultural based rural community (M[subscript age] = 15.26, Age range = 11-19 years, N = 456). Analyses examined whether associations varied as a function of adolescent gender and age.…

  3. Actively Closing the Gap? Social Class, Organized Activities, and Academic Achievement in High School

    ERIC Educational Resources Information Center

    Morris, David S.

    2015-01-01

    Participation in Organized Activities (OA) is associated with positive behavioral and developmental outcomes in children. However, less is known about how particular aspects of participation affect the academic achievement of high school students from different social class positions. Using the Education Longitudinal Study of 2002, this study…

  4. Endocrine Disease in Aged Horses.

    PubMed

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented.

  5. Therapeutics for Equine Endocrine Disorders.

    PubMed

    Durham, Andy E

    2017-02-09

    Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency.

  6. Endocrine fibroblast growth factor FGF19 promotes prostate cancer progression.

    PubMed

    Feng, Shu; Dakhova, Olga; Creighton, Chad J; Ittmann, Michael

    2013-04-15

    Prostate cancer is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that fibroblast growth factor (FGF) receptors are important in prostate cancer initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21, and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require α-Klotho (KL) and/or β-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as coreceptors along with classic FGF receptors (FGFR) to mediate potent biologic activity. Here we show that FGF19 is expressed in primary and metastatic prostate cancer tissues, where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion, and colony formation of prostate cancer cells at low ligand concentrations. FGF19 silencing in prostate cancer cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in prostate cancer cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biologic effects in prostate cancer. Our findings support the concept that therapies targeting FGFR signaling may have efficacy in prostate cancer and highlight FGF19 as a relevant endocrine FGF in this setting.

  7. ENDOCRINE DISRUPTORS AS A THREAT TO NEUROLOGICAL FUNCTION

    PubMed Central

    Weiss, Bernard

    2011-01-01

    Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. PMID:21474148

  8. Endocrine disruptors as a threat to neurological function.

    PubMed

    Weiss, Bernard

    2011-06-15

    Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer.

  9. Modeling organic nitrogen conversions in activated sludge bioreactors.

    PubMed

    Makinia, Jacek; Pagilla, Krishna; Czerwionka, Krzysztof; Stensel, H David

    2011-01-01

    For biological nutrient removal (BNR) systems designed to maximize nitrogen removal, the effluent total nitrogen (TN) concentration may range from 2.0 to 4.0 g N/m(3) with about 25-50% in the form of organic nitrogen (ON). In this study, current approaches to modeling organic N conversions (separate processes vs. constant contents of organic fractions) were compared. A new conceptual model of ON conversions was developed and combined with Activated Sludge Model No. 2d (ASM2d). The model addresses a new insight into the processes of ammonification, biomass decay and hydrolysis of particulate and colloidal ON (PON and CON, respectively). Three major ON fractions incorporated are defined as dissolved (DON) (<0.1 µm), CON (0.1-1.2 µm) and PON (41.2 µm). Each major fraction was further divided into two sub-fractions - biodegradable and non-biodegradable. Experimental data were collected during field measurements and lab experiments conducted at the ''Wschod'' WWTP (570,000 PE) in Gdansk (Poland). The accurate steady-state predictions of DON and CON profiles were possible by varying ammonification and hydrolysis rates under different electron acceptor conditions. With the same model parameter set, the behaviors of both inorganic N forms (NH4-N, NOX-N) and ON forms (DON, CON) in the batch experiments were predicted. The challenges to accurately simulate and predict effluent ON levels from BNR systems are due to analytical methods of direct ON measurement (replacing TKN) and lack of large enough database (in-process measurements, dynamic variations of the ON concentrations) which can be used to determine parameter value ranges.

  10. Quantifying the Relationship between Organic Aerosol Composition and Hygroscopicity/CCN Activity

    SciTech Connect

    Ziemann, Paul J.; Kreidenweis, Sonia M.; Petters, Markus D.

    2013-06-30

    The overall objective for this project was to provide the data and underlying process level understanding necessary to facilitate the dynamic treatment of organic aerosol CCN activity in future climate models. The specific objectives were as follows: (1) employ novel approaches to link organic aerosol composition and CCN activity, (2) evaluate the effects of temperature and relative humidity on organic aerosol CCN activity, and (3) develop parameterizations to link organic aerosol composition and CCN activity.

  11. BRCA1 is a key regulator of breast differentiation through activation of Notch signalling with implications for anti-endocrine treatment of breast cancers

    PubMed Central

    Buckley, Niamh E.; Nic An tSaoir, Caoimhe B.; Blayney, Jaine K.; Oram, Lisa C.; Crawford, Nyree T.; D’Costa, Zenobia C.; Quinn, Jennifer E.; Kennedy, Richard D.; Harkin, D. Paul; Mullan, Paul B.

