Detection of endocrine active substances in the aquatic environment in southern Taiwan using bioassays and LC-MS/MS.

Science.gov (United States)

Chen, Kuang-Yu; Chou, Pei-Hsin

2016-06-01

Endocrine active substances, including naturally occurring hormones and various synthetic chemicals have received much concern owing to their endocrine disrupting potencies. It is essential to monitor their environmental occurrence since these compounds may pose potential threats to biota and human health. In this study, yeast-based reporter assays were carried out to investigate the presence of (anti-)androgenic, (anti-)estrogenic, and (anti-)thyroid compounds in the aquatic environment in southern Taiwan. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was also used to measure the environmental concentrations of selected endocrine active substances for assessing potential ecological risks and characterizing contributions to the endocrine disrupting activities. Bioassay results showed that anti-androgenic (ND-7489 μg L(-1) flutamide equivalent), estrogenic (ND-347 ng L(-1) 17β-estradiol equivalent), and anti-thyroid activities were detected in the dissolved and particulate phases of river water samples, while anti-estrogenic activities (ND-10 μg L(-1) 4-hydroxytamoxifen equivalent) were less often found. LC-MS/MS analysis revealed that anti-androgenic and estrogenic contaminants, such as bisphenol A, triclosan, and estrone were frequently detected in Taiwanese rivers. In addition, their risk quotient values were often higher than 1, suggesting that they may pose an ecological risk to the aquatic biota. Further identification of unknown anti-androgenic and estrogenic contaminants in Taiwanese rivers may be necessary to protect Taiwan's aquatic environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of a screening system for obesogenic compounds: screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect.

Directory of Open Access Journals (Sweden)

Anna Pereira-Fernandes

Full Text Available Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds, were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA. PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound.

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

Science.gov (United States)

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

2010-01-01

The U.S. Geological Survey, in cooperation with St. Cloud State University, Minnesota Department of Health, Minnesota Pollution Control Agency, Minnesota Department of Natural Resources, Metropolitan Council Environmental Services, and the University of Minnesota, has conducted field monitoring studies and laboratory research to determine the presence of endocrine active chemicals and the incidence of endocrine disruption in Minnesota streams and lakes during 1994–2008. Endocrine active chemicals are chemicals that interfere with the natural regulation of endocrine systems, and may mimic or block the function of natural hormones in fish or other organisms. This interference commonly is referred to as endocrine disruption. Indicators of endocrine disruption in fish include vitellogenin (female egg yolk protein normally expressed in female fish) in male fish, oocytes present in male fish testes, reduced reproductive success, and changes in reproductive behavior.

Use of nuclear receptor luciferase-based bioassays to detect endocrine active chemicals in a biosolids-biochar amended soil.

Science.gov (United States)

Anderson, Carolyn G; Joshi, Geetika; Bair, Daniel A; Oriol, Charlotte; He, Guochun; Parikh, Sanjai J; Denison, Michael S; Scow, Kate M

2017-08-01

Biosolids are a potentially valuable source of carbon and nutrients for agricultural soils; however, potential unintended impacts on human health and the environment must be considered. Virtually all biosolids contain trace amounts endocrine-disrupting chemicals derived from human use of pharmaceuticals and personal care products (PPCPs). One potential way to reduce the bioavailability of PPCPs is to co-apply biosolids with biochar to soil, because biochar's chemical (e.g., aromaticity) and physical properties (e.g., surface area) give it a high affinity to bind many organic chemicals in the environment. We developed a soil-specific extraction method and utilized a luciferase-based bioassay (CALUX) to detect endocrine active chemicals in a biosolids-biochar co-amendment soil greenhouse study. Both biochar (walnut shell, 900 °C) and biosolids had positive impacts on carrot and lettuce biomass accumulation over our study period. However, the walnut shell biochar stimulated aryl hydrocarbon receptor activity, suggesting the presence of potential endocrine active chemicals in the biochar. Since the biochar rate tested (100 t ha -1 ) is above the average agronomic rate (10-20 t ha -1 ), endocrine effects would not be expected in most environmental applications. The effect of high temperature biochars on endocrine system pathways must be explored further, using both quantitative analytical tools to identify potential endocrine active chemicals and highly sensitive bioanalytical assays such as CALUX to measure the resulting biological activity of such compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analytical Methodologies for the Determination of Endocrine Disrupting Compounds in Biological and Environmental Samples

Directory of Open Access Journals (Sweden)

Zoraida Sosa-Ferrera

2013-01-01

Full Text Available Endocrine-disruptor compounds (EDCs can mimic natural hormones and produce adverse effects in the endocrine functions by interacting with estrogen receptors. EDCs include both natural and synthetic chemicals, such as hormones, personal care products, surfactants, and flame retardants, among others. EDCs are characterised by their ubiquitous presence at trace-level concentrations and their wide diversity. Since the discovery of the adverse effects of these pollutants on wildlife and human health, analytical methods have been developed for their qualitative and quantitative determination. In particular, mass-based analytical methods show excellent sensitivity and precision for their quantification. This paper reviews recently published analytical methodologies for the sample preparation and for the determination of these compounds in different environmental and biological matrices by liquid chromatography coupled with mass spectrometry. The various sample preparation techniques are compared and discussed. In addition, recent developments and advances in this field are presented.

Occurrence and distribution of pharmaceutically active and endocrine disrupting compounds in Singapore's marine environment: Influence of hydrodynamics and physical–chemical properties

International Nuclear Information System (INIS)

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

2013-01-01

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 ( R ). Principal Components Analysis revealed a strong relationship between t R 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 t R , 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. Highlights: •A field study of emerging contaminants in Singapore's coastal marine environment was conducted. •PhACs such as gemfibrozil, triclosan, carbamazepine and ibuprofen were frequently detected. •Site proximity to WWTP had little influence on ambient concentrations. •Contaminant concentrations were highly correlated to hydrodynamic residence time. •Coastal hydrodynamic behaviour greatly influences contaminant exposure risks. -- A field study demonstrates the influence of hydrodynamic residence time and physical–chemical properties on exposure risks of PhACs and EDCs in coastal marine ecosystems

Fungal Laccases Degradation of Endocrine Disrupting Compounds

Directory of Open Access Journals (Sweden)

Gemma Macellaro

2014-01-01

Full Text Available Over the past decades, water pollution by trace organic compounds (ng/L has become one of the key environmental issues in developed countries. This is the case of the emerging contaminants called endocrine disrupting compounds (EDCs. EDCs are a new class of environmental pollutants able to mimic or antagonize the effects of endogenous hormones, and are recently drawing scientific and public attention. Their widespread presence in the environment solicits the need of their removal from the contaminated sites. One promising approach to face this challenge consists in the use of enzymatic systems able to react with these molecules. Among the possible enzymes, oxidative enzymes are attracting increasing attention because of their versatility, the possibility to produce them on large scale, and to modify their properties. In this study five different EDCs were treated with four different fungal laccases, also in the presence of both synthetic and natural mediators. Mediators significantly increased the efficiency of the enzymatic treatment, promoting the degradation of substrates recalcitrant to laccase oxidation. The laccase showing the best performances was chosen to further investigate its oxidative capabilities against micropollutant mixtures. Improvement of enzyme performances in nonylphenol degradation rate was achieved through immobilization on glass beads.

Multi-class of endocrine disrupting compounds in aquaculture ecosystems and health impacts in exposed biota.

Science.gov (United States)

Ismail, Nur Afifah Hanun; Wee, Sze Yee; Aris, Ahmad Zaharin

2017-12-01

Fishes are a major protein food source for humans, with a high economic value in the aquaculture industry. Because endocrine disrupting compounds (EDCs) have been introduced into aquatic ecosystems, the exposure of humans and animals that depend on aquatic foods, especially fishes, should be seriously considered. EDCs are emerging pollutants causing global concern because they can disrupt the endocrine system in aquatic organisms, mammals, and humans. These pollutants have been released into the environment through many sources, e.g., wastewater treatment plants, terrestrial run-off (industrial activities, pharmaceuticals, and household waste), and precipitation. The use of pharmaceuticals, pesticides, and fertilizers for maintaining and increasing fish health and growth also contributes to EDC pollution in the water body. Human and animal exposure to EDCs occurs via ingestion of contaminated matrices, especially aquatic foodstuffs. This paper aims to review human EDC exposure via fish consumption. In respect to the trace concentration of EDCs in fish, types of instrument and clean-up method are of great concerns. Copyright © 2017 Elsevier Ltd. All rights reserved.

Plasma biomarkers in juvenile marine fish provide evidence for endocrine modulation potential of organotin compounds.

Science.gov (United States)

Min, Byung Hwa; Kim, Bo-Mi; Kim, Moonkoo; Kang, Jung-Hoon; Jung, Jee-Hyun; Rhee, Jae-Sung

2018-08-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), have been widely used to control marine fouling. Here, we show that organotin stimulation reduces the hormone levels in the plasma of two economically important aquaculture fish. Blood plasma samples were collected from juvenile red seabream and black rockfish exposed to environmentally realistic concentrations of TBT and TPT for 14 days. The levels of two plasma biomarkers, namely the yolk protein precursor vitellogenin (VTG) and the sex steroid 17β-estradiol (E2), were measured to determine the endocrine disrupting potential of the organotin compounds. Both organotin compounds were dose-dependently accumulated in the blood of two fish. Exposure to waterborne TBT and TBT significantly decreased the plasma VTG levels in both the juvenile fish in a dose-dependent manner. In contrast, the treatment with E2, a well-known VTG inducer, significantly increased the plasma VTG levels in both the fish. In addition, the mRNA levels of vtg were also downregulated in the liver tissues of both the fish at 100 and/or 1000 ng L -1 of TBT or TPT exposure. The plasma E2 titers were significantly suppressed at 100 and/or 1000 ng L -1 of TBT or TPT exposure for 14 days compared to their titer in the control. Since estrogen directly regulates vtg gene expression and VTG synthesis, our results reveal the endocrine disrupting potential of organotin compounds, and subsequently the endocrine modulation at early stage of fish can trigger further fluctuations in sexual differentiation, maturation, sex ration or egg production. In addition, the results demonstrate their effects on non-target organisms, particularly on animals reared in aquaculture and fisheries. Copyright © 2018 Elsevier Inc. All rights reserved.

Tributyltin: Advancing the Science on Assessing Endocrine Disruption with an Unconventional Endocrine-Disrupting Compound.

Science.gov (United States)

Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ron; Guiney, Patrick D; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P

Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated-interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

Tributyltin: Advancing the science on assessing endocrine disruption with an unconventional endocrine-disrupting compound

Science.gov (United States)

Lagadic, Laurent; Katsiadaki, Ioanna; Biever, Ronald C.; Guiney, Patrick; Karouna-Renier, Natalie; Schwarz, Tamar; Meador, James P.

2018-01-01

Tributyltin (TBT) has been recognized as an endocrine disrupting chemical (EDC) for several decades. However, only in the last decade, was its primary endocrine mechanism of action (MeOA) elucidated—interactions with the nuclear retinoid-X receptor (RXR), peroxisome proliferator-activated receptor γ (PPARγ), and their heterodimers. This molecular initiating event (MIE) alters a range of reproductive, developmental, and metabolic pathways at the organism level. It is noteworthy that a variety of MeOAs have been proposed over the years for the observed endocrine-type effects of TBT; however, convincing data for the MIE was provided only recently and now several researchers have confirmed and refined the information on this MeOA. One of the most important lessons learned from years of research on TBT concerns apparent species sensitivity. Several aspects such as the rates of uptake and elimination, chemical potency, and metabolic capacity are all important for identifying the most sensitive species for a given chemical, including EDCs. For TBT, much of this was discovered by trial and error, hence important relationships and important sensitive taxa were not identified until several decades after its introduction to the environment. As recognized for many years, TBT-induced responses are known to occur at very low concentrations for molluscs, a fact that has more recently also been observed in fish species. This review explores the MeOA and effects of TBT in different species (aquatic molluscs and other invertebrates, fish, amphibians, birds, and mammals) according to the OECD Conceptual Framework for Endocrine Disruptor Testing and Assessment (CFEDTA). The information gathered on biological effects that are relevant for populations of aquatic animals was used to construct Species Sensitivity Distributions (SSDs) based on No Observed Effect Concentrations (NOECs) and Lowest Observed Effect Concentrations (LOECs). Fish appear at the lower end of these distributions

Identifying non-point sources of endocrine active compounds and their biological impacts in freshwater lakes

Science.gov (United States)

Baker, Beth H.; Martinovic-Weigelt, Dalma; Ferrey, Mark L.; Barber, Larry B.; Writer, Jeffrey H.; Rosenberry, Donald O.; Kiesling, Richard L.; Lundy, James R.; Schoenfuss, Heiko L.

2014-01-01

Contaminants of emerging concern, particularly endocrine active compounds (EACs), have been identified as a threat to aquatic wildlife. However, little is known about the impact of EACs on lakes through groundwater from onsite wastewater treatment systems (OWTS). This study aims to identify specific contributions of OWTS to Sullivan Lake, Minnesota, USA. Lake hydrology, water chemistry, caged bluegill sunfish (Lepomis macrochirus), and larval fathead minnow (Pimephales promelas) exposures were used to assess whether EACs entered the lake through OWTS inflow and the resultant biological impact on fish. Study areas included two OWTS-influenced near-shore sites with native bluegill spawning habitats and two in-lake control sites without nearby EAC sources. Caged bluegill sunfish were analyzed for plasma vitellogenin concentrations, organosomatic indices, and histological pathologies. Surface and porewater was collected from each site and analyzed for EACs. Porewater was also collected for laboratory exposure of larval fathead minnow, before analysis of predator escape performance and gene expression profiles. Chemical analysis showed EACs present at low concentrations at each study site, whereas discrete variations were reported between sites and between summer and fall samplings. Body condition index and liver vacuolization of sunfish were found to differ among study sites as did gene expression in exposed larval fathead minnows. Interestingly, biological exposure data and water chemistry did not match. Therefore, although results highlight the potential impacts of seepage from OWTS, further investigation of mixture effects and life history factor as well as chemical fate is warranted.

Development of a new adsorbent from agro-industrial waste and its potential use in endocrine disruptor compound removal.

Science.gov (United States)

Rovani, Suzimara; Censi, Monique T; Pedrotti, Sidnei L; Lima, Eder C; Cataluña, Renato; Fernandes, Andreia N

2014-04-30

A new activated carbon (AC) material was prepared by pyrolysis of a mixture of coffee grounds, eucalyptus sawdust, calcium hydroxide and soybean oil at 800°C. This material was used as adsorbent for the removal of the endocrine disruptor compounds 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from aqueous solutions. The carbon material was characterized by scanning electron microscopy (SEM), infrared spectroscopy (FTIR), N2 adsorption/desorption curves and point of zero charge (pHPZC). Variables including the initial pH of the adsorbate solutions, adsorbent masses and contact time were optimized. The optimum range of initial pH for removal of endocrine disruptor compounds (EDC) was 2.0-11.0. The kinetics of adsorption were investigated using general order, pseudo first-order and pseudo-second order kinetic models. The Sips isotherm model gave the best fits of the equilibrium data (298K). The maximum amounts of E2 and EE2 removed at 298K were 7.584 (E2) and 7.883mgg(-1) (EE2) using the AC as adsorbent. The carbon adsorbent was employed in SPE (solid phase extraction) of E2 and EE2 from aqueous solutions. Copyright © 2014 Elsevier B.V. All rights reserved.

Endocrine disrupting compounds exposure and testis development in mammals

Science.gov (United States)

Egbowona, Biola F.; Mustapha, Olajide A.

2011-01-01

In the last few decades, there is substantial evidence that male reproductive function is deteriorating in humans and wildlife and this is associated with unintentional exposure to widely used synthetic chemicals. Subsequently, much has been done to show that certain chemicals in the environment adversely interfere with the developing fetal gonads of the laboratory animals. Some in vitro studies have demonstrated treatment-induced reproductive problems in offspring exposed to endocrine disrupting compounds (EDC) which are similar to those observed in wildlife and human population. Few EDC studies have demonstrated that there are certain periods of gestation when the developing fetus is highly sensitive and at risk of small endocrine changes. Similar observations have been made in the sewage sludge model, however, while animal studies have been insightful in providing valuable information about the range of effects that can be attributed to in utero exposure to EDCs, varying levels of maternal doses administered in different studies exaggerated extrapolation of these results to human. Thus the EDC concentration representative of fetal exposure levels is uncertain because of the complexities of its nature. So far, the level of fetal exposure can only be roughly estimated. There is substantial evidence from animal data to prove that EDCs can adversely affect reproductive development and function in male and more has accumulated on the mechanisms by which they exert their effects. This paper therefore, reviews previous studies to highlight the extent to which testis development can be disrupted during fetal life. PMID:29255381

Occurrence and distribution of pharmaceutically active and endocrine disrupting compounds in Singapore's marine environment: Influence of hydrodynamics and physical–chemical properties

Energy Technology Data Exchange (ETDEWEB)

Bayen, Stéphane [Singapore-Delft Water Alliance, National University of Singapore (Singapore); Zhang, Hui [Department of Civil and Environmental Engineering, National University of Singapore (Singapore); Desai, Malan Manish [Tropical Marine Science Institute, National University of Singapore (Singapore); Ooi, Seng Keat [Singapore-Delft Water Alliance, National University of Singapore (Singapore); Kelly, Barry C., E-mail: bckelly@nus.edu.sg [Department of Civil and Environmental Engineering, National University of Singapore (Singapore)

2013-11-15

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 (t{sub R}). Principal Components Analysis revealed a strong relationship between t{sub R} 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 t{sub R}, 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. Highlights: •A field study of emerging contaminants in Singapore's coastal marine environment was conducted. •PhACs such as gemfibrozil, triclosan, carbamazepine and ibuprofen were frequently detected. •Site proximity to WWTP had little influence on ambient concentrations. •Contaminant concentrations were highly correlated to hydrodynamic residence time. •Coastal hydrodynamic behaviour greatly influences contaminant exposure risks. -- A field study demonstrates the influence of hydrodynamic residence time and physical–chemical properties on exposure risks of PhACs and EDCs in coastal marine ecosystems.

Endocrine disrupting compounds

DEFF Research Database (Denmark)

Bøgh, I B; Christensen, P; Dantzer, V

2001-01-01

of alkylphenols, these are disseminated in the environment with sewage sludge, and domestic animals and humans are likely to be exposed via the food chain. Using the pig as an in vivo model, we studied the effect of intrauterine exposure to tertiary octylphenol (OP) on essential reproductive parameters over 3......With the growing concern that environmental chemicals might impair human and animal fertility, it is important to investigate the possible influence of these substances on sexual differentiation and genital development of mammals. Many of these substances are suspected to interfere with endocrine...... processes, and exposure during critical periods of prenatal development might affect reproductive performance over several generations. Alkylphenols and their metabolites are lipophilic substances exerting apparent estrogenic action in in vitro and in vivo testing systems. With the widespread industrial use...

Bioanalytical characterisation of multiple endocrine- and dioxin-like activities in sediments from reference and impacted small rivers

Energy Technology Data Exchange (ETDEWEB)

Kinani, Said, E-mail: said@dcmr.polytechnique.f [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France); Departement de Chimie des Mecanismes Reactionnels, Ecole Polytechnique, 91128 Palaiseau Cedex (France); Bouchonnet, Stephane, E-mail: stephane.bouchonnet@dcmr.polytechnique.f [Departement de Chimie des Mecanismes Reactionnels, Ecole Polytechnique, 91128 Palaiseau Cedex (France); Creusot, Nicolas [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France); Bourcier, Sophie [Departement de Chimie des Mecanismes Reactionnels, Ecole Polytechnique, 91128 Palaiseau Cedex (France); Balaguer, Patrick [Institut National de la Sante et de la Recherche Medicale (INSERM), U896, Montpellier, F-34298 (France); Porcher, Jean-Marc [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France); Ait-Aissa, Selim, E-mail: selim.ait-aissa@ineris.f [Unite d' Ecotoxicologie, Institut National de l' Environnement Industriel et des Risques (INERIS), BP2, F-60550 Verneuil en Halatte (France)

2010-01-15

A comprehensive evaluation of organic contamination was performed in sediments sampled in two reference and three impacted small streams where endocrine disruptive (ED) effects in fish have been evidenced. The approach combined quantitative chemical analyses of more than 50 ED chemicals (EDCs) and a battery of in vitro bioassays allowing the quantification of receptor-mediated activities, namely estrogen (ER), androgen (AR), dioxin (AhR) and pregnane X (PXR) receptors. At the most impacted sites, chemical analyses showed the presence of natural estrogens, organochlorine pesticides, parabens, polycyclic aromatic hydrocarbons (16 PAHs), bisphenol A and alkylphenols, while synthetic steroids, myco-estrogens and phyto-estrogens were not detected. Determination of toxic-equivalent amounts showed that 28-96% of estrogenic activities in bioassays (0.2-6.3 ng/g 17beta-estradiol equivalents) were explained by 17beta-estradiol and estrone. PAHs were major contributors (20-60%) to the total dioxin-like activities. Interestingly, high PXR and (anti)AR activities were detected; however, the targeted analysed compounds could not explain the measured biological activities. This study highlighted the presence of multiple organic EDCs in French river sediments subjected to mixed diffuse pollution, and argues for the need to further identify AR and PXR active compounds in the aquatic environment. - Multiple endocrine disrupting chemicals (ER, AR, AhR and PXR ligands) are detected in French river sediments using a panel of in vitro bioassays and analytical methods.

Endocrine disruptors and asthma-associated chemicals in consumer products.

Science.gov (United States)

Dodson, Robin E; Nishioka, Marcia; Standley, Laurel J; Perovich, Laura J; Brody, Julia Green; Rudel, Ruthann A

2012-07-01

Laboratory and human studies raise concerns about endocrine disruption and asthma resulting from exposure to chemicals in consumer products. Limited labeling or testing information is available to evaluate products as exposure sources. We analytically quantified endocrine disruptors and asthma-related chemicals in a range of cosmetics, personal care products, cleaners, sunscreens, and vinyl products. We also evaluated whether product labels provide information that can be used to select products without these chemicals. We selected 213 commercial products representing 50 product types. We tested 42 composited samples of high-market-share products, and we tested 43 alternative products identified using criteria expected to minimize target compounds. Analytes included parabens, phthalates, bisphenol A (BPA), triclosan, ethanolamines, alkylphenols, fragrances, glycol ethers, cyclosiloxanes, and ultraviolet (UV) filters. We detected 55 compounds, indicating a wide range of exposures from common products. Vinyl products contained > 10% bis(2-ethylhexyl) phthalate (DEHP) and could be an important source of DEHP in homes. In other products, the highest concentrations and numbers of detects were in the fragranced products (e.g., perfume, air fresheners, and dryer sheets) and in sunscreens. Some products that did not contain the well-known endocrine-disrupting phthalates contained other less-studied phthalates (dicyclohexyl phthalate, diisononyl phthalate, and di-n-propyl phthalate; also endocrine-disrupting compounds), suggesting a substitution. Many detected chemicals were not listed on product labels. Common products contain complex mixtures of EDCs and asthma-related compounds. Toxicological studies of these mixtures are needed to understand their biological activity. Regarding epidemiology, our findings raise concern about potential confounding from co-occurring chemicals and misclassification due to variability in product composition. Consumers should be able to avoid

A critical review of histopathological findings associated with endocrine and non-endocrine hepatic toxicity in fish models.

Science.gov (United States)

Wolf, Jeffrey C; Wheeler, James R

2018-04-01

Although frequently examined as a target organ for non-endocrine toxicity, histopathological evaluation of the liver is becoming a routine component of endocrine disruption studies that utilize various fish species as test subjects. However, the interpretation of microscopic liver findings can be challenging, especially when attempting to distinguish adverse changes associated with endocrine disrupting substances from those caused by systemic or direct hepatic toxicity. The purpose of this project was to conduct a critical assessment of the available peer-reviewed and grey literature concerning the histopathologic effects of reproductive endocrine active substances (EAS) and non-endocrine acting substances in the livers of fish models, and to determine if liver histopathology can be used to reliably distinguish endocrine from non-endocrine etiologies. The results of this review suggest that few compound-specific histopathologic liver effects have been identified, among which are estrogen agonist-induced increases in hepatocyte basophilia and proteinaceous intravascular fluid in adult male teleosts, and potentially, decreased hepatocyte basophilia in female fish exposed to substances that possess androgenic, anti-estrogenic, or aromatase inhibitory activity. This review also used published standardized methodology to assess the credibility of the histopathology data in each of the 117 articles that reported liver effects of treatment, and consequently it was determined that in only 37% of those papers were the data considered either highly credible or credible. The outcome of this work highlights the value of histopathologic liver evaluation as an investigative tool for EAS studies, and provides information that may have implications for EAS hazard assessment. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

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

Science.gov (United States)

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

Endocrine Disrupting Chemicals and Disease Susceptibility

Science.gov (United States)

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

2011-01-01

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. PMID:21899826

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

Science.gov (United States)

Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

2014-01-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

Science.gov (United States)

Duffy, T A; Iwanowicz, L R; McCormick, S D

2014-07-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

Biodegradation of endocrine-disrupting compounds and suppresion of estrogenic activity by ligninolytic fungi

Czech Academy of Sciences Publication Activity Database

Cajthaml, Tomáš; Křesinová, Zdena; Svobodová, Kateřina; Moeder, M.

2009-01-01

Roč. 75, č. 6 (2009), s. 745-750 ISSN 0045-6535 R&D Projects: GA MŠk LC06066; GA MŠk 2B06156; GA AV ČR KJB600200613 Institutional research plan: CEZ:AV0Z50200510 Keywords : Biodegradation * Endocrine disrupters * White rot fungi Subject RIV: EE - Microbiology, Virology Impact factor: 3.253, year: 2009

Evaluation of Endocrine Disrupting Compounds Migration in Household Food Containers under Domestic Use Conditions.

Science.gov (United States)

Sáiz, Jorge; Gómara, Belén

2017-08-09

Plasticizers and plastic monomers are commonly used in packaging. Most of them act as endocrine disrupters and are susceptible to migrate from the packaging to the food. We evaluated the migration of endocrine disrupting compounds from three different household food containers to four food simulants under different domestic treatments and for different periods of time, with the aim of reproducing real domestic conditions. The results showed that the migration to the simulants increased with the storage time, up to more than 50 times in certain cases. The heating power seemed to increase the migration processes (up to more than 30 times), and reusing containers produced an increase or decrease of the concentrations depending on the container type and the simulant. The concentrations found were lower than other concentrations reported (always less than 4000 pg/mL, down to less than 20 pg/mL), which might be a consequence of the domestic conditions used.

Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin.

Science.gov (United States)

Sheikh, Ishfaq A; Beg, Mohd A

2017-12-01

Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Copyright © 2017 John Wiley & Sons, Ltd.

Early endocrine disruptors exposure acts on 3T3-L1 differentiation and endocrine activity

Directory of Open Access Journals (Sweden)

Sofiane Boudalia

2017-06-01

Conclusion: This study confirms that EDs singularly or in mixtures, introduced during early stages of life, could affect the differentiation and the endocrine activity of adipocytes, and can act as potential factors for obesity.

Passive sampling of selected endocrine disrupting compounds using polar organic chemical integrative samplers

International Nuclear Information System (INIS)

Arditsoglou, Anastasia; Voutsa, Dimitra

2008-01-01

Two types of polar organic chemical integrative samplers (pharmaceutical POCIS and pesticide POCIS) were examined for their sampling efficiency of selected endocrine disrupting compounds (EDCs). Laboratory-based calibration of POCISs was conducted by exposing them at high and low concentrations of 14 EDCs (4-alkyl-phenols, their ethoxylate oligomers, bisphenol A, selected estrogens and synthetic steroids) for different time periods. The kinetic studies showed an integrative uptake up to 28 days. The sampling rates for the individual compounds were obtained. The use of POCISs could result in an integrative approach to the quality status of the aquatic systems especially in the case of high variation of water concentrations of EDCs. The sampling efficiency of POCISs under various field conditions was assessed after their deployment in different aquatic environments. - Calibration and field performance of polar organic integrative samplers for monitoring EDCs in aquatic environments

Bioaccumulation of pharmaceutically active compounds and endocrine disrupting chemicals in aquatic macrophytes: Results of hydroponic experiments with Echinodorus horemanii and Eichhornia crassipes.

Science.gov (United States)

Pi, N; Ng, J Z; Kelly, B C

2017-12-01

Information regarding the bioaccumulation behaviour of pharmaceutically active compounds (PhACs) and endocrine disrupting chemicals (EDCs) in aquatic plants is limited. The present study involved controlled hydroponic experiments to assess uptake and elimination rate constants (k u , k e ), bioconcentration factors (BCFs) and translocation factors (TFs) of several PhACs and EDCs in two aquatic macrophyte species, including one submerged species (Echinodorus horemanii) and one free-floating species (Eichhornia crassipes). The results revealed that the studied compounds are readily taken up in these aquatic plants. While bioconcentration factors (BCFs) and translocation factors (TFs) of the test compounds varied substantially, no discernible relationship with physicochemical properties such as octanol-water distribution coefficient (D ow ), membrane-water distribution coefficient (D mw ) and organic carbon-water partition coefficient (K oc ). Diphenhydramine and triclosan exhibited the highest degree of uptake and bioaccumulation potential. For example, the whole-plant BCF of triclosan in E. horemanii was 4390L/kg, while the whole-plant BCF of diphenhydramine in E. crassipes was 6130L/kg. BCFs of 17β-estradiol (E2), 17α-ethinylestradiol (EE2), estrone (E1) and bisphenol A (BPA) were relatively low (2-150L/kg). BCFs were generally higher in free-floating aquatic macrophyte species compared to the submerged species. For the free-floating species, E. crassipes, the majority of PhACs and EDCs were more allocated in roots compared to leaves, with TFs1). The study findings may be useful for design and implementation of phytoremediation systems, as well as aid future modeling and risk assessment initiatives for these emerging organic contaminants. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of a new adsorbent from agro-industrial waste and its potential use in endocrine disruptor compound removal

International Nuclear Information System (INIS)

Rovani, Suzimara; Censi, Monique T.; Pedrotti, Sidnei L.; Lima, Éder C.; Cataluña, Renato; Fernandes, Andreia N.

2014-01-01

Highlights: • Development of a new adsorbent from agro-industrial waste. • Characterization by chemical and spectroscopic methods. • Alternative for the treatment of effluents that contain estrogens. • The AC adsorbent was successfully employed as solid phase adsorbent for the preconcentration of E2 and EE2 from aqueous solutions. - Abstract: A new activated carbon (AC) material was prepared by pyrolysis of a mixture of coffee grounds, eucalyptus sawdust, calcium hydroxide and soybean oil at 800 °C. This material was used as adsorbent for the removal of the endocrine disruptor compounds 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from aqueous solutions. The carbon material was characterized by scanning electron microscopy (SEM), infrared spectroscopy (FTIR), N 2 adsorption/desorption curves and point of zero charge (pH PZC ). Variables including the initial pH of the adsorbate solutions, adsorbent masses and contact time were optimized. The optimum range of initial pH for removal of endocrine disruptor compounds (EDC) was 2.0–11.0. The kinetics of adsorption were investigated using general order, pseudo first-order and pseudo-second order kinetic models. The Sips isotherm model gave the best fits of the equilibrium data (298 K). The maximum amounts of E2 and EE2 removed at 298 K were 7.584 (E2) and 7.883 mg g −1 (EE2) using the AC as adsorbent. The carbon adsorbent was employed in SPE (solid phase extraction) of E2 and EE2 from aqueous solutions

Development of a new adsorbent from agro-industrial waste and its potential use in endocrine disruptor compound removal

Energy Technology Data Exchange (ETDEWEB)

Rovani, Suzimara; Censi, Monique T.; Pedrotti, Sidnei L.; Lima, Éder C.; Cataluña, Renato; Fernandes, Andreia N., E-mail: andreia.fernandes@ufrgs.br

2014-04-01

Highlights: • Development of a new adsorbent from agro-industrial waste. • Characterization by chemical and spectroscopic methods. • Alternative for the treatment of effluents that contain estrogens. • The AC adsorbent was successfully employed as solid phase adsorbent for the preconcentration of E2 and EE2 from aqueous solutions. - Abstract: A new activated carbon (AC) material was prepared by pyrolysis of a mixture of coffee grounds, eucalyptus sawdust, calcium hydroxide and soybean oil at 800 °C. This material was used as adsorbent for the removal of the endocrine disruptor compounds 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from aqueous solutions. The carbon material was characterized by scanning electron microscopy (SEM), infrared spectroscopy (FTIR), N{sub 2} adsorption/desorption curves and point of zero charge (pH{sub PZC}). Variables including the initial pH of the adsorbate solutions, adsorbent masses and contact time were optimized. The optimum range of initial pH for removal of endocrine disruptor compounds (EDC) was 2.0–11.0. The kinetics of adsorption were investigated using general order, pseudo first-order and pseudo-second order kinetic models. The Sips isotherm model gave the best fits of the equilibrium data (298 K). The maximum amounts of E2 and EE2 removed at 298 K were 7.584 (E2) and 7.883 mg g{sup −1} (EE2) using the AC as adsorbent. The carbon adsorbent was employed in SPE (solid phase extraction) of E2 and EE2 from aqueous solutions.

Steroidogenesis in vitro : towards relevant models for endocrine disruptor screening

NARCIS (Netherlands)

Roelofs, M.J.E.

2016-01-01

Starting our search for in vitro alternative methods to screen for steroidogenesis toxicity, we focused on the effects of (suggested) endocrine disrupting compounds (EDCs) on cytochrome P450 17 (CYP17) enzyme activity. CYP17 is responsible for conversion of progestagens to dehydroepiandrosterone

Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review.

Science.gov (United States)

Giulivo, Monica; Lopez de Alda, Miren; Capri, Ettore; Barceló, Damià

2016-11-01

Endocrine disrupting chemicals (EDCs) are released into the environment from different sources. They are mainly used in packaging industries, pesticides and food constituents. Clinical evidence, experimental models, and epidemiological studies suggest that EDCs have major risks for humans by targeting different organs and systems in the body (e.g. reproductive system, breast tissue, adipose tissue, pancreas, etc.). Due to the ubiquity of human exposure to these compounds the aim of this review is to describe the most recent data on the effects induced by phthalates, bisphenol A and parabens in a critical window of exposure: in utero, during pregnancy, infants, and children. The interactions and mechanisms of toxicity of EDCs in relation to human general health problems, especially those broadening the term of endocrine disruption to 'metabolic disruption', should be deeply investigated. These include endocrine disturbances, with particular reference to reproductive problems and breast, testicular and ovarian cancers, and metabolic diseases such as obesity or diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Current Limitations and Recommendations to Improve Testing for the Environmental Assessment of Endocrine Active Substances

DEFF Research Database (Denmark)

Coady, Katherine K; Biever, Ronald C; Denslow, Nancy D

2017-01-01

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 geographies, but all basically...... evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or 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...... methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen and thyroid signaling. This article is protected by copyright. All rights reserved....

Methodical approaches to managing risks for endocrine diseases evolvement in children related to impacts of environmental factors occuring on areas aimed for development

Directory of Open Access Journals (Sweden)

K.P. Luzhetskiy

2017-06-01

Full Text Available It is vital to develop systems of preventing risk-associated pathology due to constantly high levels of endocrine diseases in children exposed to chemicals with trophic effects on endocrine system (lead, cadmium, manganese, chromium, nickel, benzene, phenol, formaldehyde, benzpyrene, chlorine-organic compounds, and nitrates. Applying risk management techniques is one of the most promising trends in prevention of diseases related to environmental impacts. We offer methodical approaches based on system combination of activities at various management levels aimed at improving risk-oriented model of surveillance and control. These approaches enable allowing for detected thropic risk factors in regional social-hygienic monitoring programs, implementing algorithms of case monitoring over exposed children population, and applying contemporary prevention technologies. Social-hygienic monitoring improvement at territorial level implies stricter control and more comprehensive lists of monitored components. This can be achieved by studying compounds which form risks for endocrine system, by working out scientific-methodological grounds for accounting chemical compounds which are trophic for endocrine system, as well as by refining volumes and contents of scheduled inspections performed at high risks objects together with laboratory examination of chemical compounds including those thropic for endocrine system. Local level includes algorithms and schemes of prevention activities aimed at early detection of endocrine disorders related to chemicals impacts. When we give grounds for personified technologies of endocrine diseases prevention (alimentary disorders, physical retardation and obesity related to impacts exerted by chemicals which are trophic for endocrine system we should remember that individual programs choice is based not only on their capacity to eliminate priority compounds determining total chemical load on a person faster but also on

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

International Nuclear Information System (INIS)

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.

1986-01-01

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 [ 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

Development of a fast liquid chromatography-tandem mass spectrometry method for the determination of endocrine-disrupting compounds in waters.

Science.gov (United States)

Di Carro, Marina; Scapolla, Carlo; Liscio, Camilla; Magi, Emanuele

2010-09-01

A fast liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS) method was developed to study five endocrine-disrupting compounds (4-n-nonylphenol, bisphenol A, estrone, 17β-estradiol and 17α-ethinylestradiol) in water. Different columns were tested; the chromatographic separation of the analytes was optimized on a Pinnacle DB biphenylic column with a water-acetonitrile gradient elution, which allowed the separation of the selected endocrine-disrupting compounds (EDCs) in less than 6 min. Quantitative analysis was performed in selected reaction monitoring (SRM) mode; two transitions were chosen for each compound, using the most abundant for quantitation. Calibration curves using bisphenol A-d (16) as internal standard were drawn, showing good correlation coefficients (0.9993-0.9998). All figures of merit of the method were satisfactory; limits of detection were in the low pg range for all analytes. The method was then applied to the determination of the analytes in real water samples: to this aim, polar organic chemical integrative samplers (POCIS) were deployed in the influent and in the effluent of a drinking water treatment plant in Liguria (Italy). The EDC level was rather low in the influent and negligible in the outlet, reflecting the expected function of the treatment plant.

Effect of Endocrine Disruptor Pesticides: A Review

Directory of Open Access Journals (Sweden)

Benoit Roig

2011-06-01

Full Text Available 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.

Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Martín, Julia; Santos, Juan Luis; Aparicio, Irene, E-mail: iaparicio@us.es; Alonso, Esteban

2016-11-16

In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g{sup −1} to 6.1 ng g{sup −1}, except for hexabromocyclododecane (36 ng g{sup −1}). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g{sup −1}) and parabens (100% of samples; concentrations up to 624 ng g{sup −1}). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g{sup −1}). Hexabromocyclododecane was not detected. - Highlights: • Method for biomonitoring of endocrine-disrupting compounds in human hair. • Target compounds are commonly present in everyday products. • Method based on hair digestion and liquid chromatography-tandem mass spectrometry. • Good sensitivity, recoveries and precision and low matrix effect were obtained. �

Analytical method for biomonitoring of endocrine-disrupting compounds (bisphenol A, parabens, perfluoroalkyl compounds and a brominated flame retardant) in human hair by liquid chromatography-tandem mass spectrometry

International Nuclear Information System (INIS)

Martín, Julia; Santos, Juan Luis; Aparicio, Irene; Alonso, Esteban

2016-01-01

In this paper, a method for the determination of four groups of endocrine-disrupting compounds in human hair is proposed. Target compounds were a plastic monomer (bisphenol A), three parabens commonly used as preservatives (methylparaben, ethylparaben and propylparaben), six perfluoroalkyl compounds commonly used as water, oil and dirt repellents (perfluorooctane sulfonic acid and five perfluoroalkyl carboxylic acids, with alkyl chains from four to eight carbon atoms) and a brominated flame retardant (hexabromocyclododecane). All of them are of especial concern to human health because they are utilized in many everyday products. The method is based on hair incubation with methanol/acetic acid solution (85:15, v/v), extraction with acetone for 15 min in an ultrasonic bath and analysis by liquid chromatography-electrospray-tandem mass spectrometry in negative ionization mode. Limits of quantification in hair samples ranged from 0.6 ng g"−"1 to 6.1 ng g"−"1, except for hexabromocyclododecane (36 ng g"−"1). Recoveries were higher than 69%. Intra-day and inter-day precision, expressed as relative standard deviation, were lower than 15% and 10%, respectively. The applicability of the method was proven by analyzing the target compounds in hair samples from six volunteers. High frequencies of detection and concentrations were obtained for bisphenol A (83% of samples; concentrations up to 158 ng g"−"1) and parabens (100% of samples; concentrations up to 624 ng g"−"1). Lower concentrations were detected for the perfluoroalkyl compounds (up to 13 ng g"−"1). Hexabromocyclododecane was not detected. - Highlights: • Method for biomonitoring of endocrine-disrupting compounds in human hair. • Target compounds are commonly present in everyday products. • Method based on hair digestion and liquid chromatography-tandem mass spectrometry. • Good sensitivity, recoveries and precision and low matrix effect were obtained. • Method was successfully

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

Science.gov (United States)

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.

2017-01-01

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

Review of Bioassays for Monitoring Fate and Transport ofEstrogenic Endocrine Disrupting Compounds in Water

Energy Technology Data Exchange (ETDEWEB)

CGCampbell@lbl.gov

2004-01-30

Endocrine disrupting compounds (EDCs) are recognizedcontaminants threatening water quality. Despite efforts in sourceidentification, few strategies exist for characterization or treatment ofthis environmental pollution. Given that there are numerous EDCs that cannegatively affect humans and wildlife, general screening techniques likebioassays and biosensors provide an essential rapid and intensiveanalysis capacity. Commonly applied bioassays include the ELISA and YESassays, but promising technologies include ER-CALUXa, ELRA, Endotecta,RIANA, and IR-bioamplification. Two biosensors, Endotecta and RIANA, arefield portable using non-cellular biological detection strategies.Environmental management of EDCs in water requires integration ofbiosensors and bioassays for monitoring and assessment.

Application of biotests for the characterization of exposure pathways for endocrine disrupters from plastics; Anwendung von Biotests zur Charakterisierung der Expositionspfade fuer Umwelthormone aus Kunststoffen

Energy Technology Data Exchange (ETDEWEB)

Wagner, Martin; Oehlmann, Joerg [Frankfurt Univ., Frankfurt am Main (Germany). Abteilung Aquatische Oekotoxikologie

2011-12-15

The present project aims to characterise the exposure pathways for endocrine disruptors from plastic materials. A bioassay-based approach was employed to investigate and characterise the endocrine activity. Migration studies with food packaging and plastic preforms document the leaching of estrogen-like compounds from several types of plastic in the Yeast Estrogen Screen and the E-Screen. Additionally, anti-estrogenic activity was predominant in many samples. The detection of complex migration profiles provides evidence for the leaching of several, diverse-acting endocrine disruptors. Moreover, extracts of plastic food packaging exhibited agonistic activity on the estrogen receptor, retinoid X receptor, and vitamin D receptor. A theoretical exposure assessment for marine molluscs implies that endocrine disruptors from plastic might induce relevant effect in the environment. Within the exemplary investigation of bottled mineral water, 60% of the products were characterised as significantly estrogenic using the YES and E-Screen. These in vitro data point to the plastic packaging being one source of estrogenic contamination. An in vivo study employing the estrogen-sensitive model organism Potamopyrgus antipodarum supports this hypothesis. By using several analytical techniques (GC-MS, LC-MS/MS) we identified several well-known endocrine disruptors in bottled water and the plastic material, e.g. numerous phthalates and phenols. Moreover, potent antagonists of the estrogen and androgen receptor were extracted from bottled water. In a non-target analysis (Orbitrap-MS) a compound with the exact mass of 363.1992 [M+H{sup +}] correlated highly significantly with the biological activity. On the basis of the methods optimised and applied within the project we elaborated a set of aspects that are crucial for the applicability of bioassays to characterise the endocrine activity of complex samples. Employing a bioassay-based approach we provide evidence for the presence and

Identification of Endocrine Disruptive Effects in the Aquatic Environment - a Partial Life Cycle Study in Zebrafish

NARCIS (Netherlands)

Wester PW; Brandhof EJ van den; Vos JH; Ven LTM van der; TOX; LER

2003-01-01

In this project, an assay was developed and applied to identify hormone active substances in the aquatic environment. Laboratory fish were exposed during the reproductive and development phase to a range of established endocrine active compounds; these were estrogen (17 beta-estradiol),

Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.

Science.gov (United States)

Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

2016-01-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause masculinization in female mollusks. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30-100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2. These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intergenerational effects of endocrine-disrupting compounds: a review of the Michigan polybrominated biphenyl registry.

Science.gov (United States)

Curtis, Sarah W; Conneely, Karen N; Marder, Mary E; Terrell, Metrecia L; Marcus, Michele; Smith, Alicia K

2018-06-11

Endocrine-disrupting compounds (EDCs) are a broad class of chemicals present in many residential products that can disrupt hormone signaling and cause health problems in humans. Multigenerational cohorts, like the Michigan polybrominated biphenyl registry, are ideal for studying the effects of intergenerational exposure. Registry participants report hormone-related health problems, particularly in those exposed before puberty or those in the second generation exposed through placental transfer or breastfeeding. However, more research is needed to determine how EDCs cause health problems and the mechanisms underlying intergenerational exposure. Utilizing existing data in this registry, along with genetic and epigenetic approaches, could provide insight to how EDCs cause human disease and help to determine the risk to exposed populations and future generations.

Rapid, portable detection of endocrine disrupting chemicals through ligand-nuclear hormone receptor interactions.

Science.gov (United States)

Hunt, J Porter; Schinn, Song-Min; Jones, Matthew D; Bundy, Bradley C

2017-12-04

Endocrine disrupting chemicals (EDC) are structurally diverse compounds that can interact with nuclear hormone receptors, posing significant risk to human and ecological health. Unfortunately, many conventional biosensors have been too structure-specific, labor-intensive or laboratory-oriented to detect broad ranges of EDC effectively. Recently, several technological advances are providing more rapid, portable, and affordable detection of endocrine-disrupting activity through ligand-nuclear hormone receptor interactions. Here, we overview these recent advances applied to EDC biosensors - including cell lyophilization, cell immobilization, cell-free systems, smartphone-based signal detection, and improved competitive binding assays.

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

DEFF Research Database (Denmark)

Taxvig, Camilla; Hadrup, Niels; Boberg, Julie

2013-01-01

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......, 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...

Consensus models to predict endocrine disruption for all ...

Science.gov (United States)

Humans are potentially exposed to tens of thousands of man-made chemicals in the environment. It is well known that some environmental chemicals mimic natural hormones and thus have the potential to be endocrine disruptors. Most of these environmental chemicals have never been tested for their ability to disrupt the endocrine system, in particular, their ability to interact with the estrogen receptor. EPA needs tools to prioritize thousands of chemicals, for instance in the Endocrine Disruptor Screening Program (EDSP). Collaborative Estrogen Receptor Activity Prediction Project (CERAPP) was intended to be a demonstration of the use of predictive computational models on HTS data including ToxCast and Tox21 assays to prioritize a large chemical universe of 32464 unique structures for one specific molecular target – the estrogen receptor. CERAPP combined multiple computational models for prediction of estrogen receptor activity, and used the predicted results to build a unique consensus model. Models were developed in collaboration between 17 groups in the U.S. and Europe and applied to predict the common set of chemicals. Structure-based techniques such as docking and several QSAR modeling approaches were employed, mostly using a common training set of 1677 compounds provided by U.S. EPA, to build a total of 42 classification models and 8 regression models for binding, agonist and antagonist activity. All predictions were evaluated on ToxCast data and on an exte

Are endocrine disrupting compounds environmental risk factors for autism spectrum disorder?

