Science.gov

Sample records for estradiol congeners

  1. Estradiol Topical

    MedlinePlus

    ... a medication that is applied topically to the vagina. Estradiol is in a class of medications called ... swelling, redness, burning, irritation, or itching of the vagina vaginal discharge Some side effects can be serious. ...

  2. Atmospheric PCB congeners across Chicago

    PubMed Central

    HU, DINGFEI; LEHMLER, HANS-JOACHIM; MARTINEZ, ANDRES; WANG, KAI; HORNBUCKLE, KERI C.

    2010-01-01

    We have measured PCBs in 184 air samples collected at 37 sites in the city of Chicago using an innovative system of high-volume air samplers mounted on two health clinic vans. Here we describe results of sampling conducted from November 2006 to November 2007. The samples were analyzed for all 209 PCB congeners using a gas chromatograph with tandem mass spectrometry (GC-MS/MS). The ΣPCBs (sum of 169 peaks) in Chicago ranged from 75 pg m−3 to 5500 pg m−3 and primarily varied as a function of temperature. The congener patterns are surprisingly similar throughout the city even though the temperature-corrected concentrations vary by more than an order of magnitude. The average profile resembles a mixture of Aroclor 1242 and Aroclor 1254, and includes many congeners that have been identified as being aryl hydrocarbon receptor (AhR) agonists (dioxin-like) and/or neurotoxins. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) in air were calculated and investigated for their spatial distribution throughout the urban-industrial complex of Chicago. The NEQ concentrations are linearly correlated with ΣPCBs while the TEQ concentrations are not predictable. The findings of this study suggest that airborne PCBs in Chicago are widely present and elevated in residential communities; there are multiple sources rather than one or a few locations of very high emissions; the emission includes congeners associated with dioxin-like and neurotoxic effects and congeners associated with unidentified sources. PMID:21918637

  3. The shy prefer familiar congeners.

    PubMed

    Benhaïm, David; Ferrari, Sébastien; Chatain, Béatrice; Bégout, Marie-Laure

    2016-05-01

    The shy-bold continuum is both a fundamental aspect of human behavior and a relatively stable behavioral trait for many other species. Here we assessed whether shy individuals prefer familiar congeners, taking the European sea bass, a recently domesticated fish showing similar behavioral responses to wild fish, as a model to better understand the inter-individual variability in social behavior previously observed in this species. In the wild, the link between familiarity i.e., the preference of fish for familiar congeners and boldness could be part of the mechanism underlying shoaling formation in fish. Thirty fish were individually tested in a device designed to assess the preference for a familiar vs. an unfamiliar congener on the basis of visual cues only. An open field test (OFT) with shelter was performed on the same fish 32 days later to assess the boldness of each individual. Variables of interest included the proportion of time spent in the shelter, border and center zone of the arena and variables of activity. Variables measured in OFT were collapsed into first principal component scores using Principal Components Analysis (PCA) which allowed characterizing a shy-bold continuum. Time spent near the familiar congener was negatively correlated with boldness i.e., shy individuals spent most of the time near the familiar congener. We discuss the relevance of these findings to the understanding of the behavior of European sea bass and suggest that the link between familiarity and shyness is a general aspect of both animal and human behavior. PMID:26995491

  4. Estradiol: micrograms or milligrams

    PubMed Central

    Wickramasuriya, Nalin; Shaw, Nicholas J

    2016-01-01

    Summary Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error. Learning points Girls with primary and secondary gonadal failure require assistance with pubertal induction. Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol. Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose. Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height. PMID

  5. Drospirenone/ethinyl estradiol.

    PubMed

    Rapkin, Andrea J; Sorger, Shelley N; Winer, Sharon A

    2008-02-01

    Drospirenone 3 mg/ethinyl estradiol 20 microg (24/4) is a new unique oral contraceptive formulation that combines in a novel dosing regimen the lowest dosage of ethinyl estradiol commonly used today with drospirenone, an innovative progestin. Drospirenone is a compound closely resembling progesterone, but with the antimineralocorticoid and antiandrogenic properties of a related therapeutic agent, the diuretic, antihypertensive and androgen receptor antagonist, 17alpha-spironolactone. The prolongation of hormonally active pills in the monthly drospirenone/ethinyl estradiol cycle from 21 days to 24 days, followed by 4 days of inactive pills, is an interesting variant of the recently developed extended pill regimens (1). Recent contraceptive research has focused on improving side effect profiles and providing noncontraceptive health and lifestyle advantages. Many of these benefits are now supported with evidence-based medicine (2). Most available oral contraceptives improve cycle regularity, menstrual pain, excessive menstrual flow and acne. However, weight gain, bloating, food cravings, breast tenderness and mood alterations (especially irritability and depression and the complex of affective, behavioral and somatic symptoms of premenstrual syndrome [PMS] and the severe form of PMS, premenstrual dysphoric disorder [PMDD]) are not generally improved with the traditional oral contraceptive formulations (3). Drospirenone/ethinyl estradiol 24/4 is currently the only hormonally based contraceptive regimen with large, randomized, controlled trials demonstrating efficacy for PMDD. It has received U.S. Food and Drug Administration (FDA) indications not only for the prevention of pregnancy but also for PMDD and for moderate acne vulgaris in women who choose oral contraception for birth control (4, 5). PMID:18389090

  6. Variation in net trophic transfer efficiencies among 21 PCB congeners

    SciTech Connect

    Madenjian, C.P.; Schmidt, L.J.; Chernyak, S.M.; Elliott, R.F.; Desourcie, T.J.; Quintal, R.T.; Begnoche, L.J.; Hesselberg, R.J.

    1999-11-01

    The authors tested the hypothesis that the efficiency with which fish retain polychlorinated biphenyl (PCB) congeners from their food strongly depends on K{sub ow} and degree of chlorination of the congener. The authors used diet information, determinations of concentrations of individual PCB congeners in both coho salmon (Oncorhynchus kisutch) and their prey, and bioenergetics modeling to estimate the efficiencies with which Lake Michigan coho salmon retain various PCB congeners from their food. The retention efficiency for the tetrachloro congeners averaged 38%, whereas retention efficiencies for higher chlorinated congeners ranged from 43 to 56%. Not including tetrachloro congeners, the authors found neither decreasing nor increasing trends in the efficiencies with which the coho salmon retained the PCB congeners from their food with either increasing K{sub ow} or increasing degree of chlorination of the PCB congeners. The authors concluded that (a) for PCB congeners with 5--8 chlorine atoms/molecule, K{sub ow} and degree of chlorination had little influence on the efficiency with which coho salmon retained the various PCB congeners in their food, and (b) the efficiency with which coho salmon retained tetrachloro PCB congeners in their food appeared to be slightly lower than that for higher chlorinated PCB congeners.

  7. Variation in net trophic transfer efficiencies among 21 PCB congeners

    USGS Publications Warehouse

    Madenjian, C.P.; Schmidt, L.J.; Chernyak, S.M.; Elliott, R.F.; Desorcie, T.J.; Quintal, R.T.; Begnoche, L.J.; Hesselberg, R.J.

    1999-01-01

    We tested the hypothesis that the efficiency with which fish retain polychlorinated biphenyl (PCB) congeners from their food strongly depends on Kow and degree of chlorination of the congener. We used diet information, determinations of concentrations of individual PCB congeners in both coho salmon (Oncorhynchus kisutch) and their prey, and bioenergetics modeling to estimate the efficiencies with which Lake Michigan coho salmon retain various PCB congeners from their food. The retention efficiency for the tetrachloro congeners averaged 38%, whereas retention efficiencies for higher chlorinated congeners ranged from 43 to 56%. Not including tetrachloro congeners, we found neither decreasing nor increasing trends in the efficiencies with which the coho salmon retained the PCB congeners from their food with either increasing Kow or increasing degree of chlorination of the PCB congeners. We concluded that (a) for PCB congeners with 5−8 chlorine atoms/molecule, Kow and degree of chlorination had little influence on the efficiency with which coho salmon retained the various PCB congeners in their food, and (b) the efficiency with which coho salmon retained tetrachloro PCB congeners in their food appeared to be slightly lower than that for higher chlorinated PCB congeners.

  8. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  9. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  10. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  11. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  12. 21 CFR 201.313 - Estradiol labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Pharmacopeia under the designation “Alpha Estradiol.” The substance should no longer be referred to in drug labeling as “Alpha Estradiol.” The Food and Drug Administration would not object to label references to the... referred to the presence of “Estradiol (formerly known as Alpha Estradiol).”...

  13. Analysis of PCB congeners related to cognitive functioning in adolescents.

    PubMed

    Newman, Joan; Gallo, Mia V; Schell, Lawrence M; DeCaprio, Anthony P; Denham, Melinda; Deane, Glenn D

    2009-07-01

    To investigate the characteristics of PCBs that are linked to cognitive functioning, those congeners that were concurrently found in 271 Mohawk adolescents were grouped according to structure (dioxin-like or non-dioxin-like) and persistence (persistent or low-persistent). After the effects of the congener groups were orthogonalized, regression analyses (controlling for a number of variables found to be related to the cognitive outcomes) examined the relationship of each congener group to scores on three cognitive tests (the non-verbal Ravens Progressive Matrices, the Test of Memory and Learning, and the Woodcock Johnson-Revised). Five subtests from these cognitive tests were found to be associated with one or more PCB congener groups, most often at a moderate level. Two measures of long-term memory (Delayed Recall and Long Term Retrieval) were associated with all four congener groups. Nevertheless, examination of the role of individual congeners in the significantly related congener groups revealed that almost all congeners associated with cognitive outcomes were non-dioxin-like and ortho-substituted. A notable exception was the Ravens test where scores were associated only with dioxin-like congeners. This finding adds to the limited evidence of neurotoxic effects of dioxin-like congeners. Auditory Processing was related only to the persistent congener group. The association of the non-persistent congener group with three cognitive test scores (Delayed Recall, Long Term Retrieval and Comprehension-Knowledge) suggests that the Mohawk adolescents have experienced continuing or recent environmental exposure to PCBs that is sufficient to result in detectable cognitive decrements. Comparison of our findings with those of other human studies was limited by the relative lack of specificity of both PCB measures and cognitive outcome measures in much previous work. PMID:19465051

  14. ANALYSIS OF PCB CONGENERS RELATED TO COGNITIVE FUNCTIONING IN ADOLESCENTS

    PubMed Central

    Newman, Joan; Gallo, Mia V.; Schell, Lawrence M.; DeCaprio, Anthony P.; Denham, Melinda; Deane, Glenn D.

    2011-01-01

    To investigate the characteristics of PCBs that are linked to cognitive functioning, those congeners that were concurrently found in 271 Mohawk adolescents were grouped according to structure (dioxin-like or non-dioxin-like) and persistence (persistent or low-persistent). After the effects of the congener groups were orthogonalized, regression analyses (controlling for a number of variables found to be related to the cognitive outcomes) examined the relationship of each congener group to scores on three cognitive tests (the non-verbal Ravens Progressive Matrices, the Test of Memory and Learning, and the Woodcock Johnson – Revised). Five subtests from these cognitive tests were found to be associated with one or more PCB congener groups, most often at a moderate level. Two measures of long term memory (Delayed Recall and Long Term Retrieval) were associated with all four congener groups. Nevertheless, examination of the role of individual congeners in the significantly related congener groups revealed that almost all congeners associated with cognitive outcomes were non-dioxin-like and ortho-substituted. A notable exception was the Ravens test where scores were associated only with dioxin-like congeners. This finding adds to the limited evidence of neurotoxic effects of dioxin-like congeners. Auditory Processing was related only to the persistent congener group. The association of the non-persistent congener group with three cognitive test scores (Delayed Recall, Long Term Retrieval and Comprehension-knowledge) suggests that the Mohawk adolescents have experienced continuing or recent environmental exposure to PCBs that is sufficient to result in detectable cognitive decrements. Comparison of our findings with those of other human studies was limited by the relative lack of specificity of both PCB measures and cognitive outcome measures in much previous work. PMID:19465051

  15. Exposure to the three structurally different PCB congeners (PCB 118, 153, and 126) results in decreased protein expression and altered steroidogenesis in the human adrenocortical carcinoma cell line H295R.

    PubMed

    Tremoen, Nina Hårdnes; Fowler, Paul A; Ropstad, Erik; Verhaegen, Steven; Krogenæs, Anette

    2014-01-01

    Polychlorinated biphenyls (PCB), synthetic, persistent organic pollutants (POP), are detected ubiquitously, in water, soil, air, and sediments, as well as in animals and humans. PCB are associated with range of adverse health effects, such as interference with the immune system and nervous system, reproductive abnormalities, fetotoxicity, carcinogenicity, and endocrine disruption. Our objective was to determine the effects of three structurally different PCB congeners, PCB118, PCB 126, and PCB 153, each at two concentrations, on the steroidogenic capacity and proteome of human adrenocortical carcinoma cell line cultures (H295R) . After 48 h of exposure, cell viability was monitored and estradiol, testosterone, cortisol and progesterone secretion measured to quantify steroidogenic capacity of the cells. Two-dimensional (2D) gel-based proteomics was used to screen for proteome alterations in H295R cells in response to the PCB. Exposure to PCB 118 increased estradiol and cortisol secretion, while exposure to PCB 153 elevated estradiol secretion. PCB 126 was the most potent congener, increasing estradiol, cortisol, and progesterone secretion in exposed H295R cells. Seventy-three of the 711 spots analyzed showed a significant difference in normalized spot volumes between controls (vehicle only) and at least one exposure group. Fourteen of these protein spots were identified by liquid chromatography with mass spectroscopy (LC-MS/MS). Exposure to three PCB congeners with different chemical structure perturbed steroidogenesis and protein expression in the H295R in vitro model. This study represents an initial analysis of the effects on proteins and hormones in the H295R cell model, and additional studies are required in order to obtain a more complete understanding of the pathways disturbed by PCB congeners in H295R cells. Overall, alterations in protein regulation and steroid hormone synthesis suggest that exposure to PCB disturbs several cellular processes, including

  16. PCB congener accumulation by periphyton, herbivores, and omnivores.

    PubMed

    Hill, W R; Napolitano, G E

    1997-05-01

    The concentrations of 20 polychlorinated biphenyl (PCB) congeners were measured in periphyton, herbivorous fish (stoneroller minnows, Campostoma anomalum), and omnivorous fish (striped shiners, Luxilus chrysocephalus) in an industrially contaminated stream and a reference stream in eastern Tennessee. The sum of the concentrations of the 20 congeners, normalized by dry mass, was one to two orders of magnitude higher in stonerollers and shiners than in periphyton. Normalizing PCB concentrations by lipid mass reduced concentration differences between periphyton and stonerollers, but PCBs per unit lipid in stonerollers were still 50-350% higher than those in periphyton. Shiners had significantly higher lipid-specific PCB concentrations than did stonerollers, so a trophic hierarchy of primary producer < herbivore < omnivore was evident in lipid-specific PCB concentrations. Differences in lipid type, exposure duration, and exposure sources may account for the trophic-level differences in total PCBs. Congener profiles were roughly similar in periphyton, stonerollers, and shiners: five congeners (IUPAC numbers 101, 110, 138, 153, and 180) constituted >60% of the total mass of PCBs analyzed in all three trophic levels. However, stoneroller and shiner tissue was enriched in congeners 153, 118, and 187 relative to periphyton; congeners 153 and 187 are resistant to metabolic breakdown by monooxygenases found in fish liver. Principal component analysis of congener percentages separated periphyton from fish and distinguished between sampling locations. PMID:9175515

  17. Facial coloration tracks changes in women's estradiol.

    PubMed

    Jones, Benedict C; Hahn, Amanda C; Fisher, Claire I; Wincenciak, Joanna; Kandrik, Michal; Roberts, S Craig; Little, Anthony C; DeBruine, Lisa M

    2015-06-01

    Red facial coloration is an important social cue in many primate species, including humans. In such species, the vasodilatory effects of estradiol may cause red facial coloration to change systematically during females' ovarian cycle. Although increased red facial coloration during estrus has been observed in female mandrills (Mandrillus sphinx) and rhesus macaques (Macaca mulatta), evidence linking primate facial color changes directly to changes in measured estradiol is lacking. Addressing this issue, we used a longitudinal design to demonstrate that red facial coloration tracks within-subject changes in women's estradiol, but not within-subject changes in women's progesterone or estradiol-to-progesterone ratio. Moreover, the relationship between estradiol and facial redness was observed in two independent samples of women (N = 50 and N = 65). Our results suggest that changes in facial coloration may provide cues of women's fertility and present the first evidence for a direct link between estradiol and female facial redness in a primate species. PMID:25796069

  18. Membrane estradiol signaling in the brain

    PubMed Central

    Micevych, Paul; Dominguez, Reymundo

    2009-01-01

    While the physiology of membrane-initiated estradiol signaling in the nervous system has remained elusive, a great deal of progress has been made toward understanding the activation of cell signaling. Membrane-initiated estradiol signaling activates G proteins and their downstream cascades, but the identity of membrane receptors and the proximal signaling mechanism(s) have been more difficult to elucidate. Mounting evidence suggests that classical intracellular estrogen receptor-α (ERα) and ERβ are trafficked to the membrane to mediate estradiol cell signaling. Moreover, an interaction of membrane ERα and ERβ with metabotropic glutamate receptors has been identified that explains the pleomorphic actions of membrane-initiated estradiol signaling. This review focuses on the mechanism of actions initiated by membrane estradiol receptors and discusses the role of scaffold proteins and signaling cascades involved in the regulation of nociception, sexual receptivity and the synthesis of neuroprogesterone, an important component in the central nervous system signaling. PMID:19416735

  19. Steroid secretion following exposure of ovarian follicular cells to single congeners and defined mixture of polybrominateddibenzoethers (PBDEs), p,p'-DDT and its metabolite p,p'-DDE.

    PubMed

    Gregoraszczuk, Ewa Ł; Rak, Agnieszka; Kawalec, K; Ropstad, Erik

    2008-05-01

    The main objective of the present study was to describe in vitro effects of individual congeners of polybrominateddibenzoethers (PBDEs) (PBDE-47, 99, 100, 209), p,p'-dichlorodiphenyltrichloroethane (DDT) and p,p'-dichlorodiphenyldichloroethylene (DDE) present at the highest amount in real-life mixtures of POPs extracted from liver oil of burbot from Lake Mjøsa in Norway, and defined combinations of these compounds on steroidogenesis in porcine ovarian follicular cells. Co-culture of theca and granulosa cells (Gc) was exposed by individual congeners of PBDEs or mixture. Media samples were collected and used for cell viability and steroid determination, while cells were used for the measurement of caspase-3 activity. All investigated PBDEs congeners increased both testosterone (T) and estradiol (E2) secretion. We noted additive stimulatory action of BDE-47 and BDE-100 on both T and E2 secretion, and then inhibitory action on both of these hormones production when additionally BDE-99 and then BDE-209 were included in this mixture. The situation was different when DDT and DDE were added to the defined mixture. Stimulatory action on E2 secretion with parallel decrease of T secretion was noted. In conclusion, the data indicated: (1) stimulatory action of individual congeners of PBDEs on both E2 and T secretion by ovarian follicular cells points to stimulatory action on enzymes responsible for testosterone secretion; (2) the overall effect of a real-life mixture on the steroidogenic response in ovarian follicular cells could be dependent on the concentration of DDTs in the mixture; (3) the predicted effect of mixture, calculated based on a sum of independent action of individual congeners, was higher than that noted under the influence of defined mixture. PMID:18406082

  20. Tamoxifen induces regression of estradiol-induced mammary cancer in ACI.COP-Ept2 rat model

    PubMed Central

    Ruhlen, Rachel L.; Willbrand, Dana M.; Besch-Williford, Cynthia L.; Ma, Lixin; Shull, James D.; Sauter, Edward R.

    2012-01-01

    The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5–7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonance imaging, by 89%. Tumors expressed estrogen receptors (ER), progesterone receptor (PR), and Erbb2. ERα and PR were overexpressed in tumor compared to adjacent non-tumor mammary gland. Thus, this model is highly relevant to hormone responsive human breast cancers. PMID:18830694

  1. Nomegestrol acetate/estradiol: in oral contraception.

    PubMed

    Yang, Lily P H; Plosker, Greg L

    2012-10-01

    Nomegestrol acetate/estradiol is a combined oral contraceptive with approval in many countries. This fixed-dose combination tablet contains nomegestrol acetate, a highly selective progestogen, and estradiol, a natural estrogen. It is the first monophasic combined oral contraceptive to contain estradiol, and is taken in 28-day cycles, consisting of 24 active therapy days with 4 placebo days (i.e. 24/4-day cycles). In two large, 1-year, randomized, open-label, multicentre, phase III trials in healthy adult women (aged 18-50 years), nomegestrol acetate/estradiol was at least as effective as drospirenone/ethinylestradiol as contraceptive therapy, as the pregnancy rates in women aged 18-35 years (primary efficacy population) in terms of the Pearl Index (primary endpoint) were numerically lower with nomegestrol acetate/estradiol, although the between-group difference was not statistically significant. In both trials, nomegestrol acetate/estradiol was given in a 24/4-day cycle, and drospirenone/ethinylestradiol was given in a 21/7-day cycle. The criteria for using condoms in case of forgotten doses were less stringent in the nomegestrol acetate/estradiol group than in the drospirenone/ethinylestradiol group. Nomegestrol acetate/estradiol therapy for up to 1 year was generally well tolerated in healthy adult women, with an acceptable tolerability profile in line with that expected for a combined oral contraceptive. The most commonly reported adverse events were acne and abnormal withdrawal bleeding (most often shorter, lighter or absent periods). Overall, compared with drospirenone/ethinylestradiol, nomegestrol acetate/estradiol appeared to be associated with less favourable acne-related outcomes, and shorter, lighter or absent periods. PMID:22950535

  2. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol and related esters. 556.240 Section 556... Tolerances for Residues of New Animal Drugs § 556.240 Estradiol and related esters. No residues of estradiol, resulting from the use of estradiol or any of the related esters, are permitted in excess of the...

  3. Ethinyl Estradiol and Etonogestrel Vaginal Ring

    MedlinePlus

    ... a class of medications called combination hormonal contraceptives (birth control medications). Etonogestrel is a progestin and ethinyl estradiol ... contraceptive ring is a very effective method of birth control but does not prevent the spread of human ...

  4. Serum estradiol and coronary artery disease.

    PubMed

    Goldberg, R J; Gore, J M; Zive, M; Brady, P; Klaiber, E; Broverman, D; Ockene, I S; Dalen, J E

    1987-01-01

    Serum estradiol levels were measured in 300 men undergoing coronary angiography. Among these men, there were no significant differences in the serum estradiol levels between patients with (mean, 26.4 pg/ml) and those without (mean, 30.9 pg/ml) angiographically confirmed coronary artery disease. There were no significant differences in any of the established coronary risk factors when patients were subdivided according to the presence or absence of coronary artery disease or according to the extent of disease. In addition, no significant correlation was noted between mean serum estradiol levels and the extent of coronary artery disease as classified by the number of obstructed coronary vessels. A matched-pairs analysis was carried out in which patients who had normal coronary arteries were matched with those who had coronary artery disease on the basis of age, cigarette smoking, prior history of myocardial infarction, and body mass index. The mean serum estradiol level in the patients with coronary artery disease was 28.7 pg/ml, and the mean estradiol level was 31.4 pg/ml for the matched patients with normal coronary arteries. In addition, when serial (three) estradiol determinations were carried out in 100 patients, no association was observed between degree of estradiol variability and the occurrence and/or extent of coronary artery disease. The results of this observational study fail to support an association between serum estradiol levels and the presence or degree of coronary artery disease in men as documented by coronary angiography. PMID:3799667

  5. Differential toxicity of three PCB congeners in developing sea urchin embryos and implication of TEQ approach

    SciTech Connect

    Schweitzer, L.; Suffet, I.; Hose, J.; Bay, S.

    1995-12-31

    The relationship between body burden and toxicity of three individual PCB congeners in developing sea urchin embryos was investigated to evaluate the validity of current predictive models of PCB toxicity in an invertebrate system. The uptake and accumulation of radiolabeled PCB congeners from sea water was measured in the sea urchin embryo tissues and the relative toxicity determined. According to the toxic equivalents (TEQ) approach of assessing risk to mammals, congener 77, a nonortho-substituted congener, is predicted to be more toxic than the diortho-substituted congeners 47 and 153. Using a 72 hour embryo development assay, congener 47 was found to be at least four times as toxic as congener 77, with EC50s of 15.7 and > 72.5 mmol/kg, respectively. Congener 153, a hexachlorobiphenyl, was virtually nontoxic even at the highest dose used. Cytologic and cytogenetic anomalies were studied to find a possibly more sensitive endpoint and to suggest a mechanism of toxicity. The cytogenetic analysis revealed that the PCBs inhibited mitosis. At the highest doses, complete mitotic arrest was observed. Congener 77 was found to be at least two times more toxic than congener 153 but not as toxic as congener 47 using mitotic activity as the endpoint. Thus, the two endpoints of toxicity did not change the order in which the congeners are toxic, but established different EC50s. The relative toxicities of these congeners in this study contradict the structure-activity prediction of the mammalian-based TEQ approach.

  6. Mechanism of Polybrominated Diphenyl Ether Uptake into the Liver: PBDE Congeners Are Substrates of Human Hepatic OATP Transporters

    PubMed Central

    Pacyniak, Erik; Roth, Megan; Hagenbuch, Bruno; Guo, Grace L.