    2013-01-01

    Here, we show for the first time, that the familial breast/ovarian cancer susceptibility gene BRCA1 activates the Notch pathway in breast cells by transcriptional upregulation of Notch ligands and receptors in both normal and cancer cells. We demonstrate through chromatin immunoprecipitation assays that BRCA1 is localized to a conserved intronic enhancer region within the Notch ligand Jagged-1 (JAG1) gene, an event requiring ΔNp63. We propose that this BRCA1/ΔNp63-mediated induction of JAG1 may be important the regulation of breast stem/precursor cells, as knockdown of all three proteins resulted in increased tumoursphere growth and increased activity of stem cell markers such as Aldehyde Dehydrogenase 1 (ALDH1). Knockdown of Notch1 and JAG1 phenocopied BRCA1 knockdown resulting in the loss of Estrogen Receptor-α (ER-α) expression and other luminal markers. A Notch mimetic peptide could activate an ER-α promoter reporter in a BRCA1-dependent manner, whereas Notch inhibition using a γ-secretase inhibitor reversed this process. We demonstrate that inhibition of Notch signalling resulted in decreased sensitivity to the anti-estrogen drug Tamoxifen but increased expression of markers associated with basal-like breast cancer. Together, these findings suggest that BRCA1 transcriptional upregulation of Notch signalling is a key event in the normal differentiation process in breast tissue. PMID:23863842

  12. Passive drift or active swimming in marine organisms?

    PubMed Central

    Lumpkin, Rick; Sacco, Alexander E.; Mansfield, Katherine L.

    2016-01-01

    Predictions of organismal movements in a fluid require knowing the fluid's velocity and potential contributions of the organism's behaviour (e.g. swimming or flying). While theoretical aspects of this work are reasonably well-developed, field-based validation is challenging. A much-needed study recently published by Briscoe and colleagues in Proceedings of the Royal Society B compared movements and distribution of satellite-tracked juvenile sea turtles to virtual particles released in a data-assimilating hindcast ocean circulation model. Substantial differences observed between turtles and particles were considered evidence for an important role of active swimming by turtles. However, the experimental design implicitly assumed that transport predictions were insensitive to (i) start location, (ii) tracking duration, (iii) depth, and (iv) physical processes not depicted in the model. Here, we show that the magnitude of variation in physical parameters between turtles and virtual particles can profoundly alter transport predictions, potentially sufficient to explain the reported differences without evoking swimming behaviour. We present a more robust method to derive the environmental contributions to individual movements, but caution that resolving the ocean velocities experienced by individual organisms remains a problem for assessing the role of behaviour in organismal movements and population distributions. PMID:27974518

  13. Recent advances in organic thermally activated delayed fluorescence materials.

    PubMed

    Yang, Zhiyong; Mao, Zhu; Xie, Zongliang; Zhang, Yi; Liu, Siwei; Zhao, Juan; Xu, Jiarui; Chi, Zhenguo; Aldred, Matthew P

    2017-02-06

    Organic materials that exhibit thermally activated delayed fluorescence (TADF) are an attractive class of functional materials that have witnessed a booming development in recent years. Since Adachi et al. reported high-performance TADF-OLED devices in 2012, there have been many reports regarding the design and synthesis of new TADF luminogens, which have various molecular structures and are used for different applications. In this review, we summarize and discuss the latest progress concerning this rapidly developing research field, in which the majority of the reported TADF systems are discussed, along with their derived structure-property relationships, TADF mechanisms and applications. We hope that such a review provides a clear outlook of these novel functional materials for a broad range of scientists within different disciplinary areas and attracts more researchers to devote themselves to this interesting research field.

  14. Report on activities and attitudes of organizations active in the clinical practice guidelines field.

    PubMed Central

    Carter, A O; Battista, R N; Hodge, M J; Lewis, S; Basinski, A; Davis, D

    1995-01-01

    The organizing committee of a workshop on clinical practice guidelines (CPGs) surveyed invited organizations on their attitudes and activities related to five topics to be covered during the workshop sessions: organizational roles, priority setting, guidelines implementation, guidelines evaluation and development of a network of those active in the CPG field. Organizational roles: The national specialty societies were felt to have the largest role to play; the smallest roles were assigned to consumers, who were seen to have a role mainly in priority setting, and to industry and government, both of which were seen to have primarily a funding role. Many barriers to collaboration were identified, the solutions to all of which appeared to be better communication, establishment of common principles and clear role definitions. Priority setting: There was considerable agreement on the criteria that should be used to set priorities for CPG activities: the burden of disease on population health, the state of scientific knowledge, the cost of treatment and the economic burden of disease on society were seen as important factors, whereas the costs of guidelines development and practitioner interest in guidelines development were seen as less important. Organizations were unable to give much information on how they set priorities. Guidelines implementation: Most of the organizations surveyed did not actively try to ensure the implementation of guidelines, although a considerable minority devoted resources to implementation. The 38% of organizations that implemented guidelines actively listed a wide variety of activities, including training, use of local opinion leaders, information technology, local consensus processes and counter detailing. Guidelines evaluation: Formal evaluation of guidelines was undertaken by fewer than 13% of the responding organizations. All the evaluations incorporated assessments before and after guideline implementation, and some used primary patient