Science.gov (United States)

Moosa, Amer; Shu, Henry; Sarachana, Tewarit; Hu, Valerie W

2017-10-23

Recent research on the etiology of autism spectrum disorder (ASD) has shifted in part from a singular focus on genetic causes to the involvement of environmental factors and their gene interactions. This shift in focus is a result of the rapidly increasing prevalence of ASD coupled with the incomplete penetrance of this disorder in monozygotic twins. One such area of environmentally focused research is the association of exposures to endocrine disrupting compounds (EDCs) with elevated risk for ASD. EDCs are exogenous chemicals that can alter endogenous hormone activity and homeostasis, thus potentially disrupting the action of sex and other natural hormones at all stages of human development. Inasmuch as sex hormones play a fundamental role in brain development and sexual differentiation, exposure to EDCs in utero during critical stages of development can have lasting neurological and other physiological influences on the developing fetus and, ultimately, the child as well as adult. This review will focus on the possible contributions of EDCs to autism risk and pathogenesis by first discussing the influence of endogenous sex hormones on the autistic phenotype, followed by a review of documented human exposures to EDCs and associations with behaviors relevant to ASD. Mechanistic links between EDC exposures and aberrant neurodevelopment and behaviors are then considered, with emphasis on EDC-induced transcriptional profiles derived from animal and cellular studies. Finally, this review will discuss possible mechanisms through which EDC exposure can lead to persistent changes in gene expression and phenotype, which may in turn contribute to transgenerational inheritance of ASD. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistent organochlorine pollutants with endocrine activity and blood steroid hormone levels in middle-aged men.

Directory of Open Access Journals (Sweden)

Elise Emeville

Full Text Available 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

Endocrine potency of wastewater: Contents of endocrine disrupting chemicals and effects measured by in vivo and in vitro assays

DEFF Research Database (Denmark)

Kusk, Kresten Ole; Krüger, Tanja; Long, Manhai

2011-01-01

chemical analysis and a battery of bioassays. Influent samples, collected at the first STP grate, and effluent samples, collected after the sewage treatment, were extracted using solid phase extraction. Extracts were analyzed for the content of a range of industrial chemicals with endocrine disrupting...... properties: phthalate metabolites, parabens, industrial phenols, ultraviolet screens, and natural and synthetic steroid estrogens. The endocrine disrupting bioactivity and toxicity of the extracts were analyzed in cell culture assay for the potency to affect the function of the estrogen, androgen, aryl......Industrial and municipal effluents are important sources of endocrine disrupting compounds (EDCs) discharged into the aquatic environment. This study investigated the endocrine potency of wastewater and the cleaning efficiency of two typical urban Danish sewage treatment plants (STPs), using...

Pentachlorophenol-Induced Cytotoxic, Mitogenic, and Endocrine-Disrupting Activities in Channel Catfish, Ictalurus punctatus

Directory of Open Access Journals (Sweden)

Paul B. Tchounwou

2004-09-01

Full Text Available Pentachlorophenol (PCP is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Although it has been shown to induce systemic toxicity and carcinogenesis in several experimental studies, the literature is scarce regarding its toxic mechanisms of action at the cellular and molecular levels. Recent investigations in our laboratory have shown that PCP induces cytotoxicity and transcriptionally activates stress genes in human liver carcinoma (HepG2 cells [1]. In this research, we hypothesize that environmental exposure to PCP may trigger cytotoxic, mitogenic, and endocrine-disrupting activities in aquatic organisms including fish. To test this hypothesis, we carried out in vitro cultures of male channel catfish hepatocytes, and performed the fluorescein diacetate assay (FDA to assess for cell viability, and the Western Blot analysis to assess for vitellogenin expression following exposure to PCP. Data obtained from FDA experiments indicated a strong dose-response relationship with respect to PCP cytotoxicity. Upon 48 hrs of exposure, the chemical dose required to cause 50% reduction in cell viability (LD50 was computed to be 1,987.0 + 9.6 μg PCP/mL. The NOAEL and LOAEL were 62.5 + 10.3 μg PCP/mL and 125.0+15.2 μg PCP/mL, respectively. At lower levels of exposure, PCP was found to be mitogenic, showing a strong dose- and time-dependent response with regard to cell proliferation. Western Blot analysis demonstrated the potential of PCP to cause endocrine-disrupting activity, as evidenced by the up regulation of the 125-kDa vitellogenin protein the hepatocytes of male channel catfish.

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

Science.gov (United States)

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

Mugilid Fish Are Sentinels of Exposure to Endocrine Disrupting Compounds in Coastal and Estuarine Environments

Directory of Open Access Journals (Sweden)

Maren Ortiz-Zarragoitia

2014-09-01

Full Text Available Effects on fish reproduction can result from a variety of toxicity mechanisms first operating at the molecular level. Notably, the presence in the environment of some compounds termed endocrine disrupting chemicals (EDCs can cause adverse effects on reproduction by interfering with the endocrine system. In some cases, exposure to EDCs leads to the animal feminization and male fish may develop oocytes in testis (intersex condition. Mugilid fish are well suited sentinel organisms to study the effects of reproductive EDCs in the monitoring of estuarine/marine environments. Up-regulation of aromatases and vitellogenins in males and juveniles and the presence of intersex individuals have been described in a wide array of mullet species worldwide. There is a need to develop new molecular markers to identify early feminization responses and intersex condition in fish populations, studying mechanisms that regulate gonad differentiation under exposure to xenoestrogens. Interestingly, an electrophoresis of gonad RNA, shows a strong expression of 5S rRNA in oocytes, indicating the potential of 5S rRNA and its regulating proteins to become useful molecular makers of oocyte presence in testis. Therefore, the use of these oocyte markers to sex and identify intersex mullets could constitute powerful molecular biomarkers to assess xenoestrogenicity in field conditions.

Compounds in food packaging materials - toxicological profiling of knowns and unknowns

DEFF Research Database (Denmark)

Rosenmai, Anna Kjerstine

compounds present in these materials. Specific focus was placed on in vitroendpoints assessing endocrine activity. BPA, five BPA analogues, and 19 fluorinated substances including fluorochemical containing technical mixtures (TMs) were investigated. The in vitro assays included the androgen receptor (AR....... It is recommended to test more FCMs of paper and board with the strategy to obtain information on other potentially problematic compounds present in these materials. The presented data overall suggest that some compounds present in FCMs or suspected of being used can exert endocrine activities in vitro, though......Food contact materials (FCMs) are sources of food contamination and human chemical exposure. Some chemicals in these materials are known to cause adverse effects, but many are poorly characterized for their potential toxicological hazards making risk assessment a challenge. The aim of the project...

Polymer-immobilized ready-to-use recombinant yeast assays for the detection of endocrine disruptive compounds.

Science.gov (United States)

Bittner, Michal; Jarque, Sergio; Hilscherová, Klára

2015-08-01

Recombinant yeast assays (RYAs) constitute a suitable tool for the environmental monitoring of compounds with endocrine disrupting activities, notably estrogenicity and androgenicity. Conventional procedures require yeast reconstitution from frozen stock, which usually takes several days and demands additional equipment. With the aim of applying such assays to field studies and making them more accessible to less well-equipped laboratories, we have optimized RYA by the immobilization of Saccharomyces cerevisiae cells in three different polymer matrices - gelatin, Bacto agar, and Yeast Extract Peptone Dextrose agar - to obtain a ready-to-use version for the fast assessment of estrogenic and androgenic potencies of compounds and environmental samples. Among the three matrices, gelatin showed the best results for both testosterone (androgen receptor yeast strain; AR-RYA) and 17β-estradiol (estrogen receptor yeast strain; ER-RYA). AR-RYA was characterized by a lowest observed effect concentration (LOEC), EC50 and induction factor (IF) of 1nM, 2.2nM and 51, respectively. The values characterizing ER-RYA were 0.4nM, 1.8nM, and 63, respectively. Gelatin immobilization retained yeast viability and sensitivity for more than 90d of storage at 4°C. The use of the immobilized yeast reduced the assay duration to only 3h without necessity of sterile conditions. Because immobilized RYA can be performed either in multiwell microplates or glass tubes, it allows multiple samples to be tested at once, and easy adaptation to existing portable devices for direct in-field applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Putative effects of endocrine disrupters on pubertal development in the human

DEFF Research Database (Denmark)

Teilmann, Grete; Juul, Anders; Skakkebaek, Niels E

2002-01-01

-called endocrine disrupters. Precocious puberty has been described in several case reports of accidental exposure to oestrogenic compounds in cosmetic products, food and pharmaceuticals. Local epidemics of premature thelarche have also been suggested to be linked to endocrine disrupters. Children adopted from...... developing countries to industrialized countries often develop precocious puberty. Not only precocious puberty, but also delayed puberty can, theoretically, be associated with exposure to endocrine disrupters. While it is very plausible that endocrine disrupters may disturb pubertal development...

Overview of the Pathophysiological Implications of Organotins on the Endocrine System.

Science.gov (United States)

Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

2018-01-01

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic-pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

What Is Men's Endocrine Health?

Science.gov (United States)

... Search form Search What is Men's Endocrine Health? Men's endocrine health incorporates physical activity and sound nutrition to maintain a strong body; however, a major emphasis includes male sexuality ...

Late effects of early exposures to endocrine disrupting chemicals in rats

DEFF Research Database (Denmark)

Boberg, Julie; Hass, Ulla

2017-01-01

Endocrine disrupting compounds may interfere with tissues at critical developmental stages and give rise to cancer later in life. This talk will focus on early-life exposure to endocrine disrupting chemicals which is associated with increased risk for carcinogenesis in mammary and prostate glands...

In silico tools to aid risk assessment of endocrine disrupting chemicals

International Nuclear Information System (INIS)

Jacobs, M.N.

2004-01-01

In silico or computational tools could be used more effectively in endocrine disruptor risk assessment for prescreening potential endocrine disruptors, improving experimental in vitro screening assay design and facilitating more thorough data analyses. The in silico tools reviewed here are three-fold and include the use of: (1) nuclear receptor (NR) crystal structures and homology models to examine potential modes of ligand binding by different representative compounds; (2) multivariate principal component analyses (PCA) techniques to select best predicted cell lines for endocrine disrupting chemicals (EDC) risk assessment purposes; (3) NR quantitative structure-activity relationships (QSARs) that can be constructed from varied biological data sources, using multivariate partial least squares (PLS) techniques and specific descriptors. The cytosolic and NR examples discussed here include the Ah receptor (AhR), the human oestrogen receptor α (hERα) and the human pregnane X receptor (PXR). The varied biological data sets can be compared to give a more integrated dimension to receptor cross talk mechanisms, with further support from molecular modelling studies

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

Science.gov (United States)

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

2018-02-01

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

Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

DEFF Research Database (Denmark)

Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

2011-01-01

Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades....

SPE-HPLC purification of endocrine disrupting compounds from human serum for assessment of xenoestrogenic activity

DEFF Research Database (Denmark)

Hjelmborg, P.S.; Ghisari, Mandana; Bonefeld-Jørgensen, Eva

2006-01-01

Assessment of xenoestrogenic activity in human serum samples requires the removal of endogenous sex hormones to assure that the activity measured originates from xenobiotic compounds only. Serum samples representing high, medium and lower accumulation of persistent organic pollutants (POPs) were...... measured by ERE-CALUX was validated and considered to be a valuable tool to assess the combined ER effect of lipophilic serum POPs where additive/synergistic and agonistic/antagonistic effects are integrated giving an overall estimate of exposure and bioactivity....... for the study. MVLN cells, stably transfected with an estrogen receptor (ER) luciferase reporter vector (ERE-CALUX), were exposed to the reconstituted SPE-HPLC extracts for determination of the integrated estrogenic activity. The effects of PCBs were analyzed by direct in vitro exposure of PCBs (138, 153...

New-tools to assess the toxicological hazard of endocrine disruptor organoclorine contaminants in Mediterranean cetaceans

Energy Technology Data Exchange (ETDEWEB)

M. Cristina Fossi; Marsili, L.; Casini, S. [Dept. of Environmental Sciences, Univ. of Siena (Italy)

2004-09-15

The Mediterranean top predators, and particularly cetacean odontocetes, accumulate high concentrations of organochlorine contaminants (OCs), incurring high toxicological risk. Some organochlorine compounds, now with worldwide distribution, are known as endocrine disrupting chemicals (EDCs). Four types of organochlorine endocrine disruptors are commonly found in Mediterranean cetaceans: (1) environmental estrogens, (2) environmental androgens, (3) anti-estrogens and (4) anti-androgens. Endocrine disruptors act by mimicking sex steroid hormones, both estrogens and androgens, by binding to hormone receptors or influencing cell pathways (environmental estrogens and androgens), or by blocking and altering hormone receptor binding (anti-estrogens, antiandrogens). Environmental estrogens are the most common and most widely studied EDCs. The relative estrogenic power of these chemicals, identified by in vitro and in vivo screening methods is rather weak (10{sup -3} or less) compared with the reference power of 17-estradiol or DES. However, the high levels of organochlorine compounds detected in marine mammals, particularly in pinnipeds and odontocetes, and consequently, the high levels of organochlorines with ED capacity, cannot be ignored. Here the hypothesis that some Mediterranean cetaceans (Stenella coeruleoalba, Delphinus delphis, Tursiops truncatus and Balaenoptera physalus) are ''potentially at risk'' due to organochlorines with endocrine disrupting capacity is investigated using new non-lethal tools. As ''diagnostic'' tool we use benzo(a)pyrene monooxygenase (CYP1A1) activity in skin biopsies (non-lethal biomarker) as a potential indicator of exposure to organochlorines, with special reference to the compounds with endocrine disrupting capacity. As ''prognostic'' tool we propose the immunofluorescence technique in fibroblast cell cultures, for a qualitative and quantitative evaluation of the target

Overview of the Pathophysiological Implications of Organotins on the Endocrine System

Directory of Open Access Journals (Sweden)

Vinicius Bermond Marques

2018-03-01

Full Text Available Organotins (OTs are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic–pituitary axis, altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus or peripheral (e.g., adipose tissue mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed.

Overview of the Pathophysiological Implications of Organotins on the Endocrine System

Science.gov (United States)

Marques, Vinicius Bermond; Faria, Rodrigo Alves; Dos Santos, Leonardo

2018-01-01

Organotins (OTs) are pollutants that are used widely by industry as disinfectants, pesticides, and most frequently as biocides in antifouling paints. This mini-review presents the main evidences from the literature about morphophysiological changes induced by OTs in the mammal endocrine system, focusing on the metabolism and reproductive control. Similar to other toxic compounds, the main effects with potential health risks to humans and experimental animals are not only related to dose and time of exposure but also to age, gender, and tissue/cell exposed. Regarding the underlying mechanisms, current literature indicates that OTs can directly damage endocrine glands, as well as interfere with neurohormonal control of endocrine function (i.e., in the hypothalamic–pituitary axis), altering hormone synthesis and/or bioavailability or activity of hormone receptors in the target cells. Importantly, OTs induces biochemical and morphological changes in gonads, abnormal steroidogenesis, both associated with reproductive dysfunctions such as irregular estrous cyclicity in female or spermatogenic disorders in male animals. Additionally, due to their role on endocrine systems predisposing to obesity, OTs are also included in the metabolism disrupting chemical hypothesis, either by central (e.g., accurate nucleus and lateral hypothalamus) or peripheral (e.g., adipose tissue) mechanisms. Thus, OTs should be indeed considered a major endocrine disruptor, being indispensable to understand the main toxic effects on the different tissues and its causative role for endocrine, metabolic, and reproductive dysfunctions observed. PMID:29615977

Adipogenic Effects of a Combination of the Endocrine-Disrupting Compounds Bisphenol A, Diethylhexylphthalate, and Tributyltin

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Ronald Biemann

2014-01-01

Full Text Available Objective: The food contaminants bisphenol A (BPA, diethylhexylphthalate (DEHP, and tributyltin (TBT are potent endocrine-disrupting compounds (EDC known to interfere with adipogenesis. EDC usually act in mixtures and not as single compounds. The aim of this study was to investigate the effects of a simultaneous exposure of BPA, DEHP, and TBT on mesenchymal stem cell differentiation into adipocytes. Methods: Multipotent murine mesenchymal stem cells (C3H10T1/2 were exposed to EDC mixtures in high concentrations, i.e. MIX-high (10 µmol/l BPA, 100 µmol/l DEHP, 100 nmol/l TBT, and in environmentally relevant concentrations, i.e. MIX-low (10 nmol/l BPA, 100 nmol/l DEHP, 1 nmol/l TBT. The exposure was performed either for the entire culture time (0-12 days or at distinct stages of adipogenic differentiation. At day 12 of cell culture, the amount of adipocytes, triglyceride content (TG, and adipogenic marker gene expression were analyzed. Results: MIX-high increased the development of adipocytes and the expression of adipogenic marker genes independently of the exposure window. The total TG amount was not increased. The low-concentrated EDC mixture had no obvious impact on adipogenesis. Conclusion: In EDC mixtures, the adipogenic effect of TBT and DEHP predominates single effects of BPA. Mixture effects of EDC are not deducible from single compound experiments.

Adipogenic Effects of a Combination of the Endocrine-Disrupting Compounds Bisphenol A, Diethylhexylphthalate, and Tributyltin

Science.gov (United States)

Biemann, Ronald; Fischer, Bernd; Navarrete Santos, Anne

2014-01-01

Objective The food contaminants bisphenol A (BPA), diethylhexylphthalate (DEHP), and tributyltin (TBT) are potent endocrine-disrupting compounds (EDC) known to interfere with adipogenesis. EDC usually act in mixtures and not as single compounds. The aim of this study was to investigate the effects of a simultaneous exposure of BPA, DEHP, and TBT on mesenchymal stem cell differentiation into adipocytes. Methods Multipotent murine mesenchymal stem cells (C3H10T1/2) were exposed to EDC mixtures in high concentrations, i.e. MIX-high (10 µmol/l BPA, 100 µmol/l DEHP, 100 nmol/l TBT), and in environmentally relevant concentrations, i.e. MIX-low (10 nmol/l BPA, 100 nmol/l DEHP, 1 nmol/l TBT). The exposure was performed either for the entire culture time (0-12 days) or at distinct stages of adipogenic differentiation. At day 12 of cell culture, the amount of adipocytes, triglyceride content (TG), and adipogenic marker gene expression were analyzed. Results MIX-high increased the development of adipocytes and the expression of adipogenic marker genes independently of the exposure window. The total TG amount was not increased. The low-concentrated EDC mixture had no obvious impact on adipogenesis. Conclusion In EDC mixtures, the adipogenic effect of TBT and DEHP predominates single effects of BPA. Mixture effects of EDC are not deducible from single compound experiments. PMID:24503497

Toxicity and Estrogenic Endocrine Disrupting Activity of Phthalates and Their Mixtures

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Xueping Chen

2014-03-01

Full Text Available 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.

White rot fungi and advanced combined biotechnology with nanomaterials: promising tools for endocrine-disrupting compounds biotransformation.

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Huang, Danlian; Guo, Xueying; Peng, Zhiwei; Zeng, Guangming; Xu, Piao; Gong, Xiaomin; Deng, Rui; Xue, Wenjing; Wang, Rongzhong; Yi, Huan; Liu, Caihong

2017-10-29

Endocrine-disrupting compounds (EDCs) can interfere with endocrine systems and bio-accumulate through the food chain and even decrease biodiversity in contaminated areas. This review discusses a critical overview of recent research progress in the biotransformation of EDCs (including polychlorinated biphenyl and nonylphenol, and suspected EDCs such as heavy metals and sulfonamide antibiotics) by white rot fungi (WRF) based on techniques with an emphasis on summarizing and analyzing fungal molecular, metabolic and genetic mechanisms. Not only intracellular metabolism which seems to perform essential roles in the ability of WRF to transform EDCs, but also advanced applications are deeply discussed. This review mainly reveals the removal pathway of heavy metal and antibiotic pollutants because the single pollution almost did not exist in a real environment while the combined pollution has become more serious and close to people's life. The trends in WRF technology and its related advanced applications which use the combined technology, including biocatalysis of WRF and adsorption of nanomaterials, to degrade EDCs have also been introduced. Furthermore, challenges and future research needs EDCs biotransformation by WRF are also discussed. This research, referring to metabolic mechanisms and the combined technology of WRF with nanomaterials, undoubtedly contributes to the applications of biotechnology. This review will be of great benefit to an understanding of the trends in biotechnology for the removal of EDCs.

Comparative estrogenic activity of wine extracts and organochlorine pesticide residues in food

NARCIS (Netherlands)

Gaido, K.; Dohme, L.; Wang, F.; Chen, I.; Blankvoort, B.; Ramamoorthy, K.; Safe, S.

1998-01-01

The human diet contains industrial-derived, endocrine-active chemicals and higher levels of naturally occurring compounds that modulate multiple endocrine pathways. Hazard and risk assessment of these mixtures is complicated by noadditive interactions between different endocrine-mediated responses.

Determination of Endocrine Disrupting Compounds in surface waters by means of chromatographic techniques coupled to mass spectrometry

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M. Di Carro

2011-01-01

Full Text Available Two analytical methods were developed to study five endocrine disrupting compounds (4-n-nonylphenol, bisphenol A, estrone, 17β-estradiol and 17α-ethinylestradiol in waters. One method includes a fast liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS analysis, while the second comprise a Stir Bar Sorptive Extraction (SBSE followed by a headspace derivatization and gaschromatography-mass spectrometry (GC-MS analysis. Passive samplers POCIS (Polar Organic Chemical Integrative Samplers were used as sampling and preconcentration steps in order to reach the very low levels of the analytes in environmental waters. Both methods were then applied to the determination of the analytes in different water samples.

Ecotoxicological hazard and risk assessment of endocrine active substances.

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Leopold, Annegaaike; Roberts, Mike; Matthiessen, Peter

2017-03-01

This collection of papers provides state-of-the-art science on a complex topic that has been challenging for scientists and regulators for a long time. The papers emanated from the Society of Environmental Toxicology and Chemistry (SETAC) Pellston Workshop ® Environmental Hazard and Risk Assessment Approaches for Endocrine-Active Substances (EHRA). Forty-eight international experts met in early February 2016 to discuss whether the environmental risks posed by endocrine-disrupting substances (EDS) can be reliably assessed. The primary conclusion of the workshop was 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 assessment of EDS is scientifically sound and reliable. Integr Environ Assess Manag 2017;13:264-266. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Influence of metabolism on endocrine activities of bisphenol S.

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Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

2016-08-01

Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sources of endocrine-disrupting compounds in North Carolina waterways: a geographic information systems approach

Science.gov (United States)

Sackett, Dana K.; Pow, Crystal Lee; Rubino, Matthew J.; Aday, D.D.; Cope, W. Gregory; Kullman, Seth W.; Rice, J.A.; Kwak, Thomas J.; Law, L.M.

2015-01-01

The presence of endocrine-disrupting compounds (EDCs), particularly estrogenic compounds, in the environment has drawn public attention across the globe, yet a clear understanding of the extent and distribution of estrogenic EDCs in surface waters and their relationship to potential sources is lacking. The objective of the present study was to identify and examine the potential input of estrogenic EDC sources in North Carolina water bodies using a geographic information system (GIS) mapping and analysis approach. Existing data from state and federal agencies were used to create point and nonpoint source maps depicting the cumulative contribution of potential sources of estrogenic EDCs to North Carolina surface waters. Water was collected from 33 sites (12 associated with potential point sources, 12 associated with potential nonpoint sources, and 9 reference), to validate the predictive results of the GIS analysis. Estrogenicity (measured as 17β-estradiol equivalence) ranged from 0.06 ng/L to 56.9 ng/L. However, the majority of sites (88%) had water 17β-estradiol concentrations below 1 ng/L. Sites associated with point and nonpoint sources had significantly higher 17β-estradiol levels than reference sites. The results suggested that water 17β-estradiol was reflective of GIS predictions, confirming the relevance of landscape-level influences on water quality and validating the GIS approach to characterize such relationships.

Reproductive endocrine patterns and volatile urinary compounds of Arctictis binturong: discovering why bearcats smell like popcorn

Science.gov (United States)

Greene, Lydia K.; Wallen, Timothy W.; Moresco, Anneke; Goodwin, Thomas E.; Drea, Christine M.

2016-06-01

Members of the order Carnivora rely on urinary scent signaling, particularly for communicating about reproductive parameters. Here, we describe reproductive endocrine patterns in relation to urinary olfactory cues in a vulnerable and relatively unknown viverrid—the binturong ( Arctictis binturong). Female binturongs are larger than and dominate males, and both sexes engage in glandular and urinary scent marking. Using a large ( n = 33), captive population, we collected serum samples to measure circulating sex steroids via enzyme immunoassay and urine samples to assay volatile chemicals via gas chromatography-mass spectrometry. Male binturongs had expectedly greater androgen concentrations than did females but, more unusually, had equal estrogen concentrations, which may be linked to male deference. Males also expressed a significantly richer array of volatile chemical compounds than did females. A subset of these volatile chemicals resisted decay at ambient temperatures, potentially indicating their importance as long-lasting semiochemicals. Among these compounds was 2-acetyl-1-pyrroline (2-AP), which is typically produced at high temperatures by the Maillard reaction and is likely to be responsible for the binturong's characteristic popcorn aroma. 2-AP, the only compound expressed by all of the subjects, was found in greater abundance in males than females and was significantly and positively related to circulating androstenedione concentrations in both sexes. This unusual compound may have a more significant role in mammalian semiochemistry than previously appreciated. Based on these novel data, we suggest that hormonal action and potentially complex chemical reactions mediate communication of the binturong's signature scent and convey information about sex and reproductive state.

Evaluation of organic endocrine disruptors in water at Brazilian Multipurpose Reactor - RMB installation area

Energy Technology Data Exchange (ETDEWEB)

Silva, Larissa L.; Martins, Elâine A.J.; Cotrim, Marycel E.B.; Pires, Maria A.F., E-mail: larissa.limeira07@gmail.com, E-mail: elaine@ipen.br, E-mail: mecotrim@ipen.br, E-mail: mapires@ipen.br [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

2017-07-01

The study of pollutants with organic and inorganic characteristics in groundwater and surface waters of a given region is an important tool in the assessment of pollution. Endocrine interferers are synthetic or natural chemicals that have the ability to act on the endocrine system of humans and animals by mimetizing natural hormones and may produce adverse effects on organisms, even in low concentrations (μg or ng.L{sup -1}). Anthropic activities are the major source of input of endocrine disruptors into the environment. The Brazilian government has a project to construct a multipurpose reactor, Brazilian Multipurpose Reactor (RMB), at the Iperó city, to improve the nuclear research Brazilian capacity. The object of this research in to analyze 14 organic compounds that may be present in the groundwater and surface waters of the RMB installation area. This is an unprecedented and extremely important study for the evaluated region; since it will provide guidance on the degree of contamination of the local waters before the construction begins. The study will also make it possible to verify if the construction of the RMB will offer environmental issues to the place. For the determination of the compounds of interest, a developed and validated analytical method was used. This methodology consists of the concentration of the samples by solid phase extraction (SPE) followed by quantification by gas chromatography coupled to the mass spectrometry detector (GC/MS). The water column particulate was also evaluated by ultrasonic extraction, followed by quantification by GC/MS. The results reveal that some of the compounds were found and it was due to anthropic activities in the vicinity of the regions. By initial analysis it was possible verify river that cross the RMB area present values below 0.05 μg L{sup -1}. (author)

Evaluation of organic endocrine disruptors in water at Brazilian Multipurpose Reactor - RMB installation area

International Nuclear Information System (INIS)

Silva, Larissa L.; Martins, Elâine A.J.; Cotrim, Marycel E.B.; Pires, Maria A.F.

2017-01-01

The study of pollutants with organic and inorganic characteristics in groundwater and surface waters of a given region is an important tool in the assessment of pollution. Endocrine interferers are synthetic or natural chemicals that have the ability to act on the endocrine system of humans and animals by mimetizing natural hormones and may produce adverse effects on organisms, even in low concentrations (μg or ng.L -1 ). Anthropic activities are the major source of input of endocrine disruptors into the environment. The Brazilian government has a project to construct a multipurpose reactor, Brazilian Multipurpose Reactor (RMB), at the Iperó city, to improve the nuclear research Brazilian capacity. The object of this research in to analyze 14 organic compounds that may be present in the groundwater and surface waters of the RMB installation area. This is an unprecedented and extremely important study for the evaluated region; since it will provide guidance on the degree of contamination of the local waters before the construction begins. The study will also make it possible to verify if the construction of the RMB will offer environmental issues to the place. For the determination of the compounds of interest, a developed and validated analytical method was used. This methodology consists of the concentration of the samples by solid phase extraction (SPE) followed by quantification by gas chromatography coupled to the mass spectrometry detector (GC/MS). The water column particulate was also evaluated by ultrasonic extraction, followed by quantification by GC/MS. The results reveal that some of the compounds were found and it was due to anthropic activities in the vicinity of the regions. By initial analysis it was possible verify river that cross the RMB area present values below 0.05 μg L -1 . (author)

Comparative toxicity and endocrine disruption potential of urban and rural atmospheric organic PM1 in JEG-3 human placental cells

International Nuclear Information System (INIS)

Drooge, Barend L. van; Marqueño, Anna; Grimalt, Joan O.; Fernández, Pilar; Porte, Cinta

2017-01-01

Outdoor ambient air particulate matter and air pollution are related to adverse effects on human health. The present study assesses the cytotoxicity and ability to disrupt aromatase activity of organic PM 1 extracts from rural and urban areas at equivalent air volumes from 2 to 30 m 3 , in human placental JEG-3 cells. Samples were chemically analyzed for particle bounded organic compounds with endocrine disrupting potential, i.e. PAH, O-PAH, phthalate esters, but also for organic molecular tracer compounds for the emission source identification. Rural samples collected in winter were cytotoxic at the highest concentration tested and strongly inhibited aromatase activity in JEG-3 cells. No cytotoxicity was detected in summer samples from the rural site and the urban samples, while aromatase activity was moderately inhibited in these samples. In the urban area, the street site samples, collected close to intensive traffic, showed stronger inhibition of aromatase activity than the samples simultaneously collected at a roof site, 50 m above ground level. The cytotoxicity and endocrine disruption potential of the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning in the rural site in winter. - Highlights: • Organic extracts of outdoor ambient air PM1 showed aromatase activity inhibition in exposed human placental JEG-3 cells. • Cytotoxicity and strongest endocrine disruption was observed in rural winter samples, while lowest inhibition was observed in urban background site 50 m above a busy street. • Cytotoxicity and aromatase activity inhibition in the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning. - Organic extracts from ambient air PM 1 related to biomass burning are more cytotoxic and have stronger endocrine disruption potential than urban PM 1 .

ENDOCRINE OPHTHALMOPATHY: ETIOLOGY, PATHOGENESIS, CLINICAL PICTURE, DIAGNOSIS

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Nikonova L. V.

2018-03-01

Full Text Available The relevance of the study of endocrine ophthalmopathy is due to the high prevalence of this disease and a high risk of developing impaired vision that leads to disability of patients. This lecture presents the main genetic, immunological, clinical manifestations of endocrine ophthalmopathy in order to improve the diagnosis and treatment of this pathology. The clinical picture of endocrine ophthalmopathy is various, unique for every patient and depends on the activity and severity of the process, which requires combined etiopathogenetic therapy. The importance of timely diagnosis for endocrine ophthalmopathy with an assessment of the activity of the process for choosing the right tactics for managing patients is very high.

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

Science.gov (United States)

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. Copyright © 2011 Elsevier B.V. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

Taxvig, Camilla, E-mail: camta@food.dtu.dk [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark); Hadrup, Niels; Boberg, Julie; Axelstad, Marta [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark); Bossi, Rossana [Department of Environmental Science, Aarhus University, DK-4000 Roskilde (Denmark); Bonefeld-Jørgensen, Eva Cecilie [Department of Public Health, University of Aarhus, DK-8000 Aarhus C (Denmark); Vinggaard, Anne Marie [Division of Toxicology and Risk Assessment, National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg (Denmark)

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.

Optimization and Application of a GC-MS Method for the Determination of Endocrine Disruptor Compounds in Natural Water

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José Gustavo Ronderos-Lara

2018-06-01

Full Text Available Bisphenol A (BPA, 4-nonylphenol (4NP, estradiol (E2, and ethinylestradiol (EE2 are considered as endocrine disruptors or mutagens. These compounds are commonly called endocrine disrupter chemicals (EDCs. BPA and 4NP are widely used as plastic additives, lacquers, resins, or surfactants, while E2 is one of the predominant female sex hormones during the reproductive years, and EE2 is an estrogen derived from estradiol, used in the production of contraceptive pills. All of these can be usually found in wastewater. In Mexico, it is common for water from rivers, lakes, and canyons to be reused for different purposes. Unfortunately, there is little information on the concentration of many of the pollutants present in such bodies of water. To determine the presence of these compounds in samples of wastewater in the Apatlaco River, an accurate and reproducible method was developed by coupling gas chromatography to mass spectrometry (GC-MS. A solid-phase extraction with Chromabond RP-18 cartridges was carried out, and the elution was performed with an acetone/methanol mixture. After isolation, the solvent was removed and a silylation step was carried out using N,O-bis(trimethylsilyltrifluoroacetamide (BSTFA. Recoveries for spiked samples were between 71.8% and 111.0%. The instrumental limits of detection (IDL ranged between 24.7 and 37.0 ng mL−1. In total, 16 samples were taken in 2015 at the microbasin of the Apatlaco River, located in the state of Morelos. The maximum concentrations found were 4NP (85.5 ng mL−1, BPA (174.6 ng mL−1, E2 103.6 (ng mL−1, and EE2 (624.3 ng mL−1.

Reporter cell lines for the characterization of the interactions between nuclear receptors and endocrine disruptors

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marina egrimaldi

2015-05-01

Full Text Available Endocrine-disrupting chemicals (EDCs are exogenous substances interfering with hormone biosynthesis, metabolism, or action, and consequently causing disturbances in the endocrine system. Various pathways are activated by EDCs, including interactions with nuclear receptors (NRs which are primary targets of numerous environmental contaminants.The main NRs targeted by environmental contaminants are the estrogen (ER α, β and the androgen (AR receptors. ERs and AR have pleiotropic regulatory roles in a diverse range of tissues, notably in the mammary gland, the uterus and the prostate. Thus, dysfunctional ERs and AR signaling due to inappropriate exposure to environmental pollutants may lead to hormonal cancers and infertility. The pregnane X receptor (PXR is also recognized by many environmental molecules. PXR has a protective role of the body through its ability to regulate proteins involved in the metabolism, the conjugation and the transport of many exogenous and endogenous compounds. However, the permanent activation of this receptor by xenobiotics may lead to premature drug metabolism, the formation and accumulation of toxic metabolites and defects in hormones homeostasis. The activity of other NRs can also be affected by environmental molecules. Compounds capable of inhibiting or activating the estrogen related (ERRγ, the thyroid hormone (TRα, β, the retinoid X receptors (RXRα, β, γ and peroxisome proliferator-activated (PPAR α, γ receptors have been identified and are highly suspected to promote developmental, reproductive, neurological, or metabolic diseases in humans and wildlife.In this review we provide an overview of reporter cell lines established to characterize the human NR activities of a large panel of EDCs including natural as well as industrial compounds such as pesticides, plasticizers, surfactants, flame retardants and cosmetics.

Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

DEFF Research Database (Denmark)

Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas

2013-01-01

A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted of lectu...

Endocrine disruptors compounds, pharmaceuticals and personal care products in urban wastewater: implications for agricultural reuse and their removal by adsorption process.

Science.gov (United States)

Grassi, Mariangela; Rizzo, Luigi; Farina, Anna

2013-06-01

In the last years, a lot of emerging contaminants, such as, endocrine disruptors compounds (EDCs), pharmaceuticals, and personal care products (PPCPs) have been detected in wastewater. Because of their toxicity and possible adverse effects on the environment and humans, their release from urban wastewater treatment plants (UWWTPs) effluents should be minimized, particularly when a wastewater reuse for crops irrigation is expected. Many processes have been investigated for advanced treatment of UWWTP effluents as well as for emerging contaminant degradation; among these, adsorption process was successfully used to remove EDCs and PPCPs from wastewater. This article shortly reviews EDCs and PPCPs removal from UWWTP effluents by adsorption process using conventional and non-conventional adsorbents. The fate of EDCs and PPCPs in UWWTPs and the implications for agricultural wastewater reuse has been addressed too. In spite of the adsorption process looking to be a valuable alternative to other advanced technologies for the removal of emerging contaminants from wastewater, some gaps still remain to evaluate the actual feasibility at full scale. However, according to a few studies available in scientific literature on the use of both powdered activated carbon and granular activated carbon at full scale, adsorption process by activated carbon is a promising, potentially effective, and economically feasible solution for producing safe wastewater for agricultural reuse.

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

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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.

Endocrine disruptors induce cytochrome P450 by affecting transcriptional regulation via pregnane X receptor

International Nuclear Information System (INIS)

Mikamo, Eriko; Harada, Shingo; Nishikawa, Jun-ichi; Nishihara, Tsutomu

2003-01-01

Pregnane X receptor (PXR) is a nuclear receptor that regulates the expression of genes for cytochrome P450 3A (CYP3A), multidrug resistance 1 (MDR1), and organic anion-transporting peptide 2 (OATP2). These genes control the metabolism (CYP3A subfamily) and aspects of the pharmacokinetics (MDR1 and OATP2) of both endogenous and xenobiotic compounds. Since PXR is important in understanding the actions of endocrine disruptors (EDs), we determined the ability of suspected EDs to interact with PXR. In our study, 7 of 54 xenobiotics compounds interacted with PXR, including methoxychlor and benzophenone. All of the chemicals activated PXR in vitro and induced CYP3A mRNA in the male rat liver. In addition, CYP2C11 was also induced by some PXR agonists and converted methoxychlor into xenoestrogen. These findings suggest that some EDs affect sex hormone receptor indirectly by induction of metabolic enzyme via PXR, to produce rapidly higher concentrations of effective metabolites, leading to disturbance of the endocrine system

Potential use of Vitellogenin and Zona radiata proteins as biomarkers of endocrine disruption in Peregrine falcon exposed to organochlorine compounds (DDTs, PCBs, PCDDs and PCDFs)

Energy Technology Data Exchange (ETDEWEB)

Jimenez, B. [CSIC, Inst. of Organic Chemistry, Madrid (Spain); Mori, G.; Concejero, M.A.; Casini, S.; Fossi, M.C. [Siena Univ. (Italy)

2004-09-15

Many different classes of environmental contaminants such as industrial chemicals (e.g. alkylphenols, polychlorinated biphenyls, pesticides, PAHs, polychlorinated dibenzo-p-dioxins, and dibenzofurans), ''can cause adverse effects in the reproductive functions of intact organisms or their progenies, consequent to changes in endocrine functions'' showing a so-called Endocrine disruptor activity. Avian raptor species, such as peregrine falcon (Falco peregrinus) for their peculiar position in the food web are potentially at risk in relation to the accumulation of Persistent Organic Pollutants (POPs) and toxic metals. Recent studies carried out with Peregrine falcon (Falco peregrinus) in Spain reveal a contamination with organochlorine compounds (PCDDs, PCDFs, PCBs and DDTs) which could be responsible of the decrease of successful pairs observed during the last ten years. Thus there is a need to develop sensitive diagnostic monitoring tools for the evaluation of toxicological risk and potential effects on the reproductive function and population dynamic of avian top predator species. Two markers for the detection of EDs effects in oviparous vertebrates are induction of Vitellogenin (Vtg) and Zona Radiata Proteins (ZR). Vtg, a complex phospholipoglycoprotein, is the major egg-yolk protein precursor and is normally synthesized by females in response to estradiol. ZR together with Zona Pellucida (ZP) constitutes in birds part of the eggshell. These proteins (Vtg, ZR and ZP) are normally synthesised in the liver as a response to an estrogen signal given by Estradiol. Males and sexually undifferentiated specimens also have the Vtg and ZR genes but do not express them unless exposed to estrogenic compounds. The main aim of this preliminary study was to develop methods for the detection of Vtg and ZR in plasma obtained from peregrine falcon as a specific biomarker for the evaluation of the effects of EDCs.

Investigating apical adverse effects of four endocrine active substances in the freshwater gastropod Lymnaea stagnalis.

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Giusti, Arnaud; Lagadic, Laurent; Barsi, Alpar; Thomé, Jean-Pierre; Joaquim-Justo, Célia; Ducrot, Virginie

2014-09-15

The hermaphroditic gastropod Lymnaea stagnalis is proposed as a candidate species for the development of OECD guidelines for testing of the reprotoxicity of chemicals, including endocrine active substances (EASs). Up to now, only a few putative EASs have been tested for their reproductive toxicity in this species. In this study, we investigate the effects of four EASs with different affinities to the vertebrate estrogen and androgen receptors (chlordecone as an estrogen; cyproterone acetate, fenitrothion and vinclozolin as anti-androgens) on the reproduction of L. stagnalis in a 21-day semi-static test. Testosterone and 17α-ethinylestradiol (EE2) were used as the reference compounds. The tested EASs had no significant effect on growth and survival at the tested concentration ranges (ng to μg/L). Classical reproduction endpoints (i.e., oviposition and fecundity) were not responsive to the tested chemicals, except for chlordecone and 17α-ethinylestradiol, which hampered reproduction from 19.6 μg/L and 17.6 μg/L, respectively. The frequency of polyembryonic eggs, used as an additional endpoint, demonstrated the effects of all compounds except EE2. The molecular pathways, which are involved in such reproduction impairments, remain unknown. Our results suggest that egg quality is a more sensitive endpoint as compared to other reproductive endpoints commonly assessed in mollusk toxicity tests. Copyright © 2014 Elsevier B.V. All rights reserved.

Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

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Marcel Cerqueira Cesar Machado

Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy

DEFF Research Database (Denmark)

Larsen, Mathilde Skaarup; Bjerre, Karsten; Lykkesfeldt, Anne Elisabeth

2012-01-01

) in endocrine treated breast cancer in terms of co-expression and association with disease-free survival (DFS) in 1062 patients with ER-positive tumors. Furthermore, HER2 amplification was evaluated. We found positive associations between the phosphorylated receptors. pHER1 and pHER3 were co-expressed with one......The four human epidermal growth factor receptors (HER1-4) are involved in growth stimulation and may play a role in endocrine resistance. The receptors form dimers, leading to activation by mutual phosphorylation. Our purpose was to explore the role of the activated receptors (pHER1, pHER2, pHER3...

The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals

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Macejova Dana

2016-07-01

Full Text Available Retinoic acid (RA, an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR and rexinoid nuclear receptors (RXR, which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances. They may affect processes of reproductive system in mammals, predominantly via nuclear receptor signaling pathways. Triorganotins, such as tributyltin chloride (TBTCl and triphenyltin chloride (TPTCl, are capable to bind to RXR molecules, and thus represent potent agonists of RXR subtypes of nuclear receptors not sharing any structural characteristics with endogenous ligands of nuclear receptors. Th is article summarizes selected effects of biologically active retinoids and rexinoids on both male and female reproduction and also deals with the effects of organotin compounds evoking endocrine disrupting actions in reproduction.

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

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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.

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

DEFF Research Database (Denmark)

Gilbert, Dorothea; Mayer, Philipp; Pedersen, Mikael

2015-01-01

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...

Evaluation of yolk protein as biomarkers for endocrine disruption in molluscs

DEFF Research Database (Denmark)

Morthorst, Jane Ebsen; Holbech, Henrik; Kinnberg, Karin Lund

is also regulated by estrogens in molluscs even though it still remains unknown if and where vertebrate steroids are synthesized in molluscs and regulation of the endocrine system in molluscs is also unknown. By using our newly developed ELISA the present work investigates if yolk protein is a suitable......During recent years invertebrates and especially molluscs have received increasing attention in the field of endocrine disruption and development of OECD test guidelines to assess the effects of endocrine disrupting compounds (EDCs) in molluscs is under development. The development of standardized...... tests to detect effects of EDCs in molluscs has proved cumbersome due to lack of specific biomarkers and endpoints for endocrine effects. Intersex (presence of oocytes in the testis) and induction of vitellogenin (the yolk protein precursor in oviparous vertebrates) have been used as biomarkers for EDCs...

Determination of endocrine-disrupting compounds in drinking waters by fast liquid chromatography-tandem mass spectrometry.

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Magi, Emanuele; Scapolla, Carlo; Di Carro, Marina; Liscio, Camilla

2010-09-01

Growing attention has been recently paid to safety of food and drinking water, making necessary the adoption of policies for water sources protection and the development of sensitive and rapid analytical methods to identify micropollutants. Endocrine-disrupting compounds (EDCs) have emerged as a major issue as they alter the functioning of the endocrine system. Since ingestion of EDCs via food is considered the major exposure route, there is a growing interest in understanding EDC fate during drinking water treatment and in monitoring potential contamination of surface waters and groundwaters. In this work, a fast liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the determination of 4-n-nonylphenol (NP), bisphenol A (BPA), estrone (E1), 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) in drinking waters. In the literature analytical articles seldom provide details regarding fragmentation pathways. In this paper spectra of the five EDCs in negative ESI were interpreted with the support of accurate mass spectra acquired by a quadrupole time-of-flight instrument; fragmentation pathways were also proposed. The chromatographic separation of EDCs was optimized on a Pinnacle DB Biphenylic column with a water-acetonitrile gradient. Quantitative analysis was performed in multiple reaction monitoring (MRM) mode using bisphenol A-d(16) (BPA-d(16)) as internal standard; calibration curves showed good correlation coefficients (0.9989-0.9997). All figures of merit of the method were satisfactory; limits of detection were in the range 0.2-0.4 ng/ml. The method was applied to the determination of the analytes in waters sampled by polar organic chemical integrative samplers in a drinking water treatment plant. Rather low concentration of BPA, NP and E1 were measured in the inlet, while none of the considered EDCs was detected in the outlet. 2010 John Wiley & Sons, Ltd.

Detection of immunotoxic effects of estrogenic and androgenic endocrine disrupting compounds using splenic immune cells of the female three-spined stickleback, Gasterosteus aculeatus (L.).

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Bado-Nilles, A; Techer, R; Porcher, J M; Geffard, A; Gagnaire, B; Betoulle, S; Sanchez, W

2014-09-01

Today, the list of endocrine disrupting compounds (EDCs) in freshwater and marine environments that mimic or block endogenous hormones is expanding at an alarming rate. As immune and reproductive systems may interact in a bidirectional way, some authors proposed the immune capacities as attractive markers to evaluate the hormonal potential of environmental samples. Thus, the present work proposed to gain more knowledge on direct biological effects of natural and EDCs on female fish splenic leucocyte non-specific immune activities by using ex vivo assays. After determining the optimal required conditions to analyze splenic immune responses, seven different EDCs were tested ex vivo at 0.01, 1 and 100nM over 12h on the leucocyte functions of female three-spined stickleback, Gasterosteus aculeatus. In summary, we found that natural hormones acted as immunostimulants, whilst EDCs were immunosuppressive. Copyright © 2014 Elsevier B.V. All rights reserved.