    2010-01-01

    Polybrominated diphenyl ethers (PBDEs) are flame-retardants that upon chronic exposure enter the liver where they are biotransformed to potentially toxic metabolites. The mechanism by which PBDEs enter the liver is not known. However, due to their large molecular weights (MWs ∼485 to 1000 Da), they cannot enter hepatocytes by simple diffusion. Organic anion–transporting polypeptides (OATPs) are responsible for hepatic uptake of a variety of amphipathic compounds of MWs larger than 350 Da. Therefore, in the present study, Chinese hamster ovary cell lines expressing OATP1B1, OATP1B3, and OATP2B1 were used to test the hypothesis that OATPs expressed in human hepatocytes would be responsible for the uptake of PBDE congeners 47, 99, and 153. The results demonstrated that PBDE congeners inhibited OATP1B1- and OATP1B3-mediated uptake of estradiol-17-β-glucuronide as well as OATP2B1-mediated uptake of estrone-3-sulfate in a concentration-dependent manner. Direct uptake studies confirmed that all three PBDE congeners are substrates for the three tested hepatic OATPs. Detailed kinetic analysis revealed that OATP1B1 transported 2,2′,4,4′-tetrabromodiphenyl ether (BDE47) with the highest affinity (Km = 0.31μM) followed by 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99) (Km = 0.91μM) and 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE153) (Km = 1.91μM). For OATP1B3, the order was the same (BDE47: Km = 0.41μM; BDE99: Km = 0.70μM; BDE153: Km = 1.66μM), while OATP2B1 transported all three congeners with similar affinities (BDE47: Km = 0.81μM; BDE99: Km = 0.87μM; BDE153: Km = 0.65μM). These results clearly suggest that uptake of PBDEs via these OATPs is a mechanism responsible for liver-specific accumulation of PBDEs. PMID:20176623

  7. Biomechanical properties of osteoporotic rat femurs after different hormonal treatments: genistein, estradiol, and estradiol/progesterone

    PubMed Central

    Azboy, İbrahim; Özkaya, Mustafa; Demir, Teyfik; Demirtaş, Abdullah; Kağan Arslan, Arslan; Özkul, Emin; Akcan, Adnan; Tolunay, Tolga

    2016-01-01

    Introduction: The purpose of the study is to compare the effects of genistein, estradiol, estradiol/progesterone combination on the bone mineral density and biomechanical properties of ovariectomized rats’ bone. Methods: 50 female adult Sprague-Dawley rats were divided into five groups. Bilaterally ovaeriectomy were performed in all groups except the sham-operated group. Groups were a sham-operated group and a control group (water was given), estradiol treated group (17-β estradiol 0.015 mg/kg per day), genistein treated group (genistein 10 mg/kg per day), and an estradiol/progesterone combination group (17-β estradiol 0.015 mg/kg plus drosperinone 0.028 mg/kg per day). The water or hormones were implemented in relevant groups for eight weeks by orogasthric catheter. The bone mineral density and biomechanical properties of the femur were analyzed. Results: Genistein, estradiol, and estradiol/progesterone groups increased bone mineral density significantly compared to the control group. In diaphysis and metaphysis bending test, all groups had higher peak load values than the control group. There were statistically significant differences between the estrogen/progesterone group and control group in diaphysis bending with regard to peak load. There were statistically significant differences between the estradiol and control groups in metaphysis bending with regard to peak load. In axial rotation test, all groups had higher peak torque values than the control groups. Conclusions: Genistein, estradiol and estrogen/progesterone combination improved the biomechanical properties of the ovariectomized rat bone. Genistein which has less side effects may be considered as an alternative in the treatment of postmenopausal osteoporosis. PMID:27194109

  8. Serum estradiol levels in male cigarette smokers.

    PubMed

    Klaiber, E L; Broverman, D M; Dalen, J E

    1984-11-01

    Serum estradiol levels were compared in smoking and nonsmoking men in two separate samples. Sample I consisted of 41 young adult male volunteers ranging in age from 18 to 24 years. Twenty-three men smoked an average of 24.5 +/- 6.9 cigarettes daily. The duration of smoking averaged 5.2 +/- 2.2 years. Sample II consisted of 35 husbands who had been evaluated for infertility; they ranged in age from 19 to 49 years. Eighteen men smoked an average of 21.6 +/- 7.9 cigarettes daily. The duration of smoking averaged 11.5 +/- 4.5 years. Age, height, and weight did not differ significantly between smokers and nonsmokers within either group. Serum estradiol levels were significantly elevated in smokers compared with nonsmokers in both groups (p less than 0.001 and p less than 0.0001 in Samples I and II, respectively). No significant correlations were found between serum estradiol levels and the number of cigarettes smoked daily, or with the duration of smoking in either sample. The differences in serum estradiol levels between smokers and nonsmokers could not be attributed to the differences in marijuana and alcohol use that existed between the smokers and nonsmokers in each sample. The recent reports of elevated serum estradiol levels as a possible risk factor in coronary heart disease are discussed in view of the known relationship of cigarette smoking to coronary heart disease. PMID:6496540

  9. PCB congeners in tissues of European otter (Lutra lutra)

    SciTech Connect

    Mason, C.F.; Ratford, J.R. )

    1994-10-01

    Otters (Lutra lutra) have declined over much of their European range during the past forty years and are now absent from large areas of the lowlands of Western Europe. The most likely cause of the decline is the effects of bioaccumulating contaminants, organochlorine pesticides and PCBs having been implicated. There have been several recent studies of organochlorine residues (pesticides and PCBs) in otter tissues and scats have been used to monitor residues in otter populations. However, only from The Netherlands have data on individual PCB congeners in otter tissues and scats been reported; this Dutch otter population is now extirpated. We report a survey of PCB congeners in samples of tissues and scats from several populations of otters. 21 refs., 3 tabs.

  10. Synthesis of Am80 (tamibarotene) prodrug candidates, congeners and metabolites.

    PubMed

    Muratake, Hideaki; Amano, Yohei; Toda, Takahiro; Sugiyama, Kiyoshi; Shudo, Koichi

    2013-01-01

    Compound 1 (IT-M-07000) was previously reported as a candidate prodrug of Am80 (Tamibarotene; used to treat acute promyelocytic leukemia), and shown to be efficiently metabolized to Am80 via β-oxidation. Here, we describe in detail the synthesis of 1, together with another tetradeuterated candidate prodrug, IT-YA-00616 (2), as well as two congeners, and several metabolic intermediates of 1 previously detected in mouse plasma. PMID:23902867

  11. Serum PCB levels and congener profiles among US construction workers

    PubMed Central

    Herrick, Robert F; Meeker, John D; Hauser, Russ; Altshul, Larisa; Weymouth, George A

    2007-01-01

    Background The presence of PCB in caulking (sealant) material found in masonry buildings has been well-documented in several countries. A recent investigation of 24 buildings in the greater Boston area found that 8 buildings had high PCB levels in caulking materials used around window frames and in joints between masonry blocks. Workers removing caulking material have been shown to have elevated serum PCB levels. Methods This project compared serum PCB levels among male workers who installed and/or removed PCB-containing caulking material from buildings in the greater Boston area with reference serum PCB levels from 358 men from the same area. Serum PCB levels were measured in the same laboratory by liquid-liquid extraction, column chromatography clean-up and dual capillary column GC/microECD analysis. Results When the congener profiles were compared between the reference population and the construction workers, the serum levels of the more volatile, lighter PCBs (di-, tri-and tetrachloro, sum of IUPAC# 6–74) were substantially higher among the construction workers. One of the youngest workers had the lowest total serum PCB levels (sum of 57 congeners) of all 6 workers, but the contribution of more volatile (less chlorinated) PCB congeners (#16, 26,28,33,74,66, and 60) was markedly higher than in other 5 workers and reference men. Only this worker was working on a job that involved removing PCB caulking at the time of the blood sampling. Conclusion While the results of this pilot study are based upon small numbers (6 construction workers who handled PCB caulking), the serum PCB levels among the construction workers exceed the referents. Comparison of the congener profiles suggests that there are substantial differences between the construction workers and the general population samples. These differences, and the similarities of profiles among the construction workers strongly suggest that occupational contact with caulking material can be a major source of PCB

  12. PCBs levels and indicator congeners in children's and adolescents' hair.

    PubMed

    Liang, Baocui; Liu, Xinhui; Hou, Jing; Liang, Gang; Gong, Wenwen; Xu, Diandou; Zhang, Li

    2014-02-01

    Thirty polychlorinated biphenyl (PCB) congeners were determined in the hair samples collected from children (4-12) and adolescents (13-18) of Changchun city, Northeastern China. The mean concentrations of total PCBs and dioxin-like PCBs (dl-PCBs) in the adolescents' hair samples were 161.0 ng g(-1) and 61.7 ng g(-1), which were relatively higher than 43.7 ng g(-1) and 14.6 ng g(-1) in the children's ones. Considering gender difference, the mean concentrations in the girls' hair samples were approximately two times higher than those in the boys' ones for most PCB congeners. The pentachlorinated biphenyl was the dominant homologue. It was found that the levels of total PCBs and dl-PCBs were highly correlated with PCB 118 level in the children's hair samples, and with PCB 114 level in the adolescents' ones. The result demonstrated that the two PCB congeners could be applied as the indicators to evaluate the concentrations of total PCBs and dl-PCBs in children's and adolescents' hair, respectively. PMID:24212066

  13. Mimicking of Estradiol Binding by Flame Retardants and Their Metabolites: A Crystallographic Analysis

    PubMed Central

    Gosavi, Rajendrakumar A.; Knudsen, Gabriel A.; Birnbaum, Linda S.

    2013-01-01

    Background: Brominated flame retardants (BFRs), used in many types of consumer goods, are being studied because of concerns about possible health effects related to endocrine disruption, immunotoxicity, reproductive toxicity, and neurotoxicity. Tetrabromobisphenol A (TBBPA), the most widely used BFR, and human metabolites of certain congeners of polybrominated diphenyl ether (e.g., 3-OH-BDE-47) have been suggested to inhibit estrogen sulfotransferase, potentially affecting estrogen metabolism. Objectives: Our primary goal was to understand the structural mechanism for inhibition of the hormone-metabolizing enzyme estrogen sulfotransferase by certain BFRs. We also sought to understand various factors that facilitate the binding of flame retardants in the enzyme binding pocket. Methods: We used X-ray crystallography to obtain atomic detail of the binding modes of TBBPA and 3-OH-BDE-47 to estrogen sulfotransferase for comparison with binding of the endogenous substrate estradiol. Results: The crystal structures reveal how BFRs mimic estradiol binding as well as the various interactions between the compounds and protein residues that facilitate its binding. In addition, the structures provide insights into the ability of the sulfotransferase substrate binding pocket to accommodate a range of halogenated compounds that satisfy minimal structural criteria. Conclusions: Our results show how BFRs or their metabolites can bind to and inhibit a key hormone-metabolizing enzyme, potentially causing endocrine disruption. Citation: Gosavi RA, Knudsen GA, Birnbaum LS, Pedersen LC. 2013. Mimicking of estradiol binding by flame retardants and their metabolites: a crystallographic analysis. Environ Health Perspect 121:1194–1199; http://dx.doi.org/10.1289/ehp.1306902 PMID:23959441

  14. Distribution patterns of polychlorinated biphenyl congeners in water, sediment and biota from Midway Atoll

    SciTech Connect

    Titus, E.; Scatolini, S.; Cotter, J.; Hope, B.

    1995-12-31

    There are large gaps in the understanding of critical pathways of polychlorinated biphenyl (PCB) transfer from abiotic media into lower trophic level marine organisms and, subsequently to higher marine consumers, particularly for the North Pacific Ocean. In this study, twenty PCB congeners were quantified in surface water, sediment and tissues of marine biota taken from near-shore waters at Midway Atoll. PCB 138, 153, 180, and 187 were the most abundant congeners in all samples analyzed. Bioaccumulation was shifted in favor of higher chlorinated congeners in all species; only aquatic macrophytes displayed significant accumulation of lower chlorinated congeners. Non-ortho substituted congeners with toxic potency were below detection levels in the majority of species. Certain mono-ortho congeners, implicated in marine mammal toxicity, comprised only 4.5% of total congener load in potential forage species.

  15. Bioaccumulation of toxaphene congeners in the lake superior food web

    USGS Publications Warehouse

    Muir, D.C.G.; Whittle, D.M.; De Vault, D. S.; Bronte, C.R.; Karlsson, H.; Backus, S.; Teixeira, C.

    2004-01-01

    The bioaccumulation and biotransformation of toxaphene was examined in the food webs of Lake Superior and Siskiwit Lake (Isle Royale) using congener specific analysis as well as stable isotope ratios of carbon and nitrogen to characterize food webs. Toxaphene concentrations (calculated using technical toxaphene) in lake trout (Salvelinus namaycush) from the western basin of Lake Superior (N = 95) averaged (±SD) 889 ± 896 ng/g wet wt and 60 ± 34 ng/g wet wt in Siskiwit Lake. Major congeners in lake trout were B8-789 (P38), B8-2226 (P44), B9-1679 (P50), and B9-1025 (P62). Toxaphene concentrations were found to vary seasonally, especially in lower food web organisms in Lake Superior and to a lesser extent in Siskiwit Lake. Toxaphene concentrations declined significantly in lake herring (Coregonus artedii), rainbow smelt (Omerus mordax), and slimy sculpin (Cottus cognatus) as well as in zooplankton (> 102 &mn;m) and Mysis (Mysis relicta) between May and October. The seasonal variation may reflect seasonal shifts in the species abundance within the zooplankton community. Trophic magnification factors (TMF) derived from regressions of toxaphene congener concentrations versus δ15N were > 1 for most octa- and nonachlorobornanes in Lake Superior except B8-1413 (P26) and B9-715. Log bioaccumulation factors (BAFs) for toxaphene congeners in lake trout (ng/g lipid/ng/L dissolved) ranged from 4.54 to 9.7 and were significantly correlated with log octanol-water partition coefficients. TMFs observed for total toxaphene and congener B9-1679 in Lake Superior were similar to those in Arctic lakes, as well as to previous studies in the Great Lakes, which suggests that the bioaccumulation behavior of toxaphene is similar in pelagic food webs of large, cold water systems. However, toxaphene concentrations were lower in lake trout from Siskiwit Lake and lakes in northwestern Ontario than in Lake Superior possibly because of shorter food chains and greater reliance on zooplankton or

  16. EFFECTS OF 17B ESTRADIOL AND ETHINYL ESTRADIOL ON REPRODUCTIVE INDICATORS IN LABORATORY-EXPOSED CUNNER, TAUTOGOLABRUS ADPERSUS

    EPA Science Inventory

    Cunner (Tautogolabrus adspersus) are being studied in our laboratory to evaluate how 17 - estradiol and ethinyl estradiol affect their reproductive success. Cunner was selected because this species spawns daily, is common in estuarine areas, is easily obtainable, and is amenable ...

  17. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  18. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  19. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  20. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  1. 21 CFR 522.842 - Estradiol benzoate and testosterone propionate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol benzoate and testosterone propionate... ANIMAL DRUGS § 522.842 Estradiol benzoate and testosterone propionate. (a) Sponsors. See sponsors in... testosterone propionate (one implant consisting of 8 pellets, each pellet containing 2.5 mg estradiol...

  2. Inhibition of Estradiol Synthesis Impairs Fear Extinction in Male Rats

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole,…

  3. ELEVATION OF SERUM 17-B-ESTRADIOL IN CHANNEL CATFISH FOLLOWING INJECTION OF 17-B-ESTRADIOL, ETHYNYL ESTRADIOL, ESTRONE, ESTRIOL, AND ESTRADIOL-17B- GLUCURONIDE

    EPA Science Inventory

    17-b-Estradiol is naturally converted in numerous organisms to various derivatives/metabolites, which may be excreted from the organism into its immediate external environment. There is a paucity of data regarding the biological effects of the derivatives/metabolites on aquatic o...

  4. Fate of glucuronide conjugated estradiol in soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The reproductive hormone, 17ß-estradiol (E2), is made more water soluble (polar) in the body by attachment of glucuronide acid to E2, facilitating urinary elimination. The fate of this potentially more mobile polar form of E2 is not well understood. Soil sorption studies were conducted using [14C] 1...

  5. Evaluating alleged drinking after driving--the hip-flask defence. Part 2. Congener analysis.

    PubMed

    Iffland, R; Jones, A W

    2003-01-01

    The second part of this review describes the principles and practice of forensic congener analysis as an alternative way to evaluate claims of drinking alcohol after driving. Congener analysis was developed, perfected and practised in Germany as a way to evaluate hip-flask defences. This kind of defence challenge arises frequently when the drunk driving suspect is not apprehended at the wheel and especially after hit-and-run incidents. Besides ethanol and water, alcoholic beverages contain trace amounts of many other low-molecular substances, known collectively as the congeners, which impart the characteristic smell and taste to the drink. Importantly, the congener profile can be used to identify a particular kind of alcoholic beverage. Forensic congener analysis entails making a qualitative and quantitative analysis of ethanol, methanol, n-propanol and the isomers of butanol in blood and urine from the apprehended driver and comparing the results with the known congener profile of the alcoholic beverage allegedly consumed after driving. Interpreting the results of congener analysis requires knowledge about the absorption, distribution and elimination pattern of the congener alcohols, including their oxidation and conjugation reactions, and any metabolic interactions with ethanol. Complications arise if drinks with widely different congener profiles are consumed or if the same beverage was ingested both before and after driving. Despite these limitations, congener analysis can furnish compelling evidence to challenge or support claims of drinking alcohol after driving. PMID:12627679

  6. Inhibition of estradiol synthesis impairs fear extinction in male rats.

    PubMed

    Graham, Bronwyn M; Milad, Mohammed R

    2014-07-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole, significantly impairs extinction recall in male rats. This deficit in extinction recall is not due to state-dependent memory formation and is completely abolished by coadministration of estradiol. Our data suggest that estradiol may be just as important in the regulation of fear extinction in males as it is in females. PMID:24939838

  7. Inhibition of estradiol synthesis impairs fear extinction in male rats

    PubMed Central

    Graham, Bronwyn M.; Milad, Mohammed R.

    2014-01-01

    Emerging research has demonstrated that the sex hormone estradiol regulates fear extinction in female rodents and women. Estradiol may also regulate fear extinction in males, given its role in synaptic plasticity in both sexes. Here we report that inhibition of estradiol synthesis during extinction training, via the aromatase inhibitor fadrozole, significantly impairs extinction recall in male rats. This deficit in extinction recall is not due to state-dependent memory formation and is completely abolished by coadministration of estradiol. Our data suggest that estradiol may be just as important in the regulation of fear extinction in males as it is in females. PMID:24939838

  8. Influence of cadmium on PCB congener accumulation in quail

    SciTech Connect

    Leonzio, C.; Marsili, L.; Focardi, S. )

    1992-11-01

    Technological development this century has led to an environmental input of synthetic chemical compounds totally extraneous to natural ecosystems such as Polychlorobiphenyls (PCBs), extensively used in agriculture and industry. These xenobiotics have a high fat/water repartition coefficient, making them easily accumulated by living organisms. Their persistence and low degradability means that they are now present throughout the global ecosystem. Ubiquitous environmental contaminants also include heavy metals like Hg, As, Pb, Cd and Cr, of which Cd, an element causing functional damage to the kidney and liver in which it preferentially accumulates, is of special ecotoxicological importance. The WHO has defined an accumulation of 60 mg/kg (fresh weight), beyond which damage occurs. Cd occurs [open quotes]naturally[close quotes] in high concentrations in certain animal species including molluscs. Birds and marine mammals feeding largely on cephalopods show high levels of this metal. Many monitoring studies have also revealed high concentrations of PCBs in the same animals. The vast majority of studies on contaminants in experimental animals consider the short-, medium- and long-term effects of a single pollutant. However, the presence of synergisms and antagonisms between compounds makes it necessary to adopt a more holistic approach to the problem of environmental pollution. In order to understand if the effect of xenobiotic compounds like PCBs may be potentiated by the natural presence of cadmium in bird population, we sought preliminary information on how the presence of cadmium in the diet may influence the accumulation and metabolization of PCB congeners. The influence of Cd on PCB accumulation was investigated in Japanese quail treated experimentally with Cd and PCBs. Particular attention was paid to final congener accumulation and qualitative differences in congener composition between controls and treated birds. 15 refs., 3 figs., 1 tab.

  9. Stepping backward to improve assessment of PCB congener toxicities.

    PubMed Central

    Hansen, L G

    1998-01-01

    Polychlorinated biphenyls (PCBs) are ubiquitous global contaminants that have been intensively investigated for three decades. They are broad-acting toxicants occurring in complex mixtures and accurate risk assessment has proven to be elusive. Focusing on a limited set of end points and emphasizing a fixed set of congeners have led to more streamlined data sets that are meant to expedite hazard characterization and risk assessment for the most potent congeners--aryl hydrocarbon receptor (AhR) agonists. Unfortunately, this has made it impossible to confirm or deny significant contributions from the more prevalent components of the mixtures. PCBs may be only coincidentally present, rather than causal, in some diseases. Still, attempts to determine associations with incomplete residue data may lead to erroneous conclusions and make accurate risk assessment even more elusive. Responses not mediated through the AhR are presented and emphasize large data gaps. Dissimilar analytical reports emphasize that selection of analytes is not consistent. Collectively, these data confirm that AhR-focused objectives unintentionally created the impression that nonplanar PCBs have little if any potential for hazards to humans and wildlife. Near steady-state exposure of healthy adults are probably of minor consequence except for emerging correlations with non-Hodgkin's lymphoma; however, pulses of exposure to more labile mixtures may contribute to developmental effects without leaving a residue record. More broadly based criteria are suggested and harmonization of data collection and presentation are desirable. A more comprehensive list of PCB congeners is proposed that would provide more adequate data upon which to base associations with adverse outcomes. PMID:9539012

  10. Functionalized Congeners of P2Y1 Receptor Antagonists:

    SciTech Connect

    de Castro, Sonia; Maruoka, Hiroshi; Hong, Kunlun; Kilbey, II, S Michael; Costanzi, Stefano; Hechler, Béatrice; Gachet, Christian; Harden, T. Kendall; Jacobson, Kenneth A.

    2010-01-01

    The P2Y{sub 1} receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP. Preference for the North (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y{sub 1} receptor was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute. A series of covalently linkable N{sup 6}-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphates containing extended 2-alkynyl chains was designed, and binding affinity at the human (h) P2Y{sub 1} receptor determined. The chain of these functionalized congeners contained hydrophilic moieties, a reactive substituent, or biotin, linked via an amide. Variation of the chain length and position of an intermediate amide group revealed high affinity of carboxylic congener 8 (K{sub i} 23 nM) and extended amine congener 15 (K{sub i} 132 nM), both having a 2-(1-pentynoyl) group. A biotin conjugate 18 containing an extended {epsilon}-aminocaproyl spacer chain exhibited higher affinity than a shorter biotinylated analogue. Alternatively, click coupling of terminal alkynes of homologous 2-dialkynyl nucleotide derivatives to alkyl azido groups produced triazole derivatives that bound to the P2Y{sub 1} receptor following deprotection of the bisphosphate groups. The preservation of receptor affinity of the functionalized congeners was consistent with new P2Y{sub 1} receptor modeling and ligand docking. Attempted P2Y{sub 1} antagonist conjugation to PAMAM dendrimer carriers by amide formation or palladium-catalyzed reaction between an alkyne on the dendrimer and a 2-iodopurine-derivatized nucleotide was unsuccessful. A dialkynyl intermediate containing the chain length favored in receptor binding was conjugated to an azide-derivatized dendrimer, and the conjugate inhibited ADP-promoted human platelet aggregation. This is the first example of attaching a strategically functionalized P2Y receptor antagonist to a PAMAM dendrimer to

  11. Incubation stage and polychlorinated biphenyl (PCB) congener patterns in an altricial and precocial bird species

    USGS Publications Warehouse

    Custer, Christine M.; Custer, Thomas W.; Thyen, Stefan; Becker, Peter H.

    2014-01-01

    The composition of polychlorinated biphenyl (PCB) congeners was compared between non-incubated and embryonated eggs of tree swallows (Tachycineta bicolor) and little terns (Sterna albifrons) to determine if measurable changes in PCB congeners occurred during the embryonic period. There was no indication of changes in PCB congener patterns over the incubation period in tree swallows in 1999 and 2000 at a site with very high PCB exposure or a site with more modest PCB exposure. Additionally, congeners known to be either quickly metabolized or conserved based on experimental studies did not generally respond as predicted. Similarly, PCB congener patterns in eggs of little terns from Bottsand, Schleswig-Holstein, Germany, did not differ between non-incubated and embryonated eggs. The results from both species suggest that the stage of incubation is not an important consideration when evaluating PCB congener patterns; comparisons and assessments can be made with eggs collected at all stages of incubation.

  12. Incubation stage and polychlorinated biphenyl (PCB) congener patterns in an altricial and precocial bird species.

    PubMed

    Custer, Christine M; Custer, Thomas W; Thyen, Stefan; Becker, Peter H

    2014-12-01

    The composition of polychlorinated biphenyl (PCB) congeners was compared between non-incubated and embryonated eggs of tree swallows (Tachycineta bicolor) and little terns (Sterna albifrons) to determine if measurable changes in PCB congeners occurred during the embryonic period. There was no indication of changes in PCB congener patterns over the incubation period in tree swallows in 1999 and 2000 at a site with very high PCB exposure or a site with more modest PCB exposure. Additionally, congeners known to be either quickly metabolized or conserved based on experimental studies did not generally respond as predicted. Similarly, PCB congener patterns in eggs of little terns from Bottsand, Schleswig-Holstein, Germany, did not differ between non-incubated and embryonated eggs. The results from both species suggest that the stage of incubation is not an important consideration when evaluating PCB congener patterns; comparisons and assessments can be made with eggs collected at all stages of incubation. PMID:25213805

  13. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  14. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  15. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  16. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  17. 40 CFR 766.27 - Congeners and LOQs for which quantitation is required.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... substances containing predominantly chlorine atoms, only congeners totally chlorinated at the numbered positions need be quantified; for chemical substances containing predominantly bromine atoms, only...

  18. Total PCBs and PCB congeners in Spanish Imperial Eagle eggs

    SciTech Connect

    Hernandez, L.M.; Fernandez, M.A.; Gonzalez, M.J. )

    1989-11-01

    The Spanish Imperial Eagle Aquila (heliaca) adalberti is the only directly endangered bird of prey in Europe. Lowered reproductive success in numerous bird species has been associated with eggshell thinning and reduced production caused by DDE, the most common organochlorine residue found in wild birds. Polychlorinated biphenyls (PCBs) are usually the second most common organochlorine pollutant found in wild birds. Research to evaluate the incidence of organochlorine pollutants in the Spanish Imperial Eagle has been previously conducted. The authors have now determined the levels of total PCBs and selected PCB congeners in 34 eggs of Spanish Imperial Eagle collected at Donana National Park, Castile Plateau and Nature Park of Monfrague, since this has considerable significance when attempts are made to correlate the embryonic mortality of avian wildlife with PCB residue levels.

  19. Comparative developmental toxicity of planar PCB congeners by egg injection

    SciTech Connect

    Hoffman, D.J.; Melancon, M.J.; Eisemann, J.D.; Klein, P.N.

    1995-12-31

    The utility of egg injection studies for predicting potential embryotoxicity of PCBs and TCDD compares favorably with feeding studies. The effects of PCB congeners 3,3{prime}4,4{prime}-tetraCB (PCB 77), 2,3,3{prime},4,4{prime}-pentaCB (PCB 105), 3,3{prime},4,4{prime},5-pentaCB (PCB 126) and 2,2{prime},4,4{prime},5,5{prime}-hexaCB (PCB 153) were examined on embryonic development in chickens (Gallus gallus), northern bobwhite (Colinus virginianus), American kestrels (Falco sparverius), and common terns (Sterna hirundo) through hatching following air cell injections on day 4. The estimated LD{sub 50}s for these congeners in chickens were approximately 0.4 ppb, 2.6 ppb, 3326 ppb, and greater than 14,000 ppb, respectively; low effect levels (10--20% embryonic mortality) were 0.2 ppb, 1.2 ppb, 900 ppb, and 14,000 ppb respectively. The estimated LD{sub 50} for PCB 126 was 48 ppb for bobwhite, 65 ppb for American kestrels, and 104 ppb for common terns. The estimated LD{sub 50} for PCB 77 was 688 ppb for American kestrels. one or more hepatic microsomal cytochrome P450-linked monooxygenases including ethoxyresorufin-O-deethylase was assayed for each species. For PCB 126, the order of responsiveness of cytochrome P450 induction was: chicken > common tern > American kestrel > bobwhite, with chicken being approximately 100 times more responsive than common tern. These values are compared to existing Toxic Equivalency Factors (TEFs) including bioassay-derived ones.