  15. Long-term change in the organization of inventive activity.

    PubMed

    Lamoreaux, N R; Sokoloff, K L

    1996-11-12

    Relying on a quantitative analysis of the patenting and assignment behavior of inventors, we highlight the evolution of institutions that encouraged trade in technology and a growing division of labor between those who invented new technologies and those who exploited them commercially over the nineteenth and early-twentieth centuries. At the heart of this change in the organization of inventive activity was a set of familiar developments which had significant consequences for the supply and demand of inventions. On the supply side, the growing complexity and capital intensity of technology raised the amount of human and physical capital required for effective invention, making it increasingly desirable for individuals involved in this activity to specialize. On the demand side, the growing competitiveness of product markets induced firms to purchase or otherwise obtain the rights to technologies developed by others. These increasing incentives to differentiate the task of invention from that of commercializing new technologies depended for their realization upon the development of markets and other types of organizational supports for trade in technology. The evidence suggests that the necessary institutions evolved first in those regions of the country where early patenting activity had already been concentrated. A self-reinforcing process whereby high rates of inventive activity encouraged the evolution of a market for technology, which in turn encouraged greater specialization and productivity at invention as individuals found it increasingly feasible to sell and license their discoveries, appears to have been operating. This market trade in technological information was an important contributor to the achievement of a high level of specialization at invention well before the rise of large-scale research laboratories in the twentieth century.

  16. Multiple endocrine neoplasia type I.

    PubMed

    Beukes, E; Dent, D M; De Villiers, J C; Miller, J L

    1985-08-17

    During the 13-year period 1970-1983 only 7 cases of multiple endocrine neoplasia type I (MEN I) were seen at Groote Schuur Hospital, suggesting that the associated gene is rare in this area. Only 1 of these patients was black. Endocrine associations were as follows: hyperparathyroidism--6 cases, pituitary hypersecretion--6 cases (3 each involving growth hormone and prolactin), and pancreatic hypersecretion--3 cases (2 of gastrinoma and 1 of insulinoma). The presenting features were predictably diverse and depended on the component which manifested first. There was little difficulty in reaching a diagnosis on routine investigation. All patients with hyperparathyroidism underwent a 3 1/2-gland parathyroidectomy as the first treatment procedure, normocalcaemia being achieved in 5 cases, but persistent hypercalcaemia in the 6th suggested a supernumerary gland. A pituitary adenoma was removed in 4 cases, but persistent prolactinaemia necessitated bromocriptine therapy in 3. Successful distal pancreatectomy was undertaken in a patient with insulinoma and a patient with gastrinoma, and a further patient with gastrinoma awaits surgery. The overall prognosis in cases of MEN I appears to depend on the most aggressive component, often the pancreatic lesion; our patients have run a surprisingly benign course with only 1 late death, from hypertensive heart disease.

  17. Phenyl-functionalized magnetic palm-based powdered activated carbon for the effective removal of selected pharmaceutical and endocrine-disruptive compounds.

    PubMed

    Wong, Kien Tiek; Yoon, Yeomin; Snyder, Shane A; Jang, Min

    2016-06-01

    Triethoxyphenylsilane (TEPS)-functionalized magnetic palm-based powdered activated carbon (MPPAC-TEPS) was prepared and characterized using various spectroscopic methods, and then tested for the removal of bisphenol A, carbamazepine, ibuprofen and clofibric acid. Magnetite film on MPPAC-TEPS was homogeneously coated on the outer surface of palm-based powdered activated carbon (PPAC) through a hydrothermal co-precipitation technique. Followed by silanization of phenyl-functionalized organosilane on MPPAC's magnetic film. As results, micro/mesopore surface area and volume increased without significant pore clogging and iron (Fe) dissolution under the acidic conditions was greatly decreased. The unique structural and chemical features of MPPAC-TEPS were found to be the main reasons for the enhanced adsorption rates and removal capacities of POPs. The presence of electrolytes and different pH values greatly affected the sorption efficiencies. The dominant sorption mechanism of POPs by MPPAC-TEPS was determined to be π-π interaction (physisorption), based on thermodynamic (ΔG°) and differential scanning calorimetry (DSC). Thermal regeneration at a low temperature (350 °C) was an effective method to desorb the retained POPs and enabled to reactivate MPPAC-TEPS with sustained sorption rates and capacities, whereas PPAC was largely exhausted. As a new type of sorbent for POPs, MPPAC-TEPS has operational advantages, such as magnetic separation and stable regeneration.