Endocrine active agents: implications of adverse and non-adverse changes.

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Foster, Paul M D; McIntyre, Barry S

2002-01-01

The US Environmental Protection Agency (EPA) is currently in the process of developing screening and testing methodologies for the assessment of agents that may possess endocrine-like activity--the so-called endocrine disruptors. Moreover, the EPA has signaled its intention of placing information arising from such studies on the worldwide web. This has created significant interest in how such information may be used in risk assessment and by policymakers and the public in the potential regulation or deselection of specific chemical agents. The construction of lists of endocrine disruptors, although fulfilling the requirements of some parties, is really of little use when the nature of the response, the dose level employed, and the lifestage of the test species used are not given. Thus, we have already seen positive in vitro information available on the interaction with a receptor being used as a key indicator when the results of large, high quality in vivo studies showing no adverse changes have been ignored. Clearly a number of in vitro systems are available to ascertain chemical interaction with specific (mainly steroid) hormone receptors including a number of reporter gene assays. These assays only provide indicators of potential problems and should not be, in isolation, indicators of toxicity. Likewise, short-term in vivo screens such as the uterotrophic and Hershberger studies are frequently conducted in castrated animals and thus indicate the potential for a pharmacological response in vivo rather than an adverse effect. A number of new end points have been added to standard rodent testing protocols in the belief of providing more sensitivity to detect endocrine related changes. These include the measurement of anogenital distance (AGD), developmental landmarks [vaginal opening (VO), preputial separation (PPS)], and in some studies the counting of nipples and areolae on males. AGD, VO, and PPS are all affected by the size of the pup in which they are measured

Endocrine disrupting compounds in drinking water supply system and human health risk implication.

Science.gov (United States)

Wee, Sze Yee; Aris, Ahmad Zaharin

2017-09-01

To date, experimental and epidemiological evidence of endocrine disrupting compounds (EDCs) adversely affecting human and animal populations has been widely debated. Notably, human health risk assessment is required for risk mitigation. The lack of human health risk assessment and management may thus unreliably regulate the quality of water resources and efficiency of treatment processes. Therefore, drinking water supply systems (DWSSs) may be still unwarranted in assuring safe access to potable drinking water. Drinking water supply, such as tap water, is an additional and crucial route of human exposure to the health risks associated with EDCs. A holistic system, incorporating continuous research in DWSS monitoring and management using multi-barrier approach, is proposed as a preventive measure to reduce human exposure to the risks associated with EDCs through drinking water consumption. The occurrence of EDCs in DWSSs and corresponding human health risk implications are analyzed using the Needs, Approaches, Benefits, and Challenges (NABC) method. Therefore, this review may act as a supportive tool in protecting human health and environmental quality from EDCs, which is essential for decision-making regarding environmental monitoring and management purposes. Subsequently, the public could have sustainable access to safer and more reliable drinking water. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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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; 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 P.; Mihaich, Ellen; Odum, Jenny; Ortego, Lisa; Parrott, Joanne L.; Pickford, Daniel; Roberts, Mike; Schaefers, Christoph; Schwarz, Tamar; Solomon, Keith; Verslycke, Tim; Weltje, Lennart; Wheeler, James R.; Williams, Mike; Wolf, Jeffery C.; Yamazaki, Kunihiko

2017-01-01

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

PET and endocrine tumors

International Nuclear Information System (INIS)

Rigo, P.; Belhocine, T.; Hustinx, R.; Foidart-Willems, J.

2000-01-01

The authors review the main indications of PET examination, and specifically of 18 FDG, in the assessment of endocrine tumors: of the thyroid, of the parathyroid, of the adrenal and of the pituitary glands. Neuroendocrine tumors, gastro-entero-pancreatic or carcinoid tumors are also under the scope. Usually, the most differentiated tumors show only poor uptake of the FDG as they have a weak metabolic and proliferative activity. In the assessment of endocrine tumors, FDG-PET should be used only after most specific nuclear examinations been performed. (author)

Management of endocrine orbitopathy

International Nuclear Information System (INIS)

Kahaly, G.J.

2001-01-01

Endocrine orbitopathy is the most common extrathyroidal manifestation of Basedow's disease and is characterized by a lymphocyte infiltration of the peribulbar space. Infiltrating and activated T cells react with orbital target cells and secrete cytokines, leading to accumulation of glycosaminoglycans, interstitial edema, and enlargement of the extra ocular muscels. Interdisciplinary management is recommended for rapid diagnosis and effective therapy of patients with endocrine orbitopathy. Immunosuppressive treatment is often used initially, and by suppressing inflammatory changes, it can result in subjective and objective improvement of thyroid eye disease. (orig.) [de

Endocrine Disrupting Contaminants—Beyond the Dogma

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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

Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna.

Science.gov (United States)

Haeba, Maher H; Hilscherová, Klára; Mazurová, Edita; Bláha, Ludek

2008-05-01

Pollution-induced endocrine disruption in vertebrates and invertebrates is a worldwide environmental problem, but relatively little is known about effects of endocrine disrupting compounds (EDCs) in planktonic crustaceans (including Daphnia magna). Aims of the present study were to investigate acute 48 h toxicity and sub-chronic (4-6 days) and chronic (21 days) effects of selected EDCs in D. magna. We have investigated both traditional endpoints as well as other parameters such as sex determination, maturation, molting or embryogenesis in order to evaluate the sensitivity and possible use of these endpoints in ecological risk assessment. We have studied effects of four model EDCs (vinclozolin, flutamide, ketoconazole and dicofol) on D. magna using (i) an acute 48 h immobilization assay, (ii) a sub-chronic, 4-6 day assay evaluating development and the sex ratio of neonates, and (iii) a chronic, 21 day assay studying number of neonates, sex of neonates, molting frequency, day of maturation and the growth of maternal organisms. Acute EC50 values in the 48 h immobilization test were as follows (mg/L): dicofol 0.2, ketoconazole 1.5, flutamide 2.7, vinclozolin >3. Short-term, 4-6 day assays with sublethal concentrations showed that the sex ratio in Daphnia was modulated by vinclozolin (decreased number of neonate males at 1 mg/L) and dicofol (increase in males at 0.1 mg/L). Flutamide (up to 1 mg/L) had no effect on the sex of neonates, but inhibited embryonic development at certain stages during chronic assay, resulting in abortions. Ketoconazole had no significant effects on the studied processes up to 1 mg/L. Sex ratio modulations by some chemicals (vinclozolin and dicofol) corresponded to the known action of these compounds in vertebrates (i.e. anti-androgenicity and anti-oestrogenicity, respectively). Our study revealed that some chemicals known to affect steroid-regulated processes in vertebrates can also affect sublethal endpoints (e.g. embryonic sex determination

Two Virus Based Endocrine Disruptor Assays Effective Across Vertebrate Classes.

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The presence of hormone mimics, or endocrine disrupting compounds (EDC’s), in the environment are increasing. Sources range from agricultural run–off, pharmaceuticals in waste water, to industrial operations. Current levels of contamination are sufficient to alter sexual develo...

Childhood obesity and endocrine disrupting chemicals

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Jin Taek Kim

2017-12-01

Full Text Available The prevalence of obesity around the world has increased sharply. Strong evidence has emerged over the last decades that human exposure to numerous endocrine disrupting chemicals (EDCs is the cause of obesity and obesity-related metabolic diseases. Many EDCs are manmade chemicals that are released into the environment. EDCs are exogenous compounds that interfere with hormonal regulation and normal endocrine systems, thereby affecting the health of animals and humans. The number of chemicals belonging to EDCs is increasing and some of them are very stable; they persist in the environment (persistent organic pollutants. Although they are banned, their concentrations have been continuously increasing over time. This review gives a brief introduction to common EDCs, and evidence of harmful effects of EDCs on obesity-related diseases; we focus in particular on EDCs’ role in causing mitochondrial dysfunction.

Endocrine Disruptor Vinclozolin Induced Epigenetic Transgenerational Adult-Onset Disease

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Anway, Matthew D.; Leathers, Charles; Skinner, Michael K.

2018-01-01

The fetal basis of adult disease is poorly understood on a molecular level and cannot be solely attributed to genetic mutations or a single etiology. Embryonic exposure to environmental compounds has been shown to promote various disease states or lesions in the first generation (F1). The current study used the endocrine disruptor vinclozolin (antiandrogenic compound) in a transient embryonic exposure at the time of gonadal sex determination in rats. Adult animals from the F1 generation and all subsequent generations examined (F1–F4) developed a number of disease states or tissue abnormalities including prostate disease, kidney disease, immune system abnormalities, testis abnormalities, and tumor development (e.g. breast). In addition, a number of blood abnormalities developed including hypercholesterolemia. The incidence or prevalence of these transgenerational disease states was high and consistent across all generations (F1–F4) and, based on data from a previous study, appears to be due in part to epigenetic alterations in the male germ line. The observations demonstrate that an environmental compound, endocrine disruptor, can induce transgenerational disease states or abnormalities, and this suggests a potential epigenetic etiology and molecular basis of adult onset disease. PMID:16973726

Hormones and endocrine disruptors in human seminal plasma.

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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.

Endocrine Disrupting Chemicals (EDCs)

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... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Hormones and Health › Endocrine Disrupting Chemicals (EDCs) The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) EDCs Myth vs. ...

The Endocrine Machinery.

Science.gov (United States)

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)

Degrading Endocrine Disrupting Chemicals from Wastewater by TiO Photocatalysis: A Review

Directory of Open Access Journals (Sweden)

Jin-Chung Sin

2012-01-01

Full Text Available Widespread concerns continue to be raised about the impacts of exposure to chemical compounds with endocrine disrupting activities. To date, the percolation of endocrine disrupting chemical (EDC effluent into the aquatic system remains an intricate challenge abroad the nations. With the innovation of advanced oxidation processes (AOPs, there has been a consistent growing interest in this research field. Hence, the aim of this paper is to focus one such method within the AOPs, namely, heterogeneous photocatalysis and how it is used on the abatement of EDCs, phthalates, bisphenol A and chlorophenols in particular, using TiO2-based catalysts. Degradation mechanisms, pathways, and intermediate products of various EDCs for TiO2 photocatalysis are described in detail. The effect of key operational parameters on TiO2 photocatalytic degradation of various EDCs is then specifically covered. Finally, the future prospects together with the challenges for the TiO2 photocatalysis on EDCs degradation are summarized and discussed.

Synthesis of surface plasmon resonance (SPR) triggered Ag/TiO2 photocatalyst for degradation of endocrine disturbing compounds

International Nuclear Information System (INIS)

Leong, Kah Hon; Gan, Bee Ling; Ibrahim, Shaliza; Saravanan, Pichiah

2014-01-01

Graphical abstract: - Highlights: • Ag/TiO 2 was synthesized with aid of natural photon stimulated photoreduction. • Deposited Ag prompted well the LSPRs, Schottky barrier for visible light utilization. • Photocatalytic activity was evaluated by degrading EDCs under visible light. • 3.0 wt% Ag/TiO 2 resulted with good photocatalytic efficiency over others. - Abstract: Surface deposition of silver nanoparticles (Ag NPs) onto the 100% anatase titania (Ag/TiO 2 ) for evolution of surface plasmon resonance (SPR) was achieved sustainably with the assistance of solar energy. The preparation resulted in Ag/TiO 2 photocatalyst with varied Ag depositions (0.5 wt%, 1.0 wt%, 3.0 wt% and 5.0 wt%). All obtained photocatalysts were characterized for the evolution of SPR via crystalline phase analysis, morphology, lattice fringes, surface area and pore size characteristics, chemical composition with chemical and electronic state, Raman scattering, optical and photoluminescence properties. The deposition of synthesized Ag NPs exhibited high uniformity and homogeneity and laid pathway for effective utilization of the visible region of electromagnetic spectrum through SPR. The depositions also lead for suppressing recombination rates of electron–hole. The photocatalytic evaluation was carried out by adopting two different class of endocrine disturbing compound (EDC) i.e., amoxicillin (pharmaceutical) and 2,4-dichlorophenol (pesticide) excited with artificial visible light source. Ag/TiO 2 with Ag > 0.5 wt% exhibited significant degradation efficiency for both amoxicillin and 2,4-dichlorophenol. Thus synthesized Ag/TiO 2 revealed the implication of plasmonics on TiO 2 for the enhanced visible light photocatalytic activity

Celiac disease and endocrine autoimmunity.

Science.gov (United States)

Kahaly, George J; Schuppan, Detlef

2015-01-01

Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

Comparative toxicity and endocrine disruption potential of urban and rural atmospheric organic PM1 in JEG-3 human placental cells.

Science.gov (United States)

van Drooge, Barend L; Marqueño, Anna; Grimalt, Joan O; Fernández, Pilar; Porte, Cinta

2017-11-01

Outdoor ambient air particulate matter and air pollution are related to adverse effects on human health. The present study assesses the cytotoxicity and ability to disrupt aromatase activity of organic PM 1 extracts from rural and urban areas at equivalent air volumes from 2 to 30 m 3 , in human placental JEG-3 cells. Samples were chemically analyzed for particle bounded organic compounds with endocrine disrupting potential, i.e. PAH, O-PAH, phthalate esters, but also for organic molecular tracer compounds for the emission source identification. Rural samples collected in winter were cytotoxic at the highest concentration tested and strongly inhibited aromatase activity in JEG-3 cells. No cytotoxicity was detected in summer samples from the rural site and the urban samples, while aromatase activity was moderately inhibited in these samples. In the urban area, the street site samples, collected close to intensive traffic, showed stronger inhibition of aromatase activity than the samples simultaneously collected at a roof site, 50 m above ground level. The cytotoxicity and endocrine disruption potential of the samples were linked to combustion products, i.e. PAH and O-PAH, especially from biomass burning in the rural site in winter. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrochemical nano biosensor alarm devices for the determination of endocrine disruptor agents

International Nuclear Information System (INIS)

Iwuoha, E.; Hendricks, N.; Baker, P.

2009-01-01

The role of cytochrome P450 (CYP) enzyme systems in the detoxification of bioactive and hydrophobic xenobiotics, such as drugs, environmental pollutants, food supplements, steroids and endocrine disruptors, cannot be over-emphasized. In this study we present the development and amperometric transduction of cytochromal biosensor alarm device for the determination of endocrine disruptors. As a class II microsomal b-type heme enzyme, CYP3A4 requires the obligatory presence of electron transfer donor redox protein, NAD(P)H, and cytochrome b5 for its physiological reactivity. Optimal reconstitution assays preferably involves vesicle forming phospholipids, detergents and specialized reducing agents. Biosensor offers the possibility of observing direct electron transfer reaction of cytochrome P450-3A4 (CYP3A4) without the requirement of the enzyme's physiological redox partners (1,2). In this study, a nanobiosensor alarm device for the determination of 2,4-dichlorophenol (an endocrine disruptor and hepatocarcinogen) was developed with genetically engineered CYP3A4 imprinted on carbon electrode chips that was modified with polypyrrole-gold nanoparticles. The sensor amperometric signals resulted from the two-electron monooxygenation reaction between the ferri-heme CYP3A4 enzyme and the endocrine disruptor compound. The biosensor was interrogated electrochemically for its ability to detect and report the presence of the endocrine disruptor compound in real time. Accordingly, the response time, sensitivity, storage stability, dynamic linear range and detection limits of the device were evaluated. The biosensor alarm device had a detection limit of 43 ng/L for 2,4-dichlorophenol which is lower than the European Union limit of 300 ng/L for pesticide compounds in ground water; as well as the USA Environmental Protection Agency's drinking water equivalent level (DWEL) of 2000 ng/L (3,4). Chromatographic studies despite their tedious sample preparation and time-consuming pre

Short- and long-term temporal changes in soil concentrations of selected endocrine disrupting compounds (EDCs) following single or multiple applications of sewage sludge to pastures

International Nuclear Information System (INIS)

Rhind, S.M.; Kyle, C.E.; Ruffie, H.; Calmettes, E.; Osprey, M.; Zhang, Z.L.; Hamilton, D.; McKenzie, C.

2013-01-01

Temporal changes in soil burdens of selected endocrine disrupting compounds were determined following application to pasture of either sewage sludge or inorganic fertilizer. Soil polycyclic aromatic hydrocarbon and polychlorinated biphenyl concentrations were not altered. Changes in concentrations of diethylhexyl phthalate (DEHP) and PBDEs 47 and 99 differed with season but concentrations remained elevated for more than three weeks after application, when grazing animals are normally excluded from pasture. It is concluded that single applications of sewage sludge can increase soil concentrations of some, but not all classes of EDCs, possibly to concentrations sufficient to exert biological effects when different chemicals act in combination, but patterns of change depend on season and soil temperature. Analysis of soil from pasture subjected to repeated sludge applications, over 13 years, provided preliminary evidence of greater increases in soil burdens of all of the EDC groups measured, including all of the PBDE congeners measured. -- Highlights: •Sewage sludge or inorganic fertilizer was applied to pasture. •Soil PAH and PCB concentrations were not altered by sludge treatment. •Temporal changes in soil phthalate and PBDE differed with season. •Some soil EDC levels were elevated for more than three weeks after application. -- Effects of sewage sludge application to pastures on temporal changes in soil concentrations of endocrine disrupting compounds differ with chemical class and season

Abnormal gastrointestinal endocrine cells in patients with diabetes type 1: relationship to gastric emptying and myoelectrical activity.

Science.gov (United States)

El-Salhy, M; Sitohy, B

2001-11-01

Gastrointestinal symptoms in patients with diabetes are believed to be caused by gastrointestinal dysmotility and secretion/absorption disturbances, and the gut endocrine cells play an important part in regulating these two functions. Studies on animal models of human diabetes type I revealed abnormality in these cells, but it is unknown whether abnormality also occurs in patients with diabetes. Eleven patients with long duration of diabetes type I and organ complications, as well as gastrointestinal symptoms, were studied. Endocrine cells in different segments of the gastrointestinal tract were detected by immunocytochemistry and quantified by computerized image analysis. Gastric emptying was measured by scintigraphy and gastric myoelectric activity was determined by electrogastrography. An abnormal density of gastrointestinal endocrine cells was found in patients with diabetes. This abnormality occurred in all segments of the upper and lower gastrointestinal tract investigated, and included most of the endocrine cell types. The patients showed delayed gastric emptying, which correlated closely with the acute glucose level, but did not correlate with HbA1c. Gastric emptying also correlated closely with the density of duodenal serotonin and secretin cells. The patients exhibited bradygastrias and tachygastrias. These dysrhythmias, however, did not differ significantly from controls. The endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. The abnormality in density of the gastrointestinal endocrine cells may contribute to the development of gastrointestinal dysmotility and the symptoms encountered in patients with diabetes.

Product-to-Parent Reversion of Trenbolone: Unrecognized Risks for Endocrine Disruption

NARCIS (Netherlands)

Qu, Shen; Kolodziej, E.P.; Long, S.A.; Gloer, J.B.; Patterson, E.V.; Baltrusaitis, Jonas; Jones, G.D.; Benchetler, P.V.; Cole, E.A.; Kimbrough, K.C.; Tarnoff, M.D.; Cwiertny, D.M.

2013-01-01

Trenbolone acetate (TBA) is a high-value steroidal growth promoter often administered to beef cattle, whose metabolites are potent endocrine-disrupting compounds. We performed laboratory and field phototransformation experiments to assess the fate of TBA metabolites and their photoproducts.

Fluorinated alkyl substances and technical mixtures used in food paper-packaging exhibit endocrine-related activity in vitro.

Science.gov (United States)

Rosenmai, A K; Taxvig, C; Svingen, T; Trier, X; van Vugt-Lussenburg, B M A; Pedersen, M; Lesné, L; Jégou, B; Vinggaard, A M

2016-07-01

Migration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can be used in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum and umbilical cord blood. The specific structures of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters (PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting the need to investigate these effects. Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs of unknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, glucocorticoid, androgen, and peroxisome proliferator-activated receptor (PPAR) activity, as well as steroidogenesis in vitro and ex vivo. In general, PAPs, FTOHs, TMs, and long-chain PFCAs showed estrogenic activity through receptor activation and/or increasing 17β-estradiol levels. Furthermore, short- and long-chain PFCAs activated PPARα and PPARγ. Collectively, this means that (i) PAPs, FTOHs, and PFCAs exhibit endocrine activity through distinct and sometimes different mechanisms, (ii) two out of three tested TMs exhibited estrogenic activity, and (iii) short-chain FTOHs showed estrogenic activity and short-chain PFCAs generally activate both PPARα and PPARγ with similar potency and efficacy as long-chain PFCAs. In conclusion, several new and divergent toxicological targets were identified for different groups of PFAS. © 2016 American Society of Andrology and European Academy of Andrology.

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

Science.gov (United States)

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomarkers used in Environmental Health with focus on Endocrine Disrupters

DEFF Research Database (Denmark)

Krüger, Tanja; Ghisari, Mandana; Long, Manhai

2012-01-01

Endocrine-disrupting chemicals (EDCs) are compounds that either mimic or block endogenous hormones and can disrupt the normal function of the body. Bio-monitoring is the assessment of internal doses of EDCs and has been used for decades to provide information about exposures to chemicals giving...

Elucidation of endocrine disrupting mechanism of dioxin and related compounds for health risk assessment

Energy Technology Data Exchange (ETDEWEB)

Tohyama, Chiharu [National Institute for Environmental Studies, Tsukuba (Japan)

2004-09-15

The important point on health risk assessment for dioxins as well as environmental endocrine disruptors is that we should scientifically evaluate whether the actual exposure level from food and environment may pose a threat to human health not only for the present but also for the future generations. We formulated a research project, called CREST project with support from the Japan Science and Technology Agency, in order to obtain experimental evidence for risk assessment as well as for the mechanism of toxicity. We thus investigated the dose-response relationships of certain 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD)-like compounds for eliciting various endpoints. First, we administered TCDD or coplanar polychlorinated biphenyl (PCB) to rats and mice during the sensitive period from fertilization to birth. Second, we studied what kinds of adverse effects could be observed in terms of reproductive/developmental effects, cognitive/learning abilities and immune functions. Third, we focused on the actual toxicity phenotypes found at the whole body and organ/tissue levels by a forward toxicology approach, and tried to narrow down appropriate phenomena, to study the mechanism on the molecular basis by the reverse toxicology approach. In this presentation, I will summarize the outcome of the CREST project.

Natural compounds with herbicidal activity

Directory of Open Access Journals (Sweden)

Mariano Fracchiolla

2007-12-01

Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

Natural compounds with herbicidal activity

Directory of Open Access Journals (Sweden)

Pasquale Montemurro

2011-02-01

Full Text Available Research about phytotoxic activity of natural compounds could lead both to find new herbicidal active ingredients and to plan environmental friendly weed control strategies. Particularly, living organisms could be a source of compounds that are impossible, for their complexity, to synthesize artificially. More over, they could have alternative sites of action respect to the known chemical herbicides and, due to their origin, they should be more environmental safe. Many living organism, such as bacteria, fungi, insects, lichens and plants, are able to produce bioactive compounds. They generally are secondary metabolites or simply waste molecules. In this paper we make a review about these compounds, highlighting potential and constraints.

Endocrine-disrupting chemicals: associated disorders and mechanisms of action.

Science.gov (United States)

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.

Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action

Directory of Open Access Journals (Sweden)

Sam De Coster

2012-01-01

Full Text Available 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.

The Role of Uron and Chlorobenzene Derivatives, as Potential Endocrine Disrupting Compounds, in the Secretion of ACTH and PRL

Directory of Open Access Journals (Sweden)

Krisztian Sepp

2018-01-01

Full Text Available Uron herbicides polluting the environment represent a serious concern for environmental health and may be regarded as endocrine-disrupting compounds (EDCs, which influence the regulation of human homeostasis. We aimed to investigate the effect of EDC urons (phenuron: PU, monuron: MU, and diuron: DU and chlorobenzenes on the basal release of the adrenocorticotropic hormone (ACTH, which is a part of the adenohypophysis-adrenocortical axis. Hormone secretion in the presence of EDC was studied in two cell types: normal adenohypophysis cells (AdH and cells of prolactinomas (PRLOMA. PRLOMA was induced in female Wistar rats by subcutaneously injecting them with estrone acetate for 6 months. AdH and PRLOMA were separated from treated and untreated experimental animals, dissociated enzymatically and mechanically in order to create monolayer cell cultures, which served as an experimental in vitro model. We investigated the effects of ED agents separately and in combination on ACTH and prolactin (PRL release through the hypophyseal-adrenal axis. Hormone determination was carried out by the luminescent immunoassay and the radioimmunoassay methods. Our results showed that (1 uron agents separately did not change ACTH and PRL release in AdH culture; (2 ACTH secretion in arginine vasopressin- (AVP- activated AdH cells was significantly increased by EDC treatment; (3 ED agents increased the basal hormone release (ACTH, PRL in PRLOMA cells; and (4 EDC exposure increased ACTH release in AVP-activated PRLOMA cells. We conclude that the herbicides PU, MU, and DU carry EDC effects and show human toxicity potential.

Endocrine disruption effects in male and intersex roach (Rutilus rutilus, L.) from French rivers: An integrative approach based on subcellular to individual responses.

Science.gov (United States)

Geraudie, Perrine; Gerbron, Marie; Minier, Christophe

2017-09-01

Among the chemicals found in the aquatic environment, some have been reported to interact with the endocrine system of organisms and have been identified as endocrine disrupting compounds. In this study, we have assessed the biological effects due to environmental estrogenic compounds in adult male roach (Rutilus rutilus). Wild fish were collected in the Seine River, and one of its affluent, the Epte River in Normandy, France and impacts on endocrine and reproductive functions have been assessed. This study provides innovative data on the intersex condition in wild fish that are crucial to understand estrogenic contamination impacts and maintenance of sustainable fish population. The biomarker responses found in fish from contaminated sites included high plasmatic vitellogenin concentrations, altered steroid levels, histopathological and up to 50% intersex fish among the male. However, the overall sex ratio of the roach population indicated sign of feminization with some sites showing only 20% of males. The chemical organic contamination at the different location sites has been characterized by the levels of PAHs, PCBs and phthalates and total estrogenic activity was measured by the YES in vitro assay. Copyright © 2017 Elsevier Inc. All rights reserved.

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

DEFF Research Database (Denmark)

Matthiessen, Peter; Ankley, Gerald T.; Biever, Ronald C

2017-01-01

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...... 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...

Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds

International Nuclear Information System (INIS)

Boehme, Kathleen; Simon, Stephanie; Mueller, Stefan O.

2009-01-01

Several anthropogenous and naturally occurring substances, referred to as estrogen active compounds (EACs), are able to interfere with hormone and in particular estrogen receptor signaling. EACs can either cause adverse health effects in humans and wildlife populations or have beneficial effects on estrogen-dependent diseases. The aim of this study was to examine global gene expression profiles in estrogen receptor (ER)-proficient Ishikawa plus and ER-deficient Ishikawa minus endometrial cancer cells treated with selected well-known EACs (Diethylstilbestrol, Genistein, Zearalenone, Resveratrol, Bisphenol A and o,p'-DDT). We also investigated the effect of the pure antiestrogen ICI 182,780 (ICI) on the expression patterns caused by these compounds. Transcript levels were quantified 24 h after compound treatment using Illumina BeadChip Arrays. We identified 87 genes with similar expression changes in response to all EAC treatments in Ishikawa plus. ICI lowered the magnitude or reversed the expression of these genes, indicating ER dependent regulation. Apart from estrogenic gene regulation, Bisphenol A, o,p'-DDT, Zearalenone, Genistein and Resveratrol displayed similarities to ICI in their expression patterns, suggesting mixed estrogenic/antiestrogenic properties. In particular, the predominant antiestrogenic expression response of Resveratrol could be clearly distinguished from the other test compounds, indicating a distinct mechanism of action. Divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals Bisphenol A and o,p'-DDT, warrants a careful assessment of potential detrimental and/or beneficial effects of EACs. The characteristic expression fingerprints and the identified subset of putative marker genes can be used for screening chemicals with an unknown mode of action and for predicting their potential to exert endocrine disrupting effects

Use of external metabolizing systems when testing for endocrine disruption in the T-screen assay

International Nuclear Information System (INIS)

Taxvig, Camilla; Olesen, Pelle Thonning; Nellemann, Christine

2011-01-01

Although, it is well-established that information on the metabolism of a substance is important in the evaluation of its toxic potential, there is limited experience with incorporating metabolic aspects into in vitro tests for endocrine disrupters. The aim of the current study was a) to study different in vitro systems for biotransformation of ten known endocrine disrupting chemicals (EDs): five azole fungicides, three parabens and 2 phthalates, b) to determine possible changes in the ability of the EDs to bind and activate the thyroid receptor (TR) in the in vitro T-screen assay after biotransformation and c) to investigate the endogenous metabolic capacity of the GH3 cells, the cell line used in the T-screen assay, which is a proliferation assay used for the in vitro detection of agonistic and antagonistic properties of compounds at the level of the TR. The two in vitro metabolizing systems tested the human liver S9 mix and the PCB-induced rat microsomes gave an almost complete metabolic transformation of the tested parabens and phthalates. No marked difference the effects in the T-screen assay was observed between the parent compounds and the effects of the tested metabolic extracts. The GH3 cells themselves significantly metabolized the two tested phthalates dimethyl phthalate (DMP) and diethyl phthalate (DEP). Overall the results and qualitative data from the current study show that an in vitro metabolizing system using liver S9 or microsomes could be a convenient method for the incorporation of metabolic and toxicokinetic aspects into in vitro testing for endocrine disrupting effects.

Fluorinated alkyl substances and technical mixtures used in food paper-packaging exhibit endocrine-related activity in vitro

DEFF Research Database (Denmark)

Rosenmai, Anna Kjerstine; Taxvig, Camilla; Svingen, Terje

2016-01-01

Migration of chemicals from packaging materials to foods may lead to human exposure. Polyfluoroalkyl substances (PFAS) can be used in technical mixtures (TMs) for use in food packaging of paper and board, and PFAS have been detected in human serum and umbilical cord blood. The specific structures...... of the PFAS in TMs are often unknown, but polyfluorinated alkyl phosphate esters (PAPs) have been characterized in TMs, food packaging, and in food. PAPs can be metabolized into fluorotelomer alcohols (FTOHs) and perfluoroalkyl carboxylic acids (PFCAs). Some PFAS have endocrine activities, highlighting...... the need to investigate these effects. Herein, we studied the endocrine activity of less characterized PFAS, including short-chain PFCAs and FTOHs, PAPs, and TMs of unknown chemical composition. Long-chain PFCAs were also included. We applied seven assays covering effects on estrogen, glucocorticoid...

SECONDARY (ENDOCRINE HYPERTENSION: LECTURE

Directory of Open Access Journals (Sweden)

M. Yu. Yukina

2016-01-01

Full Text Available Hypertension is a  very common disease with high morbidity and reduction in quality of life. Endocrine disorders are the most common cause of secondary hypertension affecting ~3% of the population. Primary aldosteronism can be the cause of endocrine hypertension more often than other endocrine disorders. Other less common causes of endocrine hypertension include Cushing syndrome, pheochromocytoma, thyroid disorders, and hyperparathyroidism. Endocrine hypertension is potentially curable if the underlying cause is identified and treated accordingly. Younger age at manifestation of resistance to multiple antihypertensive drugs, together with other clinical signs of an endocrine disorder, should raise the suspicion and prompt the appropriate evaluation.

Clinical activity of fulvestrant in metastatic breast cancer previously treated with endocrine therapy and/or chemotherapy.

Science.gov (United States)

Heo, Mi Hwa; Kim, Hee Kyung; Lee, Hansang; Kim, Ji-Yeon; Ahn, Jin-Seok; Im, Young-Hyuck; Park, Yeon Hee

2018-03-16

We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy. We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016). Tumor responses were assessed every 8 weeks and at the end of treatment, as well as when disease progression was suspected. A total of 84 patients were included in this study. A median of two previous endocrine treatments had been performed; 79% of the patients had received two or more endocrine treatments. Forty-five patients (54%) had been treated with chemotherapy for MBC before the fulvestrant treatment course. Visceral metastasis was found in 49 patients (58%). The estimated median progression-free survival and overall survival were 4.4 months (95% confidence interval [CI], 3.4 to 5.5) and 32.5 months (95% CI, 17.6 to 47.4), respectively. The disease control rate was 40.5% (95% CI, 30.5 to 51.5); partial response was observed in 16% of the patients and stable disease was observed in 25% of the patients. The most frequently reported adverse reactions were mild-to-moderate grade myalgia (10.5% of the patients), injection site pain (7%), and fatigue (7%). Fulvestrant was generally well tolerated. Fulvestrant showed encouraging clinical activity and favorable feasibility in postmenopausal women with MBC who had been treated with multiple endocrine therapies and/or cytotoxic chemotherapies.

Endocrine Disrupters in Human Blood and Breast Milk: Extraction Methodologies, Cellular Uptake and Effect on Key Nuclear Receptor Functions

DEFF Research Database (Denmark)

Hjelmborg, Philip Sebastian

2010-01-01

-products from incineration plants, plastic additives, technical industry products, pesticides from the farming industry and detergent degradation products. Many of these substances can interfere with the hormonal system in organisms. The common name for these compounds is endocrine disrupters (EDCs). Some EDCs...... are persistent to degradation and are also called persistent organic pollutants (POPs). Endocrine disrupters are compounds that can interfere with an organism’s hormone system by interacting with the hormone receptors. Many of an organism’s body functions are controlled by interactions between hormones...

Endocrine disrupting chemicals: harmful substances and how to test them

Directory of Open Access Journals (Sweden)

Olea-Serrano Nicolás

2002-01-01

Full Text Available This paper presents an analysis of the opinions of different groups from: scientists, international regulatory bodies, non-governmental organizations and industry; with an interest in the problem of identifying chemical substances with endocrine disrupting activity. There is also discussion of the consequences that exposure to endocrine disruptors may have for human health, considering concrete issues related to: the estimation of risk; the tests that must be used to detect endocrine disruption; the difficulties to establish an association between dose, time of exposure, individual susceptibility, and effect; and the attempts to create a census of endocrine disruptors. Finally, it is proposed that not all hormonal mimics should be included under the single generic denomination of endocrine disruptors.

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

Science.gov (United States)

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

Environmental analysis of endocrine disrupting effects from hydrocarbon contaminants in the ecosystem. 1997 annual progress report

International Nuclear Information System (INIS)

1997-01-01

'The overall objective of the basic research grant is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. The three major lines of research include (1) a biotechnology based screening system to identify potential hormone mimics and antagonists; (2) an animal screening system to identify biomarkers of endocrine effects. and (3) a literature review to identify compounds at a variety of DOE sites that need to be examined for endocrine disrupting effects. By relating results obtained from this research project to contamination problems at various DOE sites. CBR will provide data and information on endocrine disrupting contaminants to DOE for consideration in risk analyses for determining clean-up levels and priorities needed at the sites.'

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

Energy Technology Data Exchange (ETDEWEB)

Yu, Z.; Peldszus, S.; Huck, P.M. [University of Waterloo, Waterloo, ON (Canada). NSERC Chair in Water Treatment

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.

Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.

Directory of Open Access Journals (Sweden)

Alison M Anderson

Full Text Available BACKGROUND: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. METHODOLOGY/PRINCIPAL FINDINGS: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.

In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites

Energy Technology Data Exchange (ETDEWEB)

Hamers, T.; Kamstra, J.H. [Inst. for Environmental Studies (IVM), Amsterdam (Netherlands); Sonneveld, E. [BioDetection Systems (BDS), Amsterdam (Netherlands); Murk, A.J. [Wageningen Univ., Toxicology Group, Wageningen (Netherlands); Zegers, B.N.; Boon, J.P. [Royal Netherlands Inst. for Sea Research (NIOZ), Den Burg (Netherlands); Brouwer, A. [Umea Univ., Umea (Sweden)

2004-09-15

Substantial evidence is recently becoming available that brominated flame retardants (BFRs) are potential endocrine disruptors. The toxicological profile of BFRs, however, is too incomplete and insufficient to perform human and ecological risk assessment. To fill these gaps, the EU funded research program FIRE was started in December 2002. This program aims at the identification and toxicological characterization of the most potent and environmentally relevant BFRs and their possible risk for human and wildlife health. As part of a hazard identification approach, twenty seven BFRs have been selected within the framework of FIRE for pre-screening their endocrinedisrupting potencies. Selection of test compounds was based on a maximal variation in physicochemical characteristics of BFRs within the test set, allowing the establishment of quantitative structure-activity relationships (QSARs). In addition, environmental relevance (e.g. high production volumes and persistence) and availability for testing were used as selection criteria. BFRs were tested in seven different in vitro bioassays for their potency to interfere via estrogenic, thyroidal, androgenic, progestagenic, and Ah-receptor mediated pathways. Metabolisation rates of BFRs were determined using phenobarbital-induced rat liver microsomes. Finally, the endocrine disrupting potency of the metabolites was determined in the same in vitro bio-assays and compared to the potency of the parent compounds.

Endocrine Disruptors and Leydig Cell Function

Directory of Open Access Journals (Sweden)

K. Svechnikov

2010-01-01

Full Text Available During the past decades, a large body of information concerning the effects of endocrine disrupting compounds (EDCs on animals and humans has been accumulated. EDCs are of synthetic or natural origin and certain groups are known to disrupt the action of androgens and to impair the development of the male reproductive tract and external genitalia. The present overview describes the effects of the different classes of EDCs, such as pesticides, phthalates, dioxins, and phytoestrogens, including newly synthesized resveratrol analogs on steroidogenesis in Leydig cells. The potential impact of these compounds on androgen production by Leydig cells during fetal development and in the adult age is discussed. In addition, the possible role of EDCs in connection with the increasing frequency of abnormalities in reproductive development in animals and humans is discussed.

QSAR Methods to Screen Endocrine Disruptors

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Nicola Porta

2016-08-01

Full Text Available The identification of endocrine disrupting chemicals (EDCs is one of the important goals of environmental chemical hazard screening. We report on in silico methods addressing toxicological studies about EDCs with a special focus on the application of QSAR models for screening purpose. Since Estrogen-like (ER activity has been extensively studied, the majority of the available models are based on ER-related endpoints. Some of these models are here reviewed and described. As example for their application, we screen an assembled dataset of candidate substitutes for some known EDCs belonging to the chemical classes of phthalates, bisphenols and parabens, selected considering their toxicological relevance and broad application, with the general aim of preliminary assessing their ED potential. The goal of the substitution processes is to advance inherently safer chemicals and products, consistent with the principles of green chemistry. Results suggest that the integration of a family of different models accounting for different endpoints can be a convenient way to describe ED as properly as possible and allow also both to increase the confidence of the predictions and to maximize the probability that most active compounds are correctly found.

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

Science.gov (United States)

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...

Purinergic signaling pathways in endocrine system.

Science.gov (United States)

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. Published by Elsevier B.V.

Purinergic Signaling Pathways in Endocrine System

Science.gov (United States)

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

The role of toxicology to characterize biomarkers for agrochemicals with potential endocrine activities.

Science.gov (United States)

Mantovani, Alberto; Maranghi, Francesca; La Rocca, Cinzia; Tiboni, Gian Mario; Clementi, Maurizio

2008-09-01

The paper discusses current knowledge and possible research priorities on biomarkers of exposure, effect and susceptibility for potential endocrine activities of agrochemicals (dicarboximides, ethylene bisdithiocarbammates, triazoles, etc.). Possible widespread, multiple-pathway exposure to agrochemicals highlights the need to assess internal exposure of animals or humans, which is the most relevant exposure measure for hazard and risk estimation; however, exposure data should be integrated by early indicators predictive of possible health effects, particularly for vulnerable groups such as mother-child pairs. Research need include: non-invasive biomarkers for children biomonitoring; novel biomarkers of total exposure to measure whole endocrine disrupter-related burden; characterization of biomarkers of susceptibility, including the role of markers of nutritional status; anchoring early molecular markers to established toxicological endpoints to support their predictivity; integrating "omics"-based approaches in a system-toxicology framework. As biomonitoring becomes increasingly important in the environment-and-health scenario, toxicologists can substantially contribute both to the characterization of new biomarkers and to the predictivity assessment and improvement of the existing ones.

Central control of glucose homeostasis: the brain--endocrine pancreas axis.

Science.gov (United States)

Thorens, B

2010-10-01

A large body of data gathered over the last decades has delineated the neuronal pathways that link the central nervous system with the autonomic innervation of the endocrine pancreas, which controls alpha- and beta-cell secretion activity and mass. These are important regulatory functions that are certainly keys for preserving the capacity of the endocrine pancreas to control glucose homeostasis over a lifetime. Identifying the cells involved in controlling the autonomic innervation of the endocrine pancreas, in response to nutrient, hormonal and environmental cues and how these cues are detected to activate neuronal activity are important goals of current research. Elucidation of these questions may possibly lead to new means for preserving or restoring defects in insulin and glucagon secretion associated with type 2 diabetes. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin

OpenAIRE

Brander, Susanne M.; He, Guochun; Smalling, Kelly L.; Denison, Michael S.; Cherr, Gary N.

2012-01-01

Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. We evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Men...

Changes in endocrine thymus function in patients with breast cancer under the action of combined treatment including non-specific active immunotherapy

International Nuclear Information System (INIS)

Bendyug, G.D.

1988-01-01

The state of endocrine thymus function in patients with breast cancer of the 1st-4th stage and in 31 patients with precancerous diseases is studied. It is established that considerable decrease of thymus serous factor (TSF) content in all patients is observed. Radiation- and polychemotherapy carried out decreases the endocrine thymus function. Inclusions of non-specific active immunotherapy in patients' treatment promote the increase of TSF content, that increases treatment efficiency

Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells

Science.gov (United States)

Bechard, Matthew E.; Bankaitis, Eric D.; Hipkens, Susan B.; Ustione, Alessandro; Piston, David W.; Yang, Yu-Ping; Magnuson, Mark A.; Wright, Christopher V.E.

2016-01-01

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 Neurog3TA.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+ Neurog3TA.LO progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3HI cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9+ Neurog3TA.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+ Neurog3TA.LO endocrine-biased progenitors feed production of Neurog3HI endocrine-committed cells during pancreas organogenesis. PMID:27585590

Surgical strategies in endocrine tumors

NARCIS (Netherlands)

Schreinemakers, J.M.J.

2010-01-01

Endocrine surgery has become more custom-made throughout the years. Endocrine tumors can be sporadic or develop as part of familial syndromes. Several familial syndromes are known to cause endocrine tumors. The most common are multiple endocrine neoplasia (MEN) syndromes type 1, 2A and 2B. This

Endocrine myopathy: Case-based review

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Babul Reddy Hanmayyagari

2016-01-01

Full Text Available Endocrine myopathy means muscle weakness in the presence of an abnormal endocrine state. Most of the endocrine disorders are associated with myopathy and it is usually reversible with correction of the underlying disturbance, though, there is an increasing knowledge of the metabolic effects of hormones, endocrine myopathy is a less recognized and often overlooked entity in clinical practice. Here, we describe this association in three of our patients, then, we discuss systematically about endocrine myopathy.

Assessment of the effects of the carbamazepine on the endogenous endocrine system of Daphnia magna.

Science.gov (United States)

Oropesa, A L; Floro, A M; Palma, P

2016-09-01

In the present study, the endocrine activity of the antiepileptic pharmaceutical carbamazepine (CBZ) in the crustacean Daphnia magna was assessed. To assess the hormonal activity of the drug, we exposed maternal daphnids and embryos to environmental relevant concentrations of CBZ (ranging from 10 to 200 μg/L) and to mixtures of CBZ with fenoxycarb (FEN; 1 μg/L). Chronic exposure to CBZ significantly decreased the reproductive output and the number of molts of D. magna at 200 μg/L. This compound induced the production of male offspring (12 ± 1.7 %), in a non-concentration-dependent manner, acting as a weak juvenile hormone analog. Results showed that this substance, at tested concentrations, did not antagonize the juvenoid action of FEN. Further, CBZ has shown to be toxic to daphnid embryos through maternal exposure interfering with their normal gastrulation and organogenesis stages but not producing direct embryo toxicity. These findings suggest that CBZ could act as an endocrine disruptor in D. magna as it decreases the reproductive output, interferes with sex determination, and causes development abnormality in offspring. Therefore, CBZ could directly affect the population sustainability.

Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

Energy Technology Data Exchange (ETDEWEB)

Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Efstathiou, Theo [Laboratoire Nutrinov, Technopole Atalante Champeaux, 8 rue Jules Maillard de la Gournerie, 35012 Rennes Cedex (France); Saligaut, Christian [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France); Pakdel, Farzad, E-mail: farzad.pakdel@univ-rennes1.fr [Institut de Recherche en Santé-Environnement-Travail (IRSET), Inserm UMR 1085, Team Transcription, Environment and Cancer, University of Rennes 1, 9 Avenue du Pr Léon Bernard, 35000 Rennes (France)

2017-06-15

Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as a model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and

Association between degradation of pharmaceuticals and endocrine-disrupting compounds and microbial communities along a treated wastewater effluent gradient in Lake Mead

Science.gov (United States)

Blunt, Susanna M.; Sackett, Joshua D.; Rosen, Michael R.; Benotti, Mark J.; Trenholm, Rebecca A.; Vanderford, Brett J.; Hedlund, Brian P.; Moser, Duane P.

2018-01-01

The role of microbial communities in the degradation of trace organic contaminants in the environment is little understood. In this study, the biotransformation potential of 27 pharmaceuticals and endocrine-disrupting compounds was examined in parallel with a characterization of the native microbial community in water samples from four sites variously impacted by urban run-off and wastewater discharge in Lake Mead, Nevada and Arizona, USA. Samples included relatively pristine Colorado River water at the upper end of the lake, nearly pure tertiary-treated municipal wastewater entering via the Las Vegas Wash, and waters of mixed influence (Las Vegas Bay and Boulder Basin), which represented a gradient of treated wastewater effluent impact. Microbial diversity analysis based on 16S rRNA gene censuses revealed the community at this site to be distinct from the less urban-impacted locations, although all sites were similar in overall diversity and richness. Similarly, Biolog EcoPlate assays demonstrated that the microbial community at Las Vegas Wash was the most metabolically versatile and active. Organic contaminants added as a mixture to laboratory microcosms were more rapidly and completely degraded in the most wastewater-impacted sites (Las Vegas Wash and Las Vegas Bay), with the majority exhibiting shorter half-lives than at the other sites or in a bacteriostatic control. Although the reasons for enhanced degradation capacity in the wastewater-impacted sites remain to be established, these data are consistent with the acclimatization of native microorganisms (either through changes in community structure or metabolic regulation) to effluent-derived trace contaminants. This study suggests that in urban, wastewater-impacted watersheds, prior exposure to organic contaminants fundamentally alters the structure and function of microbial communities, which in turn translates into greater potential for the natural attenuation of these compounds compared to more pristine

Contribution of the Endocrine Perspective in the Evaluation of Endocrine Disrupting Chemical Effects

DEFF Research Database (Denmark)

Bourguignon, Jean-Pierre; Juul, Anders; Franssen, Delphine

2016-01-01

Debate makes science progress. In the field of endocrine disruption, endocrinology has brought up findings that substantiate a specific perspective on the definition of endocrine disrupting chemicals (EDCs), the role of the endocrine system and the endpoints of hormone and EDC actions among other...... issues. This paper aims at discussing the relevance of the endocrine perspective with regard to EDC effects on pubertal timing. Puberty involves particular sensitivity to environmental conditions. Reports about the advancing onset of puberty in several countries have led to the hypothesis...

ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

Directory of Open Access Journals (Sweden)

P. V. Novokhatny

2014-02-01

Full Text Available Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis. Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE. Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by

Endocrine disruption in a terrestrial isopod under exposure to bisphenol A and vinclozin.

NARCIS (Netherlands)

Lemos, M.F.L.; van Gestel, C.A.M.; Soares, A.M.V.M.

2009-01-01

Background, aim, and scope In the past decade there has been an increasing awareness about the possible consequences of human and wildlife exposure to endocrine disrupting compounds (EDCs). Bisphenol A (BPA) and vinclozolin (Vz) are EDCs which impacts on vertebrates have been largely investigated.

Parental effects of endocrine disrupting compounds in aquatic wildlife: Is there evidence of transgenerational inheritance?

Science.gov (United States)

Schwindt, Adam R

2015-08-01

The effects of endocrine disrupting compounds (EDCs) on aquatic wildlife are increasingly being recognized for their complexity. Investigators have detected alterations at multiple levels of biological organization in offspring exposed to EDCs through the blood or germ line of the parents, suggesting that generational consequences of EDCs are evident. Exposure to EDCs through the parents is concerning because if the resulting phenotype of the offspring is heritable and affects fitness, then evolutionary consequences may be evident. This review summarizes the evidence for transgenerational effects of EDCs in aquatic wildlife and illustrates cases where alterations appear to be transmitted maternally, paternally, or parentally. The literature indicates that EDC exposure to the parents induces developmental, physiological, endocrinological, and behavioral changes as well as increased mortality of offspring raised in clean environments. What is lacking, however, is a clear demonstration of heritable transgenerational effects in aquatic wildlife. Therefore, it is not known if the parental effects are the result of developmental or phenotypic plasticity or if the altered phenotypes are durably passed to subsequent generations. Epigenetic changes to gene regulation are discussed as a possible mechanism responsible for EDC induced parental effects. Additional research is needed to evaluate if heritable effects of EDCs are evident in aquatic wildlife, as has been demonstrated for terrestrial mammals. Copyright © 2015 Elsevier Inc. All rights reserved.

Activation of RXR–PPAR heterodimers by organotin environmental endocrine disruptors

Science.gov (United States)

le Maire, Albane; Grimaldi, Marina; Roecklin, Dominique; Dagnino, Sonia; Vivat-Hannah, Valérie; Balaguer, Patrick; Bourguet, William

2009-01-01

The nuclear receptor retinoid X receptor-α (RXR-α)–peroxisome proliferator-activated receptor-γ (PPAR-γ) heterodimer was recently reported to have a crucial function in mediating the deleterious effects of organotin compounds, which are ubiquitous environmental contaminants. However, because organotins are unrelated to known RXR-α and PPAR-γ ligands, the mechanism by which these compounds bind to and activate the RXR-α–PPAR-γ heterodimer at nanomolar concentrations has remained elusive. Here, we show that tributyltin (TBT) activates all three RXR–PPAR-α, -γ, -δ heterodimers, primarily through its interaction with RXR. In addition, the 1.9 Å resolution structure of the RXR-α ligand-binding domain in complex with TBT shows a covalent bond between the tin atom and residue Cys 432 of helix H11. This interaction largely accounts for the high binding affinity of TBT, which only partly occupies the RXR-α ligand-binding pocket. Our data allow an understanding of the binding and activation properties of the various organotins and suggest a mechanism by which these tin compounds could affect other nuclear receptor signalling pathways. PMID:19270714

Endocrine system: part 1.

Science.gov (United States)

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.

Mitochondrial disease and endocrine dysfunction.

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Chow, Jasmine; Rahman, Joyeeta; Achermann, John C; Dattani, Mehul T; Rahman, Shamima

2017-02-01

Mitochondria are critical organelles for endocrine health; steroid hormone biosynthesis occurs in these organelles and they provide energy in the form of ATP for hormone production and trafficking. Mitochondrial diseases are multisystem disorders that feature defective oxidative phosphorylation, and are characterized by enormous clinical, biochemical and genetic heterogeneity. To date, mitochondrial diseases have been found to result from >250 monogenic defects encoded across two genomes: the nuclear genome and the ancient circular mitochondrial genome located within mitochondria themselves. Endocrine dysfunction is often observed in genetic mitochondrial diseases and reflects decreased intracellular production or extracellular secretion of hormones. Diabetes mellitus is the most frequently described endocrine disturbance in patients with inherited mitochondrial diseases, but other endocrine manifestations in these patients can include growth hormone deficiency, hypogonadism, adrenal dysfunction, hypoparathyroidism and thyroid disease. Although mitochondrial endocrine dysfunction frequently occurs in the context of multisystem disease, some mitochondrial disorders are characterized by isolated endocrine involvement. Furthermore, additional monogenic mitochondrial endocrine diseases are anticipated to be revealed by the application of genome-wide next-generation sequencing approaches in the future. Understanding the mitochondrial basis of endocrine disturbance is key to developing innovative therapies for patients with mitochondrial diseases.

Cosmetics as endocrine disruptors: are they a health risk?

Science.gov (United States)

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".

RESPONSE OF JAPANESE MEDAKA TO 17B-ESTRADIOL: A TIME COURSE OF ENDOCRINE-MEDIATED EFFECTS

Science.gov (United States)

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 ...

Update in endocrine autoimmunity.

Science.gov (United States)

Anderson, Mark S

2008-10-01

The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

Species-specific considerations in using the fish embryo test as an alternative to identify endocrine disruption.

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Schiller, Viktoria; Zhang, Xiaowei; Hecker, Markus; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

2014-10-01

A number of regulations have been implemented that aim to control the release of potentially adverse endocrine disrupters into the aquatic environment based on evidence from laboratory studies. Currently, such studies rely on testing approaches with adult fish because reliable alternatives have not been validated so far. Fish embryo tests have been proposed as such an alternative, and here we compared two species (medaka and zebrafish) to determine their suitability for the assessment of substances with estrogenic and anti-androgenic activity. Changes in gene expression (in here the phrase gene expression is used synonymously to gene transcription, although it is acknowledged that gene expression is additionally regulated, e.g., by translation and protein stability) patterns between the two species were compared in short term embryo exposure tests (medaka: 7-day post fertilization [dpf]; zebrafish: 48 and 96h post fertilization [hpf]) by using relative quantitative real-time RT-PCR. The tested genes were related to the hypothalamic-gonadal-axis and early steroidogenesis. Test chemicals included 17α-ethinylestradiol and flutamide as estrogenic and anti-androgenic reference compounds, respectively, as well as five additional substances with endocrine activities, namely bisphenol A, genistein, prochloraz, linuron and propanil. Estrogenic responses were comparable in 7-dpf medaka and 48/96-hpf zebrafish embryos and included transcriptional upregulation of aromatase b, vitellogenin 1 as well as steroidogenic genes, suggesting that both species reliably detected exposure to estrogenic compounds. However, anti-androgenic responses differed between the two species, with each species providing specific information concerning the mechanism of anti-androgenic disruption in fish embryos. Although small but significant changes in the expression of selected genes was observed in 48-hpf zebrafish embryos, exposure prolonged to 96hpf was necessary to obtain a response indicative

Adipose tissue as an endocrine organ.

Science.gov (United States)

McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

2014-02-01

Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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.

Biochemical studies on certain biologically active nitrogenous compounds

International Nuclear Information System (INIS)

Abdel kader, S.M.; El Sayed, M.M.; El Malt, E.A.; Shaker, E.S.; Abdel Aziz, H.G.

2010-01-01

Certain biologically active nitrogenous compounds such as alkaloids are widely distributed in many wild and medicinal plants such as peganum harmala L. (Phycophyllaceae). However, less literature cited on the natural compounds was extracted from the aerial parts of this plant; therefore this study was conducted on harmal leaves using several solvents. Data indicated that methanol extract was the inhibitoriest effect against some pathogenic bacteria, particularly Streptococcus pyogenus. Chromatographic separation illustrated that presence of four compounds; the most active one was the third compound (3). Elementary analysis (C, H, N) revealed that the primary chemical structure of the active antibacterial compound (C3) was: C17 H21 N3 O7 S with molecular weight 411. Spectroscopic analysis proved that coninical structure was = 1- thioformyl, 8?- D glucoperanoside- Bis- 2, 3 dihydroisopyridino pyrrol. This new compound is represented as a noval ?- carboline alkaloid compound

Immunologic Endocrine Disorders

Science.gov (United States)

Michels, Aaron W.; Eisenbarth, George S.

2010-01-01

Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

Update in Endocrine Autoimmunity

OpenAIRE

Anderson, Mark S.

2008-01-01

Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

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

Science.gov (United States)

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

Fungal treatment for the removal of endocrine disrupting compounds from reverse osmosis concentrate: Identification and monitoring of transformation products of benzotriazoles.

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Llorca, Marta; Badia-Fabregat, Marina; Rodríguez-Mozaz, Sara; Caminal, Glòria; Vicent, Teresa; Barceló, Damià

2017-10-01

The removal of 27 endocrine-disrupting compounds and related compounds (suspect effect) from a reverse osmosis concentrate using an alternative decontamination method based on a fungal treatment involving Trametes versicolor was assessed. In addition to chemical analysis, the toxicity of the treated water during the treatment was monitored using a bioluminescence inhibition test and estrogenic and anti-estrogenic tests. The compounds 1H-benzotriazole (BTZ) and two tolyltriazoles (TTZs), 4-methyl-1H-benzotriazole (4-MBTZ) and 5-methyl-1H-benzotriazole (5-MBTZ), were present in the reverse osmosis concentrate at the highest concentrations (7.4 and 12.8 μg L -1 , respectively) and were partially removed by the fungal treatment under sterile conditions (58% for BTZ and 92% for TTZs) and non-sterile conditions, although to lesser extents (32% for BTZ and 50% for TTZs). Individual biotransformation studies of BTZ and the TTZs by T. versicolor in a synthetic medium and further analysis via on-line turbulent flow chromatography coupled to an HRMS-Orbitrap allowed the tentative identification of the transformation products (TPs). Six TPs were postulated for BTZ, two TPs were postulated for 4-MBTZ, and four TPs were postulated for 5-MBTZ. Most of these TPs are suggested to have been generated by conjugation with some sugars and via the methylation of the triazole group. Only TP 148 A, postulated to be derived from the biotransformation of BTZ, was observed in the effluent of the bioreactor treating the reverse osmosis concentrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sleep and the endocrine system.

Science.gov (United States)

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. Copyright © 2015 Elsevier Inc. All rights reserved.

An overview of estrogen-associated endocrine disruption in fishes: evidence of effects on reproductive and immune physiology

Science.gov (United States)

Iwanowicz, L.R.; Blazer, V.S.

2011-01-01

Simply and perhaps intuitively defined, endocrine disruption is the abnormal modulation of normal hormonal physiology by exogenous chemicals. In fish, endocrine disruption of the reproductive system has been observed worldwide in numerous species and is known to affect both males and females. Observations of biologically relevant endocrine disruption most commonly occurs near waste water treatment plant outfalls, pulp and paper mills, and areas of high organic loading sometimes associated with agricultural practices. Estrogenic endocrine disrupting chemicals (EEDCs) have received an overwhelmingly disproportionate amount of scientific attention compared to other EDCs in recent years. In male fishes, exposure to EEDCs can lead to the induction of testicular oocytes (intersex), measurable plasma vitellogenin protein, altered sex steroid profiles, abnormal spawning behavior, skewed population sex ratios, and lessened reproductive success. Interestingly, contemporary research purports that EDCs modulate aspects of non-reproductive physiology including immune function. Here we present an overview of endocrine disruption in fishes associated with estrogenic compounds, implications of this phenomenon, and examples of EDC related research findings by our group in the Potomac River Watershed, USA.

Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations

International Nuclear Information System (INIS)

Roepke, Troy A.; Snyder, Mark J.; Cherr, Gary N.

2005-01-01

Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17β-estradiol (E 2 ), estrone (E 1 ), estriol (E 3 ), progesterone (P 4 ) and 17α-ethynylestradiol (EE 2 )). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC 50 values for a reduction in normal development was as follows: TBT L.anamesus > OCT > TBT S. p urpuratus >> E 2 > EE 2 > DDD >> BisA > P 4 > E 1 >> E 3 . The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E 2 , OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor-mediated actions. Tamoxifen, a partial ER agonist, alone inhibited development at

Antimicrobial activity of some potential active compounds against ...

African Journals Online (AJOL)

Antimicrobial activities of six potential active compounds (acetic acid, chitosan, catechin, gallic acid, lysozyme, and nisin) at the concentration of 500 g/ml against the growth of Escherichia coli, Staphylococcus aureus, Listeria innocua, and Saccharomyces cerevisiae were determined. Lysozyme showed the highest ...

[The immuno-endocrine system. A new endocrine theory: the problem of the packed transport].

Science.gov (United States)

Csaba, György

2011-05-15

Since the eighties of the last century hormone content was justified in immune cells (lymphocytes, granulocytes, monocytes, macrophages and mast cells), which produce, store and secrete these hormones. Although the amount of these materials in immune cells is relatively small, the mass of the producers (immune cells) is so large, that the phenomenon must be considered from endocrinological point of view, underlying the important differences between the "classical" and immuno-endocrine systems. Cells of the classic (built-in) endocrine system are mono-producers, while immune cells can synthesize many types of hormones (polyproducers). In addition, these cells can transport the whole hormone-producing machinery to the site of need, producing a local effect. This can be observed, for example, in the case of endorphin producing immune cells during inflammation and during early pregnancy around the chorionic villi. Hormone producing immune cells also have receptors for many hormones, so that they are poly-receivers. Via hormone producing and receiving capacity there is a bidirectional connection between the neuro-endocrine and immuno-endocrine systems. In addition, there is a network inside the immuno-endocrine system. The packed transport theory attempts to explain the mechanism and importance of the immuno-endocrine system.

Endocrine and molecular investigations in a cohort of 25 adolescent males with prominent/persistent pubertal gynecomastia.

Science.gov (United States)

Paris, F; Gaspari, L; Mbou, F; Philibert, P; Audran, F; Morel, Y; Biason-Lauber, A; Sultan, C

2016-03-01

Pubertal gynecomastia is a common condition observed in up to 65% of adolescent males. It is usually idiopathic and tends to regress within 1-2 years. In this descriptive cross-sectional study, we investigated 25 adolescent males with prominent (>B3) and/or persistent (>2 years) pubertal gynecomastia (P/PPG) to determine whether a hormonal/genetic defect might underline this condition. Endocrine investigation revealed the absence of hormonal disturbance for 18 boys (72%). Three patients presented Klinefelter syndrome and three a partial androgen insensitivity syndrome (PAIS) as a result of p.Ala646Asp and p.Ala45Gly mutations of the androgen receptor gene. The last patient showed a 17α-hydroxylase/17,20-lyase deficiency as a result of a compound heterozygous mutation of the CYP17A1 gene leading to p.Pro35Thr(P35T) and p.Arg239Stop(R239X) in the P450c17 protein. Enzymatic activity was analyzed: the mutant protein bearing the premature stop codon R239X showed a complete loss of 17α-hydroxylase and 17,20-lyase activity. The mutant P35T seemed to retain 15-20% of 17α-hydroxylase and about 8-10% of 17,20-lyase activity. This work demonstrates that P/PPG had an endocrine/genetic cause in 28% of our cases. PAIS may be expressed only by isolated gynecomastia as well as by 17α-hydroxylase/17,20-lyase deficiency. Isolated P/PPG is not always a 'physiological' condition and should thus be investigated through adequate endocrine and genetic investigations, even though larger studies are needed to better determine the real prevalence of genetic defects in such patients. © 2016 American Society of Andrology and European Academy of Andrology.

The endocrine system and sarcopenia: potential therapeutic benefits.

Science.gov (United States)

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.

Environmental Analysis of Endocrine Disrupting Effects from Hydrocarbon Contaminants in the Ecosystem - Final Report - 09/15/1996 - 09/14/2000

International Nuclear Information System (INIS)

McLachlan, John A.

2000-01-01

The three major components of the research included: (a) a biotechnology based screening system to identify potential hormone mimics and antagonists (b) an animal screening system to identify biomarkers of endocrine effects and (c) a literature review to identify compounds at various DOE sites that are potential endocrine disruptors. Species of particular interest in this study were those that can serve as sentinel species (e.g., amphibians) and thus provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. The objective of this basic research is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. Although the endocrine disrupting effects of contaminants such as dioxin and PCBs have been well characterized in both animals and humans, little is known about the capacities of other hydrocarbon contaminants to act as endocrine disruptors. Results obtained from this research project have provided information on endocrine disrupting contaminants for consideration in DOE's risk analyses for determining clean-up levels and priorities at contaminated DOE sites

Environmental Analysis of Endocrine Disrupting Effects from Hydrocarbon Contaminants in the Ecosystem - Final Report - 09/15/1996 - 09/14/2000

Energy Technology Data Exchange (ETDEWEB)

McLachlan, John A.

2000-09-14

The three major components of the research included: (a) a biotechnology based screening system to identify potential hormone mimics and antagonists (b) an animal screening system to identify biomarkers of endocrine effects and (c) a literature review to identify compounds at various DOE sites that are potential endocrine disruptors. Species of particular interest in this study were those that can serve as sentinel species (e.g., amphibians) and thus provide early warning signals for more widespread impacts on an ecosystem and its wildlife and human inhabitants. The objective of this basic research is to characterize the potential of common hydrocarbon contaminants in ecosystems to act as endocrine disruptors. Although the endocrine disrupting effects of contaminants such as dioxin and PCBs have been well characterized in both animals and humans, little is known about the capacities of other hydrocarbon contaminants to act as endocrine disruptors. Results obtained from this research project have provided information on endocrine disrupting contaminants for consideration in DOE's risk analyses for determining clean-up levels and priorities at contaminated DOE sites.

Endocrine disruptive estrogens role in electron transfer: bio-electrochemical remediation with microbial mediated electrogenesis.

Science.gov (United States)

Kumar, A Kiran; Reddy, M Venkateswar; Chandrasekhar, K; Srikanth, S; Mohan, S Venkata

2012-01-01

Bioremediation of selected endocrine disrupting compounds (EDCs)/estrogens viz. estriol (E3) and ethynylestradiol (EE2) was evaluated in bio-electrochemical treatment (BET) system with simultaneous power generation. Estrogens supplementation along with wastewater documented enhanced electrogenic activity indicating their function in electron transfer between biocatalyst and anode as electron shuttler. EE2 addition showed more positive impact on the electrogenic activity compared to E3 supplementation. Higher estrogen concentration showed inhibitory effect on the BET performance. Poising potential during start up phase showed a marginal influence on the power output. The electrons generated during substrate degradation might have been utilized for the EDCs break down. Fuel cell behavior and anodic oxidation potential supported the observed electrogenic activity with the function of estrogens removal. Voltammetric profiles, dehydrogenase and phosphatase enzyme activities were also found to be in agreement with the power generation, electron discharge and estrogens removal. Copyright © 2011 Elsevier Ltd. All rights reserved.

Endocrine emergencies in dogs and cats.

Science.gov (United States)

Koenig, Amie

2013-07-01

Success in treatment of endocrine emergencies is contingent on early recognition and treatment. Many endocrine diseases presenting emergently have nonspecific signs and symptoms. In addition, these endocrine crises are often precipitated by concurrent disease, further making early identification difficult. This article concentrates on recognition and emergency management of the most common endocrine crises in dogs and cats. Copyright © 2013 Elsevier Inc. All rights reserved.

Activity of Polyphenolic Compounds against Candida glabrata

Directory of Open Access Journals (Sweden)

Ricardo Salazar-Aranda

2015-09-01

Full Text Available Opportunistic mycoses increase the morbidity and mortality of immuno-compromised patients. Five Candida species have been shown to be responsible for 97% of worldwide cases of invasive candidiasis. Resistance of C. glabrata and C. krusei to azoles has been reported, and new, improved antifungal agents are needed. The current study was designed to evaluatethe activity of various polyphenolic compounds against Candida species. Antifungal activity was evaluated following the M27-A3 protocol of the Clinical and Laboratory Standards Institute, and antioxidant activity was determined using the DPPH assay. Myricetin and baicalein inhibited the growth of all species tested. This effect was strongest against C. glabrata, for which the minimum inhibitory concentration (MIC value was lower than that of fluconazole. The MIC values against C. glabrata for myricitrin, luteolin, quercetin, 3-hydroxyflavone, and fisetin were similar to that of fluconazole. The antioxidant activity of all compounds was confirmed, and polyphenolic compounds with antioxidant activity had the greatest activity against C. glabrata. The structure and position of their hydroxyl groups appear to influence their activity against C. glabrata.

Co-Formulants in Glyphosate-Based Herbicides Disrupt Aromatase Activity in Human Cells below Toxic Levels

Directory of Open Access Journals (Sweden)

Nicolas Defarge

2016-02-01

Full Text Available Pesticide formulations contain declared active ingredients and co-formulants presented as inert and confidential compounds. We tested the endocrine disruption of co-formulants in six glyphosate-based herbicides (GBH, the most used pesticides worldwide. All co-formulants and formulations were comparably cytotoxic well below the agricultural dilution of 1% (18–2000 times for co-formulants, 8–141 times for formulations, and not the declared active ingredient glyphosate (G alone. The endocrine-disrupting effects of all these compounds were measured on aromatase activity, a key enzyme in the balance of sex hormones, below the toxicity threshold. Aromatase activity was decreased both by the co-formulants alone (polyethoxylated tallow amine—POEA and alkyl polyglucoside—APG and by the formulations, from concentrations 800 times lower than the agricultural dilutions; while G exerted an effect only at 1/3 of the agricultural dilution. It was demonstrated for the first time that endocrine disruption by GBH could not only be due to the declared active ingredient but also to co-formulants. These results could explain numerous in vivo results with GBHs not seen with G alone; moreover, they challenge the relevance of the acceptable daily intake (ADI value for GBHs exposures, currently calculated from toxicity tests of the declared active ingredient alone.

Structure Modification of an Active Azo-Compound as a Route to New Antimicrobial Compounds

Directory of Open Access Journals (Sweden)

Simona Concilio

2017-05-01

Full Text Available Some novel (phenyl-diazenylphenols 3a–g were designed and synthesized to be evaluated for their antimicrobial activity. A previously synthesized molecule, active against bacteria and fungi, was used as lead for modifications and optimization of the structure, by introduction/removal or displacement of hydroxyl groups on the azobenzene rings. The aim of this work was to evaluate the consequent changes of the antimicrobial activity and to validate the hypothesis that, for these compounds, a plausible mechanism could involve an interaction with protein receptors, rather than an interaction with membrane. All newly synthesized compounds were analyzed by 1H-NMR, DSC thermal analysis and UV-Vis spectroscopy. The in vitro minimal inhibitory concentrations (MIC of each compound was determined against Gram-positive and Gram-negative bacteria and Candida albicans. Compounds 3b and 3g showed the highest activity against S. aureus and C. albicans, with remarkable MIC values of 10 µg/mL and 3 µg/mL, respectively. Structure-activity relationship studies were capable to rationalize the effect of different substitutions on the phenyl ring of the azobenzene on antimicrobial activity.

Endocrine therapy and urogenital outcomes among women with a breast cancer diagnosis

Science.gov (United States)

Doll, Kemi M.; Bensen, Jeannette T.; Hendrix, Laura; Anders, Carey K.; Wu, Jennifer M.; Nichols, Hazel B.

2018-01-01

Purpose Endocrine therapy for breast cancer can exacerbate menopausal symptoms. The association between endocrine therapy and common pelvic floor disorders including urinary incontinence has rarely been evaluated. We examined urogenital and sexual side effects among women with a breast cancer diagnosis, comparing endocrine therapy users to nonusers. Methods Urogenital and sexual symptoms were self-reported during the enrollment interview within the University of North Carolina Cancer Survivorship Cohort. Tumor characteristics and endocrine therapy use were collected from medical and prescription records. We calculated multivariable prevalence ratios (PR) and 95 % confidence intervals (CI) for the association of endocrine therapy (versus no endocrine therapy) and urinary incontinence, overall and by therapy type (tamoxifen or aromatase inhibitors). PROMIS Sexual Function and Satisfaction domain scores were compared across endocrine therapy groups. Results Among the 548 women with a breast cancer diagnosis, 49 % received endocrine therapy. Overall, 18 % of women reported urinary incontinence symptoms. We observed no association between urinary incontinence and endocrine therapy use overall (PR = 0.97; 95 % CI 0.67, 1.43), tamoxifen (PR = 1.20; 95 % CI 0.74, 1.96), or aromatase inhibitors (PR = 0.89; 95 % CI 0.55, 1.42), compared to no use. Approximately 55 % of women were sexually active. Sexual function scores did not vary according to endocrine therapy use, although urinary incontinence was associated with lower satisfaction scores (p = 0.05). Conclusions Our findings demonstrate a high prevalence of urinary incontinence after breast cancer diagnosis similar to the overall prevalence in older U.S. women, and this did not vary strongly according to use of endocrine therapy. PMID:27680018

[Arterial hypertension secondary to endocrine disorders].

Science.gov (United States)

Minder, Anna; Zulewski, Henryk

2015-06-01

Endocrine hypertension offers a potentially curative therapy if the underlying cause is identified and treated accordingly. In contrast to the high prevalence of arterial hypertension especially in the elderly, the classical endocrine causes remain a rare entity. Among patients with arterial hypertension the prevalence of Cushing's syndrome or pheochromocytoma is less than 1%. Primary hyperaldosteronism is more frequent with a reported prevalence of up to 9%. In order to avoid unnecessary, costly and potentially harmful evaluations and therapies due to the limited sensitivity and specificity of the critical endocrine tests it is mandatory to limit the exploration for endocrine causes to preselected patients with high pretest probability for an endocrine disorder. Younger age at manifestation of arterial hypertension or drug resistant hypertension together with other clinical signs of an endocrine disorder should raise the suspicion and prompt the appropriate evaluation.

[Dementia due to Endocrine Diseases].

Science.gov (United States)

Matsunaga, Akiko; Yoneda, Makoto

2016-04-01

Endocrine diseases affecting various organs, such as the pituitary gland, the thyroid, the parathyroid, the adrenal glands and the pancreas, occasionally cause dementia. While Alzheimer's disease (AD) is the main cause of dementia in the elderly and is untreatable, dementia caused by endocrine diseases is treatable in most cases. However, patients with dementia associated with endocrine diseases show memory impairments similar to those found in AD, often leading to misdiagnoses. Patients with endocrine diseases often present with other characteristic systemic and neuropsychiatric symptoms caused by altered hormone levels. Such neuropsychiatric symptoms include involuntary movements, depression, seizures, and muscle weakness. In these cases, abnormalities in imaging and blood or urine tests are helpful in making a differential diagnosis. As delays in the diagnosis and treatment of these patients may cause irreversible brain damage, it is imperative for clinicians to carefully exclude the possibility of latent endocrine diseases when treating patients with dementia.

Endocrine disorders in mitochondrial disease.

Science.gov (United States)

Schaefer, Andrew M; Walker, Mark; Turnbull, Douglass M; Taylor, Robert W

2013-10-15

Endocrine dysfunction in mitochondrial disease is commonplace, but predominantly restricted to disease of the endocrine pancreas resulting in diabetes mellitus. Other endocrine manifestations occur, but are relatively rare by comparison. In mitochondrial disease, neuromuscular symptoms often dominate the clinical phenotype, but it is of paramount importance to appreciate the multi-system nature of the disease, of which endocrine dysfunction may be a part. The numerous phenotypes attributable to pathogenic mutations in both the mitochondrial (mtDNA) and nuclear DNA creates a complex and heterogeneous catalogue of disease which can be difficult to navigate for novices and experts alike. In this article we provide an overview of the endocrine disorders associated with mitochondrial disease, the way in which the underlying mitochondrial disorder influences the clinical presentation, and how these factors influence subsequent management. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Synthesis, biological activity and computational studies of novel azo-compounds

International Nuclear Information System (INIS)

Ashraf, J.; Murtaza, S.; Mughal, E.U.; Sadiq, A.

2017-01-01

In the present protocol, we report the synthesis and characterization of some novel azo-compounds starting from 4-methoxyaniline and 4-aminophenazone, which were diazotized at low temperature. 4-nitrophenol, 2-aminobenzoic acid, benzamide, 4-aminobenzoic acid, resorcinol, o-bromonitrobenzene and 2-nitroaniline were used as active aromatic coupling compounds for the second step. The synthesized compounds were investigated for their potential antibacterial activities by using disc diffusion method against Escherichia coli, Shigellasonnei, Streptococcus pyrogenes, Staphylococcus aureus and Neisseria gonorrhoeae strains. They were also subjected to antioxidant activities by using DPPH method. Results revealed that the compounds of 4-methoxyaniline and 4-aminophenazone showed good antibacterial activity against all strains, where as some azo-compounds have moderate to good antioxidant activities. Furthermore, these compounds were studied by computational analysis. (author)

First characterization of the endocrine-disrupting potential of indoor gaseous and particulate contamination: comparison with urban outdoor air (France).

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Oziol, Lucie; Alliot, Fabrice; Botton, Jérémie; Bimbot, Maya; Huteau, Viviane; Levi, Yves; Chevreuil, Marc

2017-01-01

The composition of endocrine-disrupting compounds (EDCs) in the ambient air of indoor environments has already been described, but little is known about the inherent endocrine-disrupting potential of indoor air contamination. We therefore aimed to study the distribution of bioactive EDCs in the gaseous and particulate phases of indoor air using a cellular bioassay approach that integrates the interaction effects between chemicals. Organic air extracts, both gaseous and particulate, were taken from three indoor locations (office, apartment, and children's day care) in France and sampled in two different seasons in order to study their interference with the signaling of estrogen, androgen, and thyroid receptors. The experiments were also conducted on aerial extracts from an outdoor site (urban center). We found that gaseous and/or particulate extracts from all locations displayed estrogenicity, anti-androgenicity, and thyroidicity. Overall, indoor air extracts had a higher endocrine-disrupting potential compared to outdoor ones, especially during winter and in the day care. The biological activities were predominant for the gaseous extracts and tended to increase for the particulate extracts in cool conditions. In conclusion, our data confirmed the presence of bioactive EDCs in a gaseous state and highlighted their indoor origin and concentration, especially in the cold season.

A Structure-Activity Relationship (SAR Study of Neolignan Compounds with Anti-schistosomiasis Activity

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Alves Claúdio N.

2002-01-01

Full Text Available A set of eighteen neolignan derivative compounds with anti-schistosomiasis activity was studied by using the quantum mechanical semi-empirical method PM3 and other theoretical methods in order to calculate selected molecular properties (variables or descriptors to be correlated to their biological activities. Exploratory data analysis (principal component analysis, PCA, and hierarchical cluster analysis, HCA, discriminant analysis (DA and the Kth nearest neighbor (KNN method were employed for obtaining possible relationships between the calculated descriptors and the biological activities studied and predicting the anti-schistosomiasis activity of new compounds from a test set. The molecular descriptors responsible for the separation between active and inactive compounds were: hydration energy (HE, molecular refractivity (MR and charge on the C19 carbon atom (Q19. These descriptors give information on the kind of interaction that can occur between the compounds and their respective biological receptor. The prediction study was done with a new set of ten derivative compounds by using the PCA, HCA, DA and KNN methods and only five of them were predicted as active against schistosomiasis.

Intestinal endocrine cells in radiation enteritis

NARCIS (Netherlands)

Pietroletti, R.; Blaauwgeers, J. L.; Taat, C. W.; Simi, M.; Brummelkamp, W. H.; Becker, A. E.

1989-01-01

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

Endocrine system and obesity.

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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. Copyright © 2010. Published by Elsevier Inc.

The application of reporter gene assays for the detection of endocrine disruptors in sport supplements

International Nuclear Information System (INIS)

Plotan, Monika; Elliott, Christopher T.; Scippo, Marie Louise; Muller, Marc; Antignac, Jean-Philippe; Malone, Edward; Bovee, Toine F.H.; Mitchell, Samuel; Connolly, Lisa

2011-01-01

The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC 50 of 0.01 ng mL -1 and 0.16 ng mL -1 respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally active compounds the

Assessment of endocrine disruption potential of essential oils of culinary herbs and spices involving glucocorticoid, androgen and vitamin D receptors.

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Bartoňková, Iveta; Dvořák, Zdeněk

2018-04-25

Essential oils (EOs) of culinary herbs and spices are consumed on a daily basis. They are multicomponent mixtures of compounds with already demonstrated biological activities. Taking into account regular dietary intake and the chemical composition of EOs, they may be considered as candidates for endocrine-disrupting entities. Therefore, we examined the effects of 31 EOs of culinary herbs and spices on transcriptional activities of glucocorticoid receptor (GR), androgen receptor (AR) and vitamin D receptor (VDR). Using reporter gene assays in stably transfected cell lines, weak anti-androgen and anti-glucocorticoid activity was observed for EO of vanilla and nutmeg, respectively. Moderate augmentation of calcitriol-dependent VDR activity was caused by EOs of ginger, thyme, coriander and lemongrass. Mixed anti-glucocorticoid and VDR-stimulatory activities were displayed by EOs of turmeric, oregano, dill, caraway, verveine and spearmint. The remaining 19 EOs were inactive against all receptors under investigation. Analyses of GR, AR and VDR target genes by means of RT-PCR confirmed the VDR-stimulatory effects, but could not confirm the anti-glucocorticoid and anti-androgen effects of EOs. In conclusion, although we observed minor effects of several EOs on transcriptional activities of GR, AR and VDR, the toxicological significance of these effects is very low. Hence, 31 EOs of culinary herbs and spices may be considered safe, in terms of endocrine disruption involving receptors GR, AR and VDR.

The role of phytoplankton composition, biomass and cell volume in accumulation and transfer of endocrine disrupting compounds in the Southern Baltic Sea (The Gulf of Gdansk).

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Staniszewska, Marta; Nehring, Iga; Zgrundo, Aleksandra

2015-12-01

Endocrine disrupting compounds (EDCs) like bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP) are introduced to the trophic webs through among others phytoplankton. This paper describes BPA, OP and NP concentrations in phytoplankton in the Gulf of Gdansk (Southern Baltic Sea) in the years 2011-2012. The assays of BPA, OP and NP in samples were performed using HPLC with fluorescence detection. The concentrations of BPA, the most commonly used of the three compounds, were over ten times higher than OP and NP concentrations. The concentrations of the studied EDCs in phytoplankton from the Gulf of Gdansk depended on anthropogenic factors and on phytoplankton properties (species composition, biomass, volume). An increase in phytoplankton biomass did not always result in an increase of BPA, OP and NP concentrations. However, the load of the studied EDCs accumulated in phytoplankton biomass increase with a rise of biomass. An increase in BPA, OP and NP concentrations was effected by biomass growth and the proportions ofciliates, dinoflagellates, diatoms and green algae. A strong positive correlation between OP and NP concentrations and negative correlation between BPA concentrations and biomass of organisms with cells measuring <1000 μm(3) in volume results from the differing properties of these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

Radiological imaging in endocrine hypertension

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Chandan J Das

2011-01-01

Full Text Available While different generations of assays have played important role in elucidating causes of different endocrine disorders, radiological techniques are instrumental in localizing the pathology. This statement cannot be truer in any disease entity other than endocrine hypertension. This review makes an effort to highlight the role of different radiological modalities, especially ultrasonography, computed tomography and magnetic resonance imaging, in the evaluation of different causes of endocrine hypertension.

Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil

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CM Furtado

Full Text Available The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs through semi-quantitative analysis of residential water filters collected in the region of Rio dos Sinos basin, focusing on two specific classes: hormones and phenols. The solid phase extraction principle was used for the extraction of compounds and gas chromatography coupled with mass spectrometry for the separation and characterization of EDCs. Four samples of residential filters collected from public water distribution and artesian wells, from the cities of Novo Hamburgo and São Leopoldo were analysed. Using the developed methodology, it was possible to detect and comparatively quantify selected EDCs in all studied samples, which indicates the presence of these contaminants in drinking water from different sources.

Spectrum of Endocrine Disorders in Central Ghana

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Osei Sarfo-Kantanka

2017-01-01

Full Text Available 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.

Insecticidal Activity of Cyanohydrin and Monoterpenoid Compounds

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Joel R. Coats

2000-04-01

Full Text Available The insecticidal activities of several cyanohydrins, cyanohydrin esters and monoterpenoid esters (including three monoterpenoid esters of a cyanohydrin were evaluated. Topical toxicity to Musca domestica L. adults was examined, and testing of many compounds at 100 mg/fly resulted in 100% mortality. Topical LD50 values of four compounds for M. domestica were calculated. Testing of many of the reported compounds to brine shrimp (Artemia franciscana Kellog resulted in 100% mortality at 10 ppm, and two compounds caused 100% mortality at 1 ppm. Aquatic LC50 values were calculated for five compounds for larvae of the yellow fever mosquito (Aedes aegypti (L.. Monoterpenoid esters were among the most toxic compounds tested in topical and aquatic bioassays.

Mechanistic evaluation of endocrine disrupting chemicals

DEFF Research Database (Denmark)

Taxvig, Camilla

BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent for the ...... metabolising system using liver S9 mixtures or hepatic rat microsomes could be a convenient method for the incorporation of metabolic aspects into in vitro testing for endocrine disrupting effects.......BACKGROUND: This PhD project is part of the research area concerning effects of endocrine disrupters at the National Food Institute at DTU in Denmark. Endocrine disrupting chemicals (EDCs) have proved to be important for improper development of the male reproductive organs and subsequent......, to be able to detect effects and predict mixture effects. In addition, a new hypothesis have emerge concerning a potential role of exposure to endocrine disrupting chemicals, and the development of obesity and obesity related diseases. AIM: This PhD project aimed to gain more information regarding...

Estradiol and endocrine disrupting compounds adversely affect development of sea urchin embryos at environmentally relevant concentrations

Energy Technology Data Exchange (ETDEWEB)

Roepke, Troy A. [Bodega Marine Laboratory, University of California, Davis, POB 247, Bodega Bay, CA 94923 (United States); Snyder, Mark J. [Bodega Marine Laboratory, University of California, Davis, POB 247, Bodega Bay, CA 94923 (United States); Cherr, Gary N. [Bodega Marine Laboratory, University of California, Davis, POB 247, Bodega Bay, CA 94923 (United States) and Departments of Environmental Toxicology and Nutrition, One Shields Avenue, University of California, Davis, CA 95616 (United States)]. E-mail: gncherr@ucdavis.edu

2005-01-26

Environmental endocrine disrupting compounds (EDCs) are a wide variety of chemicals that typically exert effects, either directly or indirectly, through receptor-mediated processes, thus mimicking endogenous hormones and/or inhibiting normal hormone activities and metabolism. Little is known about the effects of EDCs on echinoderm physiology, reproduction and development. We exposed developing sea urchin embryos (Strongylocentrotus purpuratus and Lytechinus anamesus) to two known EDCs (4-octylphenol (OCT), bisphenol A (BisA)) and to natural and synthetic reproductive hormones (17{beta}-estradiol (E{sub 2}), estrone (E{sub 1}), estriol (E{sub 3}), progesterone (P{sub 4}) and 17{alpha}-ethynylestradiol (EE{sub 2})). In addition, we studied two non-estrogenic EDCs, tributyltin (TBT) and o,p-DDD. Successful development to the pluteus larval stage (96 h post-fertilization) was used to define EDC concentration-response relationships. The order of compound potency based on EC{sub 50} values for a reduction in normal development was as follows: TBT {sub L.anamesus} > OCT > TBT {sub S.{sub p}}{sub urpuratus} >> E{sub 2} > EE{sub 2} > DDD >> BisA > P{sub 4} > E{sub 1} >> E{sub 3}. The effect of TBT was pronounced even at concentrations substantially lower than those commonly reported in heavily contaminated areas, but the response was significantly different in the two model species. Sea urchin embryos were generally more sensitive to estrogenic EDCs and TBT than most other invertebrate larvae. Stage-specific exposure experiments were conducted to determine the most sensitive developmental periods using blastula, gastrula and post-gastrula (pluteus) stages. The stage most sensitive to E{sub 2}, OCT and TBT was the blastula stage with less overall sensitivity in the gastrula stage, regardless of concentration. Selective estrogen receptor modulators (SERMs) were added to the experiments individually and in combination with estrogenic EDCs to interfere with potential receptor

Intestinal endocrine cells in radiation enteritis

International Nuclear Information System (INIS)

Pietroletti, R.; Blaauwgeers, J.L.; Taat, C.W.; Simi, M.; Brummelkamp, W.H.; Becker, A.E.

1989-01-01

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

Endocrine pathology: past, present and future.

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Asa, Sylvia L; Mete, Ozgur

2018-01-01

Endocrine pathology is the subspecialty of diagnostic pathology which deals with the diagnosis and characterisation of neoplastic and non-neoplastic diseases of the endocrine system. This relatively young subspecialty was initially focused mainly on thyroid and parathyroid pathology, with some participants also involved in studies of the pituitary, the endocrine pancreas, and the adrenal glands. However, the endocrine system involves much more than these traditional endocrine organs and the discipline has grown to encompass lesions of the dispersed neuroendocrine cells, including neuroendocrine tumours (NETs) of the lungs, gastrointestinal tract, thymus, breast and prostate, as well as paraganglia throughout the body, not just in the adrenals. Indeed, the production of hormones is the hallmark of the endocrine system, and some aspects of gynecological/testicular, bone and liver pathology also fall into the realm of this specialty. Many of the lesions that are the focus of this discipline are increasing in incidence and their pathology is becoming more complex with increased understanding of molecular pathology and a high incidence of familial disease. The future of endocrine pathology will demand a depth of understanding of structure, function, prognosis and prediction as pathologists play a key role in the multidisciplinary care team of patients with endocrine diseases. It is anticipated that new technologies will allow increased subspecialisation in pathology and growth of this important area of expertise. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Skin Manifestations of Endocrine Diseases.

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Demirkesen, Cuyan

2015-01-01

Endocrine diseases may result in changes in cutaneous function and morphology, which cause various skin manifestations, including nonspecific or pathognomonic signs. Some of these manifestations are already known dermatologic diseases with only increased frequency in this patient group. As a result the skin may the play role of a screen displaying endocrine disorders, either due to hormone excess or deficiency. Awareness of the skin manifestations may permit prompt and adequate approach to the patients, and therefore facilitate the early diagnosis of the endocrine disease and even be life saving. Some of these manifestations may be recognized clinically, but sometimes they need to be confirmed histopathologically. In this article, many endocrine diseases and their associated skin lesions will be reviewed briefly.

Reproductive toxicity of the endocrine disrupters vinclozolin and bisphenol A in the terrestrial isopod Porcellio scaber (Latreille, 1804).

NARCIS (Netherlands)

Lemos, M.F.L.; van Gestel, C.A.M.; Soares, A.M.V.M.

2010-01-01

Endocrine Disruptor Compounds (EDCs) have been largely studied concerning their effects on vertebrates. Nevertheless, invertebrates as targets for these chemicals have been neglected and few studies are available. Specifically for edaphic invertebrates, data concerning the effects of EDCs is

Analyzing endocrine system conservation and evolution.

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Bonett, Ronald M

2016-08-01

Analyzing variation in rates of evolution can provide important insights into the factors that constrain trait evolution, as well as those that promote diversification. Metazoan endocrine systems exhibit apparent variation in evolutionary rates of their constituent components at multiple levels, yet relatively few studies have quantified these patterns and analyzed them in a phylogenetic context. This may be in part due to historical and current data limitations for many endocrine components and taxonomic groups. However, recent technological advancements such as high-throughput sequencing provide the opportunity to collect large-scale comparative data sets for even non-model species. Such ventures will produce a fertile data landscape for evolutionary analyses of nucleic acid and amino acid based endocrine components. Here I summarize evolutionary rate analyses that can be applied to categorical and continuous endocrine traits, and also those for nucleic acid and protein-based components. I emphasize analyses that could be used to test whether other variables (e.g., ecology, ontogenetic timing of expression, etc.) are related to patterns of rate variation and endocrine component diversification. The application of phylogenetic-based rate analyses to comparative endocrine data will greatly enhance our understanding of the factors that have shaped endocrine system evolution. Copyright © 2016 Elsevier Inc. All rights reserved.

EDCs DataBank: 3D-Structure database of endocrine disrupting chemicals.

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Montes-Grajales, Diana; Olivero-Verbel, Jesus

2015-01-02

Endocrine disrupting chemicals (EDCs) are a group of compounds that affect the endocrine system, frequently found in everyday products and epidemiologically associated with several diseases. The purpose of this work was to develop EDCs DataBank, the only database of EDCs with three-dimensional structures. This database was built on MySQL using the EU list of potential endocrine disruptors and TEDX list. It contains the three-dimensional structures available on PubChem, as well as a wide variety of information from different databases and text mining tools, useful for almost any kind of research regarding EDCs. The web platform was developed employing HTML, CSS and PHP languages, with dynamic contents in a graphic environment, facilitating information analysis. Currently EDCs DataBank has 615 molecules, including pesticides, natural and industrial products, cosmetics, drugs and food additives, among other low molecular weight xenobiotics. Therefore, this database can be used to study the toxicological effects of these molecules, or to develop pharmaceuticals targeting hormone receptors, through docking studies, high-throughput virtual screening and ligand-protein interaction analysis. EDCs DataBank is totally user-friendly and the 3D-structures of the molecules can be downloaded in several formats. This database is freely available at http://edcs.unicartagena.edu.co. Copyright © 2014. Published by Elsevier Ireland Ltd.

Compound Structure-Independent Activity Prediction in High-Dimensional Target Space.