  20. Polychlorinated biphenyl congener distributions in burbot: evidence for a latitude effect.

    PubMed

    Stapanian, Martin A; Madenjian, Charles P; Cott, Peter A; Rediske, Richard R; O'Keefe, James P

    2014-11-01

    The authors compared the distributions of the congeners of polychlorinated biphenyls (PCBs) detected in whole-body samples of burbot (Lota lota) from Great Slave Lake and Lake Erie. Total PCB concentrations in Great Slave Lake burbot were about one-sixtieth of the concentrations in Lake Erie burbot. Burbot from Great Slave Lake contained a higher proportion of lower-chlorinated (2-6 chlorines) congeners than did burbot from Lake Erie; the reverse occurred for more highly chlorinated (7-9 chlorines) congeners. Hexachloro congeners, followed by pentachloro congeners, dominated the proportions of total PCBs in burbot from both lakes. There were no differences between sexes in whole-body samples or between gonad and somatic tissues in the proportions of the 39 congeners and 3 sets of coeluters detected in burbot from Great Slave Lake. In contrast, there were distinct sex differences in congener distributions for older burbot from Lake Erie. The results generally supported a prediction of higher proportions of lower-chlorinated PCB homologs in organisms in remote polar areas. However, the latitudinal effect on PCB congener distribution may be more complex than that portrayed in previous studies. PMID:25088677

  1. Congener specific biotransformation and bioaccumulation of PCDDs and PCDFs from fly ash in fish

    SciTech Connect

    Sijm, D.T.H.M.; Opperhuizen, A. . Research Inst. of Toxicology, Environmental Chemistry Group); Wever, H. . Dept. of Environmental and Toxicological Chemistry)

    1993-10-01

    Biotransformation may be responsible for the lack of bioaccumulation of a number of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Goldfish (Carassius auratus) that were exposed to PCDDs and PCDFs, and piperonylbutoxide (PBO) in water bioconcentrated significantly more congeners than goldfish exposed to PCDDs and PCDFs only. Monooxygenase activity, which is responsible for the oxidation of specific PCDD and PCDF congeners in untreated fish, was inhibited by fish treated with PBO. In the PBO-treated group and in the control group, congeners with all lateral positions substituted were found. Congeners that lack chlorine substitution on one or more of the lateral positions substituted were found. Congeners that lack chlorine substitution on one or more of the lateral (2,3,7,8) positions and congeners that have all lateral positions chlorinated were found only in PBO-treated fish. Congeners that have at least one free lateral position were therefore assumed to be biotransformed. There was no relationship between the octanol/water partition coefficient and biotransformed. There was no relationship between the octanol/water partition coefficient and biotransformation of the PCDDs and PCDFs. No limitation of uptake for higher chlorinated PCDD and PCDF congeners was found.

  2. Toxicokinetics of Polybrominated Diphenyl Ether Congeners 47, 99, 100, and 153 in Mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The congener profiles of polybrominated diphenyl ethers (PBDEs) in biota samples are dominated by PBDE congeners 47, 99, 100, 153, and 154; all of which are components of the commercial pentaBDE mixtures commonly used in a variety of flammable consumer products. Very little information is available...

  3. ELECTRONIC ELASTICITY-TOXICITY RELATIONSHIPS FOR POLYCHLORINATED DIBENZO-P-DIOXIN CONGENERS. (R826166)

    EPA Science Inventory

    SCF-MO computations have been performed on tetra- to octa-chlorinated dibenzo-p-dioxin congeners (PCDD) using an MNDO-PM3 Hamiltonian. Qualitative relationships were developed between empirical, international-toxic equivalence factors for PCDD congeners and their relati...

  4. Polychlorinated biphenyl congener distributions in burbot: evidence for a latitude effect

    USGS Publications Warehouse

    Stapanian, Martin A.; Madenjian, Charles P.; Cott, Peter A.; Rediske, Richard R.; O'Keefe, James P.

    2014-01-01

    We compared the distributions of the congeners of polychlorinated biphenyls (PCBs) detected in whole-body samples of burbot (Lota lota) from Great Slave Lake and Lake Erie. Total PCB concentrations in Great Slave Lake burbot were about 1/60 of the concentrations in Lake Erie burbot. Burbot from Great Slave Lake contained a higher proportion of lower-chlorinated (2-6 chlorines) congeners than did burbot from Lake Erie; the reverse occurred for more highly chlorinated (7-9 chlorines) congeners. Hexachloro congeners, followed by pentachloro congeners, dominated the proportions of total PCB in burbot from both lakes. There were no differences between sexes in whole-body samples or between gonad and somatic tissues in the proportions of the 39 congeners and three sets of co-eluters detected in burbot from Great Slave Lake. In contrast, there were distinct sex differences in congener distributions for older burbot from Lake Erie. Our results generally supported a prediction of higher proportions of lower-chlorinated PCB homologs in organisms in remote polar areas. However, the latitudinal effect on PCB congener distribution may be more complex than that portrayed in previous studies.

  5. SENSITIVITY OF ADENOSINE TRIPHOSPHATASE IN DIFFERENT BRAIN REGIONS TO POLYCHLORINATED BIPHENYL CONGENERS

    EPA Science Inventory

    Polychlorinated biphenyl (PCBs) mixtures contain a number of different congeners, some of which have been proposed to be neuroactive. Recent studies have suggested that ortho-substituted PCBs may be neuroactive, while "dioxin-like" non-ortho-substituted congeners are not. This st...

  6. The Binding Constant of Estradiol to Bovine Serum Albumin: An Upper-Level Experiment Utilizing Tritium-Labeled Estradiol and Liquid Scintillation Counting

    ERIC Educational Resources Information Center

    Peihong Liang; Adhyaru, Bhavin; Pearson, Wright L.; Williams, Kathryn R.

    2006-01-01

    The experiment used [to the third power]H-labeled estradiol to determine the binding constant of estradiol to bovine serum albumin. Estradiol must complex with serum proteins for the transport in the blood stream because of its low solubility in aqueous systems and estradiol-protein binding constant, where K[subscript B] is important to understand…

  7. Dissipation of 17B-estradiol in composted poultry litter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of heated composting and ambient temperature poultry waste decomposition on the fate of 17ß-estradiol and testosterone were determined in separate experiments. A mixture of poultry litter, wood chips and straw was amended with [14C]17ß-estradiol or [14C]testosterone and allowed to under...

  8. Estradiol release kinetics determine tissue response in ovariectomized rats.

    PubMed

    Otto, Christiane; Kantner, Ingrid; Nubbemeyer, Reinhard; Schkoldow, Jenny; Fuchs, Iris; Krahl, Elisabeth; Vonk, Richardus; Schüler, Christiane; Fritzemeier, Karl-Heinrich; Erben, Reinhold G

    2012-04-01

    Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administration regimes. However, pulsed estradiol resulted in lower uterine weight, reduced induction of hepatic gene expression, and reduced mammary epithelial hyperplasia relative to continuous estradiol exposure. We conclude that organ responsivity is influenced by different hormone release kinetics, a fact that might be exploited to reduce undesired estradiol effects in postmenopausal women. PMID:22334713

  9. Sulfation of estradiol in human epidermal keratinocyte.

    PubMed

    Kushida, Akira; Hattori, Kenji; Yamaguchi, Nozomi; Kobayashi, Tetsuyuki; Date, Akira; Tamura, Hiroomi

    2011-01-01

    Epidermis is one of the well-known estrogen target tissues. Information regarding estrogen metabolism in epidermis is still very limited compared to that of estrogen action. In the breast cancer tissue, 17β-estradiol (E(2)) is inactivated by sulfation and the expression level of estrogen sulfotransferase (SULT1E1) is inversely correlated with its malignancy. However, there is little datum about inactivation of estradiol in skin. In order to detect and measure E(2) and its metabolites simultaneously, we established an assay method with radio HPLC. A majority of [(3)H] labeled E(2) was converted to E(2) sulfate in normal human epidermal keratinocyte (NHEK) cells. The estimated activity of sulfotransferase toward E(2) at 20 nM was 0.11±0.01 (pmol/min/mg protein). Significant induction of estrogen sulfotransferase activity was observed in calcium-differentiated NHEK cells (0.58±0.07 (pmol/min/mg protein)). The gene expression of SULT1E1 was fifteen-fold higher in differentiated keratinocyte than in proliferating keratinocyte, whereas that of steroid sulfatase was reduced. These results suggest that E(2) inactivation is primarily mediated by SULT1E1 in keratinocyte and E(2) action is likely suppressed in epidermal differentiation. PMID:21720030

  10. Evidence of latitudinal fractionation of polychlorinated biphenyl congeners along the Baltic Sea region

    SciTech Connect

    Agrell, C.; Okla, L.; Larsson, P.; Backe, C.; Wania, F.

    1999-04-15

    Annual cycles of the atmospheric concentrations of PCBs were determined at 16 (mostly rural) stations around the Baltic Sea between 1990 and 1993. The concentration levels of individual congeners were found to be influenced by their physical-chemical properties, ambient temperature, and geographical location. Median levels of PCBs were similar at all stations except at one urban site near Riga. A latitudinal gradient with higher levels in the south was found for the sum of PCB as well as for individual congeners, and the gradient was more pronounced for the low volatility congeners. As a result, the high volatility congeners increased in relative importance with latitude. Generally, PCB concentrations increased with temperature, but slopes of the partial pressure in air versus reciprocal temperature were different between congeners and between stations. In general, the low volatility congeners were more temperature dependent than the high volatility PCB congeners. Steep slopes at a sampling location indicate that the concentration in air is largely determined by diffusive exchange with soils. Lack of a temperature dependence may be due to the influence of long-range transported air masses at remote sites and due to the episodic or random nature of PCB sources at urban sites.

  11. Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

    PubMed

    Warden, Craig H; Slupsky, Carolyn; Griffey, Stephen M; Bettaieb, Ahmed; Min, Esther; Le, Anh; Fisler, Janis S; Hansen, Susan; Haj, Fawaz; Stern, Judith S

    2014-01-01

    We previously reported that a congenic rat with Brown Norway (BN) alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC). Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by (1)H nuclear magnetic resonance (NMR) spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF) level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age. PMID:24498189

  12. Differential toxicity of three polychlorinated biphenyl congeners in developing sea urchin embryos

    SciTech Connect

    Schweitzer, L.E.; Suffet, I.H.; Hose, J.E.; Bay, S.M.

    1997-07-01

    The relationship between body burden and toxicity of three individual polychlorinated biphenyl (PCB) congeners in developing sea urchin embryos was investigated to evaluate the validity of current predictive models of PCB toxicity in an invertebrate system. Body burdens of radiolabeled PCB congeners (IUPAC-47, 77, and 153) accumulated from a seawater were used to determine median effective concentrations (EC50s) for developmental and cytogenetic effects following a 72-h exposure. Congener 47, a di-ortho-substituted tetrachlorobiphenyl, was found to be at least four times more toxic than congener 77, a non-ortho-substituted (coplanar) tetrachlorobiphenyl, with EC50s of 47 and >218 mmol/kg, respectively, using an embryo development assay. This result contradicts the structure-activity prediction of the mammalian-based toxic equivalents (TEQs) approach, demonstrating the need for an ecotoxicologic model. Congener 153, a di-ortho-substituted hexachlorobiphenyl, was virtually nontoxic in terms of developmental effects at the highest dose achievable at its limit of water solubility. Cytogenetic analysis was a more sensitive method for assessing toxicity than the embryo development assay. Dose-response relationships were established with mitotic activity being the most sensitive endpoint because the PCBs appeared to inhibit mitosis. At the highest doses, complete mitotic arrest was observed. Congener 77 was found to be at least two times more toxic than congener 153 but not as toxic as congener 47 using mitotic activity as the endpoint for toxicity. Thus, the developmental and cytogenetic endpoints ranked the toxicity of the congeners similarly, but established different EC50s.

  13. A modeling approach to compare ΣPCB concentrations between congener-specific analyses

    USGS Publications Warehouse

    Gibson, Polly P.; Mills, Marc A.; Kraus, Johanna M.; Walters, David M.

    2016-01-01

    Changes in analytical methods over time pose problems for assessing long-term trends in environmental contamination by polychlorinated biphenyls (PCBs). Congener-specific analyses vary widely in the number and identity of the 209 distinct PCB chemical configurations (congeners) that are quantified, leading to inconsistencies among summed PCB concentrations (ΣPCB) reported by different studies. Here we present a modeling approach using linear regression to compare ΣPCB concentrations derived from different congener-specific analyses measuring different co-eluting groups. The approach can be used to develop a specific conversion model between any two sets of congener-specific analytical data from similar samples (similar matrix and geographic origin). We demonstrate the method by developing a conversion model for an example data set that includes data from two different analytical methods, a low resolution method quantifying 119 congeners and a high resolution method quantifying all 209 congeners. We used the model to show that the 119-congener set captured most (93%) of the total PCB concentration (i.e., Σ209PCB) in sediment and biological samples. ΣPCB concentrations estimated using the model closely matched measured values (mean relative percent difference = 9.6). General applications of the modeling approach include (a) generating comparable ΣPCB concentrations for samples that were analyzed for different congener sets; and (b) estimating the proportional contribution of different congener sets to ΣPCB. This approach may be especially valuable for enabling comparison of long-term remediation monitoring results even as analytical methods change over time. 

  14. Pharmacokinetics of furagin, a new nitrofurantoin congener, on human volunteers.

    PubMed

    Männistö, P; Karttunen, P

    1979-06-01

    The human pharmacokinetics of a nitrofurantoin congener furagin was studied after a single oral dose of 200 mg and during a 9-day continuous treatment with a dose of 100 mg t.i.d. The same dose of nitrofurantoin served as a reference medication. In the acute cross-over phase food greatly speeded up and atropine somewhat retarded the absorption of furagin, but the total absorption remained virtually unchanged as judged from the unchanged AUC values. The furagin concentrations in serum remain several hours above the MIC concentrations of many pathogenic bacteria. Despite the high concentrations in serum, the urine levels of furagin were generally lower than those of nitrofurantoin. The 24 hr recoveries in urine were 8--13% for furagin and about 36% for nitrofurantoin. In the prolonged trial furagin was absorbed and excreted in the same way as in the acute trial. On the 9th day the concentrations in serum and urine were higher than on the first day. The urinary concentrations of both furagin and nitrofurantoin always remained well above the MIC values of the most susceptible bacteria. Several volunteers complained of nightly cramps in their calves after taking furagin for some days, otherwise the side effects were minimal. PMID:468451

  15. Adenosine Amine Congener as a Cochlear Rescue Agent

    PubMed Central

    Vlajkovic, Srdjan M.; Chang, Hao; Paek, Song Yee; Chi, Howard H.-T.; Sreebhavan, Sreevalsan; Telang, Ravindra S.; Tingle, Malcolm; Housley, Gary D.; Thorne, Peter R.

    2014-01-01

    We have previously shown that adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg) was administered intraperitoneally to Wistar rats (8–10 weeks old) at intervals (6–72 hours) after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment. PMID:25243188

  16. Effects of exposure to estradiol and estradiol plus testosterone on the Mongolian gerbil (Meriones unguiculatus) female prostate.

    PubMed

    Da Silva, Diego Augusto Lopes; Zanatelli, Marianna; Shinohara, Filipe Zardini; Góes, Rejane Maira; Dos Santos, Fernanda Cristina Alcântara; Vilamaior, Patricia Simone Leite; Taboga, Sebastião Roberto

    2013-05-01

    The female prostate is a differentiated organ found in several mammal species, including humans and rodents. This gland has been related to important functions on female reproductive biology. Although the factors, which regulate prostate's development and activity are not well known, its functionality has been related to steroid hormones. It is well established that cyclic changes of estradiol and progesterone levels promote histophysiological adaptations of the whole female body. In contrast, only a few is found about those adaptations in female prostate. Thus, this study aimed to evaluate the effect of estradiol and estradiol + testosterone association on gerbil female prostate in order to verify, which hormonal associations are necessary to its homeostasis. For this, adult females had the ovaries surgically removed. After recovering, they received estradiol and estradiol + testosterone doses through 30 days, each 48 h. The prostatic tissue underwent morphological and morphometric-estereological analysis. Hormonal restriction caused great gland involution and decreased secretory activity, aspects that were reverted by exposure to estradiol and estradiol + testosterone. However, these hormones were not able to re-establish the normal prostate histoarchitecture. The immunoreaction of steroid receptors (ER-α, ER-β, and AR) responded differently among the experimental and control groups, and PCNA assay showed a decrease in epithelial cell proliferation within groups that had hormone privation. Therefore, we conclude that estradiol and testosterone are able to influence prostate morphophysiology and the maintenance of gland homeostasis depends on a balance among these and other hormones. PMID:23529937

  17. DIBROMOACETIC ACID-INDUCED ELEVATIONS OF ESTRADIOL IN THE CYCLING AND OVARIECTOMOZED/ESTRADIOL-IMPLANTED FEMALE RAT

    EPA Science Inventory

    Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations of Estradiol in Both Cycling and Ovariectomized / Estradiol-implanted Female Rats

    ABSTRACT
    Haloacetic acids are one of the principal classes of disinfection by-products generated by the chlorination of mun...

  18. KEY COMPARISON: CCQM-K25: Determination of PCB congeners in sediment

    NASA Astrophysics Data System (ADS)

    Schantz, Michele; Wise, Stephen

    2004-01-01

    Polychlorinated biphenyls (PCBs) consist of 209 possible congeners depending on the substitution of the chlorine atoms around the biphenyl molecule. PCBs have been widely used as industrial fluids, flame retardants, diluents, hydraulic fluids, and dielectric fluids for capacitors and transformers. As a class of compounds, they are environmentally stable and tend to bioaccumulate. Of the 209 possible congeners, approximately 150 congeners have been reported in the environment. Congener-specific PCB methods, which are typically based on gas chromatography (GC) with electron capture detection (ECD) or mass spectrometric (MS) detection, are designed to measure selected priority congeners, but the congeners of interest change with the study and sponsoring agency. A pilot study (CCQM-P17) for the determination of PCB congeners in sediment was organized by NIST and NRC-Canada in 2000. Ten laboratories participated in the pilot study. After discussion and critical review of the data, there was agreement that the pilot study should be followed by a Key Comparison and that the Key Comparison Reference Value (KCRV) should be derived from isotope dilution GC/MS (ID-GC/MS) based methods that had been validated in the Pilot Study. The CCQM-K25 Key Comparison study utilized a sediment sample prepared by mixing known quantities of two sediment materials to simulate a moderately contaminated sample with respect to PCBs. Nine laboratories participated in CCQM-K25 and demonstrated a high level of equivalence in capabilities for determining five PCB congeners (congener numbers 28, 101, 105, 153, and 170) in a moderately contaminated sediment using GC/MS-based methods. The amount of substance concentration for the congeners measured ranged from ~10 ng/g to ~35 ng/g. The relative expanded uncertainties of the KCRVs ranged from 2% to 5%, indicating excellent agreement among the participants that used ID-GC/MS. Results from the one laboratory that used GC/MS with a non-labeled PCB

  19. Estradiol and tamoxifen interaction at receptor sites at 37 C.

    PubMed

    Fishman, J H

    1983-09-01

    Mature rat uterine cytosol was pretreated with dextran-coated charcoal at 0 C for 2 h. This renders the subsequently formed estradiol-receptor complex thermostable at 37 C and also uncovers antiestrogen binding sites, possibly by removing an endogenous ligand. A sharp distinction is found between tamoxifen and estradiol as receptor ligands in pretreated cytosols in that tamoxifen will inhibit estradiol binding, on incubation at 37 C, only if dithiothreitol (DTT) had been included in the pretreatment solution. The presence of tamoxifen as the sole ligand in cytosol pretreated in the presence of DTT does not protect the estradiol receptor from thermal inactivation and following 37 C incubation tamoxifen is found bound exclusively to antiestrogen binding sites. Incubating the cytosol at 37 C with an equimolar mixture of estradiol and tamoxifen results in a very large increase in receptor-bound estradiol. This effect is attributed to the presence of tamoxifen complexed with antiestrogen sites. Tamoxifen in such equimolar ligand mixture binds to antiestrogen sites and is excluded from receptor sites by the estradiol, whose affinity for these sites is much greater than that of tamoxifen. PMID:6191968

  20. The influence of biotransformation on the biomagnification of polychlorobiphenyl congeners in marine mammals and birds

    SciTech Connect

    Boon, J.P.

    1994-12-31

    Results of in-vitro and in-vivo experiments and comparisons of PCB-patterns of prey and predator of field data from the North Sea are presented to explain the influence of biotransformation of PCB congeners on their biomagnification in lung-breathing marine predators. Persistent congeners are taken up proportionally to their relative contribution in prey organisms. Hence molecular descriptors do not play any role here. Metabolizability depends on the presence of vicinal hydrogen atoms and the number of ortho-Cl substituents. The maximum number ortho-Cl atoms still allowing biotransformation differs between seals, cetaceans and seabirds. The majority of congeners with a strong affinity for the Ah-receptor are metabolized in marine mammals, leaving the important question whether the observed effects on reproduction are due to parent compounds or metabolites. Starvation leads to a relative decrease of the metabolizable congeners in the overall pattern.

  1. Toxic congener-specific analysis of PCBs: assessment of toxicity in equivalents of TCDD

    SciTech Connect

    Olafsson, P.G.; Bryan, A.M.

    1987-01-01

    High resolution capillary gas chromatographic analysis of the polychlorobiphenyls (PCBs) present in snapping turtle eggs, provided quantitative data on selected toxic congeners. The concentrations of these congeners have been converted into equivalent toxic concentrations of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). The toxic equivalent factors (TEFs), necessary to effect this transformation were derived from EC/sub 50/ values (half the concentration of the toxic congener required to produce the maximum effect) for aryl hydrocarbon hydroxylase (AHH) induction associated with the corresponding toxic PCB congener or isomer. Summation of the resulting toxic equivalents provided a composite assessment of the toxicity of the PCB mixture in terms of an equivalent concentration of TCDD.

  2. The Identification of Congeners and Aliens by Drosophila Larvae

    PubMed Central

    Del Pino, Francisco; Jara, Claudia; Pino, Luis; Medina-Muñoz, María Cristina; Alvarez, Eduardo; Godoy-Herrera, Raúl

    2015-01-01

    We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles. PMID:26313007

  3. Use of herbarium data to evaluate weediness in five congeners

    PubMed Central

    Hanan-A., Ana M.; Vibrans, Heike; Cacho, N. Ivalú; Villaseñor, José L.; Ortiz, Enrique; Gómez-G., Vinicio A.

    2016-01-01

    It is often desirable to quantify a plant's relative weediness or synanthropy, that is, the degree to which a species associates with human-caused disturbance, in order to study and understand the biology, ecology and evolution of weeds and invasive plants. Herbarium specimens are among the most accessible and verifiable sources of data on distribution and habitat. However, the habitat distribution of species may not be reflected accurately by herbarium specimen data, due to well-known biases in plant collection. Here, we assess how well herbarium specimens reflect species' weediness, when compared with direct field surveys. We used five species of Melampodium (Asteraceae) and classified their degree of weediness with a modification of Nuorteva's synanthropy index, based on herbarium specimens. We then modelled the distribution of our focal species in Mexico using MaxEnt and identified a polygon of ∼3000 km2 in the state of Nayarit, Mexico, where there was a high probability of finding all five species. Systematic field searches in the target area documented all visible populations of four species along major and minor roads. Then we, again, classified their degree of weediness with the synanthropy index, based now on field data, and compared. We found that herbarium data were an accurate predictor of a species' weediness relative to its congeners despite the well-documented skew of herbarium data towards natural areas, which our data reflected as well. So, herbarium data can be used to classify species' weediness relative to each other, but not in absolute terms, if the specimens were correctly identified and none of the species were subject to particular collection bias. This study is the first attempt to compare herbarium and field data on this subject and may be relevant for other types of investigations based on herbarium data. Our work also highlights the usefulness of distribution models based on herbarium specimens. PMID:26672076

  4. The Identification of Congeners and Aliens by Drosophila Larvae.

    PubMed

    Del Pino, Francisco; Jara, Claudia; Pino, Luis; Medina-Muñoz, María Cristina; Alvarez, Eduardo; Godoy-Herrera, Raúl

    2015-01-01

    We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles. PMID:26313007

  5. Accumulation of polychlorobiphenyl congeners and p,p'-DDE at environmental concentrations by corn and beans

    SciTech Connect

    Shane, L.A.; Bush, B.

    1989-02-01

    The uptake of polychlorinated biphenyl (PCB) congeners present at low concentrations in the environment was investigated in leaf composites of four crop species and final fruits at two sites. All four species preferentially accumulated the same eight congeners, although not in the same degree or rank. No bean species demonstrated a significant increase in accumulation over time, and corn significantly reduced its PCB load over time. Mechanisms are suggested for such behavior. Fruits were 100 times less contaminated than plant leaves.

  6. Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice

    SciTech Connect

    Pacyniak, Erik; Hagenbuch, Bruno; The University of Kansas Cancer Center, Kansas City, KS ; Klaassen, Curtis D.; Lehman-McKeeman, Lois; Guo, Grace L.

    2011-11-15

    BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE) congeners detected in humans and can induce drug metabolizing enzymes in the liver. We have previously demonstrated that several human liver organic anion transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE congeners. Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not known. Therefore, the purpose of the current study was to test the hypothesis that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells transiently expressing individual Oatps and quantified the uptake of BDE47, BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice. -- Highlights: Black-Right-Pointing-Pointer PBDE congeners are substrates of OATPs expressed in human hepatocytes. Black-Right-Pointing-Pointer Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. Black-Right-Pointing-Pointer Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners in vitro. Black-Right-Pointing-Pointer In vivo Oatp1a4 plays a minor and Oatp1b2 a major role in BDE47 liver accumulation.

  7. Assessing human polychlorinated biphenyl contamination for epidemiologic studies: lessons from patterns of congener concentrations in Canadians in 1992.

    PubMed Central

    Gladen, Beth C; Doucet, Josée; Hansen, Larry G

    2003-01-01

    Humans are always exposed to mixtures of polychlorinated biphenyls (PCBs), so assessment of their health effects is complicated. Because the original sources are relatively standard mixtures that change in predictable ways while traversing the environment, there is substantial uniformity in the congener mixtures people carry. To the extent that concentrations are highly correlated, measuring multiple congeners within correlated groups would be unnecessary and estimation of separate biologic effects would be impossible. We examined correlation patterns in previously collected data on 38 congeners (and 14 other organochlorines) from 497 human milk samples from Canada from 1992. Congeners 138, 153, 156, 157, 170, 183, 187, 194, 199, and 203 were highly intercorrelated; 180 had slightly lower correlations with this group. Congeners 74, 105, and 118 were highly intercorrelated and moderately to highly correlated with the first group. Congener 99 had moderate correlations with both these groups, and congener 66 had lesser correlations with the primary group. In contrast, congeners 28, 44, 49, 60, 90/101, 128, 137, and 193 showed little correlation with any other congeners. The remaining 14 congeners were uninformative; they were quantified in fewer than 30% of samples, and varying lipid concentrations meant that those quantified were not necessarily at higher concentrations than those not quantified. In study of human health effects of PCBs, the congener pattern present in the population under study should be examined when deciding which congeners to measure; instead of solely redundant or uninformative congeners, attention should be given to other congeners that may be more useful in addressing the question of interest. PMID:12676596

  8. Trait responses of invasive aquatic macrophyte congeners: colonizing diploid outperforms polyploid

    PubMed Central

    Grewell, Brenda J.; Skaer Thomason, Meghan J.; Futrell, Caryn J.; Iannucci, Maria; Drenovsky, Rebecca E.