  18. Endocrine disruptors and female fertility: focus on (bovine) ovarian follicular physiology.

    PubMed

    Petro, E M L; Leroy, J L M R; Van Cruchten, S J M; Covaci, A; Jorssen, E P A; Bols, P E J

    2012-12-01

    Throughout the previous century, the production, use and, as a result, presence of chemicals in the environment increased enormously. Consequently, humans and animals are exposed to a wide variety of chemical substances of which some possess the ability to disrupt the endocrine system in the body, thereby denominated as "endocrine disrupting chemicals" (EDCs) or "endocrine disruptors". Because the reproductive system is a target organ for endocrine disruption, EDCs are postulated as one of the possible causes of human subfertility. Within the reproductive system, the ovarian follicle can be considered as an extremely fragile microenvironment where interactions between the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In this review, we explore how EDCs can interfere with the well-balanced conditions in the ovarian follicle. In addition, we highlight the bovine ovarian follicle as an alternative in vitro model for EDC and broader toxicology research.

  19. Diagnosis and pathology of endocrine diseases

    SciTech Connect

    Shriver, B.D.

    1988-01-01

    This book contains 22 papers under the headings of Diagnosis and Pathology of endocrine diseases. Topics covered include: Laboratory tests in the diagnosis and management of thyroid disorders, Pathology of thyroid diseases, Diagnosis of adrenourtical disease, Radiologic techniques in evaluating endocrine disorders; and the Pituitary and adrenal glands.

  20. Intestinal endocrine cells in radiation enteritis

    SciTech Connect

    Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E. )

    1989-08-01

    In this study, the intestinal endocrine cells were investigated in 13 surgical specimens affected by radiation enteritis. Endocrine cells were studied by means of Grimelius' silver staining and immunostaining for chromogranin, a general marker of endocrine cells. Positively stained cells were quantified by counting their number per unit length of muscularis mucosa. Results in radiation enteritis were compared with matched control specimens by using Student's t test. Chromogranin immunostaining showed a statistically significant increase of endocrine cells in radiation enteritis specimens compared with controls both in small and large intestine (ileum, 67.5 +/- 23.5 cells per unit length of muscularis mucosa in radiation enteritis versus 17.0 +/- 6.1 in controls; colon, 40.9 +/- 13.7 cells per unit length of muscularis mucosa in radiation enteritis versus 9.5 +/- 4.1 in controls--p less than 0.005 in both instances). Increase of endocrine cells was demonstrated also by Grimelius' staining; however, without reaching statistical significance. It is not clear whether or not the increase of endocrine cells in radiation enteritis reported in this study is caused by a hyperplastic response or by a sparing phenomenon. We should consider that increased endocrine cells, when abnormally secreting their products, may be involved in some of the clinical features of radiation enteropathy. In addition, as intestinal endocrine cells produce trophic substances to the intestine, their increase could be responsible for the raised risk of developing carcinoma of the intestine in long standing radiation enteritis.

  1. RESPONSE OF JAPANESE MEDAKA TO 17B-ESTRADIOL: A TIME COURSE OF ENDOCRINE-MEDIATED EFFECTS

    EPA Science Inventory

    Estrogenic compounds have been measured in the aquatic environment in concentrations subsequently found to affect reproduction and development in fish. Further investigations have described several endocrine-mediated events that indicate exposure of organisms to estrogens and/or ...

  2. Organizer activity of the polar cells during Drosophila oogenesis.

    PubMed

    Grammont, Muriel; Irvine, Kenneth D

    2002-11-01

    Patterning of the Drosophila egg requires the establishment of several distinct types of somatic follicle cells, as well as interactions between these follicle cells and the oocyte. The polar cells occupy the termini of the follicle and are specified by the activation of Notch. We have investigated their role in follicle patterning by creating clones of cells mutant for the Notch modulator fringe. This genetic ablation of polar cells results in cell fate defects within surrounding follicle cells. At the anterior, the border cells, the immediately adjacent follicle cell fate, are absent, as are the more distant stretched and centripetal follicle cells. Conversely, increasing the number of polar cells by expressing an activated form of the Notch receptor increases the number of border cells. At the posterior, elimination of polar cells results in abnormal oocyte localization. Moreover, when polar cells are mislocalized laterally, the surrounding follicle cells adopt a posterior fate, the oocyte is located adjacent to them, and the anteroposterior axis of the oocyte is re-oriented with respect to the ectopic polar cells. Our observations demonstrate that the polar cells act as an organizer that patterns surrounding follicle cells and establishes the anteroposterior axis of the oocyte. The origin of asymmetry during Drosophila development can thus be traced back to the specification of the polar cells during early oogenesis.

  3. [Endocrine consequences in young adult survivors of childhood cancer treatment].