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Balfer, Jenny; Hu, Ye; Bajorath, Jürgen

2014-08-01

Profiling of compound libraries against arrays of targets has become an important approach in pharmaceutical research. The prediction of multi-target compound activities also represents an attractive task for machine learning with potential for drug discovery applications. Herein, we have explored activity prediction in high-dimensional target space. Different types of models were derived to predict multi-target activities. The models included naïve Bayesian (NB) and support vector machine (SVM) classifiers based upon compound structure information and NB models derived on the basis of activity profiles, without considering compound structure. Because the latter approach can be applied to incomplete training data and principally depends on the feature independence assumption, SVM modeling was not applicable in this case. Furthermore, iterative hybrid NB models making use of both activity profiles and compound structure information were built. In high-dimensional target space, NB models utilizing activity profile data were found to yield more accurate activity predictions than structure-based NB and SVM models or hybrid models. An in-depth analysis of activity profile-based models revealed the presence of correlation effects across different targets and rationalized prediction accuracy. Taken together, the results indicate that activity profile information can be effectively used to predict the activity of test compounds against novel targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phenolic Compounds and Antioxidant Activities of Liriope muscari

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Shu Shan Du

2012-02-01

Full Text Available Five phenolic compounds, namely N-trans-coumaroyltyramine (1, N-trans-feruloyltyramine (2, N-trans-feruloyloctopamine (3, 5,7-dihydroxy-8-methoxyflavone (4 and (3S3,5,4′-trihydroxy-7-methoxy-6-methylhomoisoflavanone (5, were isolated from the fibrous roots of Liriope muscari (Liliaceae. Compounds 2–5 were isolated for the first time from the Liriope genus. Their in vitro antioxidant activities were assessed by the DPPH and ABTS scavenging methods with microplate assays. The structure-activity relationships of compounds 1–3 are discussed.

MCX based solid phase extraction combined with liquid chromatography tandem mass spectrometry for the simultaneous determination of 31 endocrine-disrupting compounds in surface water of Shanghai.

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Zhang, Hong-Chang; Yu, Xue-jun; Yang, Wen-chao; Peng, Jin-feng; Xu, Ting; Yin, Da-Qiang; Hu, Xia-lin

2011-10-15

A novel analytical method employing MCX (mixed-mode cationic exchange) based solid phase extraction (SPE) coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed to detect 31 endocrine-disrupting compounds (EDCs) in surface water samples simultaneously. The target EDCs belong to five classes, including seven estrogens, eight androgens, six progesterones, five adrenocortical hormones and five industrial compounds. In order to simultaneously concentrate the target EDCs and eliminate matrix interferences in the water samples, MCX SPE cartridges were employed for SPE, and then followed by a simple and highly efficient three-step sequential elution procedure. Two electrospray ionization (ESI) detection modes, positive (ESI+) and (ESI-), were optimized for HPLC-MS/MS analysis to obtain the highest sensitivity for all the EDCs. The limits of detection (LODs) were 0.02-1.9 ng L(-1), which are lower than or comparable to these reported in references. Wide linear ranges (LOD-100 ng L(-1) for ESI+ mode, and LOD-200 ng L(-1) for ESI- mode) were obtained with determination coefficients (R(2)) higher than 0.99 for all the compounds. With five internal standards, good recoveries (84.4-103.0%) of all the target compounds were obtained in selected surface water samples. The developed method was successfully applied to investigate the EDCs occurrence in the surface water of Shanghai by analyzing surface water samples from 11 sites. The results showed that nearly all the target compounds (30 in 31) were present in the surface water samples of Shanghai, of which three industrial compounds (4-t-OP, BPA, and BPF) showed the highest concentrations (median concentrations were 11.88-23.50 ng L(-1)), suggesting that industrial compounds were the dominating EDCs in the surface water of Shanghai, and much more attention should be paid on these compounds. Our present research demonstrated that SPE with MCX cartridges combined with HPLC-MS/MS was convenient

CE with a boron-doped diamond electrode for trace detection of endocrine disruptors in water samples.

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Browne, Damien J; Zhou, Lin; Luong, John H T; Glennon, Jeremy D

2013-07-01

Off-line SPE and CE coupled with electrochemical detection have been used for the determination of bisphenol A (BPA), bisphenol F, 4-ethylphenol, and bisphenol A diglycidyl ether in bottled drinking water. The use of boron-doped diamond electrode as an electrochemical detector in amperometric mode that provides a favorable analytical performance for detecting these endocrine-disrupting compounds, such as lower noise levels, higher peak resolution with enhanced sensitivity, and improved resistance against electrode passivation. The oxidative electrochemical detection of the endocrine-disrupting compounds was accomplished by boron-doped diamond electrode poised at +1.4 V versus Ag/AgCl without electrode pretreatment. An off-line SPE procedure (Bond Elut® C18 SPE cartridge) was utilized to extract and preconcentrate the compounds prior to separation and detection. The minimum concentration detectable for all four compounds ranged from 0.01 to 0.06 μM, having S/N equal to three. After exposing the plastic bottle water container under sunlight for 7 days, the estimated concentration of BPA in the bottled drinking water was estimated to be 0.03 μM. This proposed approach has great potential for rapid and effective determination of BPA content present in water packaging of plastic bottles that have been exposed to sunlight for an extended period of time. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Glucocorticoid-like activity of propylparaben, butylparaben, diethylhexyl phthalate and tetramethrin mixtures studied in the MDA-kb2 cell line.

Science.gov (United States)

Klopčič, Ivana; Kolšek, Katra; Dolenc, Marija Sollner

2015-01-22

Endocrine-disrupting compounds can interfere with the endocrine organs or hormone system and cause tumors, birth defects and developmental disorders in humans. The estrogen-like activity of compounds has been widely studied but little is known concerning their possible modulation of the glucocorticoid receptor. Steroidal (synthetic and natural) and non-steroidal endocrine-active compounds commonly occur as complex mixtures in human environments. Identification of such molecular species, which are responsible for modulating the glucocorticoid receptor are necessary to fully assess their risk. We have used the MDA-kb2 cell line, which expresses endogenous glucocorticoid receptor and a stably transfected luciferase reporter gene construct, to quantify the glucocorticoid-like activity of four compounds present in products in everyday use - propylparaben (PP), butylparaben (BP), diethylhexyl phthalate (DEHP) and tetramethrin (TM). We tested all possible combinations of these compounds at two concentrations (1 μM and 10 nM) and compared their glucocorticoid-like activity. At the concentration of 1 μM seven mixtures were identified to have glucocorticoid-like activity except: DEHP+TM, BP+TM, DEHP+PP+TM, BP+PP+TM. At the concentration of 10 nM only three mixtures have glucocorticoid modulatory activity: DEHP+PP, BP+PP, DEHP+BP+PP+TM. Identified glucocorticoid-like activities were between 1.25 and 1.51 fold at the concentration of 1 μM and between 1.23 and 1.44 fold at the concentration of 10 nM in comparison with the solvent control. Individually BP, PP, and DEHP had glucocorticoid-like activity of 1.60, 1.57 and 1.50 fold over the solvent control at the concentration of 1 μM. On the other hand PP and DEHP, at the concentration of 10nM, showed no glucocorticoid-like activity, while BP showed 1.44 fold. The assertion that individual glucocorticoid-like compounds do not produce harm because they are present at low, ineffective levels in humans may be irrelevant when we

The current preference for the immuno-analytical ELISA method for quantitation of steroid hormones (endocrine disruptor compounds) in wastewater in South Africa.

Science.gov (United States)

Manickum, Thavrin; John, Wilson

2015-07-01

requirements for steroid hormone quantitation. Further optimization of the sensitivity of the chemical-analytical LC-tandem mass spectrometry methods, especially for wastewater screening, in South Africa is required. Risk assessment studies showed that it was not practical to propose standards or allowable limits for the steroid estrogens E1, E2, EE2, and E3; the use of predicted-no-effect concentration values of the steroid estrogens appears to be appropriate for use in their risk assessment in relation to aquatic organisms. For raw water sources, drinking water, raw and treated wastewater, the use of bioassays, with trigger values, is a useful screening tool option to decide whether further examination of specific endocrine activity may be warranted, or whether concentrations of such activity are of low priority, with respect to health concerns in the human population. The achievement of improved quantitation limits for immuno-analytical methods, like ELISA, used for compound quantitation, and standardization of the method for measuring E2 equivalents (EEQs) used for biological activity (endocrine: e.g., estrogenic) are some areas for future EDC research.

Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

International Nuclear Information System (INIS)

Martin-Skilton, Rebeca; Lavado, Ramon; Thibaut, Remi; Minier, Christophe; Porte, Cinta

2006-01-01

Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17β-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period

Evidence of endocrine alteration in the red mullet, Mullus barbatus from the NW Mediterranean

Energy Technology Data Exchange (ETDEWEB)

Martin-Skilton, Rebeca [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Lavado, Ramon [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Thibaut, Remi [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain); Minier, Christophe [Laboratoire d' Ecotoxicologie, Universite du Havre, 25 rue Philippe Lebon, B.P. 540, F-76058 Le Havre (France); Porte, Cinta [Department of Environmental Chemistry, IIQAB-CSIC, Jordi Girona 18, 08034 Barcelona (Spain)]. E-mail: cpvqam@cid.csic.es

2006-05-15

Red mullet (Mullus barbatus) were collected from different sampling sites (NW Mediterranean) in spring and autumn, with the aim of assessing potential alterations of the endocrine system. Alkylphenols were measured in fish bile as an indicator of estrogenic exposure. Key enzymatic activities involved in both synthesis (ovarian 17{beta}-hydroxysteroid dehydrogenases and P450 aromatase) and metabolism of steroids were assessed together with histological alterations of the gonads. During the spring sampling, delayed gamete maturation, intersexuality, fibrosis, and depressed ovarian P450 aromatase activity were observed in organisms from the most polluted sites. During the autumn sampling, those effects were less evident, indicating that fish might be more susceptible to endocrine disrupting chemicals during the reproductive period. Nonetheless, enhanced glucuronidation of testosterone and estradiol was observed. Overall, this work provides first evidences of significant alterations in the endocrine system of red mullet from highly impacted areas in the NW Mediterranean. - Red mullet may be more susceptible to endocrine disruptors during the reproductive period.

Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

International Nuclear Information System (INIS)

Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

2010-01-01

Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

Your Endocrine System (For Kids)

Science.gov (United States)

... Kids / Your Endocrine System Print en español Tu sistema endocrino You might say endocrine (say: EN-doh- ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

Report of the Phase 1 of the Validation of the Fish Sexual Development Test for the Detection of Endocrine Active Substances

DEFF Research Database (Denmark)

Holbech, Henrik; Kinnberg, Karin Lund; Petersen, Gitte

This document presents the validation report (phase 1) of the Fish Sexual Development Test (FSDT). The FSDT covers a life-stage where sexual development is particularly sensitive to perturbation caused by endocrine active chemicals. The chemical exposure lasts for about 60 days, at the end of which...

Transcriptome alterations in zebrafish embryos after exposure to environmental estrogens and anti-androgens can reveal endocrine disruption.

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Schiller, Viktoria; Wichmann, Arne; Kriehuber, Ralf; Schäfers, Christoph; Fischer, Rainer; Fenske, Martina

2013-12-01

Exposure to environmental chemicals known as endocrine disruptors (EDs) is in many cases associated with an unpredictable hazard for wildlife and human health. The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable ED assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17α-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Copyright © 2013 Elsevier Inc. All rights reserved.

The OBELIX project: early life exposure to endocrine disruptors and obesity.

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Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

2011-12-01

The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

Prediction of Positions of Active Compounds Makes It Possible To Increase Activity in Fragment-Based Drug Development

Directory of Open Access Journals (Sweden)

Yoshifumi Fukunishi

2011-05-01

Full Text Available We have developed a computational method that predicts the positions of active compounds, making it possible to increase activity as a fragment evolution strategy. We refer to the positions of these compounds as the active position. When an active fragment compound is found, the following lead generation process is performed, primarily to increase activity. In the current method, to predict the location of the active position, hydrogen atoms are replaced by small side chains, generating virtual compounds. These virtual compounds are docked to a target protein, and the docking scores (affinities are examined. The hydrogen atom that gives the virtual compound with good affinity should correspond to the active position and it should be replaced to generate a lead compound. This method was found to work well, with the prediction of the active position being 2 times more efficient than random synthesis. In the current study, 15 examples of lead generation were examined. The probability of finding active positions among all hydrogen atoms was 26%, and the current method accurately predicted 60% of the active positions.

Phenolic compounds and antioxidant activity of edible flowers

Directory of Open Access Journals (Sweden)

Marta Natalia Skrajda

2017-08-01

Full Text Available Introduction: Edible flowers has been used for thousands of years. They increase aesthetic appearance of food, but more often they are mentioned in connection with biologically active substances. The main ingredient of the flowers is water, which accounts for more than 80%. In small amounts, there are also proteins, fat, carbohydrates, fiber and minerals. Bioactive substances such as carotenoids and phenolic compounds determine the functional properties of edible flowers. Aim: The aim of this work was to characterize the phenolic compounds found in edible flowers and compare their antioxidant activity. Results: This review summarizes current knowledge about the usage of edible flowers for human nutrition. The work describes the antioxidant activity and phenolic compounds of some edible flowers. Based on literature data there is a significant difference both in content of phenolic compounds and antioxidant activity between edible flowers. These difference reaches up to 3075-fold in case of antioxidant potential. Among described edible flowers the most distinguishable are roses, peonies, osmanthus fragans and sambuco nero. Conclusions: Edible flowers are the new source of nutraceuticals due to nutritional and antioxidant values.

[Disperse endocrine system and APUD concept].

Science.gov (United States)

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.

Endocrine-disrupting chemicals-Mechanisms of action on male reproductive system.

Science.gov (United States)

Sidorkiewicz, Iwona; Zaręba, Kamil; Wołczyński, Sławomir; Czerniecki, Jan

2017-07-01

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that can cause disturbances in the endocrine system and have multiple harmful effects on health by targeting different organs and systems in the human body. Mass industrial production and widespread use of EDCs have resulted in worldwide contamination. Accumulating evidence suggest that human exposure to EDCs is related to the impairment of male reproductive function and can interrupt other hormonally regulated metabolic processes, particularly if exposure occurs during early development. Investigation of studies absent in previous reviews and meta-analysis of adverse effects of EDCs on functioning of the male reproductive system is the core of this work. Four main modes of action of EDCs on male fertility have been summarized in this review. First, studies describing estrogen- pathway disturbing chemicals are investigated. Second, androgen-signaling pathway alterations and influence on androgen sensitive tissues are examined. Third, evaluation of steroidogenesis dysfunction is discussed by focusing on the steroid hormone biosynthesis pathway, which is targeted by EDCs. Last, the reportedly destructive role of reactive oxygen species (ROS) on sperm function is discussed. Spermatogenesis is a remarkably complex process, hence multiple studies point out various dysfunctions depending on the development state at which the exposure occurred. Collected data show the need to account for critical windows of exposure such as fetal, perinatal and pubertal periods as well as effects of mixtures of several compounds in future research.

Designing Endocrine Disruption Out of the Next Generation of Chemicals.

Science.gov (United States)

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

different endocrinological mechanisms through the protocol using published literature. Each was identified as endocrine active by one or more tiers. We believe that this voluntary testing protocol will be a dynamic tool to facilitate efficient and early identification of potentially problematic chemicals, while ultimately reducing the risks to public health.

Antioxidant Activity of Phenolic Compounds from Fava Bean Sprouts.

Science.gov (United States)

Okumura, Koharu; Hosoya, Takahiro; Kawarazaki, Kai; Izawa, Norihiko; Kumazawa, Shigenori

2016-06-01

Fava beans are eaten all over the world and recently, marketing for their sprouts began in Japan. Fava bean sprouts contain more polyphenols and l-3,4-dihydroxyphenylalanine (l-DOPA) than the bean itself. Our antioxidant screening program has shown that fava bean sprouts also possess a higher antioxidant activity than other commercially available sprouts and mature beans. However, the individual constituents of fava bean sprouts are not entirely known. In the present study, we investigated the phenolic compounds of fava bean sprouts and their antioxidant activity. Air-dried fava bean sprouts were treated with 80% methanol and the extract was partitioned in water with chloroform and ethyl acetate. HPLC analysis had shown that the ethyl acetate-soluble parts contained phenolic compounds, separated by preparative HPLC to yield 5 compounds (1-5). Structural analysis using NMR and MS revealed that the compounds isolated were kaempferol glycosides. All isolated compounds had an α-rhamnose at the C-7 position with different sugars attached at the C-3 position. Compounds 1-5 had β-galactose, β-glucose, α-rhamnose, 6-acetyl-β-galactose and 6-acetyl-β-glucose, respectively, at the C-3 position. The amount of l-DOPA in fava bean sprouts was determined by the quantitative (1) H NMR technique. The l-DOPA content was 550.45 mg ± 11.34 /100 g of the raw sprouts. The antioxidant activities of compounds 2-5 and l-DOPA were evaluated using the 2,2-diphenyl-1-picrylhydrazyl scavenging assay. l-DOPA showed high antioxidant activity, but the isolated kaempferol glycosides showed weak activity. Therefore, it can be suggested that l-DOPA contributed to the antioxidant activity of fava bean sprouts. © 2016 Institute of Food Technologists®

Application of Adverse Outcome Pathways to U.S. EPA's Endocrine Disruptor Screening Program.

Science.gov (United States)

Browne, Patience; Noyes, Pamela D; Casey, Warren M; Dix, David J

2017-09-01

The U.S. EPA's Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. This review describes the EDSP's use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Pathway frameworks can facilitate a weight of evidence determination of a chemical's potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304.

Prevalent flucocorticoid and androgen activity in US water sources

Science.gov (United States)

Stavreva, Diana A.; George, Anuja A.; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C.; Schiltz, R. Louis; Blazer, Vicki; Iwanowiczl, Luke R.; Hager, Gordon L.

2012-01-01

Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

Prevalent glucocorticoid and androgen activity in US water sources.

Science.gov (United States)

Stavreva, Diana A; George, Anuja A; Klausmeyer, Paul; Varticovski, Lyuba; Sack, Daniel; Voss, Ty C; Schiltz, R Louis; Blazer, Vicki S; Iwanowicz, Luke R; Hager, Gordon L

2012-01-01

Contamination of the environment with endocrine disrupting chemicals (EDCs) is a major health concern. The presence of estrogenic compounds in water and their deleterious effect are well documented. However, detection and monitoring of other classes of EDCs is limited. Here we utilize a high-throughput live cell assay based on sub-cellular relocalization of GFP-tagged glucocorticoid and androgen receptors (GFP-GR and GFP-AR), in combination with gene transcription analysis, to screen for glucocorticoid and androgen activity in water samples. We report previously unrecognized glucocorticoid activity in 27%, and androgen activity in 35% of tested water sources from 14 states in the US. Steroids of both classes impact body development, metabolism, and interfere with reproductive, endocrine, and immune systems. This prevalent contamination could negatively affect wildlife and human populations.

Simultaneous Activation of Iron- and Thiol-Based Sensor-Regulator Systems by Redox-Active Compounds.

Science.gov (United States)

Lee, Kang-Lok; Yoo, Ji-Sun; Oh, Gyeong-Seok; Singh, Atul K; Roe, Jung-Hye

2017-01-01

Bacteria in natural habitats are exposed to myriad redox-active compounds (RACs), which include producers of reactive oxygen species (ROS) and reactive electrophile species (RES) that alkylate or oxidize thiols. RACs can induce oxidative stress in cells and activate response pathways by modulating the activity of sensitive regulators. However, the effect of a certain compound on the cell has been investigated primarily with respect to a specific regulatory pathway. Since a single compound can exert multiple chemical effects in the cell, its effect can be better understood by time-course monitoring of multiple sensitive regulatory pathways that the compound induces. We investigated the effect of representative RACs by monitoring the activity of three sensor-regulators in the model actinobacterium Streptomyces coelicolor ; SoxR that senses reactive compounds directly through oxidation of its [2Fe-2S] cluster, CatR/PerR that senses peroxides through bound iron, and an anti-sigma factor RsrA that senses RES via disulfide formation. The time course and magnitude of induction of their target transcripts were monitored to predict the chemical activities of each compound in S. coelicolor . Phenazine methosulfate (PMS) was found to be an effective RAC that directly activated SoxR and an effective ROS-producer that induced CatR/PerR with little thiol-perturbing activity. p -Benzoquinone was an effective RAC that directly activated SoxR, with slower ROS-producing activity, and an effective RES that induced the RsrA-SigR system. Plumbagin was an effective RAC that activated SoxR, an effective ROS-producer, and a less agile but effective RES. Diamide was an RES that effectively formed disulfides and a weak RAC that activated SoxR. Monobromobimane was a moderately effective RES and a slow producer of ROS. Interestingly, benzoquinone induced the SigR system by forming adducts on cysteine thiols in RsrA, revealing a new pathway to modulate RsrA activity. Overall, this study showed

A multi-assay screening approach for assessment of endocrine-active contaminants in wastewater effluent samples

Energy Technology Data Exchange (ETDEWEB)

Metcalfe, Chris D., E-mail: cmetcalfe@trentu.ca [Environmental and Resource Studies, Trent University, Peterborough, ON, K9J 7B8 (Canada); Kleywegt, Sonya [Standards Development Branch, Ontario Ministry of the Environment, 40 St. Clair Ave. West, Toronto, ON, M4V 1M2 (Canada); Letcher, Robert J. [Ecotoxicology and Wildlife Health Division, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, ON, K1A 0H3 (Canada); Topp, Edward [Agriculture and Agri-Food Canada, Southern Crop Protection and Food Research Centre, London, ON, N5V 7T3 (Canada); Wagh, Purva; Trudeau, Vance L.; Moon, Thomas W. [Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, ON, K1N 6N5 (Canada)

2013-06-01

Environmental agencies must monitor an ever increasing range of contaminants of emerging concern, including endocrine disrupting compounds (EDCs). An alternative to using ultra-trace chemical analysis of samples for EDCs is to test for biological activity using in vitro screening assays, then use these assay results to direct analytical chemistry approaches. In this study, we used both analytical approaches and in vitro bioassays to characterize the EDCs present in treated wastewater from four wastewater treatment plants (WWTPs) in Ontario, Canada. Estrogen-mediated activity was assessed using a yeast estrogenicity screening (YES) assay. An in vitro competitive binding assay was used to assess capacity to interfere with binding of the thyroid hormone, thyroxine (T4) to the recombinant human thyroid hormone transport protein, transthyretin (i.e. hTTR). An in vitro binding assay with a rat peroxisome proliferator responsive element transfected into a rainbow trout gill cell line was used to evaluate binding and subsequent gene expression via the peroxisome proliferator activated receptor (PPAR). Analyses of a suite of contaminants known to be EDCs in extracts from treated wastewater were conducted using either gas chromatography with mass spectrometry (GC-MS) or liquid chromatography with tandem mass spectrometry (LC-MS/MS). Estrogenic activity was detected in the YES assay only in those extracts that contained detectable amounts of estradiol (E2). There was a positive relationship between the degree of response in the T4-hTTR assay and the amounts of polybrominated diphenyl ether (PBDE) congeners 47 and 99, triclosan and the PBDE metabolite, 4-OH-BDE17. Several wastewater extracts gave a positive response in the PPAR assay, but these responses were not correlated with the amounts of any of the EDCs analyzed by LC-MS/MS. Overall, these data indicate that a step-wise approach is feasible using a combination of in vitro testing and instrumental analysis to monitor for

A multi-assay screening approach for assessment of endocrine-active contaminants in wastewater effluent samples

International Nuclear Information System (INIS)

Metcalfe, Chris D.; Kleywegt, Sonya; Letcher, Robert J.; Topp, Edward; Wagh, Purva; Trudeau, Vance L.; Moon, Thomas W.

2013-01-01

Environmental agencies must monitor an ever increasing range of contaminants of emerging concern, including endocrine disrupting compounds (EDCs). An alternative to using ultra-trace chemical analysis of samples for EDCs is to test for biological activity using in vitro screening assays, then use these assay results to direct analytical chemistry approaches. In this study, we used both analytical approaches and in vitro bioassays to characterize the EDCs present in treated wastewater from four wastewater treatment plants (WWTPs) in Ontario, Canada. Estrogen-mediated activity was assessed using a yeast estrogenicity screening (YES) assay. An in vitro competitive binding assay was used to assess capacity to interfere with binding of the thyroid hormone, thyroxine (T4) to the recombinant human thyroid hormone transport protein, transthyretin (i.e. hTTR). An in vitro binding assay with a rat peroxisome proliferator responsive element transfected into a rainbow trout gill cell line was used to evaluate binding and subsequent gene expression via the peroxisome proliferator activated receptor (PPAR). Analyses of a suite of contaminants known to be EDCs in extracts from treated wastewater were conducted using either gas chromatography with mass spectrometry (GC-MS) or liquid chromatography with tandem mass spectrometry (LC-MS/MS). Estrogenic activity was detected in the YES assay only in those extracts that contained detectable amounts of estradiol (E2). There was a positive relationship between the degree of response in the T4-hTTR assay and the amounts of polybrominated diphenyl ether (PBDE) congeners 47 and 99, triclosan and the PBDE metabolite, 4-OH-BDE17. Several wastewater extracts gave a positive response in the PPAR assay, but these responses were not correlated with the amounts of any of the EDCs analyzed by LC-MS/MS. Overall, these data indicate that a step-wise approach is feasible using a combination of in vitro testing and instrumental analysis to monitor for

Endocrine responses to water restriction in desert sheep

International Nuclear Information System (INIS)

Ahmed, Muna M.M.

1994-01-01

For ruminants grazing in semi-arid areas, the maintenance of balanced water and energy metabolism is challenging to productivity.The metabolic effects of water restriction usually stimulate endocrine which control metabolic activity depending on the thermal environment.Radioimmunoasay technique was used to determine the level of endocrine hormones, namely thyroid stimulating hormone(TSH),thyroxine(T4) and cortisol in desert sheep.Intermittent watering every 24h, 48h and 72h increased TSH level during the morning but decreased it during the afternoon.T4 level decreased during both morning and afternoon.The cortisol level was depressed by water restriction during the morning and afternoon but showed an overlapping pattern with that of the control during the afternoon. (Author)

Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes

International Nuclear Information System (INIS)

Allera, A.; Lo, S.; King, I.; Steglich, F.; Klingmueller, D.

2004-01-01

Various pesticides, industrial pollutants and synthetic compounds, to which human populations are exposed, are known or suspected to interfere with endogenous sex hormone functions. Such interference potentially affect the development and expression of the male and female reproductive system or both. Chemicals in this class are thus referred to as endocrine disruptors (ED). This emphazises on the relevance of screening ED for a wide range of sex hormone-mimicking effects. These compounds are believed to exert influence on hormonal actions predominantly by (i) interfering with endogenous steroids in that they functionally interact with plasma membrane-located receptors as well as with nuclear receptors both for estrogens and androgens or (ii) affecting the levels of sex hormones as a result of their impact on steroid metabolizing key enzymes. Essential sex hormone-related enzymes within the endocrine system of humans are aromatase, 5α-reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase I and phase II enzymes, respectively). Using suitable human tissues and human cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals suspected of acting as ED with androgenic or antiandrogenic activity (so-called AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In addition, the respective effects of six substances were also studied as positive controls due to their well-known specific hormonal agonistic/antagonistic activities. The aim of this report and subsequent investigations is to improve human health risk assessment for AAC and other ED

Antioxidative Activities and Active Compounds of Extracts from Catalpa Plant Leaves

Directory of Open Access Journals (Sweden)

Hongyu Xu

2014-01-01

Full Text Available In order to screen the Catalpa plant with high antioxidant activity and confirm the corresponding active fractions from Catalpa ovata G. Don, C. fargesii Bur., and C. bungei C. A. Mey., total flavonoid contents and antioxidant activities of the extracts/fractions of Catalpa plant leaves were determined. The determined total flavonoid content and antioxidant activity were used as assessment criteria. Those compounds with antioxidant activity were isolated with silica gel column chromatography and ODS column chromatography. Our results showed that the total flavonoid content in C. bungei C. A. Mey. (30.07 mg/g·DW was the highest, followed by those in C. fargesii Bur. (25.55 mg/g·DW and C. ovata G. Don (24.96 mg/g·DW. According to the determination results of total flavonoid content and antioxidant activity in 3 clones of leaves of C. bungei C. A. Mey., the total flavonoid content and antioxidant activity in crude extracts from C. bungei C. A. Mey. 6 (CA6 leaves were the highest. Moreover, the results showed that the total flavonoid content and antioxidant activities of ethyl acetate (EA fraction in ethanol crude extracts in CA6 leaves were the highest, followed by n-butanol, petroleum ether (PE, and water fractions. Two flavonoid compounds with antioxidant activity were firstly isolated based on EA fraction. The two compounds were luteolin (1 and apigenin (2, respectively.

Endocrine aspects of cancer gene therapy.

Science.gov (United States)

Barzon, Luisa; Boscaro, Marco; Palù, Giorgio

2004-02-01

The field of cancer gene therapy is in continuous expansion, and technology is quickly moving ahead as far as gene targeting and regulation of gene expression are concerned. This review focuses on the endocrine aspects of gene therapy, including the possibility to exploit hormone and hormone receptor functions for regulating therapeutic gene expression, the use of endocrine-specific genes as new therapeutic tools, the effects of viral vector delivery and transgene expression on the endocrine system, and the endocrine response to viral vector delivery. Present ethical concerns of gene therapy and the risk of germ cell transduction are also discussed, along with potential lines of innovation to improve cell and gene targeting.

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

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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.

Endocrine Dysregulation in Anorexia Nervosa Update

Science.gov (United States)

2011-01-01

Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID:21976742

Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

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Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

2014-03-01

Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

Testosterone conjugating activities in invertebrates: are they targets for endocrine disruptors?

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Janer, G; Sternberg, R M; LeBlanc, G A; Porte, C

2005-02-10

Testosterone conjugation activities, microsomal acyltransferases and cytosolic sulfotransferases, were investigated in three invertebrate species, the gastropod Marisa cornuarietis, the amphipod Hyalella azteca, and the echinoderm Paracentrotus lividus. The goals of the study were to characterize steroid conjugation pathways in different invertebrate phyla and to assess the susceptibility of those processes to disruption by environmental chemicals. All three species exhibited palmitoyl-CoA: testosterone acyltransferase activity (ATAT) in the range of 100-510 pmol/min/mg protein. Despite similarities in specific activities, kinetic studies indicated that ATAT had a higher affinity for testosterone but a lower V(max) in M. cornuarietis than in P. lividus, and intermediate values were found for H. azteca. In contrast, the activity of testosterone sulfotransferase (SULT) was rather low (0.05-0.18 pmol/min/mg protein) in M. cornuarietis and H. azteca. The low activity precluded kinetic analyses and inhibition studies with these species. P. lividus digestive tube displayed high SULT activity (50-170 pmol/min/mg protein) at moderate testosterone concentrations, but was inhibited at high testosterone concentrations. The interference of model pollutants (triphenyltin (TPT), tributyltin (TBT), and fenarimol) with these conjugation pathways was investigated in vitro. Both TPT and TBT (100 microM) inhibited ATAT in P. lividus (68 and 42% inhibition, respectively), and appeared to act as non-competitive inhibitors. ATAT activity in M. cornuarietis was less affected by organotins, and a significant inhibition (20% inhibition) was detected only with TBT. Fenarimol (100 microM) did not affect ATAT in any of the species tested. Sulfation of testosterone was suppressed by the organotins as well as fenarimol when using cytosolic preparations from P. lividus. These results demonstrated the existence of interphyla differences in testosterone conjugation, and revealed that these

Aerobic biodegradation of organotin compounds in activated sludge batch reactors

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Stasinakis, Athanasios S. [Department of Environmental Studies, Water and Air Quality Laboratory, University of the Aegean, University Hill, Mytilene 81 100 (Greece)]. E-mail: astas@env.aegean.gr; Thomaidis, Nikolaos S. [Laboratory of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Zografou, Athens 157 71 (Greece); Nikolaou, Anastasia [Department of Environmental Studies, Water and Air Quality Laboratory, University of the Aegean, University Hill, Mytilene 81 100 (Greece); Kantifes, Andreas [Department of Environmental Studies, Water and Air Quality Laboratory, University of the Aegean, University Hill, Mytilene 81 100 (Greece)

2005-04-01

The biodegradation behavior of four organotin (OT) compounds, namely tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT) and triphenyltin (TPhT), was studied in lab-scale activated sludge batch reactors. The activated sludge was spiked with the OT compounds at a level of 100 {mu}g l{sup -1} as Sn. Determination of the OT compounds by GC-FPD after ethylation in the dissolved and particulate phase revealed that 24 h after the start of the experiments, almost the total of OT compounds has been removed from the dissolved phase and is associated with the suspended solids. Calculation of mass balance in batch reactors showed that OT compounds biodegradation was performed via a sequential dealkylation process. Removals due to biodegradation were differentiated according to the parent compound. In experiments with non-acclimatized biomass, a percentage of 27.1, 8.3, 73.8 and 51.3 was still present as TBT, DBT, MBT and TPhT, respectively, at the end of the experiment (18th day). Half-lives (t{sub 1/2}) of 10.2 and 5.1 days were calculated for TBT and DBT, respectively, whereas apparent t{sub 1/2} values could not be determined for MBT and TPhT (t{sub 1/2} > 18 days). The capacity of activated sludge to biodegrade OT compounds in the absence of supplemental substrate indicated that these compounds can be metabolized as single sources of carbon and energy in activated sludge systems. Excluding TBT, the presence of low concentrations of supplemental substrate did not affect the biodegradation potential of activated sludge. The acclimatization of biomass on OT compounds enhanced significantly biodegradation, resulting in significant decreases of half-lives of OT compounds. As a result in the presence of acclimatized biomass, half-lives of 1.4, 3.6, 9.8 and 5.0 days were calculated for TBT, DBT, MBT and TPhT, respectively. - The fate of organotins is assessed in activated sludge systems.

Aerobic biodegradation of organotin compounds in activated sludge batch reactors

International Nuclear Information System (INIS)

Stasinakis, Athanasios S.; Thomaidis, Nikolaos S.; Nikolaou, Anastasia; Kantifes, Andreas

2005-01-01

The biodegradation behavior of four organotin (OT) compounds, namely tributyltin (TBT), dibutyltin (DBT), monobutyltin (MBT) and triphenyltin (TPhT), was studied in lab-scale activated sludge batch reactors. The activated sludge was spiked with the OT compounds at a level of 100 μg l -1 as Sn. Determination of the OT compounds by GC-FPD after ethylation in the dissolved and particulate phase revealed that 24 h after the start of the experiments, almost the total of OT compounds has been removed from the dissolved phase and is associated with the suspended solids. Calculation of mass balance in batch reactors showed that OT compounds biodegradation was performed via a sequential dealkylation process. Removals due to biodegradation were differentiated according to the parent compound. In experiments with non-acclimatized biomass, a percentage of 27.1, 8.3, 73.8 and 51.3 was still present as TBT, DBT, MBT and TPhT, respectively, at the end of the experiment (18th day). Half-lives (t 1/2 ) of 10.2 and 5.1 days were calculated for TBT and DBT, respectively, whereas apparent t 1/2 values could not be determined for MBT and TPhT (t 1/2 > 18 days). The capacity of activated sludge to biodegrade OT compounds in the absence of supplemental substrate indicated that these compounds can be metabolized as single sources of carbon and energy in activated sludge systems. Excluding TBT, the presence of low concentrations of supplemental substrate did not affect the biodegradation potential of activated sludge. The acclimatization of biomass on OT compounds enhanced significantly biodegradation, resulting in significant decreases of half-lives of OT compounds. As a result in the presence of acclimatized biomass, half-lives of 1.4, 3.6, 9.8 and 5.0 days were calculated for TBT, DBT, MBT and TPhT, respectively. - The fate of organotins is assessed in activated sludge systems

The mast cell degranulator compound 48/80 directly activates neurons.

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Michael Schemann

Full Text Available BACKGROUND: Compound 48/80 is widely used in animal and tissue models as a "selective" mast cell activator. With this study we demonstrate that compound 48/80 also directly activates enteric neurons and visceral afferents. METHODOLOGY/PRINCIPAL FINDINGS: We used in vivo recordings from extrinsic intestinal afferents together with Ca(++ imaging from primary cultures of DRG and nodose neurons. Enteric neuronal activation was examined by Ca(++ and voltage sensitive dye imaging in isolated gut preparations and primary cultures of enteric neurons. Intraluminal application of compound 48/80 evoked marked afferent firing which desensitized on subsequent administration. In egg albumen-sensitized animals, intraluminal antigen evoked a similar pattern of afferent activation which also desensitized on subsequent exposure to antigen. In cross-desensitization experiments prior administration of compound 48/80 failed to influence the mast cell mediated response. Application of 1 and 10 µg/ml compound 48/80 evoked spike discharge and Ca(++ transients in enteric neurons. The same nerve activating effect was observed in primary cultures of DRG and nodose ganglion cells. Enteric neuron cultures were devoid of mast cells confirmed by negative staining for c-kit or toluidine blue. In addition, in cultured enteric neurons the excitatory action of compound 48/80 was preserved in the presence of histamine H(1 and H(2 antagonists. The mast cell stabilizer cromolyn attenuated compound 48/80 and nicotine evoked Ca(++ transients in mast cell-free enteric neuron cultures. CONCLUSIONS/SIGNIFICANCE: The results showed direct excitatory action of compound 48/80 on enteric neurons and visceral afferents. Therefore, functional changes measured in tissue or animal models may involve a mast cell independent effect of compound 48/80 and cromolyn.

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

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

2015-12-01

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.

The application of reporter gene assays for the detection of endocrine disruptors in sport supplements

Energy Technology Data Exchange (ETDEWEB)

Plotan, Monika; Elliott, Christopher T. [Institute of Agri-Food and Land Use, School of Biological Sciences, Queen' s University Belfast, Belfast BT95AG, Northern Ireland (United Kingdom); Scippo, Marie Louise [Department of Food Sciences, University of Liege, 4000 Liege (Belgium); Muller, Marc [Molecular Biology and Genetic Engineering GIGA-R, University of Liege, 4000 Liege (Belgium); Antignac, Jean-Philippe [LABERCA, ENVN, USC INRA 2013, BP 50707, 44 307, Nantes (France); Malone, Edward [The State Laboratory, Young' s Cross, Celbridge, Co. Kildare (Ireland); Bovee, Toine F.H. [RIKILT Institute of Food Safety, P.O. Box 230, AE Wageningen 6700 (Netherlands); Mitchell, Samuel [Agri-Food and Biosciences Institute, Belfast BT9 5PX (United Kingdom); Connolly, Lisa, E-mail: l.connolly@qub.ac.uk [Institute of Agri-Food and Land Use, School of Biological Sciences, Queen' s University Belfast, Belfast BT95AG, Northern Ireland (United Kingdom)

2011-08-26

The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC{sub 50} of 0.01 ng mL{sup -1} and 0.16 ng mL{sup -1} respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally

Radiotherapy for unresectable endocrine pancreatic carcinomas

International Nuclear Information System (INIS)

Tennvall, J.; Ljungberg, O.; Ahren, B.; Gustavsson, A.; Nillson, L.O.

1992-01-01

Surgery, when possible, is the treatment of choice for the uncommon endocrine tumours of pancreas. Unresectable cases are usually treated with cytostatic drugs or α-interferon. We describe a patient with unresectable, locally advanced endocrine pancreatic carcinoma (measuring 5 x 5 x 6 cm) that was totally cured by external radiation therapy only (40 Gy). This case together with four cases in the literature indicate that external radiation therapy should be considered in locally unresectable endocrine pancreatic carcinomas. (author)

Endocrine disruptors in bottled mineral water: total estrogenic burden and migration from plastic bottles.

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Wagner, Martin; Oehlmann, Jörg

2009-05-01

Food consumption is an important route of human exposure to endocrine-disrupting chemicals. So far, this has been demonstrated by exposure modeling or analytical identification of single substances in foodstuff (e.g., phthalates) and human body fluids (e.g., urine and blood). Since the research in this field is focused on few chemicals (and thus missing mixture effects), the overall contamination of edibles with xenohormones is largely unknown. The aim of this study was to assess the integrated estrogenic burden of bottled mineral water as model foodstuff and to characterize the potential sources of the estrogenic contamination. In the present study, we analyzed commercially available mineral water in an in vitro system with the human estrogen receptor alpha and detected estrogenic contamination in 60% of all samples with a maximum activity equivalent to 75.2 ng/l of the natural sex hormone 17beta-estradiol. Furthermore, breeding of the molluskan model Potamopyrgus antipodarum in water bottles made of glass and plastic [polyethylene terephthalate (PET)] resulted in an increased reproductive output of snails cultured in PET bottles. This provides first evidence that substances leaching from plastic food packaging materials act as functional estrogens in vivo. Our results demonstrate a widespread contamination of mineral water with xenoestrogens that partly originates from compounds leaching from the plastic packaging material. These substances possess potent estrogenic activity in vivo in a molluskan sentinel. Overall, the results indicate that a broader range of foodstuff may be contaminated with endocrine disruptors when packed in plastics.

Pesticides Provoke Endocrine Disruption A Review

International Nuclear Information System (INIS)

Aly, M.A.S.

2006-01-01

Increasing numbers of environmental chemicals,including pesticides, have the ability to produce endocrine disruption by various mechanisms. such substances may affect hormone secretion from an endocrine gland and may alter the rate of hormone elimination from the body. environmental chemicals may also disrupt regulatory feedback mechanisms that exist between two endocrine organs; or may interact with a hormone receptor either by mimicking or antagonizing the actions of the natural hormone. these chemicals are referred to endocrine disruptive chemicals (EDC's). EDC's act to alter the blood hormone levels or the subsequent action of hormones . the use of radioimmunoassay(RIA) constitutes a superior and unrivalled tool for the determination and quantification of hormones.the endocrine system participates in virtually all important functions of an organism, such as sexual differentiation before birth, sexual maturation during puberty, reproduction in adulthood, growth, metabolism, digestion, cardiovascular function and excretion. hormones are also implicated in the etiology of certain cancers of hormone- dependent tissues, such as those of the breast, uterus, and prostate gland. therefore, endocrine disruption can potentially produce widespread effects. scientists should not stick to the past belief which presumes that pesticides have limited effect on some hormones. A paradigm shift in which a wider vision of understanding of the wholesome complex effects of pesticides on the whole body rather than a narrow limited understanding should take place

Triorganotin as a compound with potential reproductive toxicity in mammals

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V.S. Delgado Filho

2011-09-01

Full Text Available Organotin compounds are typical environmental contaminants and suspected endocrine-disrupting substances, which cause irreversible sexual abnormality in female mollusks, called "imposex". However, little is known about the capability of triorganotin compounds, such as tributyltin and triphenyltin, to cause disorders in the sexual development and reproductive functions of mammals, including humans and rodents. Moreover, these compounds can act as potential competitive inhibitors of aromatase enzyme and other steroidogenic enzymes, affecting the reproductive capacity of male and female mammals. In this review, we discuss the cellular, biochemical, and molecular mechanisms by which triorganotin compounds induce adverse effects in the mammalian reproductive function.

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

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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. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phosphodiesterases in endocrine physiology and disease.

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Vezzosi, Delphine; Bertherat, Jérôme

2011-08-01

The cAMP-protein kinase A pathway plays a central role in the development and physiology of endocrine tissues. cAMP mediates the intracellular effects of numerous peptide hormones. Various cellular and molecular alterations of the cAMP-signaling pathway have been observed in endocrine diseases. Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. Indeed, PDEs are the only known mechanism for inactivation of cAMP by catalysis to 5'-AMP. It has been suggested that disruption of PDEs could also have a role in the pathogenesis of many endocrine diseases. This review summarizes the most recent advances concerning the role of the PDEs in the physiopathology of endocrine diseases. The potential significance of this knowledge can be easily envisaged by the development of drugs targeting specific PDEs.

Probing the binding of an endocrine disrupting compound-Bisphenol F to human serum albumin: insights into the interactions of harmful chemicals with functional biomacromolecules.

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Pan, Fang; Xu, Tianci; Yang, Lijun; Jiang, Xiaoqing; Zhang, Lei

2014-11-11

Bisphenol F (BPF) as an endocrine disrupting compounds (EDCs) pollutant in the environment poses a great threat to human health. To evaluate the toxicity of BPF at the protein level, the effects of BPF on human serum albumin (HSA) were investigated at three temperatures 283, 298, and 308 K by multiple spectroscopic techniques. The experimental results showed that BPF effectively quenched the intrinsic fluorescence of HSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and the binding subdomain were measured, and indicated that BPF could spontaneously bind with HSA on subdomain IIA through H-bond and van der Waals interactions. Furthermore, the conformation of HSA was demonstrably changed in the presence of BPF. The work provides accurate and full basic data for clarifying the binding mechanisms of BPF with HSA in vivo and is helpful for understanding its effect on protein function during its transportation and distribution in blood. Copyright © 2014 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

Kassotis, Christopher D.; Iwanowicz, Luke R.; Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam C.; 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. - Highlights: • Oil and gas wastewater disposal may increase endocrine disrupting activity in water. • Tested EDC activity in surface water near oil and gas wastewater injection site. • Water downstream had significantly

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

Energy Technology Data Exchange (ETDEWEB)

Kassotis, Christopher D., E-mail: christopher.kassotis@duke.edu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Iwanowicz, Luke R. [U.S. Geological Survey, Leetown Science Center, Fish Health Branch, 11649 Leetown Road, Kearneysville, WV 25430 (United States); Akob, Denise M.; Cozzarelli, Isabelle M.; Mumford, Adam C. [U.S. Geological Survey, National Research Program, 12201 Sunrise Valley Drive, MS 430, Reston, VA 20192 (United States); Orem, William H. [U.S. Geological Survey, Eastern Energy Resources Science Center, 12201 Sunrise Valley Drive, MS 956, Reston, VA 20192 (United States); Nagel, Susan C., E-mail: nagels@health.missouri.edu [Department of Obstetrics, Gynecology and Women' s Health, University of Missouri, Columbia, MO 65211 (United States)

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. - Highlights: • Oil and gas wastewater disposal may increase endocrine disrupting activity in water. • Tested EDC activity in surface water near oil and gas wastewater injection site. • Water downstream had significantly

Endocrine Diseases

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... Syndrome (PCOS) Pregnancy and Thyroid Disease Primary Hyperparathyroidism Prolactinoma Thyroid Tests Turner Syndrome Contact Us The National ... Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ...

Anti-cancer activity of compounds from Bauhinia strychnifolia stem.

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Yuenyongsawad, Supreeya; Bunluepuech, Kingkan; Wattanapiromsakul, Chatchai; Tewtrakul, Supinya

2013-11-25

The stem and root of Bauhinia strychnifolia Craib (Fabaceae family) have been traditionally used in Thailand to treat fever, alcoholic toxication, allergy and cancer. An EtOH extract of Bauhinia strychnifolia showed good inhibitory activity against several cancer cell lines including HT-29, HeLa, MCF-7 and KB. As there has been no previous reports on chemical constituents of Bauhinia strychnifolia, this study is aimed to isolate the pure compounds with anti-cancer activity. Five pure compounds were isolated from EtOH extract of Bauhinia strychnifolia stem using silica gel, dianion HP-20 and sephadex LH-20 column chromatography and were tested for their cytotoxic effects against HT-29, HeLa, MCF-7 and KB cell lines using the Sulforhodamine B (SRB) assay. Among five compounds, 3,5,7,3',5'-pentahydroxyflavanonol-3-O-α-l-rhamnopyranoside (2) possessed very potent activity against KB (IC₅₀=0.00054μg/mL), HT-29 (IC₅₀=0.00217 μg/mL), MCF-7 (IC₅₀=0.0585 μg/mL) and HeLa cells (IC₅₀=0.0692 μg/mL). 3,5,7-Trihydroxychromone-3-O-α-l-rhamnopyranoside (3) also showed good activity against HT-29 (IC₅₀=0.02366 μg/mL), KB (IC₅₀=0.0412 μg/mL) and MCF-7 (IC₅₀=0.297 μg/mL), respectively. The activity of 2 (IC₅₀=0.00054 μg/mL) against KB cell was ten times higher than that of the positive control, Camptothecin (anti-cancer drug, IC₅₀=0.0057 μg/mL). All compounds did not show any cytotoxicity with normal cells at the concentration of 1 μg/mL. This is the first report of compounds 2 and 3 on anti-cancer activity and based on the anti-cancer activity of extracts and pure compounds isolated from Bauhinia strychnifolia stem, it might be suggested that this plant could be useful for treatment of cancer. © 2013 Elsevier Ireland Ltd. All rights reserved.