    2016-01-01

    Understanding traits underlying colonization and niche breadth of invasive plants is key to developing sustainable management solutions to curtail invasions at the establishment phase, when efforts are often most effective. The aim of this study was to evaluate how two invasive congeners differing in ploidy respond to high and lowresource availability following establishment from asexual fragments. Because polyploids are expected to have wider niche breadths than diploid ancestors, we predicted that a decaploid species would have superior ability to maximize resource uptake and use, and outperform a diploid congener when colonizing environments with contrasting light and nutrient availability. A mesocosm experiment was designed to test the main and interactive effects of ploidy (diploid and decaploid) and soil nutrient availability (low and high) nested within light environments (shade and sun) of two invasive aquatic plant congeners. Counter to our predictions, the diploid congener outperformed the decaploid in the early stage of growth. Although growth was similar and low in the cytotypes at low nutrient availability, the diploid species had much higher growth rate and biomass accumulation than the polyploid with nutrient enrichment, irrespective of light environment. Our results also revealed extreme differences in time to anthesis between the cytotypes. The rapid growth and earlier flowering of the diploid congener relative to the decaploid congener represent alternate strategies for establishment and success. PMID:26921139

  9. Functionalized Congener Approach to the Design of Ligands for G Protein–Coupled Receptors (GPCRs)

    PubMed Central

    Jacobson, Kenneth A.

    2009-01-01

    Functionalized congeners, in which a chemically functionalized chain is incorporated at an insensitive site on a pharmacophore, have been designed from the agonist and antagonist ligands of various G protein–coupled receptors (GPCRs). These chain extensions enable a conjugation strategy for detecting and characterizing GPCR structure and function and pharmacological modulation. The focus in many studies of functionalized congeners has been on two families of GPCRs: those responding to extracellular purines and pyrimidines—i.e., adenosine receptors (ARs) and P2Y nucleotide receptors. Functionalized congeners of small-molecule as ligands for other GPCRs and non-G protein coupled receptors have also been designed. For example, among biogenic amine neurotransmitter receptors, muscarinic acetylcholine receptor antagonists and adrenergic receptor ligands have been studied with a functionalized congener approach. Adenosine A1, A2A, and A3 receptor functionalized congeners have yielded macromolecular conjugates, irreversibly binding AR ligands for receptor inactivation and crosslinking, radioactive probes that use prosthetic groups, immobilized ligands for affinity chromatography, and dual-acting ligands that function as binary drugs. Poly(amidoamine) dendrimers have served as nanocarriers for covalently conjugated AR functionalized congeners. Rational methods of ligand design derived from molecular modeling and templates have been included in these studies. Thus, the design of novel ligands, both small molecules and macromolecular conjugates, for studying the chemical and biological properties of GPCRs have been developed with this approach, has provided researchers with a strategy that is more versatile than the classical medicinal chemical approaches. PMID:19405524

  10. Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake whitefish (Coregonus clupeaformis) from their food

    USGS Publications Warehouse

    Madenjian, C.P.; O'Connor, D.V.; Rediske, R.R.; O'Keefe, J. P.; Pothoven, S.A.

    2008-01-01

    Lake whitefish (Coregonus clupeaformis) were fed rainbow smelt (Osmerus mordax) in four laboratory tanks over a 133-d experiment. At the start of the experiment, 10 to 14 of the fish in each tank were sacrificed, and the concentrations of 40 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 15 lake whitefish remaining in each of the four tanks at the end of the experiment as well as in the rainbow smelt fed to the lake whitefish. Each lake whitefish was weighed at the start and the end of the experiment, and the amount of food eaten by the lake whitefish during the experiment was tracked. Using these measurements, net trophic transfer efficiency (??) from the rainbow smelt to the lake whitefish in each of the four tanks was calculated for each of the 40 PCB congeners. Results showed that ?? decreased exponentially as log KOW for the congeners increased from 6 to 8. Further, ?? averaged 0.70 for the tetrachloro congeners but averaged only 0.45 for the higher chlorinated congeners. ?? 2008 SETAC.

  11. Residual congener pattern of dioxins in human breast milk in southern Vietnam.

    PubMed

    Tawara, Kenji; Nishijo, Muneko; Maruzeni, Shoko; Nakagawa, Hideaki; Kido, Teruhiko; Naganuma, Rie; Suzuki, Hiroyuki; Nhu, Dang Duc; Hung, Nguyen Ngoc; Thom, Le Thi Hong

    2011-08-01

    This study evaluated residual congener patterns of dioxin/furan (=PCDD/DF) related to tactical herbicides aerially sprayed over the regions of southern Vietnam through Operation Ranch Hand. The study focused on Cam Chinh (CC) commune, Quang Tri province (an area sprayed with tactical herbicides), and the Cam Phuc (CP) commune, Ha Tinh province (a non-sprayed area). Breast milk samples for analysis were collected in September 2002 and July 2003 from lactating primiparous and multiparous mothers born after the war (<31 years old). We found the levels of each congener in the CC commune were higher than in the CP commune, and determined specificity in the PCDD/DF congener pattern in CC commune samples by cluster analysis. The congener pattern is characterized by higher (the hexa-, the hepta-, and the octa-) chlorinated PCDD/DFs; this appears to be the same profile as that presented by pentachlorophenol (PCP), rather than 2,4,5-trichlorophenoxy acid (2,4,5-T) contaminated with 2,3,7,8-TCDD. A GC/MS study in the 1970s detected the chlorophenols 2,4-di and 2,4,6-trichlorophenol in some Agent Orange samples, which contained, like PCP, a wide variety of PCDD/DF congeners. In this context, it may be expected that certain tactical herbicides contaminated with various chlorophenol impurities, have a unique congener pattern when compared with pure 2,4,5-T formulations. PMID:21680010

  12. Trait responses of invasive aquatic macrophyte congeners: colonizing diploid outperforms polyploid.

    PubMed

    Grewell, Brenda J; Skaer Thomason, Meghan J; Futrell, Caryn J; Iannucci, Maria; Drenovsky, Rebecca E

    2016-01-01

    Understanding traits underlying colonization and niche breadth of invasive plants is key to developing sustainable management solutions to curtail invasions at the establishment phase, when efforts are often most effective. The aim of this study was to evaluate how two invasive congeners differing in ploidy respond to high and lowresource availability following establishment from asexual fragments. Because polyploids are expected to have wider niche breadths than diploid ancestors, we predicted that a decaploid species would have superior ability to maximize resource uptake and use, and outperform a diploid congener when colonizing environments with contrasting light and nutrient availability. A mesocosm experiment was designed to test the main and interactive effects of ploidy (diploid and decaploid) and soil nutrient availability (low and high) nested within light environments (shade and sun) of two invasive aquatic plant congeners. Counter to our predictions, the diploid congener outperformed the decaploid in the early stage of growth. Although growth was similar and low in the cytotypes at low nutrient availability, the diploid species had much higher growth rate and biomass accumulation than the polyploid with nutrient enrichment, irrespective of light environment. Our results also revealed extreme differences in time to anthesis between the cytotypes. The rapid growth and earlier flowering of the diploid congener relative to the decaploid congener represent alternate strategies for establishment and success. PMID:26921139

  13. 3D model of amphioxus steroid receptor complexed with estradiol

    SciTech Connect

    Baker, Michael E.; Chang, David J.

    2009-08-28

    The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen-binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER{alpha} are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER{alpha} in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR. The 3D model predicts that mutation of Glu-346 to Gln will increase the affinity of testosterone for amphioxus SR and elucidate the evolution of steroid-binding to nuclear receptors.

  14. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  15. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  16. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  17. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  18. 21 CFR 522.1940 - Progesterone and estradiol benzoate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... in calves to be processed for veal. (2) Steers—(i) Amount—(A) 200 mg progesterone and 20 mg estradiol... calves. Do not use in calves to be processed for veal. (3) Steers fed in confinement for...

  19. Association Between Preovulatory Concentrations of Estradiol and Expression of Uterine Milk Protein Precursor, Inhibin Beta A, Period 1, Proenkephalin, and Receptors for Oxytocin, Progesterone, and Estradiol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Eliminating the preovulatory surge of estradiol decreased uterine weight, uterine protein, RNA to DNA ratio, rate of protein synthesis, and embryo survival following embryo transfer in sheep. Furthermore, cows that did not exhibit standing estrus (decreased preovulatory concentrations of estradiol) ...

  20. Estradiol rapidly modulates odor responses in mouse vomeronasal sensory neurons.

    PubMed

    Cherian, S; Wai Lam, Y; McDaniels, I; Struziak, M; Delay, R J

    2014-06-01

    In rodents, many social behaviors are driven by the sense of smell. The vomeronasal organ (VNO), part of the accessory olfactory system mediates many of these chemically driven behaviors. The VNO is heavily vascularized, and is readily accessible to circulating peptide or steroid hormones. Potentially, this allows circulating hormones to alter behavior through modulating the output of the primary sensory neurons in the VNO, the vomeronasal sensory neurons (VSNs). Based on this, we hypothesized that steroid hormones, in particular 17β-estradiol, would modulate activity of VSNs. In this paper, we show that the estrogen receptors, GPR30 and ERα, were present in VSNs and that estradiol may be synthesized locally in the VNO. Our results also showed that 17β-estradiol decreased responses of isolated VSNs to dilute urine, a potent natural stimulus, with respect to current amplitudes and depolarization. Further, 17β-estradiol increased the latency of the first action potential (AP) and the AP amplitude. Additionally, calcium responses to sulfated steroids (present in the low molecular weight fraction of urine) that act as ligands for apical vomeronasal receptors were decreased by 17β-estradiol. In conclusion, we show that estradiol modulates odorant responses mediated by VSNs and hence paves the way for future studies to better understand the mechanisms by which odorant mediated behavior is altered by endocrine status of the animal. PMID:24680884

  1. Generating the Right PCB Data: Determination of Aroclors Versus PCB Congeners

    SciTech Connect

    Prignano, A.L.; Narquis, C.T.; Hyatt, J.E.

    2008-07-01

    Polychlorinated biphenyls (PCBs) are a major environmental concern due to their ubiquity and tendency to bio-accumulate, as well as their persistence and toxicity. As the cleanup of waste and contaminated soil progresses at U.S. Department of Energy (DOE) sites, the costs for accurate PCB data are increasing. PCBs are actually a broad name for a group of 209 individual compounds known as congeners. PCBs were originally produced in the United States as specific mixtures of congeners known as Aroclors. PCBs can be analyzed and quantified either as Aroclor mixtures or as individual congeners. Aroclor analysis, which is the more common analytical method applied to PCBs, has been in use for decades, and in general, most cleanup regulations are based on total PCB concentrations using Aroclor analyses. Congener analysis is relatively new to environmental cleanup and restoration due to both technical issues and associated cost. The benefits of congener analysis are that it allows a more direct analysis of the risk of the PCBs. The World Health Organization (WHO) has identified twelve specific congeners as dioxin-like with toxicity ranging from 0.00003 to 0.1 times the standard 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) toxicity. This paper defines Aroclors and congeners and compares the current application and usefulness of the two analytical methods for environmental restoration and cleanup. A strategy for the best use of the two methods to optimize overall characterization cost is presented. As part of the strategy, a method using the data from Aroclor analyses to calculate 2,3,7,8-TCDD toxicity equivalent concentrations is also presented. (authors)

  2. GENERATING THE RIGHT PCB DATA DETERMINATION OF AROCLORS VERSUS PCB CONGENERS

    SciTech Connect

    NARQUIS CT; PRIGNANO AL

    2007-11-21

    Polychlorinated biphenyls (PCBs) are a major environmental concern due to their ubiquity and tendency to bio-accumulate. as well as their persistence and toxicity. As the cleanup of waste and contaminated soil progresses at U.S. Department of Energy (DOE) sites, the costs for accurate PCB data are increasing. PCBs are actually a broad name for a group of 209 individual compounds known as congeners. PCBs were originally produced in the United States as specific mixtures of congeners known as Aroclors'. PCBs can be analyzed and quantified either as Aroclor mixtures or as individual congeners. Aroclor analysis, which is the more common analytical method applied to PCBs. has been in use for decades, and in general, most cleanup regulations are based on total PCB concentrations using Aroclor analyses. Congener analysis is relatively new to environmental cleanup and restoration due to both technical issues and associated cost. The benefits of congener analysis are that it allows a more direct analysis of the risk of the PCBs. The World Health Organization (WHO) has identified twelve specific congeners as dioxin-like with toxicity ranging from 0.00003 to 0.1 times the standard 2,3,7.8-Tetrachlorodibenzo-p-dioxin (2.3.7.8-TCDD) toxicity. This paper defines Aroclors and congeners and compares the current application and usefulness of the two analytical methods for environmental restoration and cleanup. A strategy for the best use of the two methods to optimize overall characterization cost is presented. As part of the strategy. a method using the data from Aroclor analyses to calculate 2,3,7,8-TCDD toxicity equivalent concentrations is also presented.

  3. Single and multiple congenic strains for hydrocephalus in the H-Tx rat

    PubMed Central

    Jones, Hazel C.; Chen, Gin-Fu; Yehia, Baligh R.; Carter, Barbara J.; Akins, Elizabeth J.; Wolpin, Logan C.

    2010-01-01

    The H-Tx rat has fetal-onset hydrocephalus with a complex mode of inheritance. Previously, quantitative trait locus mapping using a backcross with Fischer F344 rats demonstrated genetic loci significantly linked to hydrocephalus on Chromosomes 10, 11, and 17. Hydrocephalus was preferentially associated with heterozygous alleles on Chrs 10 and 11 and with homozygous alleles on Chr 17. This study aimed to determine the phenotypic contribution of each locus by constructing single and multiple congenic strains. Single congenic rats were constructed using Fischer F344 as the recipient strain and a marker-assisted protocol. The homozygous strains were maintained for eight generations and the brains examined for dilated ventricles indicative for hydrocephalus. No congenic rats had severe (overt) hydrocephalus. A few pups and a significant number of adults had mild disease. The incidence was significantly higher in the C10 and C17 congenic strains than in the nonhydrocephalic F344 strain. Breeding to F344 to make F.H-Tx C10 or C11 rats heterozygous for the hydrocephalus locus failed to produce progeny with severe disease. Both bicongenic and tricongenic rats of different genotype combinations were constructed by crossing congenic rats. None had severe disease but the frequency of mild hydrocephalus in adults was similar to congenic rats and significantly higher than in the F344 strain. Rats with severe hydrocephalus were recovered in low numbers when single congenic or bicongenic rats were crossed with the parental H-Tx strain. It is concluded that the genetic and epigenetic factors contributing to severe hydrocephalus in the H-Tx strain are more complex than originally anticipated. PMID:15965786

  4. Estradiol signaling via sequestrable surface receptors.

    PubMed

    Benten, W P; Stephan, C; Lieberherr, M; Wunderlich, F

    2001-04-01

    Estradiol (E(2))-signaling is widely considered to be exclusively mediated through the transcription-regulating intracellular estrogen receptor (ER) alpha and ERbeta. The aim of this study was to investigate transcription-independent E(2)-signaling in mouse IC-21 macrophages. E(2) and E(2)-BSA induce a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) of Fura-2 loaded IC-21 cells as examined by spectrofluorometry. These changes in [Ca(2+)](i) can be inhibited by pertussis toxin, but not by the ER-blockers tamoxifen and raloxifene. The E(2)-signaling initiated at the plasma membrane is mediated through neither ERalpha nor ERbeta, but rather through a novel G protein-coupled membrane E(2)-receptor as revealed by RT-PCR, flow cytometry, and confocal laser scanning microscopy. A special feature of this E(2)-receptor is its sequestration upon agonist stimulation. Sequestration depends on energy and temperature, and it proceeds through a clathrin- and caveolin-independent pathway. PMID:11250949

  5. Polychlorinated biphenyl (PCB) congener concentrations in seabirds found dead in mortality incidents around the British coast.

    PubMed

    Malcolm, H M; Osborn, D; Wright, J; Wienburg, C L; Sparks, T H

    2003-07-01

    Livers from 121 birds killed in mortality incidents in U.K. coastal waters between 1991 and 1996 were analyzed for 16 PCB congeners (IUPAC numbers 8, 18, 28, 31, 52, 77, 101, 118, 126, 128, 138, 149, 153, 169, 170, and 180). Species analyzed were guillemot (Uria aalge), shag (Phalacrocorax arisotelis), kittiwake (Rissa tridactyla), puffin (Fratercula arctica), razorbill (Alca torda), fulmar (Fulmarus glacialis), gannet (Sula bassana), and herring gull (Larus argentatus). This is the first report of PCBs in U.K. seabird tissues to be presented since 1983. Mean concentrations of total PCBs ranged from 0.47 to 15.8 mg/kg WW, similar to concentrations reported for North Sea birds during the 1970s and 1980s and lower than those reported for the same species in the Irish Sea during the late 1960s and early 1970s. The congeners generally present in the highest concentrations were (in decreasing order) 153, 138, 180, 118, and 170. Despite the birds having similar diets, both inter- and intraspecies differences in PCB congener profile were found. In guillemots from several sites on the east coast, the dominant congener was 138, compared to guillemots from the south coast, which had the more typical congener pattern found in seabirds. Some of the differences in total PCB values could be due to different causes of death, with a subsequent effect on body lipid levels. PMID:12948183

  6. Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake trout (Salvelinus namaycush) from its prey

    USGS Publications Warehouse

    Madenjian, Charles P.; David, Solomon R.; Rediske, Richard R.; O’Keefe, James P.

    2012-01-01

    Lake trout (Salvelinus namaycush) were fed bloater (Coregonus hoyi) in eight laboratory tanks over a 135-d experiment. At the start of the experiment, four to nine fish in each tank were sacrificed, and the concentrations of 75 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 10 lake trout remaining in each of the eight tanks at the end of the experiment as well as in the bloater fed to the lake trout. Each lake trout was weighed at the start and the end of the experiment, and the amount of food eaten by the lake trout was recorded. Using these measurements, net trophic transfer efficiency (γ) from the bloater to the lake trout in each of the eight tanks was calculated for each of the 75 congeners. Results showed that γ did not vary significantly with the degree of chlorination of the PCB congeners, and γ averaged 0.66 across all congeners. However,γ did show a slight, but significant, decrease as logKOW increased from 6.0 to 8.2. Activity level of the lake trout did not have a significant effect on γ.

  7. Polychlorinated biphenyl congener patterns in fish near the Hanford Site (Washington State, USA).

    PubMed

    Rodenburg, Lisa A; Delistraty, Damon; Meng, Qingyu

    2015-03-01

    It is well-known that absorption, distribution, metabolism, and excretion (ADME) processes in fish can alter polychlorinated biphenyl (PCB) congener patterns in fish, but these patterns have never been investigated using an advanced source-apportionment tool. In this work, PCB congener patterns in freshwater fish were examined with positive matrix factorization (PMF). PCB congeners were quantified via EPA Method 1668 in fillet and carcass of six species in four study areas in the Columbia River near the Hanford Site. Six factors were resolved with PMF2 software. Depletion and enhancement of PCB congeners in factors, relative to Aroclor 1254, suggested biotransformation (via cytochrome P450) and bioaccumulation in fish, respectively. Notable differences were observed among species and across study locations. For example, sturgeon and whitefish exhibited congener patterns consistent with Aroclor weathering, suggesting potential PCB metabolism in these species. In terms of location, average concentration of total PCBs for all species combined was significantly higher (P < 0.05) at Hanford 100 and 300 areas, relative to upriver and downriver study sites. Furthermore, a distinct PCB signature in sturgeon and whitefish, collected at Hanford study areas, suggests that Hanford is a unique PCB source. PMID:25621866

  8. Formation of toxic PCB congeners and PCB-solvent adducts in a sunlight irradiated cyclohexane solution of aroclor 1254

    SciTech Connect

    Lepine, F.; Milot, S.; Vincent, N. )

    1992-01-01

    Photodegradation by sunlight is an important decomposition mechanism of polychlorinated biphenyls in the environment. Photodegradation of PCBs proceeds through successive dechlorination of the biphenyl nucleus and thus modify the proportions of the various congeners in a PCB mixture. The objectives of this work is to study the effects of sunlight on a typical PCB mixture such as Aroclor 1254, in a congener specific approach in order to observe the variations in the levels of these toxic congeners in the irradiated mixture.

  9. Degradation of estradiol and ethinyl estradiol by activated sludge and by a defined mixed culture.

    PubMed

    Weber, Stefanie; Leuschner, Prisca; Kämpfer, Peter; Dott, Wolfgang; Hollender, Juliane

    2005-04-01

    The aerobic degradation of the natural hormone 17-beta-estradiol (E2) and the synthetic hormone 17-alpha-ethinyl estradiol (EE2) was investigated in batch experiments with activated sludge from a conventional and a membrane sewage treatment plant. E2 was converted to estrone (E1), the well known metabolite, and further completely transformed within 3 days. The turnover rates of E2 did not differ greatly between conventional and membrane activated sludge. EE2 was persistent in both sludges. By several transfers into fresh E2-medium an enrichment culture could be selected that used E2 as growth substrate. Further enrichment and isolation led to a defined mixed culture consisting of two strains, which were identified by a polyphasic approach as Achromobacter xylosoxidans and Ralstonia sp., respectively. The culture used E2 and E1 as growth substrates and transformed estriol (E3) and 16-alpha-hydroxyestrone but not the xenoestrogens bisphenol A, alpha-zearalenol, mestranol or EE2. The turnover rates of E2 were 0.025-0.1 microg h(-1) cfu(-1) and did not depend on the steroid concentration. PMID:15290133

  10. Enhanced osteoblast proliferation and collagen gene expression by estradiol

    SciTech Connect

    Ernest, M.; Schmid, Ch.; Froesch, E.R. )

    1988-04-01

    Estrogens play a crucial role in the development of postmenopausal osteoporosis. However, the mechanism by which estrogens exert their effects on bone is unknown. To examine possible direct effects of 17{beta}-estradiol on bone-forming cells, the authors used pure rat osteoblast-like cells in vitro as a model. Osteoblast-like cells prepared from calvaria of newborn rats were cultured serum-free in methylcellulose-containing medium for 21 days. Osteoblast-like cells proliferate selectively into clonally derived cell clusters of spherical morphorlogy. 17{beta}-Estradiol at concentrations of 0.1 nM and 1 nM enhanced osteoblast-like cell proliferation by 41% and 68% above vehicle-treated controls. The biologically inactive stereoisomer 17{alpha}-estradiol (same concentrations) had no effect. Moreover, the antiestrogen tamoxifen abolished the stimulation of osteoblast-like cell proliferation by 17{beta}-estradiol. After 21 days of culture, RNA was prepared and analyzed in a dot-hybridization assay for the abundance of pro{alpha}1(I) collagen mRNA. Steady-state mRNA levels were increased in cultures treated with 17{beta}-estradiol in a dose-dependent manner with maximal stimulation at 1 nM and 10 nM. At the same concentrations, the percentage of synthesized protein (labeled by ({sup 3}H)proline pulse) that was digestible by collagenase was increased, indicating that 17{beta}-estradiol acts as pretranslational levels to enhance synthesis of bone collagen. These data show that the osteoblast is a direct target for 17{beta}-estradiol.

  11. Comparison of nonplanar and coplanar PCB congener partitioning in seawater and bioaccumulation in blue mussels (Mytilus edulis)

    SciTech Connect

    Bergen, B.J.; Nelson, W.G.; Pruell, R.J.

    1996-09-01

    The partitioning of 18 nonplanar and three coplanar polychlorinated biphenyl (PCB) congeners was quantified in New Bedford Harbor, Massachusetts. Concurrently, bioaccumulation of these congeners was measured in blue mussels deployed for 7 and 28 d in New Bedford Harbor, and bioconcentration factors (BCFs) were calculated for each congener. The PCB concentrations measured in the dissolved and particulate fractions of seawater samples were used to calculate partition coefficients (K{sub p}) for each congener. These values were correlated with reported octanol/water partition coefficients (K{sub ow}). No significant differences (p > 0.05) were observed in the relationships between K{sub p} and K{sub ow} for the coplanar congeners relative to the nonplanar congeners. Coplanar congeners reached steady state faster than the nonplanar congeners; however, after 28 d a similar relationship was observed between BCF and K{sub ow} in coplanar and nonplanar congeners. These data indicate that coplanar PCBs partition in seawater and accumulate in mussels similarly to nonplanar PCBs with the same number of chlorines.

  12. Polychlorinated biphenyl congeners in emergent mayflies from the upper Mississippi River

    USGS Publications Warehouse

    Steingraeber, M.T.; Schwartz, T.R.; Wiener, J.G.; Lebo, J.A.

    1994-01-01

    We determined polychlorinated biphenyls (pcbs) in emergent mayflies (hexagenia bilineata) from a 1250-km reach of the upper mississippi river (umr). Total pcb concentrations (sum of 125 congeners) ranged from 0.21 To 4.1 Mu g/g of dry weight (1.2-29 mu g/g of lipid weight). Concentrations were highest in pools near the twin cities and the quad cities metropolitan areas. Longitudinal movement of pcbs was extensive downstream from the twin cities (175-320 km) but was not apparent downstream from the quad cities. The pcb composition of mayflies was relatively homogeneous throughout most of the river. However, the congener composition in mayflies from two distant locations differed markedly from the other samples and contained a greater abundance of lower molecular weight congeners. Recent pcb discharges from point and nonpoint sources may account for these differences. Emergent mayflies seem to be a useful indicator of pcb contamination of the umr.

  13. Congenic mapping and candidate sequencing of susceptibility genes for Type 1 diabetes in the NOD mouse.

    PubMed

    Ikegami, Hiroshi; Fujisawa, Tomomi; Makino, Susumu; Ogihara, Toshio

    2003-11-01

    Inheritance of type 1 diabetes is polygenic with a major susceptibility gene located in the major histocompatibility complex (MHC). In addition to MHC-linked susceptibility, a number of susceptibility genes have been mapped outside the MHC in both humans and animal models. In order to localize and identify susceptibility genes for type 1 diabetes, we have developed a series of congenic strains in which either susceptibility intervals from the NOD mouse, a mouse model of type 1 diabetes, were introgressed onto control background genes or protective intervals from control strains were introgressed onto NOD background genes. NOD. CTS-H-2 congenic mice, which possess recombinant MHC with NOD alleles at class II A and E genes, which are candidates for Idd1, revealed that Idd1 consists of multiple components, one in class II (Idd1) and the other adjacent to, but distinct from, Idd1 (Idd16). Phenotypes of NOD. IIS-Idd3 congenic mice, which share the same alleles at both Il2 and Il21 as the NOD mouse, were indistinguishable from the NOD parental strain, indicating that both Il2 and Il21 are candidates for Idd3. In contrast, NOD. IIS-Idd10 congenic mice, which share the same alleles at Fcgr1, a previous candidate for Idd10, as the NOD mouse, were protected from type 1 diabetes, suggesting that Fcgr1 may not be responsible for the Idd10 effect. These data suggest that the use of strain colony closely related to a disease model to find the same candidate mutation on different haplotypes and make congenic strains with this recombinant chromosome, termed ancestral haplotype congenic mapping, is an effective strategy for fine mapping and identification of genes responsible for complex traits. PMID:14679059

  14. Detailed PCB congener characterization of influent and effluent at New York and New Jersey WPCPs

    SciTech Connect

    Durell, G.S.; Lizotte, R.D. Jr.; Solomon, M.H.; Green, J.W.; Spadone, J.; Pires, L.

    1995-12-31

    The waste streams at 26 New York City and New Jersey water pollution control plants (WPCP) were characterized for PCB. Time-integrated influent and effluent samples were collected during normal and high (storm) flow conditions; high flow influent simulated what may by-pass the plant and be discharged through combined sewer overflows. State-of-the-art congener-specific analytical methods were used to achieve detection limits from 0.05 to 0.3 ng/L. Concentrations of 71 individual PCB congeners that constitute approximately 95% of the total PCB in Aroclors and environmental samples were determined. The PCB concentrations and congener distributions varied notably among plants. Individual congener concentrations were typically well below 1 ng/L in the effluent, with a few congeners being detected at 5 to 10 ng/L levels in some samples. The concentrations were under 1 ng/L in most influent samples, with occasional determinations above 10 ng/L. The average total PCB concentration, defined as the sum of the 71 individual congener concentrations, at the 26 WPCPs were 27, 110, and 160 ng/L for normal flow effluent, normal flow influent, and high flow influent, respectively. The results indicate that PCB levels in New York City and New Jersey WPCP discharges are generally low, with most effluent having total PCB concentrations below 0.05 {micro}g/L. The PCB levels in the influent were commonly under 0.1 {micro}g/L and became slightly elevated at most plants during storms while at some plants the increase in flow appeared to dilute the PCB in the influent. The WPCPs remove, on average, approximately 75% of the PCB received in the influent.