    PubMed

    Leroy, C; Cortet-Rudelli, C; Desailloud, R

    2015-10-01

    Endocrine complications (particularly gonadal, hypothalamic-pituitary and metabolic) of childhood cancer treatments are common in young adults. Gonadal damage may be the result of chemotherapy or radiotherapy. Fertility preservation must be systematically proposed before initiation of gonadotoxic treatment if only the child is eligible. Hypothalamic-pituitary deficiency is common after brain or total-body irradiation, the somatotropic axis is the most sensitive to irradiation. Pituitary deficiency screening must be repeated since this endocrine consequence can occur many years after treatment. Hormone replacement must be prudent particularly in case of treatment with growth hormone or steroids. Metabolic syndrome, diabetes and cardiovascular damage resulting from cancer treatments contribute to the increase of morbidity and mortality in this population and should be screened routinely even if the patient is asymptomatic. The multidisciplinary management of these adults must be organized and the role of the endocrinologist is now well established.

  4. Gastroenteropancreatic (neuro)endocrine neoplasms: the histology report.

    PubMed

    Rindi, Guido; Bordi, C; La Rosa, S; Solcia, E; Delle Fave, Gianfranco

    2011-03-01

    Based on the year 2000 World Health Organization (WHO) classification and the European Neuroendocrine Tumor Society (ENETS) grading and staging proposals, we here define the minimal guidelines for pathology reporting of (neuro)endocrine neoplasms. The macroscopical description is recommended according to standard procedures and the microscopical description according to recognized architectural and cytological features for endocrine lesions. Minimal diagnostic immunohistochemistry entails the use of chromogranin A, synaptophysin and Ki67. Other potentially useful tests are those for CD56 N-CAM, PGP 9.5 and hormones for diagnosis, the somatostatin receptor subtype 2 for potential radiodiagnostics and therapy, and transcription factors like TTF1 and CDX2, for site of origin. Grading definition is always mandatory as well as TNM staging for surgical specimens.

  5. Food protection activities of the Pan American Health Organization.

    PubMed

    1994-03-01

    One of the most widespread health problems in the Caribbean and Latin America is contaminated food and foodborne illness. The Pan American Health Organization (PAHO) has been a major force in activities to strengthen food protection. The program within the regional Program of Technical Cooperation is administered by the Veterinary Public Health program and under the guidance of the Pan American Institute for Food protection and Zoonoses in Buenos Aires, Argentina. A food action plan for 1986-90 was established at the 1986 Pan American Sanitary Conference, and extended to cover 1991-95. Program activities during the 1990s covered cholera, epidemiologic surveillance, street food vendors, shellfish poisoning, meat, national programs, information systems, air catering, food irradiation, and tourism. The action plan for 1991-95 promoted greater political support and cooperation within and between related sectors and institutions, management, and education. The aims were to organize national integrated programs, to strengthen laboratory services, to strengthen inspection services, to establish epidemiologic surveillance systems, and to promote food protection through community participation. Program activities included the initiatives of the Veterinary Public Health Program in 1991 to distribute literature on the transmission of cholera by foods. Studies were conducted in Bolivia, Colombia, and Peru on food contamination. Microbiologists received training on standard methods for detecting Vibrio cholerae in foods. A working group of experts from 10 countries examined the issues and produced a guide for investigating the incidence of foodborne disease. PAHO has contributed to the formation of an Inter-American Network for Epidemiologic Surveillance of Foodborne Diseases. PAHO has worked to improve hygienic practices among street food vendors. Seminars on paralytic shellfish poisoning were conducted in 1990; the outcome was a network working to strengthen national

  6. The molecular classification of hereditary endocrine diseases.

    PubMed

    Ye, Lei; Ning, Guang

    2015-12-01

    Hereditary endocrine diseases are an important group of diseases with great heterogeneity. The current classification for hereditary endocrine disease is mostly based upon anatomy, which is helpful for pathophysiological interpretation, but does not address the pathogenic variability associated with different underlying genetic causes. Identification of an endocrinopathy-associated genetic alteration provides evidence for differential diagnosis, discovery of non-classical disease, and the potential for earlier diagnosis and targeted therapy. Molecular diagnosis should be routinely applied when managing patients with suspicion of hereditary disease. To enhance the accurate diagnosis and treatment of patients with hereditary endocrine diseases, we propose categorization of endocrine diseases into three groups based upon the function of the mutant gene: cell differentiation, hormone synthesis and action, and tumorigenesis. Each category was further grouped according to the specific gene function. We believe that this format would facilitate practice of precision medicine in the field of hereditary endocrine diseases.

  7. Regenerative response and endocrine disrupters in crinoid echinoderms: an old experimental model, a new ecotoxicological test.