Endocrine Disruptors (Chapter 14) in Mammalian Toxicology Book

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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...

Endocrine disruptors and the breast: early life effects and later life disease.

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Macon, Madisa B; Fenton, Suzanne E

2013-03-01

Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5-27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future.

Dibutyltin Compounds Effects on PPARγ/RXRα Activity, Adipogenesis, and Inflammation in Mammalians Cells

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Flora A. Milton

2017-08-01

Full Text Available Organotins are a group of chemical compounds that have a tin atom covalently bound to one or more organic groups. The best-studied organotin is tributyltin chloride, which is an environmental pollutant and an endocrine disruptor. Tributyltin chloride has been shown to bind to PPARγ/RXRα and induces adipogenesis in different mammalian cells. However, there are few studies with other organotin compounds, such as dibutyltins. The aim of this study was to investigate the effect of dibutyltins diacetate, dichloride, dilaurate, and maleate on the transcriptional activity of the nuclear PPARγ and RXRα receptors, and on adipogenesis and inflammation. Analogous to tributyltin chloride, in reporter gene assay using HeLa cells, we observed that dibutyltins diacetate, dichloride, dilaurate, and maleate are partial agonists of PPARγ. Unlike tributyltin chloride, which is a full agonist of RXRα, dibutyltins dichloride and dilaurate are partial RXRα agonists. Additionally, the introduction of the C285S mutation, which disrupts tributyltin chloride binding to PPARγ, abrogated the dibutyltin agonistic activity. In 3T3-L1 preadipocytes, all dibutyltin induced adipogenesis, although the effect was less pronounced than that of rosiglitazone and tributyltin chloride. This adipogenic effect was confirmed by the expression of adipogenic markers Fabp4, Adipoq, and Glut4. Exposure of 3T3-L1 cells with dibutyltin in the presence of T0070907, a specific PPARγ antagonist, reduced fat accumulation, suggesting that adipogenic effect occurs through PPARγ. Furthermore, dibutyltins dichloride, dilaurate, and maleate inhibited the expression of proinflammatory genes in 3T3-L1 cells, such as Vcam1, Dcn, Fn1, S100a8, and Lgals9. Additionally, in RAW 264.7 macrophages, tributyltin chloride and dibutyltin dilaurate reduced LPS-stimulated TNFα expression. Our findings indicate that dibutyltins diacetate, dichloride, dilaurate, and maleate are PPARγ partial agonists and

Scientific Issues Relevant to Setting Regulatory Criteria to Identify Endocrine-Disrupting Substances in the European Union.

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Slama, Rémy; Bourguignon, Jean-Pierre; Demeneix, Barbara; Ivell, Richard; Panzica, Giancarlo; Kortenkamp, Andreas; Zoeller, R Thomas

2016-10-01

Endocrine disruptors (EDs) are defined by the World Health Organization (WHO) as exogenous compounds or mixtures that alter function(s) of the endocrine system and consequently cause adverse effects in an intact organism, or its progeny, or (sub)populations. European regulations on pesticides, biocides, cosmetics, and industrial chemicals require the European Commission to establish scientific criteria to define EDs. We address the scientific relevance of four options for the identification of EDs proposed by the European Commission. Option 1, which does not define EDs and leads to using interim criteria unrelated to the WHO definition of EDs, is not relevant. Options 2 and 3 rely on the WHO definition of EDs, which is widely accepted by the scientific community, with option 3 introducing additional categories based on the strength of evidence (suspected EDs and endocrine-active substances). Option 4 adds potency to the WHO definition, as a decision criterion. We argue that potency is dependent on the adverse effect considered and is scientifically ambiguous, and note that potency is not used as a criterion to define other particularly hazardous substances such as carcinogens and reproductive toxicants. The use of potency requires a context that goes beyond hazard identification and corresponds to risk characterization, in which potency (or, more relevantly, the dose-response function) is combined with exposure levels. There is scientific agreement regarding the adequacy of the WHO definition of EDs. The potency concept is not relevant to the identification of particularly serious hazards such as EDs. As is common practice for carcinogens, mutagens, and reproductive toxicants, a multi-level classification of ED based on the WHO definition, and not considering potency, would be relevant (corresponding to option 3 proposed by the European Commission). Slama R, Bourguignon JP, Demeneix B, Ivell R, Panzica G, Kortenkamp A, Zoeller RT. 2016. Scientific issues relevant

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

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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...

The molecular classification of hereditary endocrine diseases.

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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.

Combined exposure to endocrine disrupting pesticides impairs parturition and causes pup mortality in rats

DEFF Research Database (Denmark)

Hansen, Pernille Reimer; Christiansen, Sofie; Boberg, Julie

from gestational day 7 to postnatal day (PND)13 with either vehicle (control) or a mixture of the five pesticides at 25%, 50%, 75% or 100% of their individual NOAELs for causing major effects on pregnancy length and pup survival in our earlier studies. The pregnancy length was dose....... Although laboratory animal studies have shown that some endocrine disrupting pesticides can affect reproduction and sexual differentiation, individual pesticides may appear to be present in human tissues at too low levels to cause concern for adverse reproductive effects. However, recent studies in our...... laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti-androgenic effects. Here, we present results from range finding studies with combined exposure...

Rapid analysis for 567 pesticides and endocrine disrupters by GC/MS using deconvolution reporting software

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Wylie, P.; Szelewski, M.; Meng, Chin-Kai [Agilent Technologies, Wilmington, DE (United States)

2004-09-15

More than 700 pesticides are approved for use around the world, many of which are suspected endocrine disrupters. Other pesticides, though no longer used, persist in the environment where they bioaccumulate in the flora and fauna. Analytical methods target only a subset of the possible compounds. The analysis of food and environmental samples for pesticides is usually complicated by the presence of co-extracted natural products. Food or tissue extracts can be exceedingly complex matrices that require several stages of sample cleanup prior to analysis. Even then, it can be difficult to detect trace levels of contaminants in the presence of the remaining matrix. For efficiency, multi-residue methods (MRMs) must be used to analyze for most pesticides. Traditionally, these methods have relied upon gas chromatography (GC) with a constellation of element-selective detectors to locate pesticides in the midst of a variable matrix. GC with mass spectral detection (GC/MS) has been widely used for confirmation of hits. Liquid chromatography (LC) has been used for those compounds that are not amenable to GC. Today, more and more pesticide laboratories are relying upon LC with mass spectral detection (LC/MS) and GC/MS as their primary analytical tools. Still, most MRMs are target compound methods that look for a small subset of the possible pesticides. Any compound not on the target list is likely to be missed by these methods. Using the techniques of retention time locking (RTL) and RTL database searching together with spectral deconvolution, a method has been developed to screen for 567 pesticides and suspected endocrine disrupters in a single GC/MS analysis. Spectral deconvolution helps to identify pesticides even when they co-elute with matrix compounds while RTL helps to eliminate false positives and gives greater confidence in the results.

The effects of different endocrine disruptors defining compound-specific alterations of gene expression profiles in the developing testis

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López-Casas, Pedro P.; Mizrak, Sefika C.; López-Fernández, Luis A.; Paz, María; de Rooij, Dirk G.; del Mazo, Jesús

2012-01-01

Environmental contaminants considered endocrine disruptors have been shown to affect testis development and function but the mechanisms of action are not clear. We now have analyzed the effects on the transcriptome in testes of mice exposed to mono-(2-ethylhexyl)-phthalate (9.2; 46.3 or 92.7

From 'omics to otoliths: responses of an estuarine fish to endocrine disrupting compounds across biological scales.

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Brander, Susanne M; Connon, Richard E; He, Guochun; Hobbs, James A; Smalling, Kelly L; Teh, Swee J; White, J Wilson; Werner, Inge; Denison, Michael S; Cherr, Gary N

2013-01-01

Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and population decline in fishes. However, few studies have linked environmental EDC exposures with responses at multiple tiers of the biological hierarchy, including population-level effects. To this end, we undertook a four-tiered investigation in the impacted San Francisco Bay estuary with the Mississippi silverside (Menidia audens), a small pelagic fish. This approach demonstrated links between different EDC sources and fish responses at different levels of biological organization. First we determined that water from a study site primarily impacted by ranch run-off had only estrogenic activity in vitro, while water sampled from a site receiving a combination of urban, limited ranch run-off, and treated wastewater effluent had both estrogenic and androgenic activity. Secondly, at the molecular level we found that fish had higher mRNA levels for estrogen-responsive genes at the site where only estrogenic activity was detected but relatively lower expression levels where both estrogenic and androgenic EDCs were detected. Thirdly, at the organism level, males at the site exposed to both estrogens and androgens had significantly lower mean gonadal somatic indices, significantly higher incidence of severe testicular necrosis and altered somatic growth relative to the site where only estrogens were detected. Finally, at the population level, the sex ratio was significantly skewed towards males at the site with measured androgenic and estrogenic activity. Our results suggest that mixtures of androgenic and estrogenic EDCs have antagonistic and potentially additive effects depending on the biological scale being assessed, and that mixtures containing androgens and estrogens may produce unexpected effects. In summary, evaluating EDC response at multiple tiers is necessary to determine the source of disruption (lowest scale, i.e. cell line) and what the ecological impact will be (largest scale, i

Quaternary ammonium-functionalized MCM-48 mesoporous silica as a sorbent for the dispersive solid-phase extraction of endocrine disrupting compounds in water.

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Zhang, Shijuan; Lu, Fengli; Ma, Xiaoyun; Yue, Mingbo; Li, Yanxin; Liu, Jiammin; You, Jinmao

2018-07-06

MCM-48 mesoporous silica was functionalized with dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride, a quaternary ammonium salt with a long hydrophobic chain, to prepare a new sorbent for the dispersive solid-phase extraction (DSPE) of seven endocrine disrupting compounds (EDCs) including 4-hexylphenol, 4-octylphenol, 4-nonylphenol, bisphenol A, estrone, 17β-estradiol and estriol in water. A series of differently functionalized MCM-48 materials were also synthesized, and they served as reference materials to study the mechanism. The developed DSPE method was combined with HPLC with fluorescence detection to evaluate the adsorption performance. The results indicated that the quaternary ammonium-functionalized MCM-48 mesoporous silica can be used as ideal sorbent for EDCs in water with recoveries of higher than 95% due to the electrostatic interactions and hydrophobic effect. Hydrogen bonding and π-π interactions in other synthesized materials could lead to about 25-30% increase in recoveries, but the results for polyhydroxy compounds were still not satisfying. The quaternary ammonium-functionalized MCM-48 mesoporous silica was successfully applied to the DSPE of EDCs in real water samples. The optimum extraction conditions were sorbent amount, 15 mg; desorption time; 5 min; elution volume, 0.8 mL; sample pH 3.0; and salt addition, 5 g/L. The limits of detection were in the range of 1.2-2.6 ng/L, while the limits of quantitation were in the range of 4.3-8.3 ng/L. Copyright © 2018 Elsevier B.V. All rights reserved.

Effective anti-leishmanial activity of minimalist squaramide-based compounds.

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Marín, Clotilde; Ximenis, Marta; Ramirez-Macías, Inmaculada; Rotger, Carmen; Urbanova, Kristina; Olmo, Francisco; Martín-Escolano, Rubén; Rosales, María José; Cañas, Rocio; Gutierrez-Sánchez, Ramón; Costa, Antonio; Sánchez-Moreno, Manuel

2016-11-01

In order to evaluate the in vitro leishmanicidal activity of N,N'-Squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against Leishmania infantum, Leishmania braziliensis and Leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. Infectivity and cytotoxicity tests were performed on J774.2 macrophage cells using meglumine antimoniate (Glucantime) as the reference drug. Changes in metabolite excretion by 1 H-NMR and the ultrastructural alterations occurring in the parasites treated using transmission electron microscopy (TEM), was analyzed. Compounds 1, 7, 11, 14 and 17 were the more active and less toxic. Infection rates showed that the order of effectiveness was 17 > 11 > 14 > 7 for both L. infantum and L. braziliensis and in the same way, the compound 1 for L. donovani. All these compounds have altered the typical structure of the promastigotes, glycosomes and mitochondria. These severe modifications by the compounds are the ultimate reasons for the alterations observed in the excretion products. The Squaramide 17 (3-(butylamino)-4-((3-(dimetilamino)propyl)(methyl)amino)cyclobut-3-en-1,2-dione) was clearly the most efficient of all compounds. The data appear to confirm that the severe modifications generated in organelles such as glycosomes or mitochondria by the compounds are the ultimate reasons for the alterations observed in the excretion products of all species. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-leishmanial agent. Copyright © 2016. Published by Elsevier Inc.

Benzimidazoles: A biologically active compounds

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Salahuddin

2017-02-01

Full Text Available Synthesis of commercially available benzimidazole involves condensation of o-phenylenediamine with formic acid. The most prominent benzimidazole compound in nature is N-riosyldimethylbenzimidazole, which serves as a axial ligand for cobalt in vitamin B12. The benzimidazole and its derivatives play a very important role as a therapeutic agent e.g. antiulcer and anthelmintic drugs. Apart from this the benzimidazole derivatives exhibit pharmacological activities such as antimicrobial, antiviral, anticancer, anti-inflammatory, analgesic, etc. The substituted benzimidazoles are summarized in this review to know about the chemistry as well as pharmacological activities.

Endocrine system: part 2.

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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.

Intrinsic imperfections of endocrine replacement therapy

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Romijn, J. A.; Smit, J. W. A.; Lamberts, S. W. J.

2003-01-01

Hormonal substitution therapy has been extremely successful, with respect to morbidity and mortality, in the treatment of the major syndromes of endocrine insufficiency. However, many patients treated for endocrine insufficiencies still suffer from more or less vague complaints and a decreased

Antileishmanial activities of dihydrochalcones from piper elongatum and synthetic related compounds. Structural requirements for activity.

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Hermoso, Alicia; Jiménez, Ignacio A; Mamani, Zulma A; Bazzocchi, Isabel L; Piñero, José E; Ravelo, Angel G; Valladares, Basilio

2003-09-01

Two dihydrochalcones (1 and 2) were isolated from Piper elongatum Vahl by activity-guided fractionation against extracellular promastigotes of Leishmania braziliensis in vitro. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments. Derivatives 3-7 and 20 synthetic related compounds (8-27) were also assayed to establish the structural requirements for antileishmanial activity. Compounds 1-11 that proved to be more active that ketoconazol, used as positive control, were further assayed against promastigotes of Leishmania tropica and Leishmania infantum. Compounds 7 and 11, with a C(6)-C(3)-C(6) system, proved to be the most promising compounds, with IC(50) values of 2.98 and 3.65 microg/mL, respectively, and exhibited no toxic effect on macrophages (around 90% viability). Correlation between the molecular structures and antileishmanial activity is discussed in detail.

CCAR1 is required for Ngn3-mediated endocrine differentiation

International Nuclear Information System (INIS)

Lu, Chung-Kuang; Lai, Yi-Chyi; Lin, Yung-Fu; Chen, Hau-Ren; Chiang, Ming-Ko

2012-01-01

Highlights: ► We identify CCAR1 to directly interact with Ngn3. ► CCAR1 is co-localized with Ngn3 in the nucleus. ► CCAR1 cooperates with Ngn3 in activating NeuroD expression. ► CCAR1 is required for Ngn3-mediated PANC-1 transdifferentiation. -- Abstract: Neurogenin3 (Ngn3) is a basic helix-loop-helix transcription factor that specifies pancreatic endocrine cell fates during pancreas development. It can also initiate a transdifferentiation program when expressed in pancreatic exocrine and ductal cells. However, how Ngn3 initiates a transcriptional cascade to achieve endocrine differentiation is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which is a transcriptional coactivator for nuclear receptors, also interacts with Ngn3. The association between Ngn3 and CCAR1 was verified by pull-down assays and co-immunoprecipitation analyses. Using gene reporter assays, we found that CCAR1 is essential for Ngn3 to activate the expression of the reporter genes containing the NeuroD promoter. Moreover, down-regulation of endogenous CCAR1 in the PANC-1 pancreatic ductal cell line inhibits the transdifferentiation program initiated by Ngn3. CCAR1 is, therefore, a novel partner of Ngn3 in mediating endocrine differentiation.

Synthesis and anticonvulsant activity of certain chalcone based pyrazoline compounds

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Sudhakara Rao Gerapati

2015-09-01

Full Text Available Convulsions are involuntary, violent, spasmodic and prolonged contractions of skeletal muscles. That means a patient may have epilepsy without convulsions and vice versa. Epilepsy is a common neurological abnormality affecting about 1% of the world population. The primary objectives of these synthesized compounds are to suppress seizures and provide neuroprotection by minimizing the effects from seizure attacks. Here some of the chalcones and chalcone based various pyrazolines were evaluated for anticonvulsant activity. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H-NMR & Mass spectroscopy. A preliminary evaluation of the prepared compounds has indicated that some of them exhibit moderate to significant anticonvulsant activity compared to a diazepam standard1-3.  All compounds were tested for their anticonvulsant activity using maximal electroshock induced convulsions (MES in mice at a dose level of 4 mg/kg.b.w. The compounds  Ph1, Ph2 , Py2 ,Py3 and Py4 have shown  to  good anticonvulsant activity when doses are administered as 25mg/ kg.b.w  , reduced the phases of seizures severity and  found to be active and also  increased survival rate. Remaining compounds are less efficacious.

Odour-active compounds in guava (Psidium guajava L. cv. Red Suprema).

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Pino, Jorge A; Bent, Leandra

2013-09-01

Solid phase microextraction and simultaneous distillation-extraction combined with GC-FID, GC/MS, aroma extract dilution analysis and odour activity values were used to analyse volatile compounds from guava (Psidium guajava L. cv. Red Suprema) and to estimate the most odour-active compounds. The analysis led to the detection of 141 compounds, 121 of which were positively identified. The composition of guava fruit volatiles included 43 esters, 37 terpenes, 18 aldehydes, 16 alcohols, ten acids, six ketones, four furans and seven miscellaneous compounds. Seventeen odorants were considered as odour-active compounds, with (E)-β-ionone, ethyl hexanoate, ethyl butanoate, hexanal, (Z)-3-hexenal, hexyl acetate, (E)-2-hexenal and limonene contributing most to the typical guava aroma of this cultivar. © 2013 Society of Chemical Industry.

Assessment of toxic and endocrine potential of substances migrating from selected toys and baby products.

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Szczepańska, Natalia; Namieśnik, Jacek; Kudłak, Błażej

2016-12-01

Analysis of literature data shows that there is limited information about the harmful biological effects of mixture of compounds from the EDC group that are released from the surface of toys and objects intended for children and infants. One of the tools that can be used to obtain such information is appropriate bioanalytical tests. The aim of this research involved determining whether tests that use living organisms as an active element (Vibrio fischeri-Microtox®, Heterocypris incongruens-Ostrocodtoxkit F™ and the XenoScreen YES/YAS™ test of oestrogenic/androgenic activity) can be a tool for estimating the combined toxic effects induced by xenobiotics released from objects intended for children. To reproduce the conditions to which objects are exposed during their use, liquids with a composition corresponding to that of human bodily fluids (artificial sweat and saliva) were used. This research focused on the main parameters influencing the intensification of the migration process (temperature, contact time and composition of the extraction mixture). The studies aimed to estimate the endocrine potential of the extracts showed that compounds released from the surface of studied objects exhibit antagonistic androgenic activity. While on the basis of the results of Microtox® test, one can state that the largest quantity of toxic compounds are released in the first 2 h of using the object. The FTIR spectra analyses confirmed that no degradation of polymeric material took place. On the basis of the results obtained, it was unanimously concluded that contact of the object with bodily fluids may result in the release of a large number of xenobiotics, which has disadvantageous effects on the metabolic processes of the indicator organisms.

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.

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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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China

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Mingyue Zhang

2015-11-01

Full Text Available Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256 collected from children in China were measured by liquid chromatography (LC-tandem mass spectrometry (MS/MS. Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S.

An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol

International Nuclear Information System (INIS)

Frizzell, Caroline; Ndossi, Doreen; Kalayou, Shewit; Eriksen, Gunnar S.; Verhaegen, Steven; Sørlie, Morten; Elliott, Christopher T.; Ropstad, Erik; Connolly, Lisa

2013-01-01

Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1–1000 ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000 ng/ml (3.87 μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000 ng/ml (3.87 μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. - Highlights: • Alternariol was investigated for endocrine disrupting activity. • Reporter gene assays and the H295R steroidogenesis assay have been used. • An oestrogenic effect of alternariol was observed. • This can lead to an increase in expression of the progesterone receptor. • Alternariol is capable of modulating hormone production and gene expression

An in vitro investigation of endocrine disrupting effects of the mycotoxin alternariol

Energy Technology Data Exchange (ETDEWEB)

Frizzell, Caroline [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom); Ndossi, Doreen [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Sokoine University of Agriculture, Morogoro (Tanzania, United Republic of); Kalayou, Shewit [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Mekelle University College of Veterinary Medicine, Mekelle (Ethiopia); Eriksen, Gunnar S. [Norwegian Veterinary Institute, Oslo (Norway); Verhaegen, Steven [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Sørlie, Morten [Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås (Norway); Elliott, Christopher T. [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom); Ropstad, Erik [Section of Experimental Biomedicine, Norwegian School of Veterinary Science, Oslo (Norway); Connolly, Lisa, E-mail: l.connolly@qub.ac.uk [Institute for Global Food Security, School of Biological Sciences, Queen' s University Belfast, Northern Ireland (United Kingdom)

2013-08-15

Alternariol (AOH) is a mycotoxin commonly produced by Alternaria alternata on a wide range of foods. Few studies to date have been performed to evaluate the effects of AOH on endocrine activity. The present study makes use of in vitro mammalian cellular based assays and gene expression to investigate the ability of AOH to act as an endocrine disruptor by various modes of action. Reporter gene assays (RGAs), incorporating natural steroid hormone receptors for oestrogens, androgens, progestagens and glucocorticoids were used to identify endocrine disruption at the level of nuclear receptor transcriptional activity, and the H295R steroidogenesis assay was used to assess endocrine disruption at the level of gene expression and steroid hormone production. AOH exhibited a weak oestrogenic response when tested in the oestrogen responsive RGA and binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of AOH. H295R cells when exposed to 0.1–1000 ng/ml AOH, did not cause a significant change in testosterone and cortisol hormones but exposure to 1000 ng/ml (3.87 μM) AOH resulted in a significant increase in estradiol and progesterone production. In the gene expression study following exposure to 1000 ng/ml (3.87 μM) AOH, only one gene NR0B1 was down-regulated, whereas expression of mRNA for CYP1A1, MC2R, HSD3B2, CYP17, CYP21, CYP11B2 and CYP19 was up-regulated. Expression of the other genes investigated did not change significantly. In conclusion AOH is a weak oestrogenic mycotoxin that also has the ability to interfere with the steroidogenesis pathway. - Highlights: • Alternariol was investigated for endocrine disrupting activity. • Reporter gene assays and the H295R steroidogenesis assay have been used. • An oestrogenic effect of alternariol was observed. • This can lead to an increase in expression of the progesterone receptor. • Alternariol is capable of modulating hormone production and gene expression.

Endocrine disrupting alkylphenolic chemicals and other contaminants in wastewater treatment plant effluents, urban streams, and fish in the Great Lakes and Upper Mississippi River Regions.

Science.gov (United States)

Barber, Larry B; Loyo-Rosales, Jorge E; Rice, Clifford P; Minarik, Thomas A; Oskouie, Ali K

2015-06-01

Urban streams are an integral part of the municipal water cycle and provide a point of discharge for wastewater treatment plant (WWTP) effluents, allowing additional attenuation through dilution and transformation processes, as well as a conduit for transporting contaminants to downstream water supplies. Domestic and commercial activities dispose of wastes down-the-drain, resulting in wastewater containing complex chemical mixtures that are only partially removed during treatment. A key issue associated with WWTP effluent discharge into streams is the potential to cause endocrine disruption in fish. This study provides a long-term (1999-2009) evaluation of the occurrence of alkylphenolic endocrine disrupting chemicals (EDCs) and other contaminants discharged from WWTPs into streams in the Great Lakes and Upper Mississippi River Regions (Indiana, Illinois, Michigan, Minnesota, and Ohio). The Greater Metropolitan Chicago Area Waterways, Illinois, were evaluated to determine contaminant concentrations in the major WWTP effluents and receiving streams, and assess the behavior of EDCs from their sources within the sewer collection system, through the major treatment unit processes at a WWTP, to their persistence and transport in the receiving stream. Water samples were analyzed for alkylphenolic EDCs and other contaminants, including 4-nonylphenol (NP), 4-nonylphenolpolyethoxylates (NPEO), 4-nonylphenolethoxycarboxylic acids (NPEC), 4-tert-octylphenol (OP), 4-tert-octylphenolpolyethoxylates (OPEO), bisphenol A, triclosan, ethylenediaminetetraacetic acid (EDTA), and trace elements. All of the compounds were detected in all of the WWTP effluents, with EDTA and NPEC having the greatest concentrations. The compounds also were detected in the WWTP effluent dominated rivers. Multiple fish species were collected from river and lake sites and analyzed for NP, NPEO, NPEC, OP, and OPEO. Whole-body fish tissue analysis indicated widespread occurrence of alkylphenolic compounds

Endocrine disrupting alkylphenolic chemicals and other contaminants in wastewater treatment plant effluents, urban streams, and fish in the Great Lakes and Upper Mississippi River Regions

Science.gov (United States)

Barber, Larry B.; Loyo-Rosales, Jorge E.; Rice, Clifford P.; Minarik, Thomas A.; Oskouie, Ali K.

2015-01-01

Urban streams are an integral part of the municipal water cycle and provide a point of discharge for wastewater treatment plant (WWTP) effluents, allowing additional attenuation through dilution and transformation processes, as well as a conduit for transporting contaminants to downstream water supplies. Domestic and commercial activities dispose of wastes down-the-drain, resulting in wastewater containing complex chemical mixtures that are only partially removed during treatment. A key issue associated with WWTP effluent discharge into streams is the potential to cause endocrine disruption in fish. This study provides a long-term (1999-2009) evaluation of the occurrence of alkylphenolic endocrine disrupting chemicals (EDCs) and other contaminants discharged from WWTPs into streams in the Great Lakes and Upper Mississippi River Regions (Indiana, Illinois, Michigan, Minnesota, and Ohio). The Greater Metropolitan Chicago Area Waterways, Illinois, were evaluated to determine contaminant concentrations in the major WWTP effluents and receiving streams, and assess the behavior of EDCs from their sources within the sewer collection system, through the major treatment unit processes at a WWTP, to their persistence and transport in the receiving stream. Water samples were analyzed for alkylphenolic EDCs and other contaminants, including 4-nonylphenol (NP), 4-nonylphenolpolyethoxylates (NPEO), 4-nonylphenolethoxycarboxylic acids (NPEC), 4-tert-octylphenol (OP), 4-tert-octylphenolpolyethoxylates (OPEO), bisphenol A, triclosan, ethylenediaminetetraacetic acid (EDTA), and trace elements. All of the compounds were detected in all of the WWTP effluents, with EDTA and NPEC having the greatest concentrations. The compounds also were detected in the WWTP effluent dominated rivers. Multiple fish species were collected from river and lake sites and analyzed for NP, NPEO, NPEC, OP, and OPEO. Whole-body fish tissue analysis indicated widespread occurrence of alkylphenolic compounds

Taste-active compounds in a traditional Italian food: 'lampascioni'.

Science.gov (United States)

Borgonovo, Gigliola; Caimi, Sara; Morini, Gabriella; Scaglioni, Leonardo; Bassoli, Angela

2008-06-01

Nature is a rich source of taste-active compounds, in particular of plant origin, many of which have unusual tastes. Many of these are found in traditional food, where spontaneous plants are used as ingredients. Some taste-active compounds were identified in the bulbs of Muscari comosum, a spontaneous plant belonging to the family of the Liliaceae, very common in the Mediterranean area, and used in traditional gastronomy (called 'lampascioni' in South Italy). The bulbs were extracted with a series of solvents of different polarity. The different fractions were submitted to a preliminary sensory evaluation, and the most interesting ones, characterized by a strong bitter taste and some chemestetic properties, were submitted to further purification and structural analysis. From the ethereal extract, several 3-benzyl-4-chromanones and one stilbene derivative were isolated. Pure compounds were examined for their taste activity by means of sensory evaluation, and proved to be responsible for the characteristic taste of this food. Some of these compounds have been synthesized de novo to confirm their structure.

Aspartate and glutamate mimetic structures in biologically active compounds.

Science.gov (United States)

Stefanic, Peter; Dolenc, Marija Sollner

2004-04-01

Glutamate and aspartate are frequently recognized as key structural elements for the biological activity of natural peptides and synthetic compounds. The acidic side-chain functionality of both the amino acids provides the basis for the ionic interaction and subsequent molecular recognition by specific receptor sites that results in the regulation of physiological or pathophysiological processes in the organism. In the development of new biologically active compounds that possess the ability to modulate these processes, compounds offering the same type of interactions are being designed. Thus, using a peptidomimetic design approach, glutamate and aspartate mimetics are incorporated into the structure of final biologically active compounds. This review covers different bioisosteric replacements of carboxylic acid alone, as well as mimetics of the whole amino acid structure. Amino acid analogs presented include those with different distances between anionic moieties, and analogs with additional functional groups that result in conformational restriction or alternative interaction sites. The article also provides an overview of different cyclic structures, including various cycloalkane, bicyclic and heterocyclic analogs, that lead to conformational restriction. Higher di- and tripeptide mimetics in which carboxylic acid functionality is incorporated into larger molecules are also reviewed. In addition to the mimetic structures presented, emphasis in this article is placed on their steric and electronic properties. These mimetics constitute a useful pool of fragments in the design of new biologically active compounds, particularly in the field of RGD mimetics and excitatory amino acid agonists and antagonists.

First evidence of endocrine disruption in feral carp from the Ebro River

International Nuclear Information System (INIS)

Lavado, Ramon; Thibaut, Remi; Raldua, Demetrio; Martin, Rebeca; Porte, Cinta

2004-01-01

Feral carps (Cyprinus carpio) were collected in spring 2001 from five sites along the lower course of Ebro River (Spain) with the aim of investigating the existence of endocrine-disrupting effects. Several findings (low gonadosomatic index (GSI), plasmatic vitellogenin (VTG), depressed levels of testosterone, and histological alterations in gonads) detected in male carps downstream of Zaragoza's sewage treatment plant (STP) strongly suggest that the concentration of sewage effluent in the area is a major causal factor leading to the detected estrogenic effects. Important alterations (viz. delayed maturation in females, indications of arrested spermatogenesis in males) were detected in carps from Flix, a heavily industrialized area. Low ovarian P-450 aromatase and reduced glucuronidation of testosterone and estradiol in males were observed in Zaragoza and Canal Imperial de Aragon--an agricultural area--which suggest decreased estrogen synthesis, and possibly, reduced sex hormone excretion in those organisms. These results were related to some in vitro assays aimed to assess the interference of model compounds (atrazin, vinclozolin, diuron, pp'-DDE, dicofol, triphenyltin, nonylphenol, and fenarimol) with the glucuronidation of testosterone and estradiol by liver microsomal fractions. The fungicide fenarimol (10-20 μM) and nonylphenol (50 μM) were found to significantly inhibit (20%) both activities at relatively low doses. Overall, this work provides the first evidence of the existence of significant alterations of the endocrine system of carps from the medium-low course of the Ebro River and demonstrates the ability of several chemicals to modulate the inactivation of endogenous steroids

Modelling as a tool when interpreting biodegradation of micro pollutants in activated sludge systems

DEFF Research Database (Denmark)

Press-Kristensen, Kåre; Lindblom, Erik Ulfson; Henze, Mogens

2007-01-01

The aims of the present work were to improve the biodegradation of the endocrine disrupting micro pollutant, bisphenol A (BPA), used as model compound in an activated sludge system and to underline the importance of modelling the system. Previous results have shown that BPA mainly is degraded under...

The eunuchs of India: An endocrine eye opener

Directory of Open Access Journals (Sweden)

Sanjay Kalra

2012-01-01

Full Text Available There are established guidelines for the endocrine and overall treatment of transsexual persons. These guidelines provide information about the optimal endocrine management of male-to-female and female-to-male transsexual persons. India has a large community of eunuchs, also known as hijras, who are men with gender identity disorders. While this community has been studied from a social and medical point of new, no endocrine work has been done in them. This exploratory article tries to discuss the endocrine status, health, and management of the eunuchs.

Respiratory manifestations in endocrine diseases

OpenAIRE

LENCU, CODRU?A; 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 hyperthy...

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

Science.gov (United States)

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

Psychosocial approach to endocrine disease.

Science.gov (United States)

Sonino, Nicoletta; Tomba, Elena; Fava, Giovanni A

2007-01-01

In recent years, there has been growing interest in the psychosocial aspects of endocrine disease, such as the role of life stress in the pathogenesis of some conditions, their association with affective disorders, and the presence of residual symptoms after adequate treatment. In clinical endocrinology, exploration of psychosocial antecedents may elucidate the temporal relationships between life events and symptom onset, as it has been shown to be relevant for pituitary (Cushing's disease, hyperprolactinemia) or thyroid (Graves' disease) conditions, as well as the role of allostatic load, linked to chronic stress, in uncovering a person's vulnerability. After endocrine abnormalities are established, they are frequently associated with a wide range of psychological symptoms: at times, such symptoms reach the level of psychiatric illness (mainly mood and anxiety disorders); at other times, however, they can only be identified by the subclinical forms of assessment provided by the Diagnostic Criteria for Psychosomatic Research (DCPR). Indeed, in a population study, the majority of patients suffered from at least one of the three DCPR syndromes considered: irritable mood, demoralization, persistent somatization. In particular, irritable mood was found to occur in 46% of 146 patients successfully treated for endocrine conditions, a rate similar to that found in cardiology and higher than in oncology and gastroenterology. Long-standing endocrine disorders may imply a degree of irreversibility of the pathological process and induce highly individualized affective responses. In patients who showed persistence or even worsening of psychological distress upon proper endocrine treatment, the value of appropriate psychiatric interventions was underscored. As it happened in other fields of clinical medicine, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary for improving

An environmentally relevant endocrine-disrupting antiandrogen, vinclozolin, affects calling behavior of male Xenopus laevis.

Science.gov (United States)

Hoffmann, Frauke; Kloas, Werner

2010-09-01

Vinclozolin (VIN) is an antiandrogenic model substance as well as a common fungicide that can affect the endocrine system of vertebrates. The objective of this study was to investigate how VIN affects mate calling behavior of South African clawed frogs (Xenopus laevis) and whether it is effective at environmentally relevant concentrations. Male X. laevis were injected with human chorionic gonadotropin (hCG) to stimulate their androgen-controlled mate calling behavior and were treated with VIN at concentrations of 10(-6), 10(-8) and 10(-10)M. VIN at 10(-6)M reduced calling activity. Furthermore, the vocalization composition of VIN-treated X. laevis was altered. The call types advertisement calls and chirping are uttered by reproductively active males, whereas the call types growling, ticking, and rasping indicate a sexually unaroused state of a male. VIN at any of the tested concentrations led to a decrease in utterance of calls, which indicate a sexually aroused state of the males, and an increase in relative proportions of calls, indicating a sexually unaroused state of the males. Additionally, the mean duration of clicks and the number of accentuated clicks during the advertisement calls decreased at all concentrations of VIN. No significant differences were observed in any other temporal or spectral calling parameters between the treatments. This study illustrates that exposure to the antiandrogen VIN might result in a reduced reproductive success by altering mate calling behavior of X. laevis. Moreover, it suggests that the behavioral parameters examined in this study can be used as sensitive biomarkers for detecting antiandrogenic endocrine disrupting compounds in amphibians. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Glucosidase inhibitory activity and antioxidant activity of flavonoid compound and triterpenoid compound from Agrimonia Pilosa Ledeb.

Science.gov (United States)

Liu, Xi; Zhu, Liancai; Tan, Jun; Zhou, Xuemei; Xiao, Ling; Yang, Xian; Wang, Bochu

2014-01-10

In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay. The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching. These results imply that the FC and the TC could be

Cloning of the relative genes of endocrine exophthalmos

International Nuclear Information System (INIS)

Zheng, JG

2004-01-01

Aim: In order to clarify the pathogenesis of endocrine exophthalmos, and lay foundations for finding the new functions of its relative genes, the cloning of its relative genes was carried out. Methods: The thyroid tissues of 10 hyperthyroidism patients, 5 of them with endocrine exophthalmos and 5 without that, were obtained. Their mRNA were collected respectively by using Quick Prep Micro mRNA purification kit. Then the same amount of the mRNA from 5 patients with endocrine exophthalmos was added into an eppendorf tube to form a mRNA pool. And that of the 5 patients without endocrine exophthalmos was also prepared as the other pool. As a model, the pool was used to synthesize the single and double chains of cDNA through SMART Tm PCR cDNA Synthesis Kit. The double chains cDNA from the endocrine exophthalmos patients, being used as tester, and that from the patients without endocrine exophthalmos, being used as driver, were digested by restriction endonucleases Hae III to get the fragments which was less than 500 bases. The tester cDNA was ligated with adapt or 1 or 2 respectively. Then the subtractive suppressive hybridization was performed between tester and driver cDNA. And the efficacies of subtraction were measured. The differential genes between the thyroid tissues of endocrine exophthalmos and the thyroid tissues without endocrine exophthalmos were obtained through two cycles of subtractive hybridization and two cycles PCR. The differential genes were cloned into the vector of pT-Adv, and then transformed into E.coliDH5a. 48 white clonies were selected to build the subtractive suppressive library of the relative genes of endocrine exophthalmos. The primer 2 was applied for the colony PCR of the relative genes. The amplified genes were obtained and purified by using Quaqwich Spine PCR Purification Kit. According to the principle of random primer, the double chains cDNA from the thyroid tissues with or without endocrine exophthalmos were digested by Hae III

ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

OpenAIRE

P. V. Novokhatny

2014-01-01

Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study...

Scintigraphic imaging of endocrine organs

International Nuclear Information System (INIS)

Gross, M.D.; Shapiro, B.; Thrall, J.H.; Freitas, J.E.; Beierwaltes, W.H.

1984-01-01

The nuclear medicine approach to the portrayal of endocrine organs is unique; the scintigraphic images provide not only anatomic and localization information, but in many instances allow a quantitative assessment of organ function. The ability to image endocrine glands is based upon the design of radionuclides and radiopharmaceuticals with characteristics to take advantage of many unique and specific biochemical and advantage of many unique and specific biochemical and metabolic functions of these tissues. The recent introduction of new radiopharmaceutical and tracers has provided the consulting endocrinologist with imaging procedures that allow localization and functional characterization not available by other single, noninvasive diagnostic modalities. This review will serve as an update of the available techniques to image and quantitate the function of the endocrine glands using the nuclear medicine approach

Requirement for Pdx1 in specification of latent endocrine progenitors in zebrafish

Directory of Open Access Journals (Sweden)

Ellertsdottir Elin

2011-10-01

progenitor population essential for the formation of duct-associated, second wave endocrine cells. We further reveal an unexpectedly low mitotic activity in these progenitor cells, indicating that they are set aside early in development.

Update on endocrine disturbances in anorexia nervosa

DEFF Research Database (Denmark)

Støving, R K; Hangaard, J; Hagen, C

2001-01-01

The marked endocrine changes that occur in anorexia nervosa have aroused a great deal of interest, and over the last decade much research has been conducted in this field. The endocrine disturbances are not specific to this disorder, as they also occur in starvation states secondary to other causes...... of the large body of literature concerning endocrine aspects of anorexia nervosa with the main focus on the latest results, which provide leads for potential etiological theories....

Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

International Nuclear Information System (INIS)

Gradishar, William J

2016-01-01

Community-based oncologists are faced with challenges and opportunities when delivering quality patient care, including high patient volumes and diminished resources; however, there may be the potential to deliver increased patient education and subsequently improve outcomes. This review discusses the treatment of postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2- negative advanced breast cancer in order to illustrate considerations in the provision of pertinent quality education in the treatment of these patients and the management of therapy-related adverse events. An overview of endocrine-resistant breast cancer and subsequent treatment challenges is also provided. Approved treatment options for endocrine-resistant breast cancer include hormonal therapies and mammalian target of rapamycin inhibitors. Compounds under clinical investigation are also discussed

Diagnosis and pathology of endocrine diseases

International Nuclear Information System (INIS)

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

Diagnosis and pathology of endocrine diseases

Energy Technology Data Exchange (ETDEWEB)

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.

Electrocardiographic changes in the most frequent endocrine disorders associated with cardiovascular diseases. Review of the literature.

Science.gov (United States)

Costache, Irina Iuliana; Ungureanu, Maria Christina; Iliescu, D; Petriş, A; Botnariu, Gina

2015-01-01

Car- diovascular abnormalities associated with endocrine diseases are often frequent and due to complex relationships between endocrine glands (with internal secretion) and cardiovascular system (heart and vessels). Certain hormones secreted by the endocrine glands (particularly the thyroid and pituitary gland) excesses or deficiencies, are involved in morphogenesis, growth processes and activity regulation of cardiovascular system, most often in connection with the autonomic nervous system. There are also a lot of electrocardiographic changes caused by hormonal disorders that requires differential diagnosis and represents the source of erroneous diagnosis. Endocrine pathology occurred later than a heart disease, may worse heart function. Ignoring the cardiovascular events that may occur in the evolution of endo- crine diseases, may induce increased mortality due to cardiovascular complications.

Oxidative stress and the ageing endocrine system.

Science.gov (United States)

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.

Endocrine pancreatic function changes after acute pancreatitis.

Science.gov (United States)

Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

2011-10-01

This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

Endocrine Dysfunctions in Patients with Inherited Metabolic Diseases.

Science.gov (United States)

Erdöl, Şahin; Sağlam, Halil

2016-09-01

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. 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. 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. 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.

Identification and Profiling of Active Compounds from Golden Apple Snail’s Egg Pigments

Directory of Open Access Journals (Sweden)

Asadatun Abdullah

2017-08-01

Full Text Available Golden apple snail (Pomacea canaliculata has been known as rice corps pest due to high adaptability and reproductive power. Utilization of Pomacea canaliculata’s eggs as raw materials in the food and health industry is one of the efforts to eradicate the pest snail. This study was aimed to identify the active compounds contained in the extract pigments of Pomacea canaliculata’s eggs. The methods of this study were extraction of pigments using acetone and methanol, analyzing the active compound (secondary metabolite qualitatively, TLC to determine pigment components and LC-MS/MS to identify active compounds semi quantitatively. The results showed that active compounds in the methanol extract contain 11 carotenoid pigments of xanthophyl group, two carotenoid pigments of carotene group, and 2 active compounds in nonpigmented form, whereas the acetone extract contain 11 pigmentcarotenoids of xanthophyl group and 2 compounds active in non-pigment form.

Evaluation of the endocrine activity of 2,4,6-tribromophenol, benzanthrone and benzophenone-2 based on Appendix 7.8-5 of REACH guidance document

DEFF Research Database (Denmark)

Duis, Karen; Holbech, Henrik; Velasco-Santamaría, Yohana M.

Within a project funded by the German Federal Environment Agency, the practicability of Appendix 7.8-5 of REACH guidance document R.7b was evaluated using three case study substances. Shortcomings in the guidance were identified. An assessment of potential endocrine activity in aquatic vertebrates...

Bird populations as sentinels of endocrine disrupting chemicals.

Science.gov (United States)

Carere, Claudio; Costantini, David; Sorace, Alberto; Santucci, Daniela; Alleva, Enrico

2010-01-01

Exposure to endocrine disrupting chemicals (EDCs) is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED) at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

Isolation and Antimicrobial Activity of Flavonoid Compounds from Mahagony Seeds (Swietenia macrophylla, King)

Science.gov (United States)

Mursiti, S.; Supartono

2017-02-01

Flavonoid is one of the secondary metabolites compounds in mahogany seeds. Mahogany seeds can be used as an antimicrobial. This study aims to determine the antimicrobial activity of flavonoid compounds from mahogany seeds against Escherichia coli (E.coli) and Bacillus cereus (B.cereus). Isolation of flavonoid compounds done step by step. First, the maceration using n-hexane, then with methanol. The methanol extract was dissolved in ethyl acetate and aquadest, then separated. Ethyl acetate extract evaporated Flavonoid compounds were. The testing of antimicrobial activity of flavonoid compounds using the absorption method. The results showed that the antimicrobial activity of flavonoid compounds from mahogany seeds shows the inhibitory activity and provide clear zone against bacteria E.coli with value Inhibitory Regional Diameter 18.50 mm respectively, and 14.50 mm to the bacteria. Based on the results of the study, it can be concluded that flavonoid compounds from mahogany seeds have antimicrobial activity against E.coli and B.cereus.

Microsomal cytochrome P450-3A4 (CYP3A4) nanobiosensor for the determination of 2,4-dichlorophenol-An endocrine disruptor compound

International Nuclear Information System (INIS)

Hendricks, Nicolette R.; Waryo, Tesfaye T.; Arotiba, Omotayo; Jahed, Nazeem; Baker, Priscilla G.L.; Iwuoha, Emmanuel I.

2009-01-01

Cytochrome P450-3A4 (CYP3A4) is a monooxygenase enzyme that plays a major role in the detoxification of bioactive compounds and hydrophobic xenobiotics (e.g. medicines, drugs, environmental pollutants, food supplements and steroids). Physiologically the monooxygenation reactions of this class II, microsomal, b-type heme enzyme, usually requires cytochrome P450 reductase, NADPH. A novel CYP3A4 biosensor system that essentially simplified the enzymatic redox processes by allowing electron transfer between the electrode and the enzyme redox centre to occur, without any need for the physiological redox partners, was developed for the detection of 2,4-dichlorophenol (2,4-DCP), a priority environmental pollutant and an endocrine disruptor. The biosensor, GC/Naf-Co(Sep) 3+ /CYP3A4/Naf, was constructed by encapsulating CYP3A4 in a Nafion-cobalt (III) sepulchrate (Naf-Co(Sep) 3+ ) composite film on a glassy carbon (GC) electrode. The responses of the biosensor to 2,4-dichlorophenol, erythromycin (CYP3A4 native substrate) and ketoconazole (CYP 3A4 natural inhibitor) were studied by cyclic and square wave voltammetric techniques. The detection limit (DL) of the biosensor for 2,4-dichlorophenol was 0.043 μg L -1 , which is by an order of magnitude lower than the EU limit (0.3 μg L -1 ) for any pesticide compound in ground water. The biosensor's DL is lower than the U.S. Environmental Protection Agency's drinking water equivalent level (DWEL) value for 2,4-DCP, which is 2 μg L -1

[Outstanding problems of normal and pathological morphology of the diffuse endocrine system].