  15. Transdermal estradiol for postpartum depression: A promising treatment option

    PubMed Central

    Moses-Kolko, Eydie L.; Berga, Sarah L.; Kalro, Brinda; Sit, Dorothy K.Y.; Wisner, Katherine L.

    2009-01-01

    Postpartum depression (PPD) is the most common complication of childbirth and affects one out of seven childbearing women. While conventional pharmacological and psychotherapeutic antidepressant treatments are effective for PPD, a natural alternative may be preferred by postpartum women, especially those who breastfeed their infants. The treatment of PPD with synthetic forms of naturally occurring estrogen is mechanistically appealing because PPD occurs in the context of estrogen withdrawal at parturition. Preliminary evidence suggests that PPD is a disorder of hormone-related mood dysregulation (similar to perimenopausal depression) that can be effectively treated with estrogen. This review provides the basic science and clinical background as well as safety considerations to support the application of transdermal estradiol as a treatment for PPD. We conclude that estradiol treatment for PPD requires confirmation of efficacy in a randomized clinical trial prior to routine clinical use as monotherapy. Additional data regarding maternal tolerability of cyclic progestins, long-term safety of estradiol treatment, estradiol passage into breastmilk and infants, and interdisciplinary collaboration among psychiatrists and gynecologists is also needed before estradiol is used in women who decline or fail to respond to first-line antidepressant treatments, or as an augmentation of conventional antidepressant treatment. PMID:19661765

  16. The role of estradiol in male reproductive function.

    PubMed

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  17. The role of estradiol in male reproductive function

    PubMed Central

    Schulster, Michael; Bernie, Aaron M; Ramasamy, Ranjith

    2016-01-01

    Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis. Estrogen receptors, as well as aromatase, the enzyme that converts testosterone to estrogen, are abundant in brain, penis, and testis, organs important for sexual function. In the brain, estradiol synthesis is increased in areas related to sexual arousal. In addition, in the penis, estrogen receptors are found throughout the corpus cavernosum with high concentration around neurovascular bundles. Low testosterone and elevated estrogen increase the incidence of erectile dysfunction independently of one another. In the testes, spermatogenesis is modulated at every level by estrogen, starting with the hypothalamus-pituitary-gonadal axis, followed by the Leydig, Sertoli, and germ cells, and finishing with the ductal epithelium, epididymis, and mature sperm. Regulation of testicular cells by estradiol shows both an inhibitory and a stimulatory influence, indicating an intricate symphony of dose-dependent and temporally sensitive modulation. Our goal in this review is to elucidate the overall contribution of estradiol to male sexual function by looking at the hormone's effects on erectile function, spermatogenesis, and libido. PMID:26908066

  18. Congener Profiles of Polychlorinated Biphenyls in Firn and ice From Lomonosovfonna, Svalbard.

    NASA Astrophysics Data System (ADS)

    Hermanson, M. H.; Matthews, K. A.; Isaksson, E.; Muir, D. C.; Winther, J.; van de Wal, R. S.; Steig, E. J.

    2002-12-01

    In April 2000, a 60-meter ice core was drilled on Lomonosovfonna, the highest elevation ice field on Svalbard. The upper 38 meters, dating to about 1920, were analyzed for 108 polychlorinated biphenyl congeners (PCB). The objective was to identify the historic variability of congener patterns and concentration of PCB at Lomonosovfonna. PCB are known to bioaccumulate to significant concentrations in Svalbard wildlife to the extent that health of some organisms may be threatened. Knowing the input history is vital to understanding how present conditions compare to the past. Total PCB concentration in surface snow (0 to 0.5 meter) at Lomonosovfonna in 2000 was 464 pg/L, 60% of the highest concentration (777 pg/L) occurring in about the 1960s, the peak production period for PCB. The surface value was about two times greater than in the layer below (0.5 to 1 meter; 229 pg/L). The surface layer also had a greater amount of more volatile, lower molecular mass (MM) PCB congeners than found in the firn below it. Most PCB found in sub-surface (> 1 meter) Lomonosovfonna ice are from tetra-CB and penta-CB homologues (about 30% of total PCB each) with about 15% of total PCB from hexa-CB. Surface samples (<1 meter) contain more hexa-CB. PCB distribution throughout the profile is dominated by 29 congeners that comprise from 53% to 75% of total PCB, with less in the top meter than in the deeper core. Among the 29 dominant congeners are 7 (and 4 co-eluting) that make up about 25% of total PCB in the top meter and 33 to 40% in deeper layers of the core. These are PCB 49 (and 2 co-eluting PCB 43 + 37), 52, 95, 110, 118, 153 (and two co-eluting PCB, 132 + 105). Some of these congeners are among the most persistent PCB and are often found in other environmental matrices. Our results show that PCB concentrations at Lomonosovfonna are declining from peak periods and that the congener distribution may be shifting away from the 29 dominant congeners to include more high MM PCB

  19. Polychlorinated Biphenyl Congeners that Increase the Glucuronidation and Biliary Excretion of Thyroxine Are Distinct from the Congeners that Enhance the Serum Disappearance of Thyroxine

    PubMed Central

    Martin, L. A.; Wilson, D. T.; Reuhl, K. R.; Gallo, M. A.

    2012-01-01

    Polychlorinated biphenyl (PCB) congeners differentially reduce serum thyroxine (T4) in rats, but little is known about their ability to affect biliary excretion of T4. Thus, male Sprague-Dawley rats were orally administered Aroclor-1254, Aroclor-1242 (32 mg/kg per day), PCB-95, PCB-99, PCB-118 (16 mg/kg per day), PCB-126 (40 μg/kg per day), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (3.9 μg/kg per day), or corn oil for 7 days. Twenty-four hours after the last dose, [125I]T4 was administered intravenously, and blood, bile, and urine samples were collected for quantifying [125I]T4 and in bile [125I]T4 metabolites. Serum T4 concentrations were reduced by all treatments, but dramatic reductions occurred in response to Aroclor-1254, PCB-99 [phenobarbital (PB)-type congener], and PCB-118 (mixed-type congener). None of the treatments increased urinary excretion of [125I]T4. Aroclor-1254, PCB-118, TCDD, and PCB-126 (TCDD-type congener) increased biliary excretion of T4-glucuronide by 850, 756, 710, and 573%, respectively, corresponding to marked induction of hepatic UDP-glucuronosyltransferase (UGT) activity toward T4. PCB-95 and PCB-99 did not induce UGT activity; therefore, the increased biliary excretion of T4-glucuronide was related to the affinity of congeners for the aryl hydrocarbon receptor. The disappearance of [125I]T4 from serum was rapid (within 15-min) and was increased by Aroclor-1254, PCB-99 and PCB-118. Thus, reductions in serum T4 in response to PCBs did not always correspond with UGT activity toward T4 or with increased biliary excretion of T4-glucuronide. The rapid disappearance of [125I]T4 from the serum of rats treated with PB-like PCBs suggests that increased tissue uptake of T4 is an additional mechanism by which PCBs may reduce serum T4. PMID:22187485

  20. Direction of estradiol metabolism as a control of its hormonal action--uterotrophic activity of estradiol metabolites.

    PubMed

    Martucci, C; Fishman, J

    1977-12-01

    The uterotrophic activities of the catechol metabolites of estradiol 2-hydroxyestrone, 2-methoxyestrone and 2-hydroxyestradiol were measured under conditions of continuous administration of sc implanted paraffin pellets. The activity of these estrogens was compared to that of estradiol-17beta and its other principal metabolites estrone, estriol and 15alpha-hydroxyestriol (estetrol). The major catechol estrogens, 2-hydroxyestrone and 2-methoxyestrone, and the pregnancy metabolite, 15alpha-hydroxyestriol, exhibited no uterotrophic activity. The minor catecholestrogen, 2-hydroxyestradiol, showed some activity whose character was different from that exhibited by implants of estradiol, estrone and estriol all of which were equipotent uterotrophic agents. Implants of 2-hydroxyestrone in the presence of estradiol or estriol pellets did not diminish the response to the latter indicating that the 2-hydroxyestrone is not antiestrogenic under these conditions. It is concluded that the direction of estradiol metabolism can have a profound influence on the expression of peripheral hormonal activity with hydroxylation at C-2 terminating and hydroxylation at C-16 extending it. PMID:590186

  1. β-Estradiol and ethinyl-estradiol contamination in the rivers of the Carpathian Basin.

    PubMed

    Avar, Péter; Zrínyi, Zita; Maász, Gábor; Takátsy, Anikó; Lovas, Sándor; G-Tóth, László; Pirger, Zsolt

    2016-06-01

    17β-Estradiol (E2) and 17α-ethinyl estradiol (EE2), which are environmental estrogens, have been determined with LC-MS in freshwater. Their sensitive analysis needs derivatization and therefore is very hard to achieve in multiresidue screening. We analyzed samples from all the large and some small rivers (River Danube, Drava, Mur, Sava, Tisza, and Zala) of the Carpathian Basin and from Lake Balaton. Freshwater was extracted on solid phase and derivatized using dansyl chloride. Separation was performed on a Kinetex XB-C18 column. Detection was achieved with a benchtop orbitrap mass spectrometer using targeted MS analysis for quantification. Limits of quantification were 0.05 ng/L (MS1) and 0.1 ng/L (MS/MS) for E2, and 0.001 ng/L (MS1) and 0.2 ng/L (MS/MS) for EE2. River samples contained n.d.-5.2 ng/L E2 and n.d.-0.68 ng/L EE2. Average levels of E2 and EE2 were 0.61 and 0.084 ng/L, respectively, in rivers, water courses, and Lake Balaton together, but not counting city canal water. EE2 was less abundant, but it was still present in almost all of the samples. In beach water samples from Lake Balaton, we measured 0.076-0.233 E2 and n.d.-0.133 EE2. A relative high amount of EE2 was found in river Zala (0.68 ng/L) and in Hévíz-Páhoki canal (0.52 ng/L), which are both in the catchment area of Lake Balaton (Hungary). PMID:26936475

  2. Membrane-initiated estradiol actions mediate structural plasticity and reproduction

    PubMed Central

    Micevych, Paul; Christensen, Amy

    2012-01-01

    Over the years, our ideas about estrogen signaling have greatly expanded. In addition to estradiol having direct nuclear actions that mediate transcription and translation, more recent experiments have demonstrated membrane-initiated signaling. Both direct nuclear and estradiol membrane signaling can be mediated by the classical estrogen receptors, ERα and ERβ, which are two of the numerous putative membrane estrogen receptors. Thus far, however, only ERα has been shown to play a prominent role in regulating female reproduction and sexual behavior. Because ERα is a ligand-gated transcription factor and not a typical membrane receptor, trafficking to the cell membrane requires post-translational modifications. Two necessary modifications are palmitoylation and association with caveolins, a family of scaffolding proteins. In addition to their role in trafficking, caveolin proteins also serve to determine ERα interactions with metabotropic glutamate receptors (mGluRs). It is through these complexes that ERα, which cannot by itself activate G proteins, is able to initiate intracellular signaling. Various combinations of ERα-mGluR interactions have been demonstrated throughout the nervous system from hippocampus to striatum to hypothalamus to dorsal root ganglion (DRG) in both neurons and astrocytes. These combinations of ER and mGluR allow estradiol to have both facilitative and inhibitory actions in neurons. In hypothalamic astrocytes, the estradiol-mediated release of intracellular calcium stores regulating neurosteroid synthesis requires ERα-mGluR1a interaction. In terms of estradiol regulation of female sexual receptivity, activation of ERα-mGluR1a signaling complex leads to the release of neurotransmitters and alteration of neuronal morphology. This review will examine estradiol membrane signaling (EMS) activating a limbic-hypothalamic lordosis regulating circuit, which involves ERα trafficking, internalization, and modifications of neuronal morphology

  3. Estradiol Membrane-Initiated Signaling and Female Reproduction

    PubMed Central

    Micevych, Paul E; Wong, Angela May; Mittelman-Smith, Melinda Anne

    2016-01-01

    The discoveries of rapid, membrane-initiated steroid actions and central nervous system steroidogenesis have changed our understanding of the neuroendocrinology of reproduction. Classical nuclear actions of estradiol and progesterone steroids affecting transcription are essential. However, with the discoveries of membrane-associated steroid receptors, it is becoming clear that estradiol and progesterone have neurotransmitter-like actions activating intracellular events. Ultimately, membrane-initiated actions can influence transcription. Estradiol membrane-initiated signaling (EMS) modulates female sexual receptivity and estrogen feedback regulating the luteinizing hormone (LH) surge. In the arcuate nucleus, EMS activates a lordosis-regulating circuit that extends to the medial preoptic nucleus and subsequently to the ventromedial nucleus (VMH)—the output from the limbic and hypothalamic regions. Here, we discuss how EMS leads to an active inhibition of lordosis behavior. To stimulate ovulation, EMS facilitates astrocyte synthesis of progesterone (neuroP) in the hypothalamus. Regulation of GnRH release driving the LH surge is dependent on estradiol-sensitive kisspeptin (Kiss1) expression in the rostral periventricular nucleus of the third ventricle (RP3V). NeuroP activation of the LH surge depends on Kiss1, but the specifics of signaling have not been well elucidated. RP3V Kiss1 neurons appear to integrate estradiol and progesterone information which feeds back onto GnRH neurons to stimulate the LH surge. In a second population of Kiss1 neurons, estradiol suppresses the surge but maintains tonic LH release, another critical component of the estrous cycle. Together, evidence suggests that regulation of reproduction involves membrane action of steroids, some of which are synthesized in the brain. PMID:26140715

  4. Congener-specific polychlorinated biphenyl patterns in eggs of aquatic birds from the Lower Laguna Madre, Texas

    SciTech Connect

    Mora, M.A.

    1996-06-01

    Eggs from four aquatic bird species nesting in the Lower Laguna Madre, Texas, were collected to determine differences and similarities in the accumulation of congener-specific polychlorinated biphenyls (PCBs) and to evaluate PCB impacts on reproduction. Because of the different toxicities of PCB congeners, it is important to know which congeners contribute most to total PCBs. The predominant PCB congeners were 153, 138, 180, 110, 118, 187, and 92. Collectively, congeners 153, 138, and 180 accounted for 26 to 42% of total PCBs. Congener 153 was the most abundant in Caspian terns (Sterna caspia) and great blue herons (Ardea herodias) and congener 138 was the most abundant in snowy egrets (Egretta thula) and tricolored herons (Egretta tricolor). Principal component analysis indicated a predominance of higher chlorinated biphenyls in Caspian terns and great blue herons and lower chlorinated biphenyls in tricolored herons. Snowy egrets had a predominance of pentachlorobiphenyls. These results suggest that there are differences in PCB congener patterns in closely related species and that these differences are more likely associated with the species` diet rather than metabolism. Total PCBs were significantly greater (p < 0.05) in Caspian terns than in the other species. Overall, PCBs in eggs of birds from the Lower Laguna Madre were below concentrations known to affect bird reproduction.

  5. ANALYSIS OF CHIRAL PESTICIDES AND POLYCHLORINATED BIPHENYL CONGENERS IN ENVIRONMENTAL SAMPLES

    EPA Science Inventory

    Over 25 % of pesticides and other toxic organic pollutants are chiral, as are 19 of the 209 polychlorinated biphenyl (PCB) congeners; that is, they exist as two mirror image species called enantiomers (PCB enantiomers are called atropisomers). The enantiomers of a chiral compound...

  6. DIFFERENTIAL EFFECTS OF TWO LOTS OF AROCLOR 1254R: CONGENER ANALYSIS AND NEUROCHEMICAL ENDPOINTS.

    EPA Science Inventory

    Introduction
    Polychlorinated biphenyls (PCBs) are widely used in industry as heat transfer and dielectric fluids for transformers and capacitors1. PCBs were commercially produced as AroclorR mixtures in USA by the chlorination of biphenyl. Although all 209 congeners can be syn...

  7. Trait responses of invasive aquatic Ludwigia congeners (Onagraceae): effects of ploidy and resource availability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding traits underlying colonization and niche breadth of invasive plants is key to developing sustainable management solutions to curtail invasions at the establishment phase, when efforts are often most effective. The aim of this study was to evaluate how two invasive congeners differing i...

  8. MODELLING OF POLYCHLORINATED-DIOXIN AND -FURAN CONGENER PROFILES FROM MUNICIPAL WASTE COMBUSTION

    EPA Science Inventory

    The paper discusses a model, based on experimental data, that was developed to describe the profile of polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) congeners formed in the duct region of a pilot-scale combustor simulating large-scale municipal w...

  9. Thiophene congeners of morpholine and allylamine type antifungals--syntheses and biological activities.

    PubMed

    Bracher, F; Papke, T

    1995-08-01

    A thiophene analogue 8 of the antifungal drug amorolfine (1) was prepared starting from the alcohol 5. In addition, congeners of naftifine, terbinafine and butenafine, in which the naphthalene ring is replaced by a branched thienylalkyl group, wee synthesized. Of the four drug analogues only compound 9, related to terbinafine, showed significant antifungal activity. PMID:7568314

  10. CONGENER-SPECIFIC DETECTION OF DIOXINS USING JET-REMPI. (R827927)

    EPA Science Inventory

    Although 210 chemically different polychlorinated dibenzo-p-dioxin and dibenzofuran congeners can be produced during combustion, it is currently believed that fewer than 20 are toxic enough to warrant monitoring. SRI is developing a continuous emissions monitor to study...

  11. Chromatographic determination of octanol-water partition coefficients (K/sub ow/'s) for 58 polychlorinated biphenyl congeners

    SciTech Connect

    Rapaport, R.A.; Eisenreich, S.J.

    1984-03-01

    Octanol-water partition coefficients of 58 poly-chlorinated biphenyl (PCB) congeners have been determined by reverse-phase C/sub 18/ high-performance liquid chromatography (HPLC) of Aroclor 1242 and 1254 mixtures. High-resolution glass capillary gas-liquid chromatography was used for the detection of the eluted individual congeners. Some PCB congeners behaved atypically from other organics on reverse-phase HPLC, and empirically derived correction factors were used to adjust K/sub ow/ values. Congener log K/sub ow/ values for PCB's ranged from an average of 4.5 for N/sub Cl/ = 1 to 8.1 for N/sub Cl/ = 7. The environmental implications of PCB K/sub ow/ values and congener behavior on the C /sub 18/ reverse-phase column are discussed. 35 references.

  12. Toxicological consequences of feeding PCB congeners to infant rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys.

    PubMed

    Arnold, D L; Bryce, F; Mes, J; Tryphonas, H; Hayward, S; Malcolm, S

    1999-01-01

    In a study designed to minimize interspecies extrapolation of toxicological data, nine rhesus (Macaca mulatta) and 15 cynomolgus (M. fascicularis) day-old infant monkeys were separated from their dams following parturition and hand-reared using a liquid non-human primate formulation. The infants were randomly divided into a control and a treated group which received a mixture of polychlorinated biphenyl (PCB) congeners analogous to those found in breast milk from Canadian women. The concentration of congeners in the dosing media resulted in each infant receiving a total of 7.5 microg PCB congeners/kg body weight/day. The congeners were added either to the liquid formulation or to corn oil and administered to the back of the monkey's mouth for 20 weeks. Monthly blood and adipose specimens were obtained during the dosing period and then periodically until the monkey was necropsied or taken off test (minimum of 66 weeks on test) for congener analysis. Parameters such as body weight, formula consumption, tooth eruption, somatic measurements, haematology and serum biochemistry were monitored throughout the study. In addition, a qualitative evaluation of the absorption and depletion of the various congeners was undertaken as was an immunological evaluation. For the monitored parameters, very few differences were found to be statistically significant. For the immunological parameters, the only statistically differences found were a reduction over time for immunoglobulins M and G antibodies to sheep red blood cells (cyno, P = 0.025; rhesus, P = 0.002) and a treatment-related reduction in the levels of the HLA-DR cell surface marker (mean percent, P = 0.016; absolute levels, P = 0.027). There were some qualitative differences regarding absorption and depletion rates for the various congeners, but it could not be definitely ascertained whether these differences were due to species differences or dosing mode. However, statistically significant differences were found for

  13. Comparative Biological Effects and Potency of 17a- and 17ß-Estradiol In Fathead Minnows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol is the most potent natural estrogen commonly found in anthropogenically altered environments and has been the focus of many toxicological laboratory studies. However, fewer aquatic toxicological data on the effects of 17a-estradiol, a diastereoisomer of 17ß-estradiol, exists in the li...

  14. Disposition of toxic PCB congeners in snapping turtle eggs: expressed as toxic equivalents of TCDD

    SciTech Connect

    Bryan, A.M.; Stone, W.B.; Olafsson, P.G.

    1987-11-01

    Studies of snapping turtles, taken from the region of the Upper Hudson River, in New York State, revealed exceedingly high levels of PCBs in the adipose tissue. There is evidence to suggest that large reserves of fat provide protection against chlorinated hydrocarbon toxicity. Such storage may protect snapping turtle eggs from disposition of toxic PCB congeners and account for the apparent absence of reports regarding detrimental effects on the hatchability of eggs from turtles living in the vicinity of the upper Hudson River. The present study was undertaken to determine if indeed these eggs are protected against disposition of toxic PCB congeners by the presence of large reserves of fat. Although tissue volumes play an important role in determining the initial site of disposition, the major factor controlling the elimination of these compounds involves metabolism. For simple halogenated benzenes as well as for more complex halogenated biphenyls, oxidative metabolism catalyzed by P-448, occurs primarily at the site of two adjacent unsubstituted carbon atoms via arene oxide formation leading to the formation of water soluble metabolites. Toxicological studies have demonstrated that the most toxic PCB congeners, isosteriomers of tetrachlorodibenzo-p-dioxin (TCDD), require no metabolic activation. These compounds have chlorine atoms in the meta and para positions of both rings. It may be concluded that the structures of PCB congeners and isomers which favor induction of cytochrome P-448 are also those which are toxic and resist metabolism. It is the objective of the present study to determine if the heavy fat bodies of the female turtle provide a sufficiently large sink to retain the toxic congeners and prevent their incorporation into the eggs.

  15. Comparison of PBDE congeners as inducers of oxidative stress in zebrafish.

    PubMed

    Usenko, Crystal Y; Abel, Erika L; Kudela, Molly; Janise, Annie; Bruce, Erica D

    2015-05-01

    A proposed primary pathway through which polybrominated diphenyl ethers (PBDEs) disrupt normal biological functions is oxidative stress. In the present study, 4 PBDE congeners were evaluated for their potential to initiate oxidative stress in zebrafish during development: BDE 28, BDE 47, BDE 99, and BDE 100. N-acetylcysteine (NAC) was used to increase intracellular glutathione concentrations and only decreased the effects of BDE 28 at 10 ppm and 20 ppm and BDE 47 at 20 ppm. N-acetylcysteine coexposure did not alter the rates of mortality or curved body axis compared with PBDE exposure alone. The activity of glutathione-S-transferase (GST) was not altered at 24 h postfertilization (hpf), but increased following 10 ppm BDE 28 exposure at 120 hpf. Transcription of several genes associated with stress was also evaluated. At 24 hpf, cytochrome c oxidase subunit 6a (COX6a) transcription was up-regulated in embryos exposed to BDE 99, and BDE 28 exposure up-regulated the transcription of Glutathione-S-transferase-pi (GSTpi). At 24 hpf, glutamate-cysteine ligase (GCLC) was slightly down-regulated by all congeners evaluated. At 120 hpf, TNF receptor-associated protein 1 (TRAP1) and COX6A were up-regulated by all congeners, however GSTpi was down-regulated by all congeners. The results of quantitative real-time transcription polymerase chain reaction are mixed and do not strongly support a transcriptional response to oxidative stress. According to the authors' data, PBDEs do not induce oxidative stress. Oxidative stress may occur at high exposure concentrations; however, this does not appear to be a primary mechanism of action for the PBDE congeners tested. PMID:25663549

  16. A High-Speed Congenic Strategy Using First-Wave Male Germ Cells

    PubMed Central

    Ogonuki, Narumi; Inoue, Kimiko; Hirose, Michiko; Miura, Ikuo; Mochida, Keiji; Sato, Takahiro; Mise, Nathan; Mekada, Kazuyuki; Yoshiki, Atsushi; Abe, Kuniya; Kurihara, Hiroki; Wakana, Shigeharu; Ogura, Atsuo

    2009-01-01

    Background In laboratory mice and rats, congenic breeding is essential for analyzing the genes of interest on specific genetic backgrounds and for analyzing quantitative trait loci. However, in theory it takes about 3–4 years to achieve a strain carrying about 99% of the recipient genome at the tenth backcrossing (N10). Even with marker-assisted selection, the so-called ‘speed congenic strategy’, it takes more than a year at N4 or N5. Methodology/Principal Findings Here we describe a new high-speed congenic system using round spermatids retrieved from immature males (22–25 days of age). We applied the technique to three genetically modified strains of mice: transgenic (TG), knockin (KI) and N-ethyl-N-nitrosourea (ENU)-induced mutants. The donor mice had mixed genetic backgrounds of C57BL/6 (B6)∶DBA/2 or B6∶129 strains. At each generation, males used for backcrossing were selected based on polymorphic marker analysis and their round spermatids were injected into B6 strain oocytes. Backcrossing was repeated until N4 or N5. For the TG and ENU-mutant strains, the N5 generation was achieved on days 188 and 190 and the proportion of B6-homozygous loci was 100% (74 markers) and 97.7% (172/176 markers), respectively. For the KI strain, N4 was achieved on day 151, all the 86 markers being B6-homozygous as early as on day 106 at N3. The carrier males at the final generation were all fertile and propagated the modified genes. Thus, three congenic strains were established through rapid generation turnover between 41 and 44 days. Conclusions/Significance This new high-speed breeding strategy enables us to produce congenic strains within about half a year. It should provide the fastest protocol for precise definition of the phenotypic effects of genes of interest on desired genetic backgrounds. PMID:19333383

  17. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Estradiol and related esters. 556.240 Section 556.240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD...

  18. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Estradiol and related esters. 556.240 Section 556.240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD...

  19. 21 CFR 556.240 - Estradiol and related esters.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Estradiol and related esters. 556.240 Section 556.240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD...

  20. Fate of 17B-estradiol in anaerobic lagoon digesters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fate of [14C]17B-estradiol ([14C]E2) was monitored for 42 d in triplicate 10 L anaerobic digesters. Total radioactive residues (TRR) decreased rapidly in the liquid layer of the digesters and reached a steady-state value of 19-24% of the initial dose after 4 days. LC/MS/MS analyses of the liqu...

  1. Fate of estradiol and testosterone in anaerobic lagoon digestors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Laboratory-scale lagoon digestors were constructed, and the fate of 14C-labelled 17ß-estradiol (E2) and testosterone (Test) were monitored for 42 d anaerobically under biological and sterile conditions. Hormone levels decreased in the liquid layer and increased in the sludge with time. At 42 d, 16-2...