    PubMed

    Candia Carnevali, M D

    2005-01-01

    The regenerative phenomena that reproduce developmental processes in adult organisms and are regulated by endocrine and neurohumoral mechanisms can provide new sensitive tests for monitoring the effects of exposure to anthropogenic chemicals such as endocrine disrupter (ED) contaminants. These pollutants in fact can be bioaccumulated by the organisms, causing dysfunctions in steroid hormone production/metabolism and activities and inducing dramatic effects on reproductive competence, development and growth in many animals, man included. Current research is exploring the effects of exposure to different classes of compounds well known for their ED activity, such as polychlorinated biphenyls (PCBs), nonylphenols and organotins, on regenerative potential of echinoderms, a relatively unexplored and promising applied approach which offers the unique chance to study physiological developmental processes in adult animals. The selected test species is the crinoid Antedon mediterranea, which represents a valuable experimental model for investigation into the regenerative process from the macroscopic to the molecular level. The present study employs an integrated approach which combines exposure experiments, chemical analysis and biological analysis utilizing classical methods of light (LM) and electron (TEM and SEM) microscopy and immunocytochemistry. The experiments were carried out on experimentally induced arm regenerations in controlled conditions with exposure concentrations comparable to those of moderately polluted coastal zones in order to reproduce common conditions of exposure to environmental contaminants. The results of the exposure tests were analysed in terms of effects at the whole organism, at the tissue and cellular level, and possible sites of action of EDs. Our results show that prolonged exposure to these compounds significantly affects the regenerative mechanisms by inducing appreciable anomalies in terms of regeneration times, overall growth, general

  8. DNA methylation of oestrogen-regulated enhancers defines endocrine sensitivity in breast cancer

    PubMed Central

    Stone, Andrew; Zotenko, Elena; Locke, Warwick J.; Korbie, Darren; Millar, Ewan K. A.; Pidsley, Ruth; Stirzaker, Clare; Graham, Peter; Trau, Matt; Musgrove, Elizabeth A.; Nicholson, Robert I.; Gee, Julia M. W.; Clark, Susan J.

    2015-01-01

    Expression of oestrogen receptor (ESR1) determines whether a breast cancer patient receives endocrine therapy, but does not guarantee patient response. The molecular factors that define endocrine response in ESR1-positive breast cancer patients remain poorly understood. Here we characterize the DNA methylome of endocrine sensitivity and demonstrate the potential impact of differential DNA methylation on endocrine response in breast cancer. We show that DNA hypermethylation occurs predominantly at oestrogen-responsive enhancers and is associated with reduced ESR1 binding and decreased gene expression of key regulators of ESR1 activity, thus providing a novel mechanism by which endocrine response is abated in ESR1-positive breast cancers. Conversely, we delineate that ESR1-responsive enhancer hypomethylation is critical in transition from normal mammary epithelial cells to endocrine-responsive ESR1-positive cancer. Cumulatively, these novel insights highlight the potential of ESR1-responsive enhancer methylation to both predict ESR1-positive disease and stratify ESR1-positive breast cancer patients as responders to endocrine therapy. PMID:26169690

  9. Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator.

    PubMed

    Kleszczyński, Konrad; Hardkop, Lena H; Fischer, Tobias W

    2011-01-01

    Melatonin or N-acetyl-5-methoxytryptamine, is a compound derived from tryptophan that is found in all organisms from single cells to vertebrates and the human. It is one of the most evolutionarily conserved and pleiotropic hormone still active in humans and has been implicated in vital skin functions such as hair growth, fur pigmentation as well as melanoma control. Being a main secretory product of the pineal gland, melatonin regulates seasonal biorhythms, reproductive mechanisms or mammary gland metabolism. Due to its wide range endocrine properties it is also recognized to modulate numerous additional functions ranging from scavenging free radicals, immunomodulation-mediated DNA repair, wound healing, involvement in gene expression connected with circadian clocks and modulation of secondary endocrine signaling including prolactin release. Recently, apart from above mentioned entities, it was shown that melatonin suppresses ultraviolet (UV)-induced damage in human skin and human derived cell lines (e.g., keratinocytes, fibroblasts). The magnitude of UV-induced damage is mediated apparently by various molecular mechanisms related to generation of reactive oxygen species (ROS), apoptosis and mitochondrial-mediated cell death which are all counteracted or modulated by melatonin. We provide here an update of the relevant protective effects and molecular mechanisms of action of melatonin in the skin.

  10. Esterification of vertebrate like steroids in molluscs: a target of endocrine disruptors?

    PubMed

    Giusti, Arnaud; Joaquim-Justo, Célia

    2013-11-01

    Alterations of the reproductive organs of gastropod molluscs exposed to pollutants have been reported in natural populations for more than 40 years. In some cases, these impacts have been linked to exposure to endocrine-disrupting chemicals (EDCs), which are known to induce adverse impacts on vertebrates, mainly by direct binding to steroid receptors or by altering hormone synthesis. Investigations on the mechanisms of action of endocrine disruptors in molluscs show that EDCs induce modifications of endogenous titres of androgens (e.g., testosterone, androstenedione) and oestrogens (e.g., 17ß-oestradiol). Alterations of the activity of enzymes related to steroid metabolism (i.e., cytochrome P-450 aromatase, acyltransferases) are also often observed. In bivalves and gastropods, fatty acid esterification of steroids might constitute the major regulation of androgen and oestrogen homeostasis. The present review indicates that metabolism of steroid hormones to fatty acid esters might be a target of synthetic EDCs. Alterations of this process would impact the concentrations of free, potentially bioactive, form of steroids.