Science.gov (United States)

Iaglov, V V; Iaglova, N V

2011-01-01

The diffuse endocrine system (DES)--a mosaic-cellular endoepithelial gland--is the biggest part of the human endocrine system. Scientists used to consider cells of DES as neuroectodermal. According to modem data cells of DES are different cytogenetic types because they develop from the different embryonic blastophyllum. So that any hormone-active tumors originated from DES of the digestive, respiratory and urogenital system shouldn't be considered as neuroendocrinal tumors. The basic problems of DES morphology and pathology are the creation of scientifically substantiated histogenetic classification of DES tumors.

Reproductive endocrine-disrupting effects of triclosan: Population exposure, present evidence and potential mechanisms

International Nuclear Information System (INIS)

Wang, Cai-Feng; Tian, Ying

2015-01-01

Triclosan has been used as a broad-spectrum antibacterial agent for over 40 years worldwide. Increasing reports indicate frequent detection and broad exposure to triclosan in the natural environment and the human body. Current laboratory studies in various species provide strong evidence for its disrupting effects on the endocrine system, especially reproductive hormones. Multiple modes of action have been suggested, including disrupting hormone metabolism, displacing hormones from hormone receptors and disrupting steroidogenic enzyme activity. Although epidemiological studies on its effects in humans are mostly negative but conflicting, which is typical of much of the early evidence on the toxicity of EDCs, overall, the evidence suggests that triclosan is an EDC. This article reviews human exposure to triclosan, describes the current evidence regarding its reproductive endocrine-disrupting effects, and discusses potential mechanisms to provide insights for further study on its endocrine-disrupting effects in humans. - Highlights: • Triclosan is widely detected in human urine, blood and breast milk. • Laboratory studies suggest reproductive endocrine-disrupting effects of triclosan. • Laboratory studies suggest estrogenic properties of triclosan. • There are three potential mechanisms regarding the estrogenic effect of triclosan. • Prospective epidemiological studies on vulnerable populations are needed. - This review summarizes current evidence on human exposure to triclosan, and its reproductive endocrine-disrupting effects and potential mechanisms.

THE ANTIBACTERIAL ACTIVITY OF WATER APPLE LEAVES ACTIVE COMPOUND (Syzygium zeylanicum AGAINST Escherichia coli AND Staphylococcus aureus

Directory of Open Access Journals (Sweden)

- Hamidah

2017-07-01

Full Text Available Escherichia coli is one of the bacteria that cause infections in the human digestive tract such as diarrhea, while Staphylococcus aureus is one of the bacteria that cause infections in the skin injury such as boils and pimples. This study used Syzygium zeylanicum leaves because it has potential as a antibacterial because it contains active compounds. This study aimed was determine the antibacterial activity of the fraction and the active compound in Syzygium zeylanicum leaves against Escherichia coli and Staphylococcus aureus. Research conducted on November 2015 to January 2016. The method used in this research were extraction by maceration, fractionation by liquid fractionation, antibacterial activity test, and determination of minimum inhibitory concentration with the diffusion method and isolation of active compounds by column chromatography method. The bacteria used in this test are Escherichia coli and Staphylococcus aureus. Data are presented in tabular form based on the average value of the inhibition diameter and deviation standard. The results of this research showed the water methanol active fraction against the bacteria that used in this test. The methanol water fraction had obtained one antibacterial compound in bottle 1,3,5 which shows the value of tannin Rf 0,416. The minimum inhibitory concentration of water methanol of water apple leaves is 1000 µg/mL for Escherichia coli and 500 µg/mL for  Staphylococcus aureus. The minimum  inhibitory concentration of the active  compound  to  Escherichia  coli  and  Staphylococcus  aureus  in  500  µg/mL.  The fraction and the active compound of water apple leaves have an antibacterial activity with Escherichia coli and Staphylococcus aureus and the active compound is tannin.

Pediatric endocrine surgery development

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Ivan I. Dedov

2017-12-01

Full Text Available Department of pediatric surgery at the Endocrinology Research Centre has been around for nearly two years. During operation, surgical treatment has received more than 500 patients with various endocrine disorders. The article discusses modern diagnostic approaches and surgical options for diseases included in the new direction of pediatric surgery – endocrine surgery in children. There are discussions about options for radical treatment of Graves disease in children, positive and negative aspects of surgical and radioactive iodine treatment. Is own stats of postoperative hyperparathyroidism. Is proposed to optimize the algorithm of actions in identifying thyroid nodules in children. In primary hyperparathyroidism, the emphasis is on the complexity of the postoperative management of patients related to the feature of children’s age in determining the severity of the reactions on the water-electrolyte disorders. Separately reviewed the literature of the adrenal glands diseases in children, demonstrating their own clinical cases which required surgical intervention. The authors describe the possibilities of modern neurosurgical equipment in the Endocrinology Research Centre in operations on the pituitary gland in children. Patients of different age groups performed transnasal transsphenoidal removal of tumors of the chiasm-sellar region using endoscopic assistance. The article also cited research data of pancreas diseases and their surgical treatment. Much attention is paid to the gender section of endocrine surgery in children. Discusses the tactics in disorders of sex development, gonadal tumors in children, diseases of the breast. In conclusion outlines the prospects for the development of endocrine surgery in children.

Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test

NARCIS (Netherlands)

Jomaa, B.; Hermsen, S.A.B.; Kessels, M.Y.; Berg, van den J.H.J.; Peijenburg, A.C.M.; Aarts, J.M.M.J.G.; Piersma, A.H.; Rietjens, I.

2014-01-01

Zebrafish embryos were exposed to concentration ranges of selected thyroid-active model compounds in order to assess the applicability of zebrafish-based developmental scoring systems within an alternative testing strategy to detect the developmental toxicity of thyroid-active compounds. Model

Trauma and the endocrine system.

Science.gov (United States)

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. Copyright © 2010 SEEN. Published by Elsevier Espana. All rights reserved.

The multigenerational effects of water contamination and endocrine disrupting chemicals on the fitness of Drosophila melanogaster.

Science.gov (United States)

Quesada-Calderón, Suany; Bacigalupe, Leonardo Daniel; Toro-Vélez, Andrés Fernando; Madera-Parra, Carlos Arturo; Peña-Varón, Miguel Ricardo; Cárdenas-Henao, Heiber

2017-08-01

Water pollution due to human activities produces sedimentation, excessive nutrients, and toxic chemicals, and this, in turn, has an effect on the normal endocrine functioning of living beings. Overall, water pollution may affect some components of the fitness of organisms (e.g., developmental time and fertility). Some toxic compounds found in polluted waters are known as endocrine disruptors (ED), and among these are nonhalogenated phenolic chemicals such as bisphenol A and nonylphenol. To evaluate the effect of nonhalogenated phenolic chemicals on the endocrine system, we subjected two generations (F0 and F1) of Drosophila melanogaster to different concentrations of ED. Specifically, treatments involved wastewater, which had the highest level of ED (bisphenol A and nonylphenol) and treated wastewater from a constructed Heliconia psittacorum wetland with horizontal subsurface water flow (He); the treated wastewater was the treatment with the lowest level of ED. We evaluated the development time from egg to pupa and from pupa to adult as well as fertility. The results show that for individuals exposed to treated wastewater, the developmental time from egg to pupae was shorter in individuals of the F1 generation than in the F0 generation. Additionally, the time from pupae to adult was longer for flies growing in the H. psittacorum treated wastewater. Furthermore, fertility was lower in the F1 generation than in the F0 generation. Although different concentrations of bisphenol A and nonylphenol had no significant effect on the components of fitness of D. melanogaster (developmental time and fertility), there was a trend across generations, likely as a result of selection imposed on the flies. It is possible that the flies developed different strategies to avoid the effects of the various environmental stressors.

Effects of endocrine disruptors on prosobranch snails (Mollusca: Gastropoda) in the laboratory. Part II: Triphenyltin as a xeno-androgen.

Science.gov (United States)

Schulte-Oehlmann, U; Tillmann, M; Markert, B; Oehlmann, J; Watermann, B; Scherf, S

2000-12-01

In laboratory experiments the effects of suspected endocrine disrupting chemicals on freshwater and marine prosobranch species were analysed. In this second of three publications the responses of the freshwater ramshorn snail Marisa cornuarietis and of two marine prosobranchs (the dogwhelk Nucella lapillus and the netted whelk Hinia reticulata) to the xeno-androgenic model compound triphenyltin (TPT) are presented. Marisa and Nucella were exposed via water (nominal concentrations 5-500 ng TPT-Sn/L) and Hinia via sediments (nominal concentrations 50-500 micrograms TPT-Sn/kg dry wt.) for up to 4 months. Female ramshorn snails but not the two marine species developed imposex in a time and concentration dependent manner (EC10 4 months: 12.3 ng TPT-Sn/L) with a comparable intensity as described for tributyltin. TPT reduced furthermore the fecundity of Marisa at lower concentrations (EC10 4 months: 5.59 ng TPT-Sn/L) with a complete inhibition of spawning at nominal concentrations > or = 250 ng TPT-Sn/L (mean measured +/- SD: > or = 163 +/- 97.0 ng TPT-Sn/L). The extension of the pallial sex organs (penis with accessory structures and prostate gland) of male ramshorn snails and dogwhelks were reduced by up to 25% compared to the control but not in netted whelks. Histopathological analyses for M. cornuarietis and H. reticulata provide evidence for a marked impairment of spermatogenesis (both species) and oogenesis (only netted whelks). The test compound induced a highly significant and concentration independent increase in the incidence of hyperplasia on gills, osphradia and other organs in the mantle cavity of N. lapillus indicating a carcinogenic potential of TPT. The results show that prosobranchs are sensitive to endocrine disruption at environmentally relevant concentrations of TPT. Also, M. cornuarietis is a promising candidate for a future organismic invertebrate system to identify endocrine-mimetic test compounds.

Relationship structure-antioxidant activity of hindered phenolic compounds

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Weng, X. C.

2014-12-01

Full Text Available The relationship between the structure and the antioxidant activity of 21 hindered phenolic compounds was investigated by Rancimat and DPPH· tests. 3-tert-butyl-5-methylbenzene-1,2-diol is the strongest antioxidant in the Rancimat test but not in the DPPH· test because its two hydroxyl groups have very strong steric synergy. 2,6-Ditert-butyl-4-hydroxy-methylphenol exhibits a strong antioxidant activity as 2,6-ditertbutyl- 4-methoxyphenol does in lard. 2,6-Ditert-butyl-4- hydroxy-methylphenol also exhibits stronger activity than 2-tert-butyl-4- methoxyphenol. The methylene of 2,6-ditert-butyl-4-hydroxy-methylphenol can provide a hydrogen atom to active free radicals like a phenolic hydroxyl group does because it is greatly activated by both the aromatic ring and hydroxyl group. Five factors affect the antioxidant activities of the phenolic compounds: how stable the phenolic compound free radicals are after providing hydrogen atoms; how many hy drogen atoms each of the phenolic compounds can provide; how fast the phenolic compounds provide hydrogen atoms; how easily the phenolic compound free radicals can combine with more active free radicals, and whether or not a new antioxidant can form after the phenolic compound provides hydrogen atoms.La relación entre estructura y la actividad antioxidante de 21 compuestos fenólicos con impedimentos estéricos fue investigado mediante ensayos con Rancimat y DPPH·. El 3-terc-butil-5-metilbenceno-1,2-diol es el antioxidante más potente en los ensayos mediante Rancimat pero no mediante ensayos con DPPH·, porque sus dos grupos hidroxilo tienen una fuerte sinergia estérica. El 2,6-Di-terc-butil-4-hidroxi-metil-fenol mostró una actividad antioxidante tan fuerte como el 2,6-di-ter-butil-4-metoxifenol en ensayos con manteca de cerdo. El 2,6-di-terc-butil-4-hidroxi-metilfenol también mostró una actividad más fuerte que el 2-terc-butil-4-metoxifenol. El grupo metileno del 2,6-di-ter-butil-4-hidroxi

Guidance Document on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption

DEFF Research Database (Denmark)

Satya, Sneha; Wade, Mike; Hass, Ulla

This guidance document was developed as a follow-up to the workshop on OECD countries’ activities regarding testing, assessment and management of endocrine disrupters, which was held in Copenhagen (Denmark) on 22-24 September 2010 (see document No. 118 published in the Series on Testing and Asses......This guidance document was developed as a follow-up to the workshop on OECD countries’ activities regarding testing, assessment and management of endocrine disrupters, which was held in Copenhagen (Denmark) on 22-24 September 2010 (see document No. 118 published in the Series on Testing...... on testing and assessment of endocrine disrupters (EDTA AG). In November 2010, comments were requested from the WNT, the EDTA AG, the Task Force on Hazard Assessment and experts involved in the assessment of chemicals. The EDTA AG addressed the comments from the WNT at a meeting held in April 2011...... the conclusions and next steps recommended in the draft guidance document are sensible and helpful when assessed in light of comprehensive datasets. The draft guidance document and the three case studies were reviewed again and revised at a meeting of the EDTA AG in December 2011. The draft guidance document...

Endocrine effects of contaminated sediments on the freshwater snail Potamopyrgus antipodarum in vivo and in the cell bioassays in vitro.

Science.gov (United States)

Mazurová, E; Hilscherová, K; Jálová, V; Köhler, H-R; Triebskorn, R; Giesy, J P; Bláha, L

2008-09-17

Lake Pilnok located in the black coal-mining region Ostrava-Karvina, Czech Republic, contains sediments highly contaminated with powdered waste coal. Moreover, population of the endangered species of narrow-clawed crayfish Pontastacus leptodactylus with high proportion of intersex individuals (18%) was observed at this site. These findings motivated our work that aimed to evaluate contamination, endocrine disruptive potency using in vitro assays and in vivo effects of contaminated sediments on reproduction of sediment-dwelling invertebrates. Chemical analyses revealed low concentrations of persistent chlorinated compounds and heavy metals but concentrations of polycyclic aromatic hydrocarbons (PAH) were high (sum of 16 PAHs 10 microg/g dw). Organic extracts from sediments caused significant in vitro AhR-mediated activity in the bioassay with H4IIE-luc cells, estrogenicity in MVLN cells and anti-androgenicity in recombinant yeast assay, and these effects could be attributed to non-persistent compounds derived from the waste coal. We have also observed significant in vivo effects of the sediments in laboratory experiments with the Prosobranchian euryhaline mud snail Potamopyrgus antipodarum. Sediments from Lake Pilnok as well as organic extracts of the sediments (externally added to the control sediment) significantly affected fecundity during 8 weeks of exposure. The effects were stimulations of fecundity at lower concentrations at the beginning of the experiment followed by inhibitions of fecundity and general toxicity. Our study indicates presence of chemicals that affected endocrine balance in invertebrates, and emphasizes the need for integrated approaches combining in vitro and in vivo bioassays with identification of chemicals to elucidate ecotoxicogical impacts of contaminated sediment samples.

Data-Driven Derivation of an "Informer Compound Set" for Improved Selection of Active Compounds in High-Throughput Screening.

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Paricharak, Shardul; IJzerman, Adriaan P; Jenkins, Jeremy L; Bender, Andreas; Nigsch, Florian

2016-09-26

Despite the usefulness of high-throughput screening (HTS) in drug discovery, for some systems, low assay throughput or high screening cost can prohibit the screening of large numbers of compounds. In such cases, iterative cycles of screening involving active learning (AL) are employed, creating the need for smaller "informer sets" that can be routinely screened to build predictive models for selecting compounds from the screening collection for follow-up screens. Here, we present a data-driven derivation of an informer compound set with improved predictivity of active compounds in HTS, and we validate its benefit over randomly selected training sets on 46 PubChem assays comprising at least 300,000 compounds and covering a wide range of assay biology. The informer compound set showed improvement in BEDROC(α = 100), PRAUC, and ROCAUC values averaged over all assays of 0.024, 0.014, and 0.016, respectively, compared to randomly selected training sets, all with paired t-test p-values agnostic fashion. This approach led to a consistent improvement in hit rates in follow-up screens without compromising scaffold retrieval. The informer set is adjustable in size depending on the number of compounds one intends to screen, as performance gains are realized for sets with more than 3,000 compounds, and this set is therefore applicable to a variety of situations. Finally, our results indicate that random sampling may not adequately cover descriptor space, drawing attention to the importance of the composition of the training set for predicting actives.

Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

Science.gov (United States)

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

2013-12-12

Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic

Assessment of A Simple Compound-Saving Method To Study Insecticidal Activity of Natural Extracts and Pure Compounds Against Mosquito Larvae.

Science.gov (United States)

Falkowski, Michaël; Jahn-Oyac, Arnaud; Ferrero, Emma; Issaly, Jean; Eparvier, Véronique; Girod, Romain; Rodrigues, Alice M S; Stien, Didier; Houël, Emeline; Dusfour, Isabelle

2016-12-01

Research on natural insecticides has intensified with the spread of resistance to chemicals among insects, particularly disease vectors. To evaluate compounds, the World Health Organization (WHO) has published standardized procedures. However, those may be excessively compound-consuming when it comes to assessing the activity of natural extracts and pure compounds isolated in limited amount. As part of our work on the discovery of new mosquito larvicides from Amazonian plants, we developed a compound-saving assay in 5-ml glass tubes instead of WHO larval 100-ml cups. Comparing activity of synthetic and natural chemicals validated the glass tube assay. Raw data, lethal doses that kill 50% (LD 50 ) and 90% (LD 90 ) at 24 and 48 h, were highly correlated (0.68 natural extracts and molecules, identifying active compounds using 10 times less material than in the WHO protocol.

Arterial and venous thrombosis in endocrine diseases

NARCIS (Netherlands)

van Zaane, Bregje; Stuijver, Danka J. F.; Squizzato, Alessandro; Gerdes, Victor E. A.

2013-01-01

Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency,

QSAR Models for Reproductive Toxicity and Endocrine Disruption Activity

Directory of Open Access Journals (Sweden)

Marjan Vračko

2010-03-01

Full Text Available Reproductive toxicity is an important regulatory endpoint, which is required in registration procedures of chemicals used for different purposes (for example pesticides. The in vivo tests are expensive, time consuming and require large numbers of animals, which must be sacrificed. Therefore an effort is ongoing to develop alternative In vitro and in silico methods to evaluate reproductive toxicity. In this review we describe some modeling approaches. In the first example we describe the CAESAR model for prediction of reproductive toxicity; the second example shows a classification model for endocrine disruption potential based on counter propagation artificial neural networks; the third example shows a modeling of relative binding affinity to rat estrogen receptor, and the fourth one shows a receptor dependent modeling experiment.

Anti-human rhinoviral activity of polybromocatechol compounds isolated from the rhodophyta, Neorhodomela aculeata.

Science.gov (United States)

Park, Soon-Hye; Song, Jae-Hyoung; Kim, Taejung; Shin, Woon-Seob; Park, Gab Man; Lee, Seokjoon; Kim, Young-Joo; Choi, Pilju; Kim, Heejin; Kim, Hui-Seong; Kwon, Dur-Han; Choi, Hwa Jung; Ham, Jungyeob

2012-10-01

An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2-6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC₅₀) of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC₅₀ of 7.11 μg/mL, and anti-HRV3 activity, with an IC₅₀ of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

Estrogenic effects of marijuana smoke condensate and cannabinoid compounds

International Nuclear Information System (INIS)

Lee, Soo Yeun; Oh, Seung Min; Chung, Kyu Hyuck

2006-01-01

Chronic exposure to marijuana produces adverse effects on the endocrine and reproductive systems in humans; however, the experimental evidence for this presented thus far has not been without controversy. In this study, the estrogenic effect of marijuana smoke condensate (MSC) was evaluated using in vitro bioassays, viz., the cell proliferation assay, the reporter gene assay, and the ER competitive binding assay. The results of these assays were compared with those of three major cannabinoids, i.e., THC, CBD, and CBN. The estrogenic effect of MSC was further confirmed by the immature female rat uterotrophic assay. MSC stimulated the estrogenicity related to the ER-mediated pathway, while neither THC, CBD, nor CBN did. Moreover, treatment with 10 and 25 mg/kg MSC induced significant uterine response, and 10 mg/kg MSC resulted in an obvious change in the uterine epithelial cell appearance. MSC also enhanced the IGFBP-1 gene expression in a dose-dependent manner. To identify the constituents of MSC responsible for its estrogenicity, the MSC fractionated samples were examined using another cell proliferation assay, and the estrogenic active fraction was analyzed using GC-MS. In the organic acid fraction that showed the strongest estrogenic activity among the seven fractions of MSC, phenols were identified. Our results suggest that marijuana abuse is considered an endocrine-disrupting factor. Furthermore, these results suggest that the phenolic compounds contained in MSC play a role in its estrogenic effect

Antibacterial and antifungal activity of sulfur-containing compounds from Petiveria alliacea L.

Science.gov (United States)

Kim, Seokwon; Kubec, Roman; Musah, Rabi A

2006-03-08

A total of 18 organosulfur compounds originating from Petiveria alliacea L. roots have been tested for their antibacterial and antifungal activities. These represent compounds occurring in fresh homogenates as well as those present in various macerates, extracts and other preparations made from Petiveria alliacea. Of the compounds assayed, the thiosulfinates, trisulfides and benzylsulfinic acid were observed to be the most active, with the benzyl-containing thiosulfinates exhibiting the broadest spectrum of antimicrobial activity. The effect of plant sample preparation conditions on the antimicrobial activity of the extract is discussed.

Bird populations as sentinels of endocrine disrupting chemicals

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Claudio Carere

2010-03-01

Full Text Available Exposure to endocrine disrupting chemicals (EDCs is a widespread phenomenon in nature. Although the mechanisms of action of EDCs are actively studied, the consequences of endocrine disruption (ED at the population level and the adaptations evolved to cope with chronic EDC exposure have been overlooked. Birds probably represent the animal taxon most successfully adapted to synanthropic life. Hence, birds share with humans a similar pattern of exposure to xenobiotics. In this article, we review case studies on patterns of behaviour that deviate from the expectation in bird species exposed to EDCs. We provide behavioural and ecological parameters to be used as endpoints of ED; methodological requirements and caveats based on species-specific life-history traits, behavioural repertoires, developmental styles, and possibility of captive breeding; a list of species that could be used as sentinels to assess the quality of man-made environment.

Endocrine Abnormalities in Patients with Chronic Kidney Disease.

Science.gov (United States)

Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

2015-01-01

In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

Endocrine dysfunction among adult patients with tuberculosis: An African experience

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Davis Kibirige

2014-01-01

Full Text Available A broad spectrum of endocrine conditions has been reported among adult patients with tuberculosis in Africa. This review aims to describe the magnitude and pathogenesis of the following endocrinopathies among patients with tuberculosis in Africa: adrenal insufficiency, diabetes mellitus, disorders of calcium and vitamin D metabolism, thyroid dysfunction and hypogonadism. PubMed database and Google scholar were used to search for the relevant published English language studies and case reports relating to endocrine abnormalities and tuberculosis in Africa up to July 2013. The search terms used were endocrine dysfunction, endocrine abnormalities, adrenal insufficiency, diabetes mellitus, thyroid dysfunction, hypogonadism, disorders of calcium and vitamin D metabolism, tuberculosis, Africa. Reference lists of the identified articles were further used to identify other studies. Adrenal insufficiency, diabetes mellitus and calcium-vitamin D abnormalities were the most prevalent and frequently reported endocrine disorders among adult patients with tuberculosis in Africa. A meticulous endocrine evaluation among tuberculosis patients with suspected endocrine abnormalities should be encouraged in Africa and other high TB endemic regions. Treatment of these endocrine disorders has generally been shown to improve quality of life and reduce mortality.

Multiple endocrine diseases in dogs: 35 cases (1996-2009).

Science.gov (United States)

Blois, Shauna L; Dickie, Erica; Kruth, Stephen A; Allen, Dana G

2011-06-15

To characterize a population of dogs from a tertiary care center with 2 or more endocrine disorders, including the specific disorders and time intervals between diagnosis of each disorder. Retrospective case series. 35 dogs with 2 or more endocrine disorders. Medical records were reviewed, and the following was recorded: clinical signs, physical examination findings, and the results of CBC, serum biochemical analysis, urinalysis, aerobic bacterial culture of urine samples, endocrine testing, diagnostic imaging, and necropsy. 35 dogs with more than 1 endocrine disorder were identified. Seventy-seven percent (27/35) of the dogs were male, and the mean age at the time of diagnosis of the first endocrinopathy was 7.9 years. Miniature Schnauzer was the most common breed. Twenty-eight of 35 (80%) dogs had 2 disorders; 7 (20%) had 3 disorders. The most common combinations of disorders included diabetes mellitus and hyperadrenocorticism in 57.1 % (20/35) of dogs; hypoadrenocorticism and hypothyroidism in 22.9% (8/35) of dogs; and diabetes mellitus and hypothyroidism in 28.6% (10/35) of dogs. A mean of 14.5 months elapsed between diagnosis of the first and second endocrine disorders, whereas there was a mean of 31.1 months between diagnosis of the first and third endocrine disorders. Results suggested that the occurrence of multiple endocrine disorders was uncommon in dogs. The most common combinations of endocrine disorders in this population of dogs were diabetes mellitus and hyperadrenocorticism, followed by hypoadrenocorticism and hypothyroidism.

Epicardial adipose tissue in endocrine and metabolic diseases.

Science.gov (United States)

Iacobellis, Gianluca

2014-05-01

Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

The clandestine organs of the endocrine system.

Science.gov (United States)

Garcia-Reyero, Natàlia

2018-02-01

This review analyzes what could be regarded as the "clandestine organs" of the endocrine system: the gut microbiome, the immune system, and the stress system. The immune system is very closely related to the endocrine system, with many intertwined processes and signals. Many researchers now consider the microbiome as an 'organ' that affects the organism at many different levels. While stress is certainly not an organ, it affects so many processes, including endocrine-related processes, that the stress response system deserved a special section in this review. Understanding the connections, effects, and feedback mechanisms between the different "clandestine organs" and the endocrine system will provide us with a better understanding of how an organism functions, as well as reinforce the idea that there are no independent organs or systems, but a complex, interacting network of molecules, cells, tissues, signaling pathways, and mechanisms that constitute an individual. Published by Elsevier Inc.

High levels of endocrine pollutants in US streams during low flow due to insufficient wastewater dilution

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Rice, Jacelyn; Westerhoff, Paul

2017-08-01

Wastewater discharges from publicly owned treatment works are a significant source of endocrine disruptors and other contaminants to the aquatic environment in the US. Although remaining pollutants in wastewater pose environmental risks, treated wastewater is also a primary source of stream flow, which in turn is critical in maintaining many aquatic and riparian wildlife habitats. Here we calculate the dilution factor--the ratio of flow in the stream receiving discharge to the flow of wastewater discharge--for over 14,000 receiving streams in the continental US using streamflow observations and a spatially explicit watershed-scale hydraulic model. We found that wastewater discharges make up more than 50% of in-stream flow for over 900 streams. However, in 1,049 streams that experienced exceptional low-flow conditions, the dilution factors in 635 of those streams fell so low during those conditions that the safety threshold for concentrations of one endocrine disrupting compound was exceeded, and in roughly a third of those streams, the threshold was exceeded for two compounds. We suggest that streams are vulnerable to public wastewater discharge of contaminants under low-flow conditions, at a time when wastewater discharges are likely to be most important for maintaining stream flow for smaller sized river systems.

SLEEP APNEA IN ENDOCRINE DISORDERS

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I. V. Misnikova

2016-01-01

Full Text Available In the recent years, an association between sleep apnea and a  number of endocrine diseases has been established. The secretion of many hormones after falling asleep is considerably changed, compared to the period of wakefulness. In patients with endocrine disorders, abnormal hormonal secretion and its pathological consequences may contribute to sleep apnea. Sleep fragmentation and intermittent hypoxia arising in sleep apnea result in a decrease in insulin sensitivity, which contributes to the development of type 2 diabetes mellitus. The prevalence of sleep apnea increases in acromegaly, which may affect the risk of cardio-pulmonary complications. There is an association between sleep apnea and testosterone treatment in men, as well as in postmenopausal women. Sleep apnea in hypothyroidism is most frequently related to the development of hypothyroidism per se and can therefore be reversed with thyroid hormone replacement therapy. Timely detection and treatment of sleep apnea in patients with endocrine disorders can improve their survival prognosis and quality of life.

Endocrine manifestations in celiac disease.

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Freeman, Hugh James

2016-10-14

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.

Levels and distributions of organic pollutants in subtidal sediments from the Loire estuary: Are there any relationships with TTR-binding activity?

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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.

Biologically Active Macrocyclic Compounds – from Natural Products to Diversity‐Oriented Synthesis

DEFF Research Database (Denmark)

Madsen, Charlotte Marie; Clausen, Mads Hartvig

2011-01-01

Macrocyclic compounds are attractive targets when searching for molecules with biological activity. The interest in this compound class is increasing, which has led to a variety of methods for tackling the difficult macrocyclization step in their synthesis. This microreview highlights some recent...... developments in the synthesis of macrocycles, with an emphasis on chemistry developed to generate libraries of putative biologically active compounds....

Neurocutaneous spectrum of multiple endocrine neoplasia-1

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Shireen Furtado

2012-01-01

Full Text Available Multiple endocrine neoplasia type I or Wermer syndrome is characterized by primary hyperparathyroidism, enteropancreatic endocrine tumor, and a pituitary pathology. A 35-year-old male presented with visual field defects, hyperprolactinemia, and hypogonadism. He also had multiple infraumbilical skin-colored nodules. A syndromal association of Wermer syndrome was derived using the dermal, pituitary, parathyroid, and gastrointestinal hormonal manifestations of the tumor. The radiological and histological findings of lesion which underwent biopsy are discussed. The presence of collagenomas, lipomas, and hypopigmented macules in a patient with neuroendocrine symptoms should raise the suspicion of an underlying multiple endocrine neoplasia.

Morphological and transcriptomic effects of endocrine modulators on the gonadal differentiation of chicken embryos: The case of tributyltin (TBT).

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Scheider, Jessica; Afonso-Grunz, Fabian; Jessl, Luzie; Hoffmeier, Klaus; Winter, Peter; Oehlmann, Jörg

2018-03-01

Morphological malformations induced by tributyltin (TBT) exposure during embryonic development have already been characterized in various taxonomic groups, but, nonetheless, the molecular processes underlying these changes remain obscure. The present study provides the first genome-wide screening for differentially expressed genes that are linked to morphological alterations of gonadal tissue from chicken embryos after exposure to TBT. We applied a single injection of TBT (between 0.5 and 30 pg as Sn/g egg) into incubated fertile eggs to simulate maternal transfer of the endocrine disruptive compound. Methyltestosterone (MT) served as a positive control (30 pg/g egg). After 19 days of incubation, structural features of the gonads as well as genome-wide gene expression profiles were assessed simultaneously. TBT induced significant morphological and histological malformations of gonadal tissue from female embryos that show a virilization of the ovaries. This phenotypical virilization was mirrored by altered expression profiles of sex-dependent genes. Among these are several transcription and growth factors (e.g. FGF12, CTCF, NFIB), whose altered expression might serve as a set of markers for early identification of endocrine active chemicals that affect embryonic development by transcriptome profiling without the need of elaborate histological analyses. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Advances in the development of AMPK-activating compounds.

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Sriwijitkamol, Apiradee; Musi, Nicolas

2008-10-01

AMP-activated protein kinase (AMPK) is an energy sensing enzyme that controls glucose and lipid metabolism. This review summarizes the present data on AMPK as a pharmacologic target for the treatment of metabolic disorders. The mechanisms governing AMPK activity and how this enzyme controls different metabolic pathways are reviewed briefly, and details about the effect that AMPK activators have on glucose metabolism are provided. Evidence obtained using the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) suggests that AMPK promotes glucose transport into skeletal muscles and that this enzyme inhibits hepatic glucose production. AICAR also induces fatty acid oxidation in muscle and inhibits cholesterol synthesis in the liver. The metabolic effects of AICAR on glucose and lipid metabolism indicate that AMPK may be a good pharmacologic target for the treatment of type 2 diabetes and hypercholesterolemia. Novel AMPK-specific compounds are allowing researchers to examine whether this enzyme is a useful pharmacologic target for the treatment of human disease and whether chronic activation of AMPK will be safe.

ANTIBACTERIAL COMPOUNDS ACTIVITY OF MANGROVE LEAF EXTRACT RHIZOPHORA MUCRONATA ON AEROMONAS HYDROPHYLA

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Panjaitan M.A.P.

2018-01-01

Full Text Available Pathogenic bacterial infections such as A.hydrophyla in fish cultivation are common problems. A.hydrophyla belongs to a group of bacteria resistant to more than one type of antibiotic. This study aims to determine the antibacterial activity of R.mucronata mangrove leaf extract and to identify potential antibacterial compounds. The research procedure includes extraction, compound refinement, phytochemical test, antibacterial activity test, and KBM-KHM Test. The results show that the antibacterial ability possessed by R.mucronata leaves crude extract increased after the extract was purified utilizing separating funnel. The lowest concentration of methanol fraction extract capable of inhibiting A.hydrophyla (KHM growth was at 8.25±0.39 ppm, while the lowest concentration of A.hydrophyla was 32.99±1.56 ppm. Bioactive compounds contained in methanol R.mucronata leaves extract are alkaloid compounds, flavonoids, and tannins. Out of the three compounds detected, antibacterial activity is thought to be derived from flavonoid and tannin compounds.

Endocrine and Metabolic Aspects of OSA

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Ravinder Goswami

2014-03-01

Full Text Available Obstructive sleep apnea (OSA is characterized by repeated spells of apnea.Collapsibility of hypopharynx due to multiple factors involving pharyngeal dilatormuscles and deposition of fat or fluid in the surrounding soft tissues are importantcontributing factors in its pathogenesis. OSA commonly affects obese individuals.Males are more commonly affected than the females probably due to the disturbingeffect of testosterone on sleep.The impact of OSA on human health include disturbances in endocrine and metabolicsystem affecting hypothalamic-pituitary-gonadal axis, adrenocorticotrophic-cortisolaxis, growth hormone, antidiuretic hormones and insulin resistance. There is atendency for predisposition of the metabolic syndrome or its components includingglycemic dysregulation, hypertension, hyperlipidemia and physical parameters relatedto adiposity. On the other hand, several endocrine disorders such as hypothyroidism,growth hormone excess, polycystic ovarian disease and testosterone replacement areassociated with increased prevalence of OSA.There is limited information on the effect of treatment of OSA by continuous positiveairway pressure (CPAP on the endocrine and metabolic disturbances. There is a needto conduct randomized controlled trials using CPAP therapy in patients with OSA andto study its cause and effect relationship with endocrine and metabolic disturbances.

Plasma thymidine kinase-1 activity predicts outcome in patients with hormone receptor positive and HER2 negative metastatic breast cancer treated with endocrine therapy.

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Bonechi, Martina; Galardi, Francesca; Biagioni, Chiara; De Luca, Francesca; Bergqvist, Mattias; Neumüller, Magnus; Guarducci, Cristina; Boccalini, Giulia; Gabellini, Stefano; Migliaccio, Ilenia; Di Leo, Angelo; Pestrin, Marta; Malorni, Luca

2018-03-27

The aim of this study was to investigate if thymidine kinase-1 (TK1), a well-known proliferation marker, could represent a valid circulating biomarker to identify hormone receptor positive (HR+)/HER2 negative (HER2neg) metastatic breast cancer (MBC) patients most likely to benefit from endocrine therapy (ET). We used the DiviTum™ assay to analyze TK1 activity in cell lysates of three HR+/HER2neg BC cell lines and in plasma of 31 HR+/HER2neg MBC patients receiving ET. Blood samples were collected at treatment initiation, after one month and at disease progression. CTCs count and ESR1 / PIK3CA mutations in circulating tumor DNA were performed and correlated with TK1 activity. TK1 activity was reduced in the two endocrine-sensitive cell lines after 2 days of treatment. In patients, high baseline TK1 activity correlated with CTCs positivity (p-value=0.014). Patients with low baseline levels of TK1 activity had a significantly better PFS compared to those with high baseline TK1 activity (p-value=0.012). Patients with an early drop of TK1 activity after one month of treatment had a significantly better PFS compared to those who experienced an increase (p-value=0.0026). Our study suggests that TK1 could be a potential prognostic, predictive and monitoring marker of early ET response in HR+/HER2neg MBC patients.

Factors associated with cancer-related fatigue in breast cancer patients undergoing endocrine therapy in an urban setting: a cross-sectional study

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Huang Xu

2010-08-01

Full Text Available Abstract Background Fatigue is prevalent in breast cancer survivors and has profound effects on daily life. The interference of fatigue with endocrine therapy may be difficult to separate. This study investigates the prevalence and severity of fatigue and identifies the demographic, clinical, and lifestyle factors associated with cancer-related fatigue (CRF in breast cancer patients undergoing endocrine therapy in an urban area. Methods Women with stage I-IIIA breast cancer were recruited and asked to participate (n = 371 in the study. The 315 women who responded to the questionnaire (84.9%, 54 (17.1% had completed endocrine therapy and 261 (82.9% were still undergoing endocrine therapy. The patients had been diagnosed at an average of 31 months prior to recruitment (range, 7 to 60 months; the average age was 48 (range, 33 to 72 years. The 11-point scale and Visual Analog Scale (VAS were employed to quantify the level of fatigue experienced by the patients. Logistic regression analyses and a trend test method were performed to evaluate factors associated with CRF. Results Among the 315 patients, 189 (60% had experienced or were experiencing CRF during endocrine therapy. Logistic regression analysis was performed to identify factors associated with CRF, including BMI (body mass index, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet. Factors unrelated to CRF were age, marital status, treatment, endocrine therapy drugs, alcohol intake, and smoking. The trend test method revealed an association between physical activity and dietary level and the intensity of CRF. Conclusions The present findings suggest that fatigue is an important problem in the majority of breast cancer patients during endocrine therapy. We found that BMI, clinical stage, menopausal status, duration of endocrine therapy, physical activity, and diet are associated with fatigue. Future research should focus on the impact factors of CRF

Tailoring endocrine treatment for early breast cancer

NARCIS (Netherlands)

Fontein, Duveken Berthe Yvonne

2014-01-01

This thesis describes several important aspects of adjuvant endocrine therapy for postmenopausal women with endocrine-sensitive, early-stage breast cancer. In our ongoing efforts to tailor treatment so as to provide the best possible care to each of our patients, we studied the influence of various

Microsomal cytochrome P450-3A4 (CYP3A4) nanobiosensor for the determination of 2,4-dichlorophenol-An endocrine disruptor compound

Energy Technology Data Exchange (ETDEWEB)

Hendricks, Nicolette R.; Waryo, Tesfaye T.; Arotiba, Omotayo; Jahed, Nazeem; Baker, Priscilla G.L. [SensorLab, Department of Chemistry, University of Western Cape, Moderddam Road, Bellville, Cape Town 7535 (South Africa); Iwuoha, Emmanuel I. [SensorLab, Department of Chemistry, University of Western Cape, Moderddam Road, Bellville, Cape Town 7535 (South Africa)], E-mail: eiwuoha@uwc.ac.za

2009-02-28

Cytochrome P450-3A4 (CYP3A4) is a monooxygenase enzyme that plays a major role in the detoxification of bioactive compounds and hydrophobic xenobiotics (e.g. medicines, drugs, environmental pollutants, food supplements and steroids). Physiologically the monooxygenation reactions of this class II, microsomal, b-type heme enzyme, usually requires cytochrome P450 reductase, NADPH. A novel CYP3A4 biosensor system that essentially simplified the enzymatic redox processes by allowing electron transfer between the electrode and the enzyme redox centre to occur, without any need for the physiological redox partners, was developed for the detection of 2,4-dichlorophenol (2,4-DCP), a priority environmental pollutant and an endocrine disruptor. The biosensor, GC/Naf-Co(Sep){sup 3+}/CYP3A4/Naf, was constructed by encapsulating CYP3A4 in a Nafion-cobalt (III) sepulchrate (Naf-Co(Sep){sup 3+}) composite film on a glassy carbon (GC) electrode. The responses of the biosensor to 2,4-dichlorophenol, erythromycin (CYP3A4 native substrate) and ketoconazole (CYP 3A4 natural inhibitor) were studied by cyclic and square wave voltammetric techniques. The detection limit (DL) of the biosensor for 2,4-dichlorophenol was 0.043 {mu}g L{sup -1}, which is by an order of magnitude lower than the EU limit (0.3 {mu}g L{sup -1}) for any pesticide compound in ground water. The biosensor's DL is lower than the U.S. Environmental Protection Agency's drinking water equivalent level (DWEL) value for 2,4-DCP, which is 2 {mu}g L{sup -1}.

Anti-Human Rhinoviral Activity of Polybromocatechol Compounds Isolated from the Rhodophyta, Neorhodomela aculeata

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Hui-Seong Kim

2012-10-01

Full Text Available An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1 and five polybromocatechols (2–6 by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC50 of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC50 of 7.11 μg/mL, and anti-HRV3 activity, with an IC50 of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

Schedule for Rating Disabilities; the Endocrine System. Final rule.

Science.gov (United States)

2017-11-02

This document amends the Department of Veterans Affairs (VA) Schedule for Rating Disabilities (VASRD) by revising the portion of the Schedule that addresses endocrine conditions and disorders of the endocrine system. The effect of this action is to ensure that the VASRD uses current medical terminology and to provide detailed and updated criteria for evaluation of endocrine disorders.

Endocrine causes of nonalcoholic fatty liver disease.

Science.gov (United States)

Marino, Laura; Jornayvaz, François R

2015-10-21

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

The Relationship between the Ionic Composition of the Environment and the Secretory Activity of the Endocrine Cell Types of Stannius Corpuscles in the Teleost Gasterosteus aculeatus

NARCIS (Netherlands)

Wendelaar Bonga, S.E.; Greven, J.A.A.; Veenhuis, M.

1976-01-01

The corpuscles of Stannius of threespined sticklebacks contain two glandular cell types of presumed endocrine nature. To elucidate the function of both cell types the secretory activity of the cells was studied in fully adapted seawater and freshwater fishes and in specimens transferred from sea

Syndromes that Link the Endocrine System and Genitourinary Tract.

Science.gov (United States)

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.

The influence of internal irradiation on the endocrine system and the importance of its functional state for the development of late sequelae

International Nuclear Information System (INIS)

Dedov, V.I.; Norets, T.A.

1981-01-01

The problem of choosing and proving criteria for the estimation of their biological effect at the level of organism results from the necessity to clarify the danger of incorporation of low doses of radioactive compounds. Therefore the importance of changes in the functional state of the endocrine system for the development of late sequelae following internal irradiation was investigated. Male and female rats were injected once with 1.22x10 4 Bq/g body weight 75 Se-selenomethionine. In the blood plasma the content of thyroxine, corticosterone, testosterone, and estradiol was determined. Moreover, the conditions of adaptation and reparation processes as well as of the reproductive function were checked. A long time afterwards the male rats showed a suppression of the functions of the endocrine system which led to a suppression of the adaptive and repairing processes and of the reproductive function, to a decrease in body weight and dynamic activity. In female animals such phenomena did never occur; that is probably connected to the weakly pronounced changes in the hormonal state. The results allow to propose the hormonal state as a criterion for evaluation of the biological effect of internal irradiation. (author)

Activity-Guided Isolation of Antioxidant Compounds from Andrographis stenophylla Leaf

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Neelaveni Thangavel

2010-01-01

Full Text Available The antioxidant potency of various extracts of Andrographis stenophylla leaf was evaluated in vitro using ferric thiocyanate method. Reductive ability and free radical scavenging activity of the extracts were also investigated. Amounts of phenolic compounds in each of the extracts were determined using Folin-Ciocalteau reagent and compared to observe the correlation between antioxidant activities and total phenolic content. Methanol extract exhibited maximum antioxidant activity and was found to contain 2% of total phenolic compounds. Methanol extract was subjected to column chromatographic separation over silica gel G using ethyl acetate: formic acid: acetic acid: water. Fractions thus obtained were screened for their antioxidant activity. Among the eleven fractions screened, fraction C was more active than the standard butylated hydroxyanisole. Fraction C on further fractionation with n-butanol: acetic acid: water afforded two flavanoids namely acacetine and isosakuranetine. Fraction A was also shown to possess good antioxidant activity which was developed using TLC and indicated the presence of a terpenoid, Andrographolide. The structures of the isolated compounds were confirmed by UV, IR, MS, 1H and 13C NMR spectral data. This is the first report wherein Andrographolide, Acacetine and Isosakuranetine are isolated from Andrographis stenophylla leaf.

The application of PET in endocrine tumors

International Nuclear Information System (INIS)

Yuan Zhibin

2003-01-01

There are wide application of PET in endocrine tumors, including thyroid cancer, parathyroid adenoma, pheochromocytoma and neuroblastoma. Many papers concluded that in diagnosing endocrine tumors, PET does not show apparent advantages comparing with traditional radionuclide imaging methods. But as a useful complementary method, its clinical value has been recognized

Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System

NARCIS (Netherlands)

Autrup, Herman; Barile, Frank A.; Blaauboer, Bas J.; Degen, Gisela H.; Dekant, Wolfgang; Dietrich, Daniel; Domingo, Jose L.; Gori, Gio Batta; Greim, Helmuth; Hengstler, Jan G.; Kacew, Sam; Marquardt, Hans; Pelkonen, Olavi; Savolainen, Kai; Vermeulen, Nico P.

The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can be

Principles of Pharmacology and Toxicology Also Govern Effects of Chemicals on the Endocrine System

DEFF Research Database (Denmark)

Autrup, Herman; Barile, Frank A; Blaauboer, Bas J

2015-01-01

The present debate on chemicals with Hormonal activity, often termed 'endocrine disruptors', is highly controversial and includes challenges of the present paradigms used in toxicology and in hazard identification and risk characterization. In our opinion, chemicals with hormonal activity can be ...

Cryptic antifungal compounds active by synergism with polyene antibiotics.