  2. Fate of glucuronide conjugated estradiol in the environment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The fate and transport of conjugated reproductive hormones, which are polar compared to parent hormones, are little understood. Laboratory bench-scale soil (Hamar; Sandy, mixed, frigid typic Endoaquolls) sorption studies were conducted using [14C] 17ß-estradiol-3-glucuronide for a range of concentra...

  3. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  4. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  5. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  6. 21 CFR 522.2478 - Trenbolone acetate and estradiol benzoate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ANIMAL DRUGS § 522.2478 Trenbolone acetate and estradiol benzoate. (a) Specifications. Each implant dose...) For an implant as described in paragraph (a)(1) of this section: (A) Amount. 200 mg trenbolone acetate... feed efficiency. (C) Limitations. Implant subcutaneously in ear only. Safety and effectiveness have...

  7. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  8. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  9. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  10. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  11. 21 CFR 862.1260 - Estradiol test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Estradiol test system. 862.1260 Section 862.1260 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  12. Neurotensin enhances estradiol induced DNA synthesis in immature rat uterus

    SciTech Connect

    Mistry, A.; Vijayan, E.

    1985-05-27

    Systemic administration of Neurotensin, a tridecapeptide, in immature rats treated with estradiol benzoate significantly enhances uterine DNA synthesis as reflected by the incorporation of /sup 3/H-thymidine. The peptide may have a direct action on the uterus. Substance P, a related peptide, had no effect on uterine DNA synthesis. 18 references, 4 tables.

  13. Estradiol valerate and alcohol intake: dose-response assessments

    PubMed Central

    Quirarte, Gina L; Reid, Larry D; de la Teja, I Sofía Ledesma; Reid, Meta L; Sánchez, Marco A; Díaz-Trujillo, Arnulfo; Aguilar-Vazquez, Azucena; Prado-Alcalá, Roberto A

    2007-01-01

    Background An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. Results With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. Conclusion The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries. PMID:17335585

  14. Empirical modeling of an in vitro activity of polychlorinated biphenyl congeners and mixtures.

    PubMed Central

    Svendsgaard, D J; Ward, T R; Tilson, H A; Kodavanti, P R

    1997-01-01

    The goal of this research is to predict an in vitro activity of polychlorinated biphenyl (PCB) congeners and their mixtures and to describe the relationship between this activity and chemical structure. The test system used multiple PCB concentrations on each cell culture plate in a repeated measures design, which improved precision for comparing between concentration levels. A weighted regression that accounted for this experimental design feature was used in fitting a nonlinear dose-response exponential model to the PCB concentration-activity data from an in vitro test system in which 3H-phorbol ester binding was measured in cerebellar granule cells exposed to different PCB congeners to test for their effects on protein kinase C translocation. The model allowed for the minimum level to be less than control, a common slope, and the estimation of the log of the concentration that produces an activity 50% above the control activity (E50) for 36 congeners and 3 commercial mixtures. Next, a weighted logistic regression using a second order response model in the variables Clortho, Clpara, and Clmeta was used to relate the estimated log E50s to indicators of chemical structure. This model was preferred over models that might seem more mechanistically based because in internal validation, it attained a smaller PRESS statistic (the sum of squares between all observed and predicted observations) than other models. Evidently, this second order model makes more efficient use of parameters than other models considered. Plots of the predictions of the logistic second order response model versus log Kow confirm the usual pattern that congeners with intermediate levels of log Kow are the more active. The data of three commercial mixtures were included in this regression by assuming a common combination index (ratio of observed E50 to predicted E50, assuming dose addition). The logistic model suggests that congeners with one, two, or three chlorine substitutions at the ortho

  15. ESTRADIOL AND THE ESTRADIOL METABOLITE, 2-HYDROXYESTRADIOL, ACTIVATE AMP-ACTIVATED PROTEIN KINASE IN C2C12 MYOTUBES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Systemic loss of estradiol (E2) during menopause is associated with increased adiposity which can be prevented with E2 replacement. Rodent studies suggest that E2, or lack of, is a key mediator in menopause-related metabolic changes. We have previously demonstrated that E2 treatment produces a rap...

  16. The Orientation and Dynamics of Estradiol and Estradiol Oleate in Lipid Membranes and HDL Disc Models

    PubMed Central

    Vogel, Alexander; Scheidt, Holger A.; Feller, Scott E.; Metso, Jari; Badeau, Robert M.; Tikkanen, Matti J.; Wähälä, Kristiina; Jauhiainen, Matti; Huster, Daniel

    2014-01-01

    Estradiol (E2) and E2 oleate associate with high-density lipoproteins (HDLs). Their orientation in HDLs is unknown. We studied the orientation of E2 and E2 oleate in membranes and reconstituted HDLs, finding that E2 and E2 oleate are membrane-associated and highly mobile. Our combination of NMR measurements, molecular dynamics simulation, and analytic theory identifies three major conformations where the long axis of E2 assumes a parallel, perpendicular, or antiparallel orientation relative to the membrane’s z-direction. The perpendicular orientation is preferred, and furthermore, in this orientation, E2 strongly favors a particular roll angle, facing the membrane with carbons 6, 7, 15, and 16, whereas carbons 1, 2, 11, and 12 point toward the aqueous phase. In contrast, the long axis of E2 oleate is almost exclusively oriented at an angle of ∼60° to the z-direction. In such an orientation, the oleoyl chain is firmly inserted into the membrane. Thus, both E2 and E2 oleate have a preference for interface localization in the membrane. These orientations were also found in HDL discs, suggesting that only lipid-E2 interactions determine the localization of the molecule. The structural mapping of E2 and E2 oleate may provide a design platform for specific E2-HDL-targeted pharmacological therapies. PMID:24988346

  17. Relationship between ovarian reserve and preovulatory estradiol during a fixed-time AI protocol in beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estradiol production is essential for reproductive efficiency. This study compared numbers of follicles in beef cows that did or did not have elevated preovulatory estradiol during a fixed-time AI (FTAI) protocol. In experiment 1, 5 low estradiol (LowE2) and 5 high estradiol (HighE2) cows were slaug...

  18. Polychlorinated biphenyl (PCB) congener effects on the longevity of the housefly

    SciTech Connect

    Tehseen, W.M.; Hansen, L.G.; Schaeffer, D.J. )

    1992-01-01

    The microsomal monooxygenase system in the housefly is well-characterized, active, inducible and inhibited by the same types of compounds as in vertebrate systems. Flies metabolize PCBs to polar products and retain congeners from a commercial mixture in proportions consistent with PCB biotransformation and elimination in vertebrates. Although TCDD has been shown to have a high affinity for, and be an effective agonist of the juvenile hormone receptor in insects, toxic manifestations in adult insects may differ from those in certain highly sensitive vertebrate species. This study was undertaken to determine if the housefly bioassay could effectively compare the net adverse biological activity of a group of PCB congeners independent of Ah receptor effects.

  19. A facile microwave-assisted protocol for rapid synthesis of N-acetylneuraminic acid congeners

    PubMed Central

    Saludes, Jonel P.; Sahoo, Dhananjaya; Monreal, I. Abrrey

    2014-01-01

    We developed a simple, rapid and efficient microwave irradiation-assisted protocol that is 1- to 2-orders of magnitude faster than conventional techniques, providing an expedient access to the sialic acid congeners Neu5Ac1Me (1), Neu5Acβ1,2Me2 (2), Neu5Ac1Me O-peracetate (3) and 4,5-oxazoline of Neu5Ac2en1Me O-peracetate (4). PMID:24678239

  20. Investigations into the effects of PCB congeners on reproduction in lake trout from the Great Lakes

    USGS Publications Warehouse

    Mac, Michael J.; Schwartz, T.R.

    1992-01-01

    Eggs of feral lake trout collected in Lake Michigan were reared under laboratory conditions and monitored for egg hatchability, physical abnormalities, and survival of fry. Subsamples of eggs were also analyzed for PCB congeners. A negative correlation was found between egg hatchability and total PCBs but expressing PCB dose as dioxin equivalents did not produce as strong a correlation. No other measure of reproductive success correlated significantly with PCB concentration in the egg.

  1. In silico predictive studies of mAHR congener binding using homology modelling and molecular docking.

    PubMed

    Panda, Roshni; Cleave, A Suneetha Susan; Suresh, P K

    2014-09-01

    The aryl hydrocarbon receptor (AHR) is one of the principal xenobiotic, nuclear receptor that is responsible for the early events involved in the transcription of a complex set of genes comprising the CYP450 gene family. In the present computational study, homology modelling and molecular docking were carried out with the objective of predicting the relationship between the binding efficiency and the lipophilicity of different polychlorinated biphenyl (PCB) congeners and the AHR in silico. Homology model of the murine AHR was constructed by several automated servers and assessed by PROCHECK, ERRAT, VERIFY3D and WHAT IF. The resulting model of the AHR by MODWEB was used to carry out molecular docking of 36 PCB congeners using PatchDock server. The lipophilicity of the congeners was predicted using the XLOGP3 tool. The results suggest that the lipophilicity influences binding energy scores and is positively correlated with the same. Score and Log P were correlated with r = +0.506 at p = 0.01 level. In addition, the number of chlorine (Cl) atoms and Log P were highly correlated with r = +0.900 at p = 0.01 level. The number of Cl atoms and scores also showed a moderate positive correlation of r = +0.481 at p = 0.01 level. To the best of our knowledge, this is the first study employing PatchDock in the docking of AHR to the environmentally deleterious congeners and attempting to correlate structural features of the AHR with its biochemical properties with regards to PCBs. The result of this study are consistent with those of other computational studies reported in the previous literature that suggests that a combination of docking, scoring and ranking organic pollutants could be a possible predictive tool for investigating ligand-mediated toxicity, for their subsequent validation using wet lab-based studies. PMID:23081860

  2. Inhalation and Dietary Exposure to PCBs in Urban and Rural Cohorts via Congener-Specific Measurements

    PubMed Central

    2015-01-01

    Polychlorinated biphenyls (PCBs) are a group of 209 persistent organic pollutants, whose documented carcinogenic, neurological, and respiratory toxicities are expansive and growing. However, PCB inhalation exposure assessments have been lacking for North American ambient conditions and lower-chlorinated congeners. We assessed congener-specific inhalation and dietary exposure for 78 adolescent children and their mothers (n = 68) in the Airborne Exposure to Semi-volatile Organic Pollutants (AESOP) Study. Congener-specific PCB inhalation exposure was modeled using 293 measurements of indoor and outdoor airborne PCB concentrations at homes and schools, analyzed via tandem quadrupole GS-MS/MS, combined with questionnaire data from the AESOP Study. Dietary exposure was modeled using Canadian Total Diet Survey PCB concentrations and National Health and Nutrition Examination Survey (NHANES) food ingestion rates. For ∑PCB, dietary exposure dominates. For individual lower-chlorinated congeners (e.g., PCBs 40+41+71, 52), inhalation exposure was as high as one-third of the total (dietary+inhalation) exposure. ∑PCB inhalation (geometric mean (SE)) was greater for urban mothers (7.1 (1.2) μg yr–1) and children (12.0 (1.2) μg yr–1) than for rural mothers (2.4 (0.4) μg yr–1) and children (8.9 (0.3) μg yr–1). Schools attended by AESOP Study children had higher indoor PCB concentrations than did homes, and account for the majority of children’s inhalation exposure. PMID:25510359

  3. Bioaccumulation profiles of polychlorinated biphenyl congeners and organochlorine pesticides in Ganges River dolphins

    SciTech Connect

    Senthilkumar, K.; Kannan, K.; Sinha, R.K.; Tanabe, S.; Giesy, J.P.

    1999-07-01

    Isomer-specific concentrations of polychlorinated biphenyls (PCBs) including non-, mono-, and di-ortho-substituted congeners, DDT and its metabolites, hexachlorocyclohexane (HCH) isomers, chlordane compounds, and hexachlorobenzene (HCB) were determined in river dolphin blubber and prey fishes collected during 1993 through 1996 from the River Ganges in India. Concentrations of organochlorines were also measured in the milk and liver of dolphins, benthic invertebrates, and sediments. The DDTs and PCBs were the predominant compounds found in dolphin tissues and fish that comprise the diet of dolphins. Concentrations of DDTs and PCBs in the blubber of dolphins were in the range of 30 to 120 and 1.5 to 25 {micro}g/g, lipid weight, respectively. Penta- and hexachlorobiphenyls collectively accounted for 68 to 80% of the total PCB concentrations in river dolphins. Hexachlorobiphenyl congener 138 (2.2{prime}, 3,4,4{prime},5{prime}-) was the most abundant in dolphin blubber and prey fishes. The isomer/congener pattern of PCBs and organchlorine pesticides suggested that there is less metabolism due to cytochrome P450 enzymes in Ganges river dolphins than in marine or terrestrial mammals. The mean 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) estimated in river dolphin blubber was greater than those that can cause adverse effects in mink. Comparison of organochlorine concentrations in river dolphins with those of the values reported for samples analyzed during 1988 through 1992 suggested that the contamination by these compounds has increased in the River Ganges.

  4. PCB patterns in herring and pike with special regard to co-planar congeners

    SciTech Connect

    Alsberg, T.; Wit, C. de; Eriksson, U.; Jaernberg, U.; Bignert, A.; Olsson, M.

    1995-12-31

    This study investigates the patterns of PCB in two aquatic organisms, herring and pike. The aim is to establish a basis for a model for estimating the levels of co-planar PCBs from the concentrations of nonplanar congeners. The chosen fish populations reflect differences in species, age, habitat (locations) and time of catch, as well as differences in total PCB concentrations. More stable patterns would be presumed, the more homogeneous the population. Herring were sampled at two locations, one in the Bothnian Bay (Harufjaerden) and one in the Southern Baltic (Utlaengan). Two age classes were sampled at each location, 2- and 6-year olds, respectively at Utlaengan, and 2- and 5-year olds, respectively at Harufjaerden. Pike were sampled from Lake Bolmen in southern Sweden in 1992, and pike from the same location but sampled in 1971 were taken from the specimen bank. Ten individuals per population were analyzed. Thirteen PCB congeners were determined, namely PCBs 28, 52, 77, 101, 105, 118, 126, 1 38, 153, 156, 157, 169, 180, thus including the seven PCBs that are measured in the national monitoring program, in addition to three monoortho and three non-ortho PCBs. Regarding the possibility of creating a model for calculating the concentrations of the planar PCBs from those of the non-planar, the results look promising for PCB-126 and PCB-169, whereas PCB-77 shows a lower correlation to the non-planar congeners.

  5. Behavioral effects of pre- and postnatal exposure to individual polychlorinated biphenyl congeners in rats

    SciTech Connect

    Holene, E.; Bernhoft, A.; Engen, P.; Nafstad, I. |; Skaare, J.U. |; Sagvolden, T.

    1995-06-01

    Rats were exposed in utero and through mother`s milk either to the coplanar PCB congener 3,3{prime},4,4{prime},5-CB (IUPAC no. 126) or to the mono-ortho-substituted PCB congener 2,3{prime},4,4{prime},5-CB (IUPAC no. 118). The different groups of mothers were exposed to 1 and 5 mg/kg body weight of PCB 118, and 2 {mu}g/kg b.w. of PCB 126 every second day from day 10 to day 20 of gestation. The exposure did not affect the body weight of the dams or the size, weight, sex ratio, or physical development of the offspring. Operant behavioral testing revealed that the PCB-exposed offspring showed both poorer visual discrimination and higher activity level than did the controls. The coplanar PCB 126 congener was the most potent treatment. These results show that both PCB 118 and PCB 126 produced significant neurotoxic effects in the offspring of exposed females in absence of clinical maternotoxic and fetotoxic effects.

  6. Exposure to mercury and Aroclor 1268 congeners in least terns (Sternula antillarum) in coastal Georgia, USA.

    PubMed

    Robinson, Gabrielle L; Mills, Gary L; Lindell, Angela H; Schweitzer, Sara H; Hernandez, Sonia M

    2015-08-01

    Concentrations of total mercury and the rare PCB mixture Aroclor 1268 in least terns (Sternula antillarum), a colonially-nesting, piscivorous seabird, in the Turtle River estuary and other coastal sites in Georgia, USA, were investigated. The Turtle River estuary is the location of the Linden Chemical Plant (LCP) Superfund site, a site prioritized by USA law for immediate remediation, where industries released effluent containing these contaminants until 1994. Aroclor 1268 is a highly-chlorinated PCB mixture that was used and released exclusively at the LCP site and nowhere else in the south eastern USA. High concentrations of Aroclor 1268 congeners and mercury have been documented in biota local to LCP, but no studies report concentrations in high trophic level, piscivorous birds such as least terns. We collected feathers and feces from chicks, and eggs from adults, at nesting colonies along the Georgia coast to analyze contaminant loads (in dry weight ppb). Mean Aroclor 1268 mixture concentrations in eggs (≤16,329 ppb) were highest at colonies in and just outside LCP, and decreased with increasing distance (up to 110 km) from LCP, but the Aroclor 1268 signature congener mixture was present at all sites. Mercury concentrations in eggs (≤3370 ppb), feathers (≤5950 ppb), and feces (≤417 ppb), were present at all sites, but did not vary significantly among sites. This report confirms the extensive dispersal of Aroclor 1268 congeners (approximately 110 km north and 70 km south of its point source) via bioaccumulation and trophic transfer. PMID:26166752

  7. Screening for planar chlorobiphenyl congeners in marine biota by HPLC/PDA

    SciTech Connect

    Krahn, M.M.; Ylitalo, G.M.; Buzitis, J.; Sloan, C.A.; Boyd, D.T.; Chan, S.L.; Varanasi, U.

    1994-12-31

    A rapid method has been developed to screen for the dioxin-like planar chlorobiphenyl (CB) congeners, as well as certain other CBs and DDTs, in tissue samples from marine biota. Following extraction, the analytes were separated from interfering compounds on a gravity-flow column packed with acidic, basic and neutral silica gel. Subsequently, the planar CB congeners were resolved from the DDTs and other CBs by HPLC on Cosmosil PYE analytical columns cooled to 9 C and were measured by an ultraviolet (UV) photodiode array (PDA) detector. Individual analytes were identified by comparing their UV spectra and retention to those of reference standards and analyte purity was established by comparing spectra within a peak to the apex spectrum. The HPLC/PDA method was tested with tissue samples from fish, shellfish and marine mammals. Concentrations of the planar CB congeners, as well as certain other CBs and DDTs, in samples determined by screening compared favorably with those in the same samples analyzed by a comprehensive method. The screening method required about 20% of the time needed for the comprehensive analyses. The authors demonstrated the utility of the HPLC/PDA method by determining CBs and DDTs in edible tissue from a variety of seafood species; preliminary results from this survey will be presented.

  8. Coplanar polychlorinated biphenyl congeners in shark livers from the north-western African Atlantic ocean

    SciTech Connect

    Serrano, R.; Fernandez, M.A.; Hernandez, L.M.

    1997-01-01

    Polychlorinated biphenyls have been widely used by industry throughout the world since 1930. Although their use has been banned in many countries since the late 1970s, they still represent an important class of priority pollutants due to their persistence. Most open uses of these chemicals have been severely curtailed in industrialized nations, but a considerable fraction of past productions is probably still cycling in the ecosphere. In recent years, attention has been focused on the toxicity of PCBs, especially of those congeners showing similar toxicity as the polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). It has been shown that PCB congeners` toxicity largely depends on the chlorine substitution pattern. The most toxic PCB cogeners are those with two para chlorines, at least two meta chlorines and 0-2 ortho chlorines. These so-called {open_quotes}coplanar{close_quotes} (non- mono- and di-ortho) PCB cogeners are able to obtain planar conformation. Recently, toxic equivalence factors have been assigned to coplanar PCBs. Thus determination of individual PCB cogeners is important for evaluating the toxic potentials of PCB residues in, for example, wildlife. This paper presents preliminary results of a study looking at levels of PCB congeners, including coplanar ones, in the liver of six shark species, collected in the North African Atlantic Ocean. 15 refs., 2 figs., 2 tabs.

  9. Bioaccumulation of PCB congeners by blue mussels (Mytilus edulis) deployed in New Bedford Harbor, Massachusetts

    SciTech Connect

    Bergen, B.J. . Environmental Research Lab., Science Applications International Corp.); Nelson, W.G.; Pruell, R.J. . Environmental Research Lab.)

    1993-09-01

    Blue mussels (Mytilus edulis) were deployed to monitor the levels of bioavailable contaminants during a pilot dredging project in New Bedford Harbor (NBH), Massachusetts. Dissolved and particulate seawater samples also were collected periodically during these deployments. Polychlorinated biphenyl (PCB) congener concentrations in both mussel tissue and seawater samples were among the quantified contaminants. Large differences in the dissolved and particulate PCB concentrations in seawater and tissue residue concentrations in mussels were observed along a gradient from the upper harbor to Buzzards Bay. Bioconcentration factors (BCFs) were calculated for six PCB congenors at two stations in NBH and a reference site in Buzzards Bay. Equations were generated relating the log BCF to the log octanol/water partition coefficient (K[sub ow]) for these congeners. A consistent relationship was found between dissolved PCB congener concentrations and tissue concentrations in the mussels. This study demonstrates the utility of the blue mussel as a monitoring organism for quantifying bioavailable contaminants in seawater and for relating PCB tissue residues with seawater concentrations.

  10. Distinguishing PCB Isomeric Congeners with their Gas Chromatographic and Mass Spectrometric Ortho Effect using Comprehensive Gas Chromatography

    EPA Science Inventory

    The 209 polychlorinated biphenyl (PCB) congeners and associated nine isomeric groups (nine groups of PCBs with the same degree of chlorination) have been long recorded as high endocrine disrupting chemicals in the environment. Difficult analytical problems exist, in those frequen...

  11. DIFFERENTIAL EFFECTS OF POLYCHLORINATED BIPHENYL CONGENERS ON PHOSPHOINOSITIDE HYDROLYSIS AND PROTEIN KINASE C TRANSLOCATION IN RAT CEREBELLAR GRANULE CELLS

    EPA Science Inventory

    Previous reports from our laboratory have suggested that the neuroactivity of some polychlorinated biphenyl (PCB) congeners is associated with perturbations in cellular Ca2+-homeostasis. o characterize the neurochemical effects of PCBs further, the present experiments found that ...

  12. Endocrine disrupter--estradiol--in Chesapeake Bay tributaries.

    PubMed

    Dorabawila, Nelum; Gupta, Gian

    2005-04-11

    Exogenous chemicals that interfere with natural hormonal functions are considered endocrine disrupting chemicals (EDCs). Estradiol (17beta-estradiol or E2) is the most potent of all xenoestrogens. Induction of vitellogenin (VTG) production in male fish occurs at E2 concentrations as low as 1 ng l-1. E2 reaches aquatic systems mainly through sewage and animal waste disposal. Surface water samples from ponds, rivers (Wicomico, Manokin and Pocomoke), sewage treatment plants (STPs), and coastal bays (Assawoman, Monie, Chincoteague, and Tangier Sound-Chesapeake Bay) on the Eastern Shore of Maryland were analyzed for E2 using enzyme linked immuno-sorbent assay (ELISA). E2 concentrations in river waters varied between 1.9 and 6.0 ng l-1. Highest E2 concentrations in river waters were observed immediately downstream of STPs. E2 concentrations in all the coastal bays tested were 2.3-3.2 ng l-1. PMID:15811666

  13. Estradiol Upregulates c-FLIPlong Expression in Anterior Pituitary Cells.

    PubMed

    Jaita, G; Zárate, S; Ferraris, J; Gottardo, M F; Eijo, G; Magri, M L; Pisera, D; Seilicovich, A

    2016-04-01

    Anterior pituitary cell turnover depends on a tight balance between proliferation and apoptosis. We have previously shown that estrogens sensitize anterior pituitary cells to pro-apoptotic stimuli. c-FLIP (cellular-FLICE-inhibitory-protein) isoforms are regulatory proteins of apoptosis triggered by death receptors. c-FLIPshort isoform competes with procaspase-8 inhibiting its activation. However, c-FLIPlong isoform may have a pro- or anti-apoptotic function depending on its expression level. In the present study, we explored whether estrogens modulate c-FLIP expression in anterior pituitary cells from ovariectomized (OVX) rats and in GH3 cells, a somatolactotrope cell line. Acute administration of 17β-estradiol to OVX rats increased c-FLIPlong expression in the anterior pituitary gland without changing c-FLIPshort expression as assessed by Western blot. Estradiol in vitro also increased c-FLIPlong expression in anterior pituitary cells but not in GH3 cells. As determined by flow cytometry, the percentage of anterior pituitary cells expressing c-FLIP was higher than in GH3 cells. However, c-FLIP fluorescence intensity in GH3 cells was higher than in anterior pituitary cells. FasL increased the percentage of TUNEL-positive GH3 cells incubated either with or without estradiol suggesting that the pro-apoptotic action of Fas activation is estrogen-independent. Our results show that unlike what happens in nontumoral pituitary cells, estrogens do not modulate either c-FLIPlong expression or FasL-induced apoptosis in GH3 cells. The stimulatory effect of estradiol on c-FLIPlong expression could be involved in the sensitizing effect of this steroid to apoptosis in anterior pituitary cells. The absence of this estrogenic action in tumor pituitary cells could be involved in their tumor-like behavior. PMID:26566102

  14. Determination of estriol, estradiol, estrone, and progesterone in cosmetic products.

    PubMed

    Hubinger, Jean C

    2015-01-01

    This report describes the development and validation of a reverse phase high-performance liquid chromatography (HPLC) method with UV detection for the determination of the hormones estriol, estradiol, estrone, and progesterone in topically applied products. The developed method was then used to conduct a postmarket survey of consumer products for these hormones. Each product was first mixed with Celite and then extracted with methanol. Extracts were cleaned on a Waters Oasis HLB solid phase extraction cartridge, and then analyzed using reversed phase HPLC. The analytes were separated using an Agilent Zorbax Eclipse XDB C8 (5 μm, 250 mm by 4.6 mm) analytical column and detected by their absorbance at 230 nm. Chromatographic separation was achieved by a 1.0-ml/min linear gradient from 30% acetonitrile and 70% water to 80% acetonitrile and 20% water over 30 min. A final 5 min hold time and a re-equilibration time of 10 min were used to prepare the column for subsequent analysis. Recovery from two different brand lotions spiked with three different levels of estriol, estradiol, estrone, and progesterone ranged from 81.8% to 101%. In this study, a total of 70 cosmetic products were surveyed. Twenty two (63%) of the 35 products were labeled as containing an estrogen and/ or progesterone and also provided quantitative label information about the hormone ingredient. The most frequently labeled hormones were progesterone (66%), estriol (46%), estradiol (11%), and estrone (6%). Six products labeled as containing estriol were found to contain estradiol. An estrogen and/or progesterone were found in 34 products at concentrations ranging from 86.0 to 26,800 μg/g. Progesterone was not found in one product labeled as containing this hormone. An additional 35 products, which did not list hormones on their labels, were analyzed and estrogen or progesterone was not detected in these products. PMID:26454975

  15. Transdermal estradiol treatment during breastfeeding: maternal and infant serum concentrations.

    PubMed

    Pinheiro, Emily; Bogen, Debra L; Hoxha, Denada; Wisner, Katherine L

    2016-04-01

    We examined estradiol (E2) and estrone (E1) concentrations in breastfeeding mother-infant dyads. The mothers had postpartum depression and were participants in a randomized clinical trial with three treatments (transdermal E2, sertraline, and placebo). Neither infant E1 and E2 concentrations nor infant growth differed across the treatments. Transdermal E2 administration of 50 to 200 mcg/day for breastfeeding women did not affect infant E1 or E2 concentrations or infant growth. PMID:25956588

  16. Estradiol induces functional inactivation of p53 by intracellular redistribution.

    PubMed

    Molinari, A M; Bontempo, P; Schiavone, E M; Tortora, V; Verdicchio, M A; Napolitano, M; Nola, E; Moncharmont, B; Medici, N; Nigro, V; Armetta, I; Abbondanza, C; Puca, G A

    2000-05-15

    Estrogen treatment of MCF-7 cells grown in serum-free medium induced a modification of the intracellular distribution of p53 protein. Western blot analysis and immunofluorescence staining showed that p53 was localized in the nucleus of untreated cell and that after 48 h of hormone treatment, it was mostly localized in the cytoplasm. This effect was blocked by the antiestrogen ICI182,780. Intracellular redistribution of p53 was correlated to a reduced expression of the WAF1/CIP1 gene product and to the presence of degradation fragments of p53 in the cytosol. Estradiol treatment prevented the growth inhibition induced by oligonucleotide transfection, simulating DNA damage. This observation indicated that the wild-type p53 gene product present in the MCF-7 cell could be inactivated by estradiol through nuclear exclusion to permit the cyclin-dependent phosphorylation events leading to the G1-S transition. In addition, the estradiol-induced inactivation of p53 could be involved in the tumorigenesis of estrogen-dependent neoplasm. PMID:10825127

  17. High Levels of Structural Diversity Observed in Microcystins from Microcystis CAWBG11 and Characterization of Six New Microcystin Congeners

    PubMed Central

    Puddick, Jonathan; Prinsep, Michèle R.; Wood, Susanna A.; Kaufononga, Sangata A. F.; Cary, Stephen Craig; Hamilton, David P.