  11. QSAR modeling and prediction of the endocrine-disrupting potencies of brominated flame retardants.

    PubMed

    Papa, Ester; Kovarich, Simona; Gramatica, Paola

    2010-05-17

    In the European Union REACH regulation, the chemicals with particularly harmful behaviors, such as endocrine disruptors (EDs), are subject to authorization, and the identification of safer alternatives to these chemicals is required. In this context, the use of quantitative structure-activity relationships (QSAR) becomes particularly useful to fill the data gap due to the very small number of experimental data available to characterize the environmental and toxicological profiles of new and emerging pollutants with ED behavior such as brominated flame retardants (BFRs). In this study, different QSAR models were developed on different responses of endocrine disruption measured for several BFRs. The multiple linear regression approach was applied to a variety of theoretical molecular descriptors, and the best models, which were identified from all of the possible combinations of the structural variables, were internally validated for their performance using the leave-one-out (Q(LOO)(2) = 73-91%) procedure and scrambling of the responses. External validation was provided, when possible, by splitting the data sets in training and test sets (range of Q(EXT)(2) = 76-90%), which confirmed the predictive ability of the proposed equations. These models, which were developed according to the principles defined by the Organization for Economic Co-operation and Development to improve the regulatory acceptance of QSARs, represent a simple tool for the screening and characterization of BFRs.

  12. Endocrine-related genes are altered by antibacterial agent triclosan in Chironomus riparius aquatic larvae.

    PubMed

    Martínez-Paz, Pedro; Morales, Mónica; Urien, Josune; Morcillo, Gloria; Martínez-Guitarte, José Luis

    2017-06-01

    Triclosan (TCS) is an antibacterial agent widely used in personal care and consumer products and commonly detected in aquatic ecosystems. In the present study, the effects of TCS on endocrine-related genes of Chironomus riparius aquatic larvae, a reference organism in aquatic toxicology, were evaluated. Twenty-four-hour in vivo exposures at 10µg/L, 100µg/L, and 1000µg/L TCS revealed that this xenobiotic was able to alter the transcriptional activity of ecdysone receptor gene (EcR), the ultraspiracle gene (usp), the estrogen-related receptor gene (ERR), and the E74 early ecdysone-inducible gene, as measured by real-time RT-PCR. Moreover, the hsp70 gene, a heat shock protein gene, was upregulated after exposure to TCS. The results of the present work provide the first evidence of the potential disruptive effects of TCS in endocrine-related genes suggesting a mode of action that mimics ecdysteroid hormones in insects.

  13. Early Life Exposure to Ractopamine Causes Endocrine-Disrupting Effects in Japanese Medaka (Oryzias latipes).

    PubMed

    Sun, Liwei; Wang, Sisi; Lin, Xia; Tan, Hana; Fu, Zhengwei

    2016-02-01

    β-Agonists, which are used as human pharmaceuticals or feed additives, have been detected in aquatic environments. β-Agonists have also been proposed for use in aquaculture. However, there are limited data available regarding the adverse effects of β-agonists in aquatic organisms. In this study, ractopamine was selected as the representative β-agonist, and medaka embryos were exposed at concentrations ranging from 5 to 625 μg/L for 44 days. In contrast to what has been found in mammals, ractopamine caused no growth response in medaka. However, the transcriptional changes of genes related to the hypothalamic-pituitary-gonadal (HPG) axis, especially in females, suggested that β-agonists may have the potential to disrupt the endocrine system. Moreover, genes involved in anti-oxidative activity or detoxification were affected in a gender-specific manner. These findings, particularly the effects on the endocrine system of fish, will advance our understanding of the ecotoxicity of β-agonists.

  14. Investigation of potential endocrine disrupting effects of mosquito larvicidal Bacillus thuringiensis israelensis (Bti) formulations.

    PubMed

    Maletz, Sibylle; Wollenweber, Marc; Kubiak, Katharina; Müller, Annett; Schmitz, Stefan; Maier, Dieter; Hecker, Markus; Hollert, Henner