Science.gov (United States)

Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

2016-04-01

The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

International Nuclear Information System (INIS)

Kandhasamy, Subramani; Ramanathan, Giriprasath; Muthukumar, Thangavelu; Thyagarajan, SitaLakshmi; Umamaheshwari, Narayanan; Santhanakrishnan, V P; Sivagnanam, Uma Tiruchirapalli; Perumal, Paramasivan Thirumalai

2017-01-01

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a–5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: (1T46)) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48 h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the

Nanofibrous matrixes with biologically active hydroxybenzophenazine pyrazolone compound for cancer theranostics

Energy Technology Data Exchange (ETDEWEB)

Kandhasamy, Subramani [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India); Ramanathan, Giriprasath [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Muthukumar, Thangavelu [Department of Clinical and Experimental Medicine (IKE), Division of Neuro and Inflammation Sciences (NIV), Linkoping University (Sweden); Thyagarajan, SitaLakshmi [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Umamaheshwari, Narayanan [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India); Santhanakrishnan, V P [Department of Plant Biotechnology, TNAU, Coimbatore, Tamilnadu (India); Sivagnanam, Uma Tiruchirapalli, E-mail: suma67@gmail.com [Bioproducts Lab, CSIR-Central Leather Research Institute, Chennai 600020, Tamilnadu (India); Perumal, Paramasivan Thirumalai, E-mail: ptperumal@gmail.com [Organic Chemistry Division, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, Tamilnadu (India)

2017-05-01

The nanomaterial with the novel biologically active compounds has been actively investigated for application in cancer research. Substantial use of nanofibrous scaffold for cancer research with potentially bioactive compounds through electrospinning has not been fully explored. Here, we describe the series of fabrication of nanofibrous scaffold loaded with novel potential biologically active hydroxybenzo[a]phenazine pyrazol-5(4H)-one derivatives were designed, synthesized by a simple one-pot, two step four component condensation based on Michael type addition reaction of lawsone, benzene-1,2-diamine, aromatic aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one as the substrates. The heterogeneous solid state catalyst (Fe (III) Y-Zeolite) could effectively catalyze the reaction to obtain the product with high yield and short reaction time. The synthesized compounds (5a–5p) were analyzed by NMR, FTIR and HRMS analysis. Compound 5c was confirmed by single crystal XRD studies. All the compounds were biologically evaluated for their potential inhibitory effect on anticancer (MCF-7, Hep-2) and microbial (MRSA, MTCC 201 and FRCA) activities. Among the compounds 5i exhibited the highest levels of inhibitory activity against both MCF-7, Hep-2 cell lines. Furthermore, the compound 5i (BPP) was evaluated for DNA fragmentation, flow cytometry studies and cytotoxicity against MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. In addition, molecular docking (PDB ID: (1T46)) studies were performed to predict the binding affinity of ligand with receptor. Moreover, the synthesized BPP compound was loaded in to the PHB-PCL nanofibrous scaffold to check the cytotoxicity against the MCF-7, Hep-2 and NIH 3T3 fibroblast cell lines. The in vitro apoptotic potential of the PHB-PCL-BPP nanofibrous scaffold was assessed against MCF-7, Hep-2 cancerous cells and fibroblast cells at 12, 24 and 48 h respectively. The nanofibrous scaffold with BPP can induce apoptosis and also suppress the

Synthesis, Characterization, and Antimicrobial Activities of Coordination Compounds of Aspartic Acid

Directory of Open Access Journals (Sweden)

T. O. Aiyelabola

2016-01-01

Full Text Available Coordination compounds of aspartic acid were synthesized in basic and acidic media, with metal ligand M : L stoichiometric ratio 1 : 2. The complexes were characterized using infrared, electronic and magnetic susceptibility measurements, and mass spectrometry. Antimicrobial activity of the compounds was determined against three Gram-positive and three Gram-negative bacteria and one fungus. The results obtained indicated that the availability of donor atoms used for coordination was a function of the pH of the solution in which the reaction was carried out. This resulted in varying geometrical structures for the complexes. The compounds exhibited a broad spectrum of activity and in some cases better activity than the standard.

Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma

NARCIS (Netherlands)

Heikens, J.; Michiels, E. M.; Behrendt, H.; Endert, E.; Bakker, P. J.; Fliers, E.

1998-01-01

The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25

Proteomic analysis of the reproductive organs of the hermaphroditic gastropod Lymnaea stagnalis exposed to different endocrine disrupting chemicals.

Directory of Open Access Journals (Sweden)

Arnaud Giusti

Full Text Available 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

Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

International Nuclear Information System (INIS)

Guo, Shiguang; Mao, Li; Ji, Feng; Wang, Shouguo; Xie, Yue; Fei, Haodong; Wang, Xiao-dong

2016-01-01

Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. - Highlights: • Compound 13 (C13) attenuates dexamethasone (Dex)-induced osteoblast cell death. • C13-induced cytoprotective effect against Dex in osteoblasts requires AMPK activation. • Forced AMPK activation protects osteoblasts from Dex, nullifying C13's activities. • C13 increases NADPH activity and inhibits Dex-induced oxidative stress in osteoblasts.

Activating AMP-activated protein kinase by an α1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death

Energy Technology Data Exchange (ETDEWEB)

Guo, Shiguang [Department of Intensive Care Unit, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Mao, Li [Department of Endocrinology, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Ji, Feng, E-mail: huaiaifengjidr@163.com [Department of Orthopedics, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Wang, Shouguo; Xie, Yue; Fei, Haodong [Department of Orthopedics, Huai' an First People' s Hospital, Nanjing Medical University, Huai' an (China); Wang, Xiao-dong, E-mail: xiaodongwangsz@163.com [The Center of Diagnosis and Treatment for Children' s Bone Diseases, The Children' s Hospital Affiliated to Soochow University, Suzhou (China)

2016-03-18

Excessive glucocorticoid (GC) usage may lead to non-traumatic femoral head osteonecrosis. Dexamethasone (Dex) exerts cytotoxic effect to cultured osteoblasts. Here, we investigated the potential activity of Compound 13 (C13), a novel α1 selective AMP-activated protein kinase (AMPK) activator, against the process. Our data revealed that C13 pretreatment significantly attenuated Dex-induced apoptosis and necrosis in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. AMPK activation mediated C13′ cytoprotective effect in osteoblasts. The AMPK inhibitor Compound C, shRNA-mediated knockdown of AMPKα1, or dominant negative mutation of AMPKα1 (T172A) almost abolished C13-induced AMPK activation and its pro-survival effect in osteoblasts. On the other hand, forced AMPK activation by adding AMPK activator A-769662 or exogenous expression a constitutively-active (ca) AMPKα1 (T172D) mimicked C13's actions and inhibited Dex-induced osteoblast cell death. Meanwhile, A-769662 or ca-AMPKα1 almost nullified C13's activity in osteoblast. Further studies showed that C13 activated AMPK-dependent nicotinamide adenine dinucleotide phosphate (NADPH) pathway to inhibit Dex-induced reactive oxygen species (ROS) production in MC3T3-E1 cells and primary murine osteoblasts. Such effects by C13 were almost reversed by Compound C or AMPKα1 depletion/mutation. Together, these results suggest that C13 alleviates Dex-induced osteoblast cell death via activating AMPK signaling pathway. - Highlights: • Compound 13 (C13) attenuates dexamethasone (Dex)-induced osteoblast cell death. • C13-induced cytoprotective effect against Dex in osteoblasts requires AMPK activation. • Forced AMPK activation protects osteoblasts from Dex, nullifying C13's activities. • C13 increases NADPH activity and inhibits Dex-induced oxidative stress in osteoblasts.

Antibacterial Activity of Phenolic Compounds Against the Phytopathogen Xylella fastidiosa

OpenAIRE

Maddox, Christina E.; Laur, Lisa M.; Tian, Li

2010-01-01

Xylella fastidiosa is a pathogenic bacterium that causes diseases in many crop species, which leads to considerable economic loss. Phenolic compounds (a group of secondary metabolites) are widely distributed in plants and have shown to possess antimicrobial properties. The anti-Xylella activity of 12 phenolic compounds, representing phenolic acid, coumarin, stilbene and flavonoid, was evaluated using an in vitro agar dilution assay. Overall, these phenolic compounds were effective in inhibiti...

Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents

OpenAIRE

Agrawal, Amit; Robertson, John FR; Cheung, KL

2006-01-01

Abstract Background High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced ...

Endocrine neoplasms in familial syndromes of hyperparathyroidism.

Science.gov (United States)

Li, Yulong; Simonds, William F

2016-06-01

Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. © 2016 Society for Endocrinology.

Highlighting Indication of extracorporeal membrane oxygenation in endocrine emergencies.

Science.gov (United States)

Chao, Anne; Wang, Chih-Hsien; You, Hao-Chun; Chou, Nai-Kwoun; Yu, Hsi-Yu; Chi, Nai-Hsin; Huang, Shu-Chien; Wu, I-Hui; Tseng, Li-Jung; Lin, Ming-Hsien; Chen, Yih-Sharng

2015-08-24

Extracorporeal membrane oxygenation (ECMO) has been repeatedly used to rescue patients with cardiopulmonary arrest. However, its clinical utility in endocrine emergencies remains unclear. Herein, we describe a case series of 12 patients presenting with refractory shock secondary to endocrine emergencies who were rescued by ECMO support. Patients were identified between 2005 and 2012 from our ECMO registry. The diagnostic distribution was as follows: pheochromocytoma crisis (n = 4), thyroid storm (n = 5), and diabetic ketoacidosis (n = 3). The initial presentation of pheochromocytoma crisis was indistinguishable from acute myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension and limb ischemia. Thyroid storm was characterized by hyperbilirubinemia and severe gastrointestinal bleeding, whereas neurological symptoms were common in diabetic ketoacidosis. The clinical outcomes of patients with endocrine emergencies were compared with those of 80 cases with AMI who received ECMO because of cardiogenic shock. The cardiac function and the general conditions showed a significantly faster recovery in patients with endocrine emergencies than in those with AMI. We conclude that ECMO support can be clinically useful in endocrine emergencies. The screening of endocrine diseases should be considered during the resuscitation of patients with refractory circulatory shock.

Efficiencies of freshwater and estuarine constructed wetlands for phenolic endocrine disruptor removal in Taiwan.

Science.gov (United States)

Hsieh, Chi-Ying; Yang, Lei; Kuo, Wen-Chien; Zen, Yi-Peng

2013-10-01

We examined the distribution and removal efficiencies of phenolic endocrine disruptors (EDs), namely nonylphenol diethoxylates (NP2EO), nonylphenol monoethoxylates (NP1EO), nonylphenol (NP), and octylphenol (OP), in wastewater treated by estuarine and freshwater constructed wetland systems in Dapeng Bay National Scenic Area (DBNSA) and along the Dahan River in Taiwan. Water samples were taken bimonthly at 30 sites in three estuarine constructed wetlands (Datan, Pengcun and Linbian right bank (A and B)) in DBNSA, for eight sampling campaigns. The average removal efficiencies were in the range of 3.13-97.3% for wetlands in DBNSA. The highest average removal occurred in the east inlet to the outlet of the Tatan wetland. The most frequently detected compound was OP (57.7%), whose concentration was up to 1458.7 ng/L in DBNSA. NP was seen in only 20.5% of the samples. The temporal variation of EDs showed a decrease across seasons, where summer>spring>winter>autumn in these constructed wetlands. The removal efficiencies of EDs by estuarine wetlands, in decreasing order, were Datan>Pengcun>Linbian right bank in DBNSA. Water samples collected at 18 sites in three freshwater constructed wetlands (Daniaopi, Hsin-Hai I, and Hsin-Hai II) along the riparian area of Dahan River. NP2EO was the most abundant compound, with a concentration of up to 11,200 ng/L. Removal efficiencies ranged from 55% to 91% for NP1EO, NP2EO, and NP in Hsin-Hai I. The average removal potential of EDs in freshwater constructed wetlands, in decreasing order, was Hsin-Hai II>Daniaopi>Hsin-Hai I constructed wetlands. The lowest concentrations of the selected compounds were observed in the winter. The highest removal efficiency of the selected phenolic endocrine disruptors was achieved by Hsin-Hai I wetland. The calculated risk quotients used to evaluate the ecological risk were up to 30 times higher in the freshwater wetlands along Dahan River than in the estuarine (DBNSA) constructed wetlands, indicating

Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil

OpenAIRE

Furtado,CM; von Mühlen,C

2015-01-01

The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs) are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs thr...

Antiplasmodial activity of some phenolic compounds from ...

African Journals Online (AJOL)

Background: Plasmodium falciparum, one of the causative agents of malaria, has high adaptability through mutation and is resistant to many types of anti-malarial drugs. This study presents an in vitro assessment of the antiplasmodial activity of some phenolic compounds isolated from plants of the genus Allanblackia.

Yeast Estrogen Screen Assay as a Tool for Detecting Estrogenic Activity in Water Bodies

Directory of Open Access Journals (Sweden)

Mirjana Bistan

2012-01-01

Full Text Available The presence of endocrine-disrupting compounds in wastewater, surface water, groundwater and even drinking water has become a major concern worldwide, since they negatively affect wildlife and humans. Therefore, these substances should be effectively removed from effluents before they are discharged into surface water to prevent pollution of groundwater, which can be a source of drinking water. Furthermore, an efficient control of endocrine-disrupting compounds in wastewater based on biological and analytical techniques is required. In this study, a yeast estrogen screen (YES bioassay has been introduced and optimized with the aim to assess potential estrogenic activity of waters. First, assay duration, concentration of added substrate to the assay medium and wavelength used to measure the absorbance of the substrate were estimated. Several compounds, such as 17-β-estradiol, 17-α-ethinylestradiol, bisphenol A, nonylphenol, genisteine, hydrocortisone, dieldrin, atrazine, methoxychlor, testosterone and progesterone were used to verify its specificity and sensitivity. The optimized YES assay was sensitive and responded specifically to the selected estrogenic and nonestrogenic compounds in aqueous samples. Potential estrogenicity of influent and effluent samples of two wastewater treatment plants was assessed after the samples had been concentrated by solid-phase extraction (SPE procedure using Oasis® HLB cartridges and methanol as eluting solvent. Up to 90 % of relative estrogenic activity was detected in concentrated samples of influents to wastewater treatment plants and estrogenic activity was still present in the concentrated effluent samples. We found that the introduced YES assay is a suitable screening tool for monitoring the potential estrogenicity of effluents that are discharged into surface water.

Application of endocrine disruptor screening program fish short-term reproduction assay: Reproduction and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus) exposed to Bermuda pond sediment.

Science.gov (United States)

Fort, Douglas J; Mathis, Michael; Fort, Chelsea E; Fort, Hayley M; Bacon, Jamie P

2015-06-01

A modified tier 1 Endocrine Disruptor Screening Program (EDSP) 21-d fish short-term reproduction assay (FSTRA) was used to evaluate the effects of sediment exposure from freshwater and brackish ponds in Bermuda on reproductive fecundity and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus). Reproductively active male and female fish were exposed to control sediment and sediment from 2 freshwater ponds (fathead minnow) and 2 marine ponds (killifish) contaminated with polyaromatic hydrocarbons and metals via flow-through exposure for 21 d. Reproductive fecundity was monitored daily. At termination, the status of the reproductive endocrine system was assessed by the gonadosomatic index, gonadal histology, plasma steroids (estrogen [E2], testosterone [T], and 11-ketotestosterone [11-KT]), steroidogenic enzymes (aromatase and combined 3β/17β -hydroxysteroid dehydrogenase [3β/17β-HSD]), and plasma vitellogenin (VTG). Decreased reproductive fecundity, lower male body weight, and altered endocrinological measures of reproductive status were observed in both species. Higher plasma T levels in female minnows and 11-KT levels in both male and female minnows and female killifish exposed to freshwater and brackish sediments, respectively. Decreased female E2 and VTG levels and gonadal cytochrome P19 (aromatase) activity were also found in sediment exposed females from both species. No effect on female 3β/17β-HSD activity was found in either species. The FSTRA provided a robust model capable of modification to evaluate reproductive effects of sediment exposure in fish. © 2015 SETAC.

Appetite-Controlling Endocrine Systems in Teleosts

Science.gov (United States)

Rønnestad, Ivar; Gomes, Ana S.; Murashita, Koji; Angotzi, Rita; Jönsson, Elisabeth; Volkoff, Hélène

2017-01-01

Mammalian studies have shaped our understanding of the endocrine control of appetite and body weight in vertebrates and provided the basic vertebrate model that involves central (brain) and peripheral signaling pathways as well as environmental cues. The hypothalamus has a crucial function in the control of food intake, but other parts of the brain are also involved. The description of a range of key neuropeptides and hormones as well as more details of their specific roles in appetite control continues to be in progress. Endocrine signals are based on hormones that can be divided into two groups: those that induce (orexigenic), and those that inhibit (anorexigenic) appetite and food consumption. Peripheral signals originate in the gastrointestinal tract, liver, adipose tissue, and other tissues and reach the hypothalamus through both endocrine and neuroendocrine actions. While many mammalian-like endocrine appetite-controlling networks and mechanisms have been described for some key model teleosts, mainly zebrafish and goldfish, very little knowledge exists on these systems in fishes as a group. Fishes represent over 30,000 species, and there is a large variability in their ecological niches and habitats as well as life history adaptations, transitions between life stages and feeding behaviors. In the context of food intake and appetite control, common adaptations to extended periods of starvation or periods of abundant food availability are of particular interest. This review summarizes the recent findings on endocrine appetite-controlling systems in fish, highlights their impact on growth and survival, and discusses the perspectives in this research field to shed light on the intriguing adaptations that exist in fish and their underlying mechanisms. PMID:28458653

The role of phytoplankton composition, biomass and cell volume in accumulation and transfer of endocrine disrupting compounds in the Southern Baltic Sea (The Gulf of Gdansk)

International Nuclear Information System (INIS)

Staniszewska, Marta; Nehring, Iga; Zgrundo, Aleksandra

2015-01-01

Endocrine disrupting compounds (EDCs) like bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP) are introduced to the trophic webs through among others phytoplankton. This paper describes BPA, OP and NP concentrations in phytoplankton in the Gulf of Gdansk (Southern Baltic Sea) in the years 2011–2012. The assays of BPA, OP and NP in samples were performed using HPLC with fluorescence detection. The concentrations of BPA, the most commonly used of the three compounds, were over ten times higher than OP and NP concentrations. The concentrations of the studied EDCs in phytoplankton from the Gulf of Gdansk depended on anthropogenic factors and on phytoplankton properties (species composition, biomass, volume). An increase in phytoplankton biomass did not always result in an increase of BPA, OP and NP concentrations. However, the load of the studied EDCs accumulated in phytoplankton biomass increase with a rise of biomass. An increase in BPA, OP and NP concentrations was effected by biomass growth and the proportions ofciliates, dinoflagellates, diatoms and green algae. A strong positive correlation between OP and NP concentrations and negative correlation between BPA concentrations and biomass of organisms with cells measuring <1000 μm"3 in volume results from the differing properties of these compounds. - Highlights: • The concentration of BPA was higher than OP, NP in phytoplankton. • The concentration of BPA, OP, NP depended on phytoplankton properties. • The load of BPA, OP, NP accumulated with phytoplankton increase with a rise of the biomass. • Ciliates, dinoflagellates, diatoms, green algae accumulated the most BPA, OP, NP. • Higher biomass of smaller volume organisms more accumulated OP, NP and less BPA. - The study has shown that factors affecting concentration of BPA, NP and OP were: species composition, biomass, volume and location of sampling station.

Radiosensitization of Escherichia coli and Salmonella typhi in presence of active compounds

International Nuclear Information System (INIS)

Lacroix, M.; Chiasson, F.; Borsa, J.; Ouattara, B.

2004-01-01

The radiosensitization of Escherichia coli and Salmonella typhi in ground beef was evaluated in the presence of 18 active compounds. Medium fat ground beef (23% fat) was inoculated with E. coli or S. typhi and each active compound was added separately at various concentrations. For E. coli, the most efficient compounds were trans-cinnamaldehyde, thymol and thyme. For S. typhi, the most efficient compounds was trans-cinnamaldehyde, carvacrol and thymol. The addition of tetrasodium pyrophosphate, carvacrol and ascorbic acid had no effect on the irradiation sensitivity of E. coli. For S. typhi, only ascorbic acid had no effect

Radiosensitization of Escherichia coli and Salmonella typhi in presence of active compounds

Energy Technology Data Exchange (ETDEWEB)

Lacroix, M. E-mail: monique.lacroix@inrs-iaf.uquebec.ca; Chiasson, F.; Borsa, J.; Ouattara, B

2004-10-01

The radiosensitization of Escherichia coli and Salmonella typhi in ground beef was evaluated in the presence of 18 active compounds. Medium fat ground beef (23% fat) was inoculated with E. coli or S. typhi and each active compound was added separately at various concentrations. For E. coli, the most efficient compounds were trans-cinnamaldehyde, thymol and thyme. For S. typhi, the most efficient compounds was trans-cinnamaldehyde, carvacrol and thymol. The addition of tetrasodium pyrophosphate, carvacrol and ascorbic acid had no effect on the irradiation sensitivity of E. coli. For S. typhi, only ascorbic acid had no effect.

Toxicology of perfluorinated compounds

Energy Technology Data Exchange (ETDEWEB)

Stahl, Thorsten [Hessian State Laboratory, Wiesbaden (Germany); Mattern, Daniela; Brunn, Hubertus [Hessian State Laboratory, Giessen (Germany)

2011-12-15

Perfluorinated compounds [PFCs] have found a wide use in industrial products and processes and in a vast array of consumer products. PFCs are molecules made up of carbon chains to which fluorine atoms are bound. Due to the strength of the carbon/fluorine bond, the molecules are chemically very stable and are highly resistant to biological degradation; therefore, they belong to a class of compounds that tend to persist in the environment. These compounds can bioaccumulate and also undergo biomagnification. Within the class of PFC chemicals, perfluorooctanoic acid and perfluorosulphonic acid are generally considered reference substances. Meanwhile, PFCs can be detected almost ubiquitously, e.g., in water, plants, different kinds of foodstuffs, in animals such as fish, birds, in mammals, as well as in human breast milk and blood. PFCs are proposed as a new class of 'persistent organic pollutants'. Numerous publications allude to the negative effects of PFCs on human health. The following review describes both external and internal exposures to PFCs, the toxicokinetics (uptake, distribution, metabolism, excretion), and the toxicodynamics (acute toxicity, subacute and subchronic toxicities, chronic toxicity including carcinogenesis, genotoxicity and epigenetic effects, reproductive and developmental toxicities, neurotoxicity, effects on the endocrine system, immunotoxicity and potential modes of action, combinational effects, and epidemiological studies on perfluorinated compounds). (orig.)

Endocrine-disrupting Chemicals: Review of Toxicological Mechanisms Using Molecular Pathway Analysis

Science.gov (United States)

Yang, Oneyeol; Kim, Hye Lim; Weon, Jong-Il; Seo, Young Rok

2015-01-01

Endocrine disruptors are known to cause harmful effects to human through various exposure routes. These chemicals mainly appear to interfere with the endocrine or hormone systems. As importantly, numerous studies have demonstrated that the accumulation of endocrine disruptors can induce fatal disorders including obesity and cancer. Using diverse biological tools, the potential molecular mechanisms related with these diseases by exposure of endocrine disruptors. Recently, pathway analysis, a bioinformatics tool, is being widely used to predict the potential mechanism or biological network of certain chemicals. In this review, we initially summarize the major molecular mechanisms involved in the induction of the above mentioned diseases by endocrine disruptors. Additionally, we provide the potential markers and signaling mechanisms discovered via pathway analysis under exposure to representative endocrine disruptors, bisphenol, diethylhexylphthalate, and nonylphenol. The review emphasizes the importance of pathway analysis using bioinformatics to finding the specific mechanisms of toxic chemicals, including endocrine disruptors. PMID:25853100

Endocrine manifestations of celiac disease

Directory of Open Access Journals (Sweden)

R Philip

2012-01-01

Full Text Available Background: Celiac disease can have extra gastrointestinal tract (GIT presentations, most of which are endocrine. The aim of this study was to present patients diagnosed to have celiac disease from an endocrine department and to study the prevalence of endocrinopathies in celiac disease. Materials and Methods: A total of 36 patients from the endocrinology department (LLRM Medical College, Meerut between January 2011 and July 2012 and who were diagnosed to have celiac disease were included in the study. Results: Short stature was the commonest presentation (25%, other presentations included short stature and delayed puberty (20%, delayed puberty (11%, screening for celiac disease in type-1 DM patients (17%, rickets (6%, anemia not responding to oral therapy (6%, type-1 DM with recurrent hypoglycaemia (6%, and osteomalacia (3%. The endocrine manifestations include (after complete evaluation short stature (58%, delayed puberty (31%, elevated alkaline phospahatase (67%, low calcium (22%, X-rays suggestive of osteomalacia or rickets (8%, capopedal spasm (6%, and night blindness (6%. Anti-TPO antibody positivity was found in 53%, hypothyroidism in 28%, subclinical hypothyroidism in 17%, and type-1 DM in 25% of the patients. A total of 14% patients had no GI symptoms. Conclusion: Celiac disease is an endocrine disrupter as well as the great masquerader having varied presentations including short stature, delayed puberty, and rickets. Some patients who have celiac disease may not have any GI symptoms, making the diagnosis all the more difficult. Also, there is significant incidence of celiac disease with hypothyroidism and type-1 DM, making screening for it important in these diseases.

Distribution and accumulation of endocrine-disrupting chemicals and pharmaceuticals in wastewater irrigated soils in Hebei, China

International Nuclear Information System (INIS)

Chen Feng; Ying Guangguo; Kong Lingxiao; Wang Li; Zhao Jianliang; Zhou Lijun; Zhang Lijuan

2011-01-01

This study investigated the occurrence of 43 emerging contaminants including 9 endocrine-disrupting chemicals and 34 pharmaceuticals in three sites in Hebei Province, north China. Each site has a wastewater irrigated plot and a separate groundwater irrigated plot for comparison purpose. The results showed that the concentrations of the target compounds in the wastewater irrigated soils were in most cases higher than those in the groundwater irrigated soils. Among the 43 target compounds, nine compounds bisphenol-A, triclocarban, triclosan, 4-nonylphenol, salicylic acid, oxytetracycline, tetracycline, trimethoprim and primidone were detected at least once in the soils. Preliminary environmental risk assessment showed that triclocarban might pose high risks to terrestrial organisms while the other detected compounds posed minimal risks. Irrigation with wastewater could lead to presence or accumulation of some emerging contaminants to some extent in irrigated soils. - Highlights: → Some EDCs and PPCPs were detected in the wastewater irrigated soils. → Application of reclaimed water could lead to accumulation of some compounds. → Groundwater has been contaminated by some compounds. → Triclocarban posed high risks to soil organisms. - Application of reclaimed wastewater on agricultural land could lead to the presence or accumulation of wastewater-related contaminants in soils.

Distribution and accumulation of endocrine-disrupting chemicals and pharmaceuticals in wastewater irrigated soils in Hebei, China

Energy Technology Data Exchange (ETDEWEB)

Feng, Chen [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Ying Guangguo, E-mail: guangguo.ying@gmail.com [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Lingxiao, Kong [Institute of Plant Protection, Hebei Academy of Agriculture and Forestry Science, Baoding 07100 (China); Li, Wang; Jianliang, Zhao; Lijun, Zhou; Lijuan, Zhang [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China)

2011-06-15

This study investigated the occurrence of 43 emerging contaminants including 9 endocrine-disrupting chemicals and 34 pharmaceuticals in three sites in Hebei Province, north China. Each site has a wastewater irrigated plot and a separate groundwater irrigated plot for comparison purpose. The results showed that the concentrations of the target compounds in the wastewater irrigated soils were in most cases higher than those in the groundwater irrigated soils. Among the 43 target compounds, nine compounds bisphenol-A, triclocarban, triclosan, 4-nonylphenol, salicylic acid, oxytetracycline, tetracycline, trimethoprim and primidone were detected at least once in the soils. Preliminary environmental risk assessment showed that triclocarban might pose high risks to terrestrial organisms while the other detected compounds posed minimal risks. Irrigation with wastewater could lead to presence or accumulation of some emerging contaminants to some extent in irrigated soils. - Highlights: > Some EDCs and PPCPs were detected in the wastewater irrigated soils. > Application of reclaimed water could lead to accumulation of some compounds. > Groundwater has been contaminated by some compounds. > Triclocarban posed high risks to soil organisms. - Application of reclaimed wastewater on agricultural land could lead to the presence or accumulation of wastewater-related contaminants in soils.

Myopathies of endocrine disorders: A prospective clinical and biochemical study

Directory of Open Access Journals (Sweden)

Vikas Sharma

2014-01-01

Full Text Available Introduction: Major categories of endocrine myopathy include those associated with: Adrenal dysfunction (as in Cushing′s disease or steroid myopathy; thyroid dysfunction (as in myxedema coma or thyrotoxic myopathy; vitamin D deficiency; parathyroid dysfunction; and pituitary dysfunction. Steroid myopathy is the most common endocrine myopathy. Objective: To study the etiology, varied presentations, and outcome after therapy of patients with endocrine myopathies. Materials and Methods: Myopathy was evaluated by the standard clinical procedures: Detailed clinical history, manual muscle strength testing, and creatine phosphokinase (CPK. Endocrine disorders were diagnosed as per clinical features and biochemical parameters. The treatment was given to patients as per underlying endocrine disease. Myopathy was assessed before and after treatment. Results: Out of the 37 patients who were diagnosed with endocrine myopathies, thyroid dysfunction was the most common cause (17 cases, followed by vitamin D deficiency in nine, adrenal dysfunction in six, parathyroid dysfunction in three, and pituitary dysfunction in two. Some patients had atypical presentation (repeated falls in one, tongue fasciculations in one, neck weakness in five, one with ptosis and facial weakness, asymmetrical onset in one, and calf hypertrophy in one. The serum creatine kinase (CK concentration did not correlate with muscle weakness. Following the treatment regimen which was specific for a given myopathy, 26 patients recovered fully. Conclusion: We found varied clinical presentations of endocrine myopathies. All the patients with neuromuscular complaints should be investigated for endocrine causes because significant number of them recovers fully with specific treatment.

Endocrine and metabolic disorders associated with human immune deficiency virus infection.

Science.gov (United States)

Unachukwu, C N; Uchenna, D I; Young, E E

2009-01-01

Many reports have described endocrine and metabolic disorders in the human immunodeficiency virus (HIV) infection. This article reviewed various reports in the literature in order to increase the awareness and thus the need for early intervention when necessary. Data were obtained from MEDLINE, Google search and otherjournals on 'HIV, Endocrinopathies/Metabolic Disorders' from 1985 till 2007. Studies related to HIV associated endocrinopathies and metabolic disorders in the last two decades were reviewed. Information on epidemiology, pathogenesis, diagnosis and treatment of the target organ endocrinopathies and metabolic disorders in HIV/AIDS were extracted from relevant literature. Endocrine and metabolic disturbances occur in the course of HIV infection. Pathogenesis includes direct infection of endocrine glands by HIV or opportunistic organisms, infiltration by neoplasms and side effects of drugs. Adrenal insufficiency is the commonest HIV endocrinopathy with cytomegalovirus adrenalitis occurring in 40-88% of cases. Thyroid dysfunction may occur as euthyroid sick syndrome or sub-clinical hypothyroidism. Hypogonadotrophic dysfunction accounts for 75% of HIV-associated hypogonadism, with prolonged amenorrhoea being three times more likely in the women. Pancreatic dysfunction may result in hypoglycaemia or diabetes mellitus (DM). Highly active antiretroviral therapy (HAART) especially protease inhibitors has been noted to result in insulin resistance and lipodystrophy. Virtually every endocrine organ is involved in the course of HIV infection. Detailed endocrinological and metabolic evaluation and appropriate treatment is necessary in the optimal management of patients with HIV infection in our environment.

Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens

DEFF Research Database (Denmark)

Boberg, Julie; Mandrup, Karen; Jacobsen, Pernille Rosenskjold

2013-01-01

Dietary phytoestrogens may prevent certain human diseases, but endocrine activity has been reported in animal studies. Sprague-Dawley rats were exposed perinatally to a 1-, 10- or 100-fold “high human dietary intake” mixture of 12 phytoestrogens consisting of mainly the lignan secoisolarici resinol...... genes in testis and prostate were unaffected. Decreased serum estradiol was seen in genistein-exposed dams. This study indicated adverse effects at high intake levels in rats, but does not provide evidence for risk of phytoestrogen-mediated endocrine disruption at normal human dietary consumption levels...

Copper, manganese, zinc and magnesium content in endocrine organs of horses, cattle and pigs

Energy Technology Data Exchange (ETDEWEB)

Stoeckl, W; Weiser, M

1968-07-01

In horses, cattle and pigs the content of copper, manganese, zinc and magnesium was determined in the pituitary, adrenal, thyroid, pancreas, ovary and thymus, and the mean values and standard deviations were determined. Within the same animal there were considerable variations of each element as between the different endocrine glands and similar significant differences from one animal to another. These results are not extensive enough to permit any conclusion on the relationship of the examined elements to the endocrine function or their influence on the enzyme activity. 1 table.

Effect of vanadium compounds on acid phosphatase activity

OpenAIRE

Vescina, Cecilia M.; Sálice, Viviana C.; Cortizo, Ana María; Etcheverry, Susana B.

1996-01-01

The direct effect of different vanadium compounds on acid phosphatase (ACP) activity was investigated. Vanadate and vanadyl but not pervanadate inhibited the wheat germ ACP activity. These vanadium derivatives did not alter the fibroblast Swiss 3T3 soluble fraction ACP activity. Using inhibitors of tyrosine phosphatases (PTPases), the wheat germ ACP was partially characterized as a PTPase. This study suggests that the inhibitory ability of different vanadium derivatives to modulate ACP activi...

Sarcopenia and Age-Related Endocrine Function

Directory of Open Access Journals (Sweden)

Kunihiro Sakuma

2012-01-01

Full Text Available Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia.

Nigerian Endocrine Practice

African Journals Online (AJOL)

The journal accepts original contributions related to the practice and science of clinical endocrinology, articles updating the clinical endocrinologist on current areas of interest in the diagnosis and treatment of endocrine disorders, articles discussing dilemma facing endocrinologists in the clinical, social, and ethical arena of ...

Improved removal of estrogenic and pharmaceutical compounds in sewage effluent by full scale granular activated carbon: impact on receiving river water.

Science.gov (United States)

Grover, D P; Zhou, J L; Frickers, P E; Readman, J W

2011-01-30

Sewage effluents are widely recognised as the main source of emerging contaminants, such as endocrine disrupting chemicals (EDCs) and pharmaceuticals in surface waters. A full-scale granular activated carbon (GAC) plant has been installed as an advanced technology for the removal of these contaminants, in a major sewage treatment works (STW) in South-West England as part of the UK National Demonstration Programme for EDCs. This study presented for the first time, an assessment of the impact of a recently commissioned, post-tertiary GAC plant in the removal of emerging contaminants in a working STW. Through regular sampling followed by solid-phase extraction and analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS), a significant reduction in the concentrations of steroidal estrogens was observed (>43-64%). In addition, significant reductions were observed for many of the pharmaceutical compounds such as mebeverine (84-99%), although the reduction was less dramatic for some of the more widely used pharmaceuticals analysed, including carbamazepine and propranolol (17-23%). Copyright © 2010 Elsevier B.V. All rights reserved.

REST represses a subset of the pancreatic endocrine differentiation program

DEFF Research Database (Denmark)

Martin, David; Kim, Yung-Hae; Sever, Dror

2015-01-01

in neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic...... endocrine cells, which are molecularly close to neurons. We show that Rest is widely expressed in pancreas progenitors and that it is down-regulated in differentiated endocrine cells. Sustained expression of REST in Pdx1(+) progenitors impairs the differentiation of endocrine-committed Neurog3...

Biologically Active Compounds of Plant Foods: Prospective Impact ...

African Journals Online (AJOL)

On the other hand, other biologically active compounds impair health by ... of essential elements through different mechanisms and giving astringent taste, odor, ... The health benefits of selected substances from Ethiopian food crops need to ...

Synthesis of Some Novel Thiadiazole Derivative Compounds and Screening Their Antidepressant-Like Activities

Directory of Open Access Journals (Sweden)

Nafiz Öncü Can

2018-03-01

Full Text Available Novel thiadiazole derivatives were synthesized through the reaction of acetylated 2-aminothiadiazole and piperazine derivatives. The chemical structures of the compounds were clarified by Infrared Spectroscopy (IR, 1H Nuclear Magnetic Resonance Spectroscopy (1H-NMR, 13C Nuclear Magnetic Resonance Spectroscopy (13C-NMR and Electronspray Ionisation Mass Spectroscopy (ESI-MS spectroscopic methods. Antidepressant-like activities were evaluated by the tail-suspension (TST and modified forced swimming (MFST methods. Besides, possible influence of the test compounds on motor activities of the animals were examined by activity cage tests. In the TST, administration of the compounds 2c, 2d, 2e, 2f, 2g and 2h significantly decreased the immobility time of mice regarding the control values. Further, in the MFST, the same compounds reduced the total number of immobility behaviors while increasing swimming performance. However, no change was observed in the total number of climbing behaviors. These data suggested that compounds 2c, 2d, 2e, 2f, 2g and 2h possess notable antidepressant-like activities. Reference drug fluoxetine (10 mg/kg was also exhibited its antidepressant activity, as expected. No significant difference was seen between the locomotor activity values of the test groups signifying that observed antidepressant-like activities are specific. Theoretical calculation of absorption, distribution, metabolism, excretion (ADME properties for the obtained compounds were performed and obtained data supported the antidepressant-like potential of these novel thiadiazole derivatives.

Selected endocrine disrupting compounds (vinclozolin, flutamide, ketoconazole and dicofol): Effects on survival, occurrence of males, growth, molting and reproduction of Daphnia magna

Czech Academy of Sciences Publication Activity Database

Haeba, M. H.; Hilscherová, Klára; Mazurová, E.; Bláha, Luděk

2008-01-01

Roč. 15, č. 3 (2008), s. 222-227 ISSN 0944-1344 Institutional research plan: CEZ:AV0Z60050516 Keywords : Daphnia magna * dicofol * endocrine disruption Subject RIV: EF - Botanics Impact factor: 2.492, year: 2008

Treatment of wastewater and sludge, and decomposition of endocrine disrupting chemicals with radiation

International Nuclear Information System (INIS)

Kudo, Hisaaki

2006-01-01

This country report describes the past and current research activities in Japan on radiation treatment of wastewater and sludge carried out by early 90s, and decomposition of endocrine disrupting chemicals that is going-on. (author)

Examining the biodegradation of endocrine disrupting bisphenol A and nonylphenol in WWTPs

DEFF Research Database (Denmark)

Press-Kristensen, Kåre; Lindblom, Erik Ulfson; Schmidt, Jens Ejbye

2008-01-01

The aim of this work was to examine biodegradation of the endocrine disrupting chemicals bisphenol A (BPA) and nonylphenol (NP) in activated sludge. Experiments were performed in a pilot wastewater treatment plant (WWTP) in Copenhagen, Denmark. During standard operation the BPA concentration...

Conserved genetic pathways controlling the development of the diffuse endocrine system in vertebrates and Drosophila.

Science.gov (United States)

Hartenstein, Volker; Takashima, Shigeo; Adams, Katrina L

2010-05-01

The midgut epithelium is formed by absorptive enterocytes, secretory cells and endocrine cells. Each of these lineages is derived from the pluripotent progenitors that constitute the embryonic endoderm; the mature midgut retains pools of self-renewing stem cells that continue to produce all lineages. Recent findings in vertebrates and Drosophila shed light on the genetic mechanism that specifies the fate of the different lineages. A pivotal role is played by the Notch signaling pathway that, in a manner that appears to be very similar to the way in which Notch signaling selects neural progenitors within the neurectoderm, distinguishes the fate of secretory/endocrine cells and enterocytes. Proneural genes encoding bHLH transcription factors are expressed and required in prospective endocrine cells; activation of the Notch pathways restricts the number of these cells and promotes enterocyte development. In this review we compare the development of the intestinal endocrine cells in vertebrates and insects and summarize recent findings dealing with genetic pathways controlling this cell type. Copyright 2009. Published by Elsevier Inc.

Role of ozone and granular activated carbon in the removal of mutagenic compounds.

Science.gov (United States)

Bourbigot, M M; Hascoet, M C; Levi, Y; Erb, F; Pommery, N

1986-01-01

The identification of certain organic compounds in drinking water has led water treatment specialists to be increasingly concerned about the eventual risks of such pollutants to the health of consumers. Our experiments focused on the role of ozone and granular activated carbon in removing mutagenic compounds and precursors that become toxic after chlorination. We found that if a sufficient dose of ozone is applied, its use does not lead to the creation of mutagenic compounds in drinking water and can even eliminate the initial mutagenicity of the water. The formation of new mutagenic compounds seems to be induced by ozonation that is too weak, although these mutagens can be removed by GAC filtration. Ozone used with activated carbon can be one of the best means for eliminating the compounds contributing to the mutagenicity of water. A combined treatment of ozone and activated carbon also decreases the chlorine consumption of the treated water and consequently reduces the formation of chlorinated organic compounds. PMID:3816720

Estrogenic compounds decrease growth hormone receptor abundance and alter osmoregulation in Atlantic salmon

Science.gov (United States)

Lerner, Darren T.; Sheridan, Mark A.; McCormick, Stephen D.

2012-01-01

Exposure of Atlantic salmon smolts to estrogenic compounds is shown to compromise several aspects of smolt development. We sought to determine the underlying endocrine mechanisms of estrogen impacts on the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis. Smolts in freshwater (FW) were either injected 3 times over 10 days with 2 μg g−1 17β-estradiol (E2) or 150 μg g−1 4-nonylphenol (NP). Seawater (SW)-acclimated fish received intraperitoneal implants of 30 μg g−1 E2 over two weeks. Treatment with these estrogenic compounds increased hepatosomatic index and total plasma calcium. E2 and NP reduced maximum growth hormone binding by 30–60% in hepatic and branchial membranes in FW and SW, but did not alter the dissociation constant. E2 and NP treatment decreased plasma levels of IGF-I levels in both FW and SW. In FW E2 and NP decreased plasma GH whereas in SW plasma GH increased after E2 treatment. Compared to controls, plasma chloride concentrations of E2-treated fish were decreased 5.5 mM in FW and increased 10.5 mM in SW. There was no effect of NP or E2 on gill sodium–potassium adenosine triphosphatase (Na+/K+-ATPase) activity in FW smolts, whereas E2 treatment in SW reduced gill Na+/K+-ATPase activity and altered the number and size of ionocytes. Our data indicate that E2 downregulates the GH/IGF-I-axis and SW tolerance which may be part of its normal function for reproduction and movement into FW. We conclude that the mechanism of endocrine disruption of smolt development by NP is in part through alteration of the GH/IGF-I axis via reduced GH receptor abundance.

Endocrine disruption mechanism of o,p'-DDT in mature male tilapia (Oreochromis niloticus)

International Nuclear Information System (INIS)

Leanos-Castaneda, Olga; Kraak, Glen van der; Rodriguez-Canul, Rossanna; Gold, G.

2007-01-01

The aim of the present study was to evaluate, in vivo, the potential of o,p'-DDT to disrupt the endocrine system of mature male tilapia. In particular, the possibility that o,p'-DDT effects were mediated directly via the estrogen receptor (ER). Compounds with known ability to bind to the ER were employed: estradiol to induce and tamoxifen to inhibit the estrogenic effects result of the activation of the ER. In addition, an aromatase inhibitor, 4-hydrxyandrostenedione (4-OHA), was used to assess the ability of o,p'-DDT to induce estrogenic effects in a surrounding of low estradiol concentration. The effects of estradiol and o,p'-DDT were studied alone or in the presence of tamoxifen or 4-OHA at the end of a 12-day period of exposure. The main endpoints measured were plasma alkaline-labile phosphorous (ALP; an indirect indicator of vitellogenin), estradiol, testosterone and o,p'-DDT. It was found that o,p'-DDT was able to induce the vitellogenesis (measured as plasma ALP increase) and decrease the circulating levels of estradiol and testosterone. Interestingly, o,p'-DDT kept this ability in whole fish with low concentrations of estradiol which would exclude endogenous estradiol as indirect mediator of the estrogenic effects induced by o,p'-DDT. In addition, the plasma concentration of o,p'-DDT, instead of that of estradiol, was closely related to the plasma ALP increase induced by o,p'-DDT. This indicates that o,p'-DDT could have directly activated the vitellogenesis. The antiestrogenic action of tamoxifen to inhibit the vitellogenesis and the decrease on plasma estradiol induced by o,p'-DDT indicates that o,p'-DDT can bind directly to the ER. In conclusion, this in vivo study shows that o,p'-DDT has the potential to disrupt the endocrine system and strongly supports that the estrogenic actions of o,p'-DDT involve binding to the ER

Endocrine function over time in patients with myotonic dystrophy type 1

DEFF Research Database (Denmark)

Dahlqvist, Julia Rebecka; Ørngreen, M C; Witting, N

2015-01-01

BACKGROUND AND PURPOSE: Patients with myotonic dystrophy type 1 (DM1) have an increased incidence of endocrine dysfunction. In this study, the temporal evolution of endocrine dysfunction in patients with DM1 was investigated. METHODS: Endocrine function was assessed in 68 patients with DM1, in whom...... endocrine function had been followed, on average, for 8 years. The endocrine function was assessed by measuring the concentration of hormones and metabolites in blood and by validating libido with questionnaires. RESULTS: At baseline, 30 of the 68 patients presented with at least one hormonal dysfunction....... When re-evaluated after 8 years, 57 of 68 patients had endocrine dysfunction. Diabetic patients had increased from one to four. At follow-up, hyperparathyroidism occurred in 25% and abnormal thyroid-stimulating hormone in 21%, compared with 14% and 9% at baseline. Sixteen of 33 men had increased...

Integrative assessment of enantioselectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids

Energy Technology Data Exchange (ETDEWEB)

Zhao Meirong [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Chen Fang [College of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou 310018 (China); Wang Cui; Zhang Quan [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Gan Jianying [Department of Environmental Sciences, University of California, Riverside, CA 92521 (United States); Liu Weiping, E-mail: wliu@zjut.edu.c [Research Center of Environmental Science, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China)

2010-05-15

The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (-)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study. - Chiral contaminants should consider multiple effects and relate directions of enantioselectivity to their interplaying processes.

Integrative assessment of enantioselectivity in endocrine disruption and immunotoxicity of synthetic pyrethroids

International Nuclear Information System (INIS)

Zhao Meirong; Chen Fang; Wang Cui; Zhang Quan; Gan Jianying; Liu Weiping

2010-01-01

The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (-)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study. - Chiral contaminants should consider multiple effects and relate directions of enantioselectivity to their interplaying processes.

Paediatric Endocrine Disorders at the University College Hospital ...

African Journals Online (AJOL)

Background: Until recently, most published research focus more on infectious diseases and malnutrition giving the impression that endocrine disorders are uncommon. Reports on endocrine disorders in children in developing countries are few compared to developed countries reflecting the different level of prevalence in ...

Ductuloinsular tumors of the pancreas - Endocrine tumors with entrapped nonneoplastic ductules

NARCIS (Netherlands)

van Eeden, Susanne; de Leng, Wendy W. J.; Offerhaus, G. Johan A.; Morsink, Folkert H.; Weterman, Marian A. J.; de Krijger, Ronald R.; Klöppel, Günter; Klimstra, David S.

2004-01-01

Rare pancreatic neoplasms have been reported that show both endocrine and exocrine differentiation in the neoplastic components. In addition, pancreatic endocrine tumors may contain small, cytologically bland ductules intimately admixed with the endocrine component. It was recently suggested that

Tumors of the endocrine/neuroendocrine system: an overview.