    2014-01-01

    Microcystins (MCs) are cyclic peptides produced by cyanobacteria, which can be harmful to humans and animals when ingested. Differences in the coding of the non-ribosomal peptide synthetase/polyketide synthase enzyme complex responsible for microcystin production have resulted in more than 100 microcystin variants being reported to date. The microcystin diversity of Microcystis CAWBG11 was investigated using matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography-mass spectrometry. This revealed that CAWBG11 simultaneously produced 21 known microcystins and six new congeners: [Asp3] MC-RA, [Asp3] MC-RAba, [Asp3] MC-FA, [Asp3] MC-WA, MC-FAba and MC-FL. The new congeners were putatively characterized by tandem mass spectrometry and chemical derivatization. A survey of the microcystin congeners produced by 49 cyanobacterial strains documented in scientific literature showed that cyanobacteria generally produce four microcystin congeners, but strains which produce up to 47 microcystin congeners have been reported. Microcystis CAWBG11 (which produces at least 27 congeners) was positioned in the top ten percentile of the strains surveyed, and showed fluidity of the amino acids incorporated into both position two and position four. PMID:25402827

  18. Genetic interaction between hyperglycemic QTLs is manifested under a high calorie diet in OLETF-derived congenic rats.

    PubMed

    Fukumura, Tomoe; Kose, Hiroyuki; Takeda, Chiyo; Kurita, Yuko; Ochiai, Kazuhiko; Yamada, Takahisa; Matsumoto, Kozo

    2011-01-01

    The condition of hyperglycemia results from multiple genetic and environmental factors. In recent years much progress has been made with regards to the search for candidate genes involved in the expression of various common diseases including type 2 diabetes. However less is known about the specific genetic and environmental connections that are important for the development of the disease. In the present study, we used hyperglycemic congenic rats to address this issue. When given a normal diet, two hyperglycemic QTLs (quantitative trait locus), Nidd2/of and Nidd10/of, showed mild obesity and/or increased blood glucose in the oral glucose tolerance test. In a double congenic strain possessing both loci, these indices were not significantly different from those of either single congenic strain. In contrast, the double congenic strain fed a high-calorie diet showed significantly greater body weight than the single congenic strains or normoglycemic control rats. Although postprandial glucose levels of the double congenic rat were not further aggravated even on the high fat diet, it was notable that the postprandial insulin levels were drastically elevated. From these results, we constructed a novel model animal especially for the study of prediabetic hyperinsulemia, in which two QTLs and an additional dietary condition are involved. This may help to shed light on the genetic basis and gene-to-diet interaction during the early stage of type 2 diabetes. PMID:21512267

  19. Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen-stimulated prolactin secretion in incubated rat pituitaries.

    PubMed

    Aguilar, R; Bellido, C; Garrido-Gracia, J C; Alonso, R; Sánchez-Criado, J E

    2006-04-01

    In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX) has two agonist effects in the rat pituitary: induction of progesterone receptor (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of pituitaries from TX-treated rats. The present experiments investigated whether PR-independent PRL release into the incubation medium of pituitaries from TX-treated ovariectomized (OVX) rats was affected by E2, and the effect of different ER ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in pituitaries collected from estradiol benzoate- and TX-treated OVX rats was studied. It was found that: i) incubation with E2 supressed the PRL releasing effect of injected TX; ii) whereas coincubation with the pure anti-E type II ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked by addition of E2 to the medium. Taken together, these data argue in favor of the presence of specific membrane recognition sites for E in the lactotrope involved in steroid-specific E2 inhibition of TX-stimulated PRL secretion. PMID:16595727

  20. Role of astroglia in the neuroplastic and neuroprotective actions of estradiol.

    PubMed

    Azcoitia, Iñigo; Santos-Galindo, María; Arevalo, María A; Garcia-Segura, Luis M

    2010-12-01

    Astrocyte-neuron cross-talk is an essential component of the mechanisms involved in the neuroendocrine and neuroprotective actions of estradiol. Astrocytes express estrogen receptors, show morphological and functional modifications in response to estradiol and participate in the hormonal regulation of synaptic plasticity and neuroendocrine events. In addition, estradiol interferes with the activation of astrocytes under pathological conditions, modulating the release of neurotrophic factors and inflammatory molecules by these cells. Furthermore, under neurodegenerative conditions, astrocytes synthesize estradiol, which acts as a local neuroprotectant. The actions of estradiol on astrocytes can be imitated by selective estrogen receptor modulators. Some of these molecules, which are free of the peripheral risks associated with estrogen therapy, exert estradiol-like anti-inflammatory actions on astrocytes and are potential therapeutic candidates for the control of reactive astrogliosis. PMID:21143654

  1. Rapid Direct Action of Estradiol in GnRH Neurons: Findings and Implications

    PubMed Central

    Kenealy, Brian P.; Terasawa, E.

    2011-01-01

    Estradiol plays a pivotal role in the control of gonadotropin-releasing hormone (GnRH) neuronal function and female reproduction. While positive and negative feedback actions of estradiol that enhance and suppress release of GnRH and LH are primarily mediated through estrogen receptor alpha located in interneurons, a series of recent studies in our laboratory indicate that rapid excitatory actions of estradiol also directly modify GnRH neuronal activity. We observed this phenomenon in cultured primate GnRH neurons, but similar rapid direct actions of estradiol are also described in cultured GnRH neurons and green fluorescent protein-labeled GnRH neurons of mice. Importantly, rapid direct action of estradiol in GnRH neurons is mediated through membrane or membrane associated receptors, such as GPR30, STX-sensitive receptors, and ERβ. In this review, possible implications of this rapid estradiol action in GnRH neurons are discussed. PMID:22654841

  2. Dose-dependent regulation of cell proliferation and collagen degradation by estradiol on ligamentum flavum

    PubMed Central

    2014-01-01

    Background Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum. Methods Primary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated. Results In our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17β-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10-9 M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol. Conclusions The results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum. PMID:25022571

  3. TEMPORAL AND CONCENTRATION DEPENDENT ESTRADIOL EFFECTS ON NEURAL PATHWAYS MEDIATING SEXUAL RECEPTIVITY

    PubMed Central

    Micevych, Paul; Sinchak, Kevin

    2013-01-01

    The acceptance of estradiol signaling through receptors found in the cell membrane, as well as, the nucleus has provided for a re-examination of timing and location of estradiol actions on neural circuits mediating sexual receptivity (lordosis). Estradiol membrane signaling involves the transactivation of metabotropic glutamate receptors (mGluR) that transduce steroid information through PKC signaling cascades producing rapid activation of lordosis regulating circuits. It has been known for some time that estradiol initially produces an inhibition of the medial preoptic nucleus (MPN). We have demonstrated that underlying this inhibition is estradiol acting in the arcuate nucleus to induce β-endorphin release which inhibits the MPN through a μ-opioid receptor mechanism. This transient inhibition is relieved by either subsequent progesterone treatment or longer exposure to higher doses of estradiol to facilitate lordosis behavior. We review recent findings about estradiol membrane signaling inducing dendritic spine formation in the arcuate nucleus that is critical for estradiol induction of sexual receptivity. Moreover, we discuss the evidence that in addition to ERα, several other putative membrane estrogen receptors facilitate lordosis behavior through regulation of the arcuate nucleus. These include the GRP30 and the STX activated Gq-mER. Finally, we report on the importance of GABA acting at GABAB receptors for estradiol membrane signaling that regulates lordosis circuit activation and sexual receptivity. PMID:24028299

  4. The formation at 37 C of a nondissociable receptor-estradiol complex.

    PubMed

    Fishman, J H; Fishman, J

    1985-08-30

    The receptor-estradiol complex formed in rat uterine cytosol when heated at 37 C converts from a dissociable to a nondissociable form. The conversion is best observed in cytosols pretreated with charcoal at 0 C which renders the subsequently formed receptor-estradiol complexes thermostable at 37 C. In the presence of dithiothreitol the heated complex remains dissociable. Tamoxifen does not form nondissociable complexes with the estradiol receptor. It is proposed that the nondissociable form of the receptor complex is a required phase in the mechanism of estradiol action. PMID:2412556

  5. A Comparison of the Effects of Transdermal Estradiol and Estradiol Valerate on Endometrial Receptivity in Frozen-thawed Embryo Transfer Cycles: A Randomized Clinical Trial

    PubMed Central

    Davar, Robab; Janati, Sima; Mohseni, Fereshteh; Khabazkhoob, Mehdi; Asgari, Soheila

    2016-01-01

    Background: The purpose of this study was to determine the optimal endometrial preparation protocol by comparing the clinical outcome of two methods of endometrial preparation in frozen-thawed embryo transfer (FET) cycles, including that is, oral estradiol and 17ß-estradiol transdermal patch. Methods: In this randomized controlled trial, women underwent either conventional IVF or intracytoplasmic sperm injection (ICSI) who had at least two top-quality embryos appropriate for cryopreservation and frozen embryos from previous cycles. In the study group (n=45), 17-B estradiol transdermal patches 100 μg were applied from the second day of the cycle and continued every other day. Then, each patch was removed after four days. In the control group (n=45), oral estradiol valerate 6 mg was started at the same time and continued daily. Results: There was a significant difference in estradiol level on the day of progesterone administration and the day of embryo transfer between the two groups (p= 0.001 in both), but no significant difference was observed between them in biochemical and clinical pregnancy rates (32.6% vs. 33.3%, p=1.000 and 30.2% vs. 33.3%, p=0.810, respectively). Conclusion: It is suggested that estradiol transdermal patches be used instead of oral estradiol in FET cycles. Due to the reduced costs, drug dose, and emotional stress as well as the simplicity of the protocol for patients. PMID:27141464

  6. Potentially estrogenic polychlorinated biphenyls congeners serum levels and its relation with lung cancer.

    PubMed

    Recio-Vega, Rogelio; Mendez-Henandez, Alejandra; Gabriel, Antonio Padua Y; Jacobo-Avila, Antonio; Portales-Castanedo, Arnulfo; Hernandez-Gonzalez, Sandra; Gallegos-Arreola, Martha Patricia; Ocampo-Gomez, Guadalupe

    2013-09-01

    Lung cancer is the most common cancer in the world. The main cause of lung cancer is cigarette smoke; however, other important genetic and environmental risk factors play a significant role in the development of lung cancer. Among these factors, occupational and accidental exposure to polychlorinated biphenyls (PCBs) has been associated with an increased risk in lung cancer, suggesting that PCBs could be potent carcinogens. The aim of the present study was to investigate the association between PCB exposure levels, CYP1A1 polymorphisms and the risk of lung cancer. This study enrolled newly diagnosed lung cancer patients. Environmental and occupational information related to the patients studied was collected. Blood samples were taken for the measurement of serum levels of 20 PCB congeners and for CYP1A1 polymorphism analysis. The serum levels of two PCB congeners with potential estrogenic activity were higher in lung cancer patients. The risk of lung cancer was found to correlate with age, gender, smoking history and with agricultural workers, as well as with congener 18. No differences were found in the frequency of CYP1A1 polymorphisms. Furthermore, we did not find a correlation between CYP1A1 polymorphisms and PCB serum levels. The high levels of PCB with estrogenic activity found in our cases, could promote lung cancer inducing cell proliferation in non-neoplastic and neoplastic lung cells via ERβ; inducing the formation of DNA adducts, producing oxidative stress with the subsequent DNA damage and increasing the endogenous catechol levels by catechol-O-methyl transferase (COMT) inhibition. PMID:22729568

  7. Deposition history of polychlorinated biphenyls to the Lomonosovfonna Glacier, Svalbard: a 209 congener analysis.

    PubMed

    Garmash, Olga; Hermanson, Mark H; Isaksson, Elisabeth; Schwikowski, Margit; Divine, Dmitry; Teixeira, Camilla; Muir, Derek C G

    2013-01-01

    A 37 m deep ice core representing 1957-2009 and snow from 2009 to 2010 were collected on the Lomonosovfonna glacier, Svalbard (78.82° N; 17.43° E) and analyzed for 209 polychlorinated biphenyl (PCB) congeners using high-resolution mass spectrometry. Congener profiles in all samples showed the prevalence of tetra- and pentachlorobiphenyls, dominated in all samples by PCB-44, PCB-52, PCB-70 + PCB-74, PCB-87 + PCB-97, PCB-95, PCB-99, PCB-101, and PCB-110. The ∑PCB flux varied over time, but the peak flux, ∼19 pg cm(-2) year(-1) from 1957 to 1966, recurred in 1974-1983, 1998-2009, and 2009-2010. The minimum was 5.75 pg cm(-2) year(-1) in 1989-1998, following a 15 year decline. Peak ∑PCB fluxes here are lower than measured in the Canadian Arctic. The analysis of all 209 congeners revealed that PCB-11 (3,3'-dichlorobiphenyl) was present in all samples, representing 0.9-4.5% of ∑PCB. PCB-11 was not produced in a commercial PCB product, and its source to the Arctic has not been well-characterized; however, our results confirm that the sources to Lomonosovfonna have been active since 1957. The higher fluxes of ∑PCB correspond to periods when average 5 day air mass back trajectories have a frequency of 8-10% and reach 60° N or beyond over northern Europe and western Russia or the North Sea into the U.K. PMID:24073820

  8. Accumulation of PCB congeners in nestling tree swallows (Tachycineta bicolor) on the Hudson River, New York

    USGS Publications Warehouse

    Echols, K.R.; Tillitt, D.E.; Nichols, J.W.; Secord, A.L.; McCarty, J.P.

    2004-01-01

    Tree swallows (Tachycineta bicolor) were used as a sentinel species to monitor the contamination and bioavailability of polychlorinated biphenyls (PCBs) in the Hudson River watershed. Several tree swallow nest box colonies around and downstream from Hudson Falls, NY, were studied. Tree swallow eggs, adults, and 5-, 10-, and 15-day-old nestlings were collected and analyzed for 103 PCB congeners. Emergent insects collected by net (primarily Odonata) or as a food bolus (primarily Diptera) taken from the mouths of adult tree swallows returning to the nest were analyzed in the same manner. Total PCB concentrations (wet weight) in eggs from two contaminated sites ranged from 9000 to 25 000 ng/g and accumulated to 32 000 and 96 000 ng/g in 15-day-old nestling at two contaminated sites. The congener patterns of PCBs in eggs, nestlings, and adults were compared to those found in emergent insects (Odonata and Diptera) using principal components analysis. The PCB patterns of the biota differed from that of Aroclor technical mixtures. PCB patterns in adult tree swallows were similar to those in eggs, while the patterns in dietary insects were similar to nestling tree swallows. Uptake rate constants were determined for tree swallow nestlings and compared between the two contaminated sites. The estimated PCB congener uptake rate constants were 0.008-0.02 d-1 based on uptake in nestlings until day 15 post-hatch. The rate constants were comparable between the two study areas and may be used to predict nestling contamination at other locations. Our studies confirm the utility of nestling tree swallows to evaluate localized PCB contamination.

  9. Concentration levels and congener profiles of polychlorinated biphenyls, pentachlorobenzene, and hexachlorobenzene in commercial pigments.

    PubMed

    Anezaki, Katsunori; Nakano, Takeshi

    2014-01-01

    The concentration levels and congener profiles of polychlorinated biphenyls (PCBs), pentachlorobenzene (PeCBz), and hexachlorobenzene (HxCBz) were assessed in commercially available organic pigments. Among the azo-type pigments tested, PCB-11, which is synthesized from 3,3'-dichlorobendizine, and PCB-52, which is synthesized from 2,2',5,5'-tetrachlorobendizine, were the major congeners detected. It is speculated that these were byproducts of chlorobendizine, which has a very similar structure. The total PCB concentrations in this type of pigment ranged from 0.0070 to 740 mg/kg. Among the phthalocyanine-type pigments, highly chlorinated PCBs, mainly composed of PCB-209, PeCBz, and HxCBz were detected. Their concentration levels ranged from 0.011 to 2.5 mg/kg, 0.0035 to 8.4 mg/kg, and 0.027 to 75 mg/kg, respectively. It is suggested that PeCBz and HxCBz were formed as byproducts and converted into PCBs at the time of synthesizing the phthalocyanine green. For the polycyclic-type pigments that were assessed, a distinctive PCB congener profile was detected that suggested an impact of their raw materials and the organic solvent used in the pigment synthesis. PCB pollution from PCB-11, PCB-52, and PCB-209 pigments is of particular concern; therefore, the monthly variations in atmospheric concentrations of these pollutants were measured in an urban area (Sapporo city) and an industrial area (Muroran city). The study detected a certain level of PCB-11, which is not included in PCB technical mixtures, and revealed continuing PCB pollution originating from pigments in the ambient air. PMID:23852585

  10. Sexual Cycle of Cryptococcus neoformans var. grubii and Virulence of Congenic a and α Isolates

    PubMed Central

    Nielsen, Kirsten; Cox, Gary M.; Wang, Ping; Toffaletti, Dena L.; Perfect, John R.; Heitman, Joseph

    2003-01-01

    Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and α mating types has been reported for two varieties (C. neoformans var. neoformans, serotype D, and C. neoformans var. gattii, serotypes B and C), yet the vast majority of infections involve a distinct variety (C. neoformans var. grubii, serotype A) that has been thought to be clonal and restricted to the α mating type. We recently identified the first serotype A isolate of the a mating type which had been thought to be extinct (strain 125.91). Here we report that this unusual strain can mate with a subset of pathogenic serotype A strains to produce a filamentous dikaryon with fused clamp connections, basidia, and viable recombinant basidiospores. One meiotic segregant mated poorly with the serotype A reference strain H99 but robustly with a crg1 mutant that lacks a regulator of G protein signaling and is hyperresponsive to mating pheromone. This meiotic segregant was used to create congenic a and α mating type serotype A strains. Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and α mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the α mating type to increased virulence in congenic serotype D strains. Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence. PMID:12933823

  11. A mass spectroscopic method for analysis of AHH-inducing and other polychlorinated biphenyl congeners and selected pesticides in fish

    USGS Publications Warehouse

    Schmidt, Larry J.; Hesselberg, Robert J.

    1992-01-01

    The 209 polychlorinated biphenyl (PCB) congeners exhibit a wide range in toxicity to fish, birds, and mammals. This paper discusses the use of gas chromatography/mass spectrometry negative chemical ionization (GC/MS-NCI) to quantify congeners of highly suspected toxicity such as IUPAC #77 (3,3',4,4'-tetrachlorobiphenyl) and #126 (3,3',4,4',5-pentachlorobiphenyl). GC/MS analysis time needed to produce the necessary resolution was reduced to 1 h per sample or standard, allowing an autosampler to inject 12 samples in 24 hours, plus 12 standards/QC samples. Identification and quantification of some 60+ congeners and several selected pesticides and estimation of total PCBs are also possible within the 1 h analysis. For congeners of high chlorination (penta through octa), the method exhibited excellent sensitivity, such that we could not locate a fish which exhibited PCB levels below our calibrated quantitation range. NCI was not as sensitive for mono through tri and for some tetrachlorinated PCB congeners, an exception being PCB #77, for which sensitivity was of the same order as for the more highly chlorinated biphenyls. Long term stability was excellent. Over a 6-mo period, results of replicate analyses for PCB congeners and pesticides in a composited sample of lake trout (Salvelinus namaycush) from Lake Michigan had a relative standard deviation of 12% of the mean. Over the same time period, mean recoveries for samples spiked at concentrations similar to those in Lake Michigan lake trout were 90-102%. Response was linear over a wide range of concentrations for each of the analyzed compounds. This method is now being used for routine analysis of PCB congeners and selected pesticides in our laboratory.

  12. Acute toxicity of PCB congeners to Daphnia magma and Pimephales promelas

    SciTech Connect

    Dillon, T.M. ); Burton, W.D.S. )

    1991-02-01

    The acute toxicity (EC50/LC50) of commercial PCB mixtures has been reported to range from 2.0 to 283 ug/L. Because PCBs are very hydrophobic most biological studies have utilized a carrier solvent to facilitate introduction of PCBs into aqueous solution. As a result, biological effects are often reported at exposure concentrations exceeding water solubility. The purpose of this work was to evaluate the comparative toxicity of selected PCB congeners without carrier solvents. These tests were conducted on early life stages of two sensitive freshwater organisms, Daphnia magna and Pimephales promelas.

  13. The dioxin contamination incident in Ireland, 2008: analytical results and congener patterns.

    PubMed

    Tlustos, C; Sheridan, M; O'Sullivan, D; Anderson, W; Flynn, A

    2012-01-01

    A porcine fat sample taken as part of the national residues monitoring programme in 2008 led to the detection of a major feed contamination incidence in the Republic of Ireland. The source of the contamination was traced back to the use of contaminated oil in a direct-drying feed operation system. Congener profiles in animal fat and feed samples showed a high level of consistency and pinpointed the likely source of fuel contamination to be a highly chlorinated commercial PCB mixture. PMID:22035259

  14. Energy metabolism and hindbrain AMPK: regulation by estradiol.

    PubMed

    Briski, Karen P; Ibrahim, Baher A; Tamrakar, Pratistha

    2014-03-01

    Nerve cell energy status is screened within multiple classically defined hypothalamic and hindbrain components of the energy balance control network, including the hindbrain dorsal vagal complex (DVC). Signals of caudal DVC origin have a physiological role in glucostasis, e.g., maintenance of optimal supply of the critical substrate fuel, glucose, through control of motor functions such as fuel consumption and gluco-counterregulatory hormone secretion. A2 noradrenergic neurons are a likely source of these signals as combinatory laser microdissection/high-sensitivity Western blotting reveals expression of multiple biomarkers for metabolic sensing, including adenosine 5'-monophosphate-activated protein kinase (AMPK). Hypoglycemia elicits estradiol-dependent sex differences in A2 AMPK activation as phospho-AMPK (pAMPK) expression is augmented in male and ovariectomized (OVX) female, but not estrogen-replaced, OVX rats. This dichotomy may reflect, in part, estradiol-mediated up-regulation of glycolytic and tricarboxylic acid cycle enzyme expression during hypoglycemia. Our new model for short-term feeding abstinence has physiological relevance to planned (dieting) or unplanned (meal delay) interruption of consumption in modern life, which is negatively correlated with appetite control and obesity, and is useful for investigating how estrogen may mitigate the effects of disrupted fuel acquisition on energy balance via actions within the DVC. Estradiol reduces DVC AMPK activity after local delivery of the AMP mimic, 5-aminoimidazole-4-carboxamide-riboside, or cessation of feeding for 12 h but elevates pAMPK expression when these treatments are combined. These data suggest that estrogen maintains cellular energy stability over periods of suspended fuel acquisition and yet optimizes, by DVC AMPK-dependent mechanisms, counter-regulatory responses to metabolic challenges that occur during short-span feeding abstinence. PMID:25372736

  15. Nomegestrol acetate-17b-estradiol for oral contraception

    PubMed Central

    Burke, Anne

    2013-01-01

    Oral contraceptives remain a popular method of contraception over 50 years after their introduction. While safe and effective for many women, the failure rate of oral contraception is about 8%. Concerns about the risk of venous thromboembolism continue to drive the search for the safest oral contraceptive formulations. The oral contraceptive NOMAC-E2 contains nomegestrol acetate (NOMAC) 2.5 mg + 17b-estradiol (E2) 1.5 mg. The approved dosing regimen is 24 days of active hormone, followed by a 4-day hormone-free interval. NOMAC is a progestin derived from testosterone, which has high bioavailability, rapid absorption, and a long half-life. Estradiol, though it has a lower bioavailability, has been successfully combined with NOMAC in a monophasic oral contraceptive. Two recently published randomized controlled trials demonstrate that NOMAC-E2 is an effective contraceptive, with a Pearl Index less than one pregnancy per 100 woman-years. The bleeding pattern on NOMAC-E2 is characterized by fewer bleeding/spotting days, shorter withdrawal bleeds, and a higher incidence of amenorrhea than the comparator oral contraceptive containing drospirenone and ethinyl estradiol. The adverse event profile appears to be acceptable. Few severe adverse events were reported in the randomized controlled trials. The most common adverse events were irregular bleeding, acne, and weight gain. Preliminary studies suggest that NOMAC-E2 does not seem to have negative effects on hemostatic and metabolic parameters. While no one oral contraceptive formulation is likely to be the optimum choice for all women, NOMAC-E2 is a formulation with effectiveness comparable with that of other oral contraceptives, and a reassuring safety profile. PMID:23836965

  16. Nomegestrol acetate-17b-estradiol for oral contraception.

    PubMed

    Burke, Anne

    2013-01-01

    Oral contraceptives remain a popular method of contraception over 50 years after their introduction. While safe and effective for many women, the failure rate of oral contraception is about 8%. Concerns about the risk of venous thromboembolism continue to drive the search for the safest oral contraceptive formulations. The oral contraceptive NOMAC-E2 contains nomegestrol acetate (NOMAC) 2.5 mg + 17b-estradiol (E2) 1.5 mg. The approved dosing regimen is 24 days of active hormone, followed by a 4-day hormone-free interval. NOMAC is a progestin derived from testosterone, which has high bioavailability, rapid absorption, and a long half-life. Estradiol, though it has a lower bioavailability, has been successfully combined with NOMAC in a monophasic oral contraceptive. Two recently published randomized controlled trials demonstrate that NOMAC-E2 is an effective contraceptive, with a Pearl Index less than one pregnancy per 100 woman-years. The bleeding pattern on NOMAC-E2 is characterized by fewer bleeding/spotting days, shorter withdrawal bleeds, and a higher incidence of amenorrhea than the comparator oral contraceptive containing drospirenone and ethinyl estradiol. The adverse event profile appears to be acceptable. Few severe adverse events were reported in the randomized controlled trials. The most common adverse events were irregular bleeding, acne, and weight gain. Preliminary studies suggest that NOMAC-E2 does not seem to have negative effects on hemostatic and metabolic parameters. While no one oral contraceptive formulation is likely to be the optimum choice for all women, NOMAC-E2 is a formulation with effectiveness comparable with that of other oral contraceptives, and a reassuring safety profile. PMID:23836965

  17. Polychlorinated biphenyl (PCB) exposure assessment by multivariate statistical analysis of serum congener profiles in an adult Native American population.

    PubMed

    DeCaprio, Anthony P; Johnson, Glenn W; Tarbell, Alice M; Carpenter, David O; Chiarenzelli, Jeffrey R; Morse, Gayle S; Santiago-Rivera, Azara L; Schymura, Maria J

    2005-07-01

    The major determinants of human polychlorinated biphenyl (PCB) body burden include the source and route of exposure and the toxicokinetic processes occurring after uptake. However, the relative importance of each factor for individual subjects cannot currently be determined. The present study characterizes levels and patterns of PCB congeners in a large cohort of adult Akwesasne Mohawks with historical PCB exposure. Total serum PCB ranged from 0.29 to 48.32 ng/g and was higher in adult men than in women (median of 3.81 vs. 2.94 ng/g). The mean serum congener profile for the full cohort was dominated by persistent penta- to hepta-chlorinated biphenyls; several labile congeners were also prominent. In order to provide additional information on individual body burden determinants, multivariate exploratory data analysis techniques were applied to the congener-specific serum PCB data. A self-training receptor model, polytopic vector analysis (PVA), was employed to determine the number, composition, and relative proportions of independent congener patterns that contributed to the overall serum PCB profile for each Mohawk subject. PVA identified five such patterns, each of which was characterized by a unique mix of congeners. One pattern observed in a limited number of Mohawks was similar to those reported for air sampled near contaminated sediment deposits at Akwesasne and for volatilized Aroclor 1248 and is hypothesized to reflect recent inhalation exposure in these subjects. A second pattern was consistent with unaltered Aroclor 1254. A third pattern, resembling Aroclor 1262 but without labile congeners, was correlated with age and is interpreted as representing a lifetime PCB accumulation profile. The final two patterns were dominated by subsets of major persistent congeners and are hypothesized to reflect intermediate bioaccumulation profiles and/or differences in individual toxicokinetics. The results confirm the utility of a multivariate exploratory analysis

  18. HT update: spotlight on estradiol/norethindrone acetate combination therapy

    PubMed Central

    Casey, Colleen L; Murray, Christine A

    2008-01-01

    The goal of postmenopausal hormone therapy is to alleviate the symptoms that are associated with the loss of estrogen. Many formulations of estrogen and progestin are available, depending on the needs and circumstances of each individual woman. For postmenopausal women, the choice of whether or not to begin therapy requires knowledge of the risks and benefits of estrogen and/or progestin replacement. The purpose of this review is to describe the risks and benefits of hormonal therapy, focusing on estradiol/norethindrone acetate combination therapy. PMID:18488874

  19. Patterns of Salivary Estradiol and Progesterone across the Menstrual Cycle

    PubMed Central

    GANDARA, BEATRICE K.; LERESCHE, LINDA; MANCL, LLOYD

    2007-01-01

    The aim of this study was to characterize the normality of menstrual cycles on the basis of progesterone and estradiol levels in self-collected saliva samples. Twenty-two women, ages 19–40 years, self-collected whole unstimulated saliva specimens each morning for two consecutive menstrual cycles. On the basis of presence/timing of hormone peaks, two investigators classified 24 cycles as normal, 10 as likely normal, and 10 as clearly not normal with respect to expected profiles. Our results show that whole saliva samples collected at home on a daily basis provide a noninvasive, feasible method of determining menstrual cycle profiles. PMID:17435149

  20. Congener-specific extraction and separation of coplanar PCBs from soil using SPME and capillary GC/MS

    SciTech Connect

    Woolley, C.L.; Mani, V.; Shirey, R.E.; Desorcie, J.L.

    1995-12-31

    The persistence and widespread environmental occurrence of polychlorinated biphenyls (PCBs) in the air, waterways and industrial facilities has created a need for quantitative and qualitative analysis of Aroclor-like mixtures. Although there are 209 possible PCB concerns, only a limited number have shown toxic activity similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The World Health Organization recently released a list of the 13 most toxic PCB congeners. Each was rated by its Toxic Equivalency Factor relative to TCDD. These 13 PCB congeners belong to the class of toxic coplanar compounds. These congeners commonly contain chlorosubstitutions in the 3,3{prime},4,4{prime} or 3,4,4{prime} or 3{prime},4,4{prime} positions and either 0, 1, or 2 chloro-substituents in the ortho positions. A new capillary column containing a bonded octylmethyl polysiloxane stationary phase (SPB-Octyl) was evaluated for its propensity to separate coplanar PCB congeners. Solid phase microextraction (SPME), a solvent-free method for extracting volatiles and semi-volatiles from drinking water, waste water, soil and sludge was used to extract PCBs from soil. GC-ECD and GC-MS separations of PCB ladened soils were examined via SPME on the SPB-Octyl column. An approach for selective extraction of coplanar PCB congeners by SPME will be described.

  1. SAR of Sponge-Inspired Hemibastadin Congeners Inhibiting Blue Mussel PhenolOxidase.

    PubMed

    Niemann, Hendrik; Hagenow, Jens; Chung, Mi-Young; Hellio, Claire; Weber, Horst; Proksch, Peter

    2015-05-01

    Hemibastadin derivatives, including the synthetically-derived 5,5'-dibromohemibastadin-1 (DBHB), are potent inhibitors of blue mussel phenoloxidase (PO), which is a key enzyme involved in the firm attachment of this invertebrate to substrates and, thus, a promising molecular target for anti-fouling research. For a systematic investigation of the enzyme inhibitory activity of hemibastadin derivatives, we have synthesized nine new congeners, which feature structural variations of the DBHB core structure. These structural modifications include, e.g., different halogen substituents present at the aromatic rings, different amine moieties linked to the (E)-2-(hydroxyimino)-3-(4-hydroxyphenyl)propionic acid, the presence of free vs. substituted aromatic hydroxyl groups and a free vs. methylated oxime group. All compounds were tested for their inhibitory activity towards the target enzyme in vitro, and IC50 values were calculated. Derivatives, which structurally closely resemble sponge-derived hemibastadins, revealed superior enzyme inhibitory properties vs. congeners featuring structural moieties that are absent in the respective natural products. This study suggests that natural selection has yielded structurally-optimized antifouling compounds. PMID:25988522

  2. DNA barcoding of Nilssonia congeners corroborates existence of wild N. nigricans in northeast India.

    PubMed

    Kundu, Shantanu; Laskar, Boni Amin; Venkataraman, Krishnamoorthy; Banerjee, Dhriti; Kumar, Vikas

    2016-07-01

    DNA barcode data of soft-shell turtles is limited in global DNA database while it is completely lacking for the highly debated species Nilssonia nigricans. We employed DNA barcoding technique to discriminate the species cluster for Nilssonia congeners, especially for the highly debated N. nigricans from different localities of northeast India. Sampling across the region included a few live specimens from wild, market sold carcass specimens, and a few dry carapaces meant for home decoration purpose. The generated sequences (621 bp of mtCOI) of dry carapaces showed 99-100% homology with the generated sequences of morphologically identified N. nigricans. The COI barcode sequences of N. nigricans (n = 12) showed 3.8% mean genetic divergence with N. hurum (n = 3), 10% with N. gangetica (n = 4), and 9.2% with N. formosa (GenBank sequences). Similarly, the mtCytb sequences of the dry carapace and live specimens of N. nigricans were 99-100% homologous with the conspecific database sequences and formed specific clusters. The inferred Neighbor-Joining (NJ), Maximum Likelihood (ML), and Bayesian (BA) phylogeny based on partial mtCOI gene efficiently discriminated all the congeners of Nilssonia into specific clusters and, therefore, it was helpful to detect the existence of N. nigricans. PMID:26057013

  3. Linking habitat use of Hudson River striped bass to accumulation of polychlorinated biphenyl congeners

    SciTech Connect

    Ashley, J.T.F.; Secor, D.H.; Zlokovitz, E.; Wales, S.Q.; Baker, J.E.

    2000-03-15

    Since 1976, the commercial striped bass fishery in the Hudson River (NY) has been closed due to total polychlorinated biphenyl (t-PCB) concentrations that exceed the US Food and Drug Administration's advisory level of 2 {micro}g/g-wet weight. Extensive monitoring of Hudson River striped bass demonstrated much more variability in t-PCB levels among individual striped bass than could be explained by their age, sex, or lipid contents. To investigate the possible role of differential habitat use among subpopulations of striped bass in controlling their PCB exposures, 70 fish collected throughout the Hudson River estuary and Long Island Sound in 1994--1995 were analyzed for PCB congeners, and their lifetime migration behaviors were estimated by otolith microchemistry. The mean salinity encountered during the fish's last growth season prior to capture was inversely correlated with the t-PCB body burden. Striped bass permanently residing in fresh and oligohaline portions of the estuary adjacent to known PCB sources had elevated t-PCB levels and congeneric patterns with higher proportions of di-, tri-, and tetrachlorobiphenyls. Conversely, fish spending the majority of their life in more saline waters of the estuary or migrating frequently throughout the salinity gradient contained lower PCB levels composed of more highly chlorinated congeners. The approach used in this study allows habitat use to be incorporated into exposure assessments for anadromous fish species such as striped bass.

  4. Toxic cell concentrations of three polychlorinated biphenyl congeners in the green alga, Selenastrum capricornutum

    SciTech Connect

    Mayer, P. |; Halling-Soerensen, B.; Nyholm, N.; Sijm, D.T.H.M.

    1998-09-01

    Algal growth inhibition tests were performed with the unicellular green alga Selenastrum capricornutum and three {sup 14}C-labeled polychlorinated biphenyl (PCB) congeners. Toxicity was related to external aqueous concentrations and additionally to internal algal bound PCB concentrations. Estimates of the concentrations at 50% effectiveness (EC50s) for the three PCB congeners ranged within a factor of 17 when based on measured aqueous concentrations. When based on internal toxicant concentrations the corresponding range was 6.7 to 14.3 mmol/kg wet weight. Thus, changing the basis from external to internal concentrations reduced the range by almost one order of magnitude. Additional toxic cell concentrations of five monoaromatic compounds and S. capricornutum were calculated from literature data to be in the same order of magnitude as the experimental toxic cell concentrations for the PCBs, whereas EC50 values for all substances ranged by more than four orders of magnitude. The experimental and calculated data indicate that observed differences in the estimated EC50 values were mainly due to differences in bioconcentration behavior rather than to different intrinsic toxicities. These findings are in agreement with the concept of baseline toxicity, meaning that a number of hydrophobic organics exerts their acute toxicity by one relatively nonspecific mode of action.

  5. Enhanced accumulation of PCB congeners by Baltic Sea blue mussels, Mytilus edulis, with increased algae enrichment

    SciTech Connect

    Gilek, M.; Bjoerk, M.; Broman, D.; Kautsky, N.; Naef, C.

    1996-09-01

    The objective of this study was to examine if natural variations in the quantity of phytoplankton-derived particulate and dissolved organic carbon influences the accumulation of polychlorinated biphenyls (PCBs) in the tissues of Baltic Sea blue mussels (Mytilus edulis L.). In a laboratory flow-through experiment the authors exposed M. edulis to the technical PCB mixture Aroclor{reg_sign} 1248 for 21 d at three different enrichments of the unicellular green algae Chlamydomonas sp., 0.10, 0.16, and 0.32 mg particulate organic carbon (POC)/L. Tissue and water concentrations were determined for seven PCB congeners and 21-d bioaccumulation factors were calculated against total water concentrations. Contrary to what would be expected, an increase in algae enrichment from 0.10 to 0.32 mg POC/L resulted in an enhanced PCB accumulation by a factor of approx. 2. This increase in PCB accumulation was more pronounced for PCB congeners with lower hydrophobicity. These observations have implications for the design of laboratory accumulation studies and potentially for PCB accumulation and cycling in field populations of suspension-feeding mussels in response to changes in eutrophication status.

  6. SAR of Sponge-Inspired Hemibastadin Congeners Inhibiting Blue Mussel PhenolOxidase

    PubMed Central

    Niemann, Hendrik; Hagenow, Jens; Chung, Mi-Young; Hellio, Claire; Weber, Horst; Proksch, Peter

    2015-01-01

    Hemibastadin derivatives, including the synthetically-derived 5,5′-dibromohemibastadin-1 (DBHB), are potent inhibitors of blue mussel phenoloxidase (PO), which is a key enzyme involved in the firm attachment of this invertebrate to substrates and, thus, a promising molecular target for anti-fouling research. For a systematic investigation of the enzyme inhibitory activity of hemibastadin derivatives, we have synthesized nine new congeners, which feature structural variations of the DBHB core structure. These structural modifications include, e.g., different halogen substituents present at the aromatic rings, different amine moieties linked to the (E)-2-(hydroxyimino)-3-(4-hydroxyphenyl)propionic acid, the presence of free vs. substituted aromatic hydroxyl groups and a free vs. methylated oxime group. All compounds were tested for their inhibitory activity towards the target enzyme in vitro, and IC50 values were calculated. Derivatives, which structurally closely resemble sponge-derived hemibastadins, revealed superior enzyme inhibitory properties vs. congeners featuring structural moieties that are absent in the respective natural products. This study suggests that natural selection has yielded structurally-optimized antifouling compounds. PMID:25988522

  7. Coating effects on the glass adsorption of polychlorinated biphenyl (PCB) congeners.

    PubMed

    Lung, S C; Altshul, L M; Ford, T E; Spengler, J D

    2000-12-01

    The effects of coating materials on polychlorinated biphenyl (PCB) adsorption in aqueous solution were assessed in an attempt to minimize PCB sorption loss during sampling processes. A coating material, which enhances PCB adsorption and allows adsorbed PCBs to be readily extracted by solvents, can act as a sampling concentrator to reduce PCB losses from both adsorption and evaporation. Several coating materials were evaluated, including paraffin oil, silicone oil, dimethyldichlorosilane (Sylon-CT), Prosil 28 and polydimethylsiloxane (PDS) with viscosity 0.65, 50 (PDS 50), and 500 (PDS 500) cSt. PDS and silicone oil enhanced adsorption for all five congeners examined (IUPAC No. 28, 52, 101, 138, and 180). Sylon-CT, paraffin oil and Prosil 28 had inconsistent effects on adsorption of different congeners. Desorption of adsorbed PCBs onto all coating types was assessed. The recovery efficiency of extracting PCBs with solvents was enhanced greatly with all coatings as opposed to non-coated surfaces, with the exception of paraffin oil. Coating with silicon oil, PDS 50, and 500 resulted in virtually 100% recovery of adsorbed PCBs. It was also found that Teflon containers were poor substitutes for glass containers and failed to minimize PCB losses. Among the materials studied, the best coating that could be used as a sampling concentrator was PDS 500. PMID:11061308

  8. Pyrolysis of MWI fly ash -- effect on dioxin-like congeners.

    PubMed

    Hung, Pao Chen; Chen, Qing Hui; Chang, Moo Been

    2013-08-01

    Removal and destruction of dioxin-like congeners, including polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs), from fly ash were investigated at varying pyrolysis temperatures and reaction times and using calcium-based additives. Destruction efficiencies based on TEQ and mass both increase with rising treatment temperature. However, additional low chlorinated PCDD/Fs were formed significantly by dechlorination of high chlorinated PCDD/Fs, at pyrolysis temperatures of 250 and 300°C. Surprisingly, lower destruction efficiencies were realized in the presence of Ca-based additive, compared with those without additive, and TEQ values of fly ash into which CaO was introduced increased, compared with the raw ash, due to significant formation of low chlorinated PCDD/Fs (4-5 Cl). However, complex interactions among unburned carbon, sulfur and metals in the fly ash collected in this study make it difficult to pinpoint the exact causes. The results obtained in this study indicate that degradation and formation of dioxin-like congeners take place simultaneously in pyrolysis process, such as formation of low chlorinated PCDD/Fs via dechlorination of highly chlorinated PCDD/Fs. PMID:23714152

  9. Effects of estradiol on neural responses to social signals in female túngara frogs.

    PubMed

    Chakraborty, Mukta; Burmeister, Sabrina S

    2015-11-01

    Estradiol plays an important role in mediating changes in female sexual behavior across reproductive cycles. In the túngara frog [Physalaemus (=Engystomops) pustulosus], the relationship between gonadal activity and female sexual behavior, as expressed by phonotaxis, is mediated primarily by estradiol. Estradiol receptors are expressed in auditory and motivational brain areas and the hormone could serve as an important modulator of neural responses to conspecific calls. To better understand how estradiol modifies neural responses to conspecific social signals, we manipulated estradiol levels and measured expression of the immediate early gene egr-1 in the auditory midbrain, thalamus and limbic forebrain in response to conspecific or heterospecific calls. We found that estradiol and conspecific calls increased egr-1 expression in the auditory midbrain and limbic forebrain, but in the thalamus, only conspecific calls were effective. In the preoptic area, estradiol enhanced the effect of the conspecific call on egr-1 expression, suggesting that the preoptic area could act as a hormonal gatekeeper to phonotaxis. Overall, the results suggest that estradiol has broad influences on the neural circuit involved in female reproduction, particularly those implicated in phonotaxis. PMID:26449971

  10. Dissipation and transformation of 17B-estradiol-17-sulfate in soil-water systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogen conjugates are known to be precursors of endocrine-disrupting free estrogens, e.g. 17B-estradiol (E2) and estrone (E1), in the environment. This study investigated the fate of a sulfate conjugated estrogen, 17B-estradiol-17-sulfate (E2-17S), in agricultural soils using laboratory batch stu...

  11. THE PATHOBIOLOGY OF 17B-ESTRADIOL IN SUMMER FLOUNDER, PARALICHTYS DENTATUS

    EPA Science Inventory

    Estradiol has been shown to cause increased vitellogenin (VtG) concentrations in male fish. The intent of this study was to evaluate the pathobiology associated with exposure to 17 -estradiol (E2) on liver, gonad, and kidney tissues of summer flounder, Paralichthys dentatus. Juve...

  12. Effects of preovulatory estradiol concentration on embryo survival and pregnancy establishment in beef cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of estradiol during the preovulatory period on embryo survival and pregnancy establishment has not been characterized in beef cows. We hypothesized that preovulatory estradiol is important for embryo survival and pregnancy establishment in beef cows. In order to establish the importance o...

  13. Exogenous estradiol alters gonadal growth and timing of temperature sex determination in gonads of sea turtle.

    PubMed

    Díaz-Hernández, Verónica; Marmolejo-Valencia, Alejandro; Merchant-Larios, Horacio

    2015-12-01

    Temperature sex determining species offer a model for investigating how environmental cues become integrated to the regulation of patterning genes and growth, among bipotential gonads. Manipulation of steroid hormones has revealed the important role of aromatase in the regulation of the estrogen levels involved in temperature-dependent sex determination. Estradiol treatment counteracts the effect of male-promoting temperature, but the resulting ovarian developmental pattern differs from that manifested with the female-promoting temperature. Hypoplastic gonads have been reported among estradiol-treated turtles; however the estradiol effect on gonadal size has not been examined. Here we focused on the sea turtle Lepidochelys olivacea, which develops hypoplastic gonads with estradiol treatment. We studied the effect of estradiol on cell proliferation and on candidate genes involved in ovarian pattern. We found this effect is organ specific, causing a dramatic reduction in gonadal cell proliferation during the temperature-sensitive period. Although the incipient gonads resembled tiny ovaries, remodeling of the medullary cords and down-regulation of testicular factor Sox9 were considerably delayed. Contrastingly, with ovarian promoting temperature as a cue, exogenous estradiol induced the up-regulation of the ovary factor FoxL2, prior to the expression of aromatase. The strong expression of estrogen receptor alpha at the time of treatment suggests that it mediates estradiol effects. Overall results indicate that estradiol levels required for gonadal growth and to establish the female genetic network are delicately regulated by temperature. PMID:26465360

  14. Application of fly ash as an adsorbent for Estradiol in animal waste.

    PubMed

    Norris, Pauline; Hagan, Stephanie; Cohron, Martin; Zhao, Houying; Pan, Wei-Ping; Li, Kawang

    2015-09-15

    The contamination of agricultural ground with estrogen compounds through application of animal wastes is a present concern. At the same time, current uses for waste fly ash having high carbon content are limited. To help mitigate these problems, we examine using waste fly ash as a useful adsorbent for Estradiol in pig waste digests. In this study, Estradiol was added to vials containing water and fly ash from several different power plants. After an extraction process, the amount of Estradiol in the water was measured. Commercial activated carbon was also used for comparison purposes. Vials containing varying concentrations of Estradiol and no trapping material were used as a control. The results from this study indicate that fly ash can be used as a trapping material for Estradiol in water, but that commercially available activated carbon can trap about an order of magnitude more Estradiol than the fly ash and that the effects of the fly ash matrix can both inhibit and promote the solvation of Estradiol into water depending possibly upon pH and cation concentration effects. In addition, preliminary extraction studies using pig waste digest indicate that fly ash can be used as adsorbent for Estradiol present in pig waste. PMID:26150373

  15. Modeling of Coupled Degradation, Sorption, and Transport of 17beta-Estradiol in Undisturbed Soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of 17 beta-estradiol in the environment, even at part-per trillion concentrations, may raise significant concern regarding the health of aquatic organisms. Once 17 beta-estradiol is released into the environment from human and animal sources, its fate and transport is controlled by fact...

  16. Luteinizing hormone secretion as influenced by age and estradiol in the prepubertal gilt

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The aim of this study was to determine if there is an age related reduction in the sensitivity of the negative feedback action of estradiol on luteinizing hormone (LH) secretion in the prepubertal gilt. Ovariectomized gilts at 90 (n = 12), 150 (n = 11) or 210 (n = 12) days of age received estradiol ...

  17. Ultrasound and estradiol plasma levels in threatened abortion.

    PubMed

    Melis, G B; Strigini, F; Fruzzetti, F; Paoletti, A M; Battistelli, P; Boldrini, A

    1984-01-01

    Ultrasound examination and unconjugated estriol assay were performed in 111 women with threatened abortion between the 6th and the 20th week of pregnancy. In viable pregnancies, fetal echoes and fetal heart movements were always observed by sonar from the 10th week onward and estradiol levels always increased above 30 pg/ml from the 13th week. Both ultrasound and estriol assay showed high percentages of uncertain prognostic indication on pregnancy outcome when examinations were performed during the first weeks of pregnancy. However, in the same period estriol levels higher than 30 pg/ml were always correlated with the favourable outcome of pregnancy, since no abortion occurred in subjects with detectable estriol values. During the second trimester ultrasound and estradiol results were normal in all viable pregnancies, while they were abnormal in 71.4% of pregnancies which failed to continue. Estriol values were always undetectable when fetuses could not be identified by sonar or they were dead. These data seem to demonstrate that both methods have similar prognostic value in patients with threatened abortion. However both sonar examination and estriol levels sometimes failed in predicting subsequent pregnancy interruptions, suggesting that abortions were not related to either fetal or placental alterations. PMID:6395604

  18. Sampling the Hudson River estuary for PCBs using multiplate artificial substrate samplers and congener-specific gas chromatography in 1991

    SciTech Connect

    Bush, B. . Wadsworth Center for Labs. and Research State Univ. of New York, Albany, NY . School of Public Health); Dzurica, S. . School of Public Health); Wood, L.; Madrigal, E.C. . Wadsworth Center for Labs. and Research)

    1994-08-01

    During the summer of 1991, multiplate artificial substrate samplers were deployed at five locations in the Hudson River from Troy to Poughkeepsie, New York. The sedimentary material that collected on these plates was fractionated and analyzed using a congener-specific method for PCB content. The results were compared intrasite, intersite, and across time. The authors found no difference between the PCB congener distribution patterns in the coarse and fine fractions, as determined by linear regression. They also found little evidence of intersite differentiation--they found no discernible difference in PCB congener distribution, but they did find a difference in magnitude. The 1991 results were then compared to the results from a previous study conducted from 1977 to 1985. They found that over the studied 120 km stretch of the river there has been a 3.7 [+-] 1.2% per annum decline in PCB multiplate residue since 1983.

  19. Congener-specific accumulation and trophic transfer of polychlorinated biphenyls in spider crab food webs revealed by stable isotope analysis.

    PubMed

    Bodin, N; Le Loc'h, F; Caisey, X; Le Guellec, A-M; Abarnou, A; Loizeau, V; Latrouite, D

    2008-01-01

    Polychlorobiphenyls (PCB) and stable isotopes (delta15N and delta13C) were analyzed in the spider crab (Maja brachydactyla) food web from the Iroise Sea (Western Brittany) and the Seine Bay (Eastern English Channel). PCB concentrations were all significantly higher in organisms from the Seine Bay than those from the Iroise Sea. PCB patterns were strongly related to the feeding mode of the species, and increased influence of higher chlorinated congeners was highlighted with trophic position of the organisms. PCB concentrations (lipid normalized) were significantly related to the isotopically derived trophic level (TL) in spider crab food webs. The highest trophic magnification factors (TMFs) were calculated for the congeners with 2,4,5-substitution, and were lower in the Seine Bay compared to the Iroise Sea. The confrontation of PCB and TL data also revealed biotransformation capacity of decapod crustaceans for specific congeners based on structure-activity relations. PMID:17544187

  20. Antigenotoxic effect of allicin against estradiol-17beta-induced genotoxic damage in cultured mammalian cells.

    PubMed

    Siddique, Yasir Hasan; Beg, Tanveer; Ara, Gulshan; Gupta, Jyoti; Afzal, Mohammad

    2010-07-01

    Antigenotoxic activity of allicin, one of the sulphur compounds of garlic (Allium sativum) which possesses antioxidant and thiol disulphide exchange activity, was studied against estradiol-17beta-induced genotoxic damage using chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) as parameters. Approximately 10, 20 and 40 microM of estradiol-17beta was tested for its genotoxic effect in the presence of metabolic activation and was found to be genotoxic at 20 and 40 microM. Approximately 20 microM of estradiol-17beta was treated along with 5, 10 and 15 microM of allicin, separately, in the presence of metabolic activation. Similar treatments were given with 40 microM of estradiol-17beta. Treatments along with allicin result in the reduction of CAs and SCEs, suggesting its anti-genotoxic activity in human lymphocytes in vitro against estradiol-17beta-induced genotoxic damage. PMID:20582805

  1. A long-term study of anaerobic dechlorination of PCB congeners by sediment microorganisms pathways and mass balance

    SciTech Connect

    Rhee, G.Y.; Sokol, R.C.; Bush, B. . Wadsworth Center for Labs. and Research); Bethoney, C.M. . School of Public Health, New York State Dept. of Health)

    1993-10-01

    Reductive dechlorination of PCBs by Hudson River sediment microorganisms was investigated using individual congeners, 2,3,4,2[prime],4[prime],5[prime]-, 2,4,5,2[prime],4[prime],5[prime]-, 2,3,4,5,6-, 2,4,2[prime],4[prime]-, and 3,4,3[prime],4[prime]-chlorobiphenyls (CBPs) in long-term studies lasting 15 to 20 months. The dechlorination of 2,3,4,2[prime],4[prime],5[prime]-CBP yielded 2,4,5,2[prime],4[prime]-, 2,4,2[prime],4[prime]-, 2,4,2[prime],5[prime]-, and 2,4,2[prime],5[prime]-, and 2,4,2[prime]-CBPs; notably absent was 2,2[prime]-CBP. Yet, the total molar concentration of all congeners decreased with time and at 15 months accounted for only 25% of the