    2015-12-01

    Bti is successfully used as a biological control agent for mosquito control. It has proven to be ecological friendly, and thus, is used in ecologically sensitive habitats. Recent investigations of groundwater in Germany have detected estrogenic activity in five consecutive groundwater wells in a region where Bti is applied. Therefore, it was suspected that this compound can act as an environmental xenoestrogen. In the present study, five Bti formulations as well as the active ingredient, VectoBac® TP (TP), were investigated regarding their estrogenic activity using the LYES and ER CALUX® assays. Furthermore, their steroidogenesis disruption properties were studied using the H295R Steroidogenesis Assay. Additionally, field samples from a Bti application area as well as samples from an artificial pond were examined. Three of the Bti formulations and the active ingredient TP showed significant estrogenic activity in the LYES (up to 52 ng·l(-1) estradiol equivalents (EEQ) in the 18-fold concentration) and/or the ER CALUX® (up to 1 ng·EEQ·l(-1) in the 18-fold concentration). In the H295R significant but weak effects with no dose-response-relationship on the production of estradiol, and 21-hydroxyprogesterone (WDG) as well as testosterone (TP) by H295R cells could be observed. The field samples as well as the samples from the artificial pond showed no significant increase of estrogenic activity after application of TP or WDG in the ER CALUX®. With the exception of the controlled laboratory experiments with direct application of Bti to the utilized in vitro test systems the present study did not reveal any significant effects of Bti on endocrine functions that would indicate that the application of Bti could cause adverse endocrine effects to organisms in aquatic ecosystems. Instead, our results support previous studies that the use of Bti products against mosquitos would be safe even for sensitive habitats such as conservation areas.

  15. A Multiplex Human Syndrome Implicates a Key Role for Intestinal Cell Kinase in Development of Central Nervous, Skeletal, and Endocrine Systems

    PubMed Central

    Lahiry, Piya; Wang, Jian; Robinson, John F.; Turowec, Jacob P.; Litchfield, David W.; Lanktree, Matthew B.; Gloor, Gregory B.; Puffenberger, Erik G.; Strauss, Kevin A.; Martens, Mildred B.; Ramsay, David A.; Rupar, C. Anthony; Siu, Victoria; Hegele, Robert A.

    2009-01-01

    Six infants in an Old Order Amish pedigree were observed to be affected with endocrine-cerebro-osteodysplasia (ECO). ECO is a previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems. Autozygosity mapping and sequencing identified a previously unknown missense mutation, R272Q, in ICK, encoding intestinal cell kinase (ICK). Our results established that R272 is conserved across species and among ethnicities, and three-dimensional analysis of the protein structure suggests protein instability due to the R272Q mutation. We also demonstrate that the R272Q mutant fails to localize at the nucleus and has diminished kinase activity. These findings suggest that ICK plays a key role in the development of multiple organ systems. PMID:19185282

  16. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of experience to improve screening and testing for endocrine active chemicals

    EPA Science Inventory

    Outline of the presentationEDCs – from 1991 to 1996 – Wingspread and Our Stolen Future 1996 – FQPA and SDWA mandates endocrine screening 1996-1998 – EDSTAC (the assays, debates over modes of action included) The final battery – EAT in vivo and in vit...

  17. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of experience to improve screening and testing for endocrine active chemicals.@@

    EPA Science Inventory

    In 1996 the Food Quality Protection and Safe Drinking Water Acts instructed the USEPA to determine “…whether the pesticide chemical may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine effects;"*...

  18. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of experience to improve screening and testing for endocrine active chemicals.

    EPA Science Inventory

    In 1996 the Food Quality Protection and Safe Drinking Water Acts instructed the USEPA to determine “…whether the pesticide chemical may have an effect in humans that is similar to an effect produced by a naturally occurring estrogen or other endocrine effects;"*...

  19. A Two-Tiered-Testing Decision Tree for Assays in the USEPA-EDSP Screening Battery: Using 15 years of Experience to Improve Screening and Testing for Endocrine Active Chemicals##

    EPA Science Inventory

    This product is a brief description of the oral presentation given by Dr LE Gray Jr at the meeting for the T4 workshop report-Lessons learned, challenges, ansd opportunities: The U.S. Endocrine Disruptor Scrrening Program published in the journal ALTEX, edited by the Swiss Societ...

  20. Endocrine disturbances in suprasellar germinomas.

    PubMed

    Buchfelder, M; Fahlbusch, R; Walther, M; Mann, K

    1989-03-01

    The authors have investigated hypothalamic-pituitary function in 8 patients (aged 9-27 years) with surgically and histologically proven suprasellar germinomas. Diabetes insipidus was found in 7 patients. All the patients had hypogonadism and hypocortisolism as judged by dynamic endocrine testing. Hypothyroidism was found in 6. Moreover, growth hormone secretion, as assessed by insulin-induced hypoglycemia, was defective in all patients. Comparison of results of insulin-induced hypoglycemia testing and stimulation tests by CRH and GHRH suggested that all patients had a primary suprahypophyseal lesion rather than a primary pituitary defect. The authors conclude that suprasellar germinomas, although uncommon, should be included in the differential diagnosis of juvenile suprasellar tumours and in cases suggestive of idiopathic diabetes insipidus, even if neuroradiological investigation fails to demonstrate a discrete tumour.

  1. Endocrine Consequences of Anorexia Nervosa

    PubMed Central

    Misra, Madhusmita; Klibanski, Anne

    2014-01-01

    Summary Anorexia nervosa (AN) is prevalent in adolescents and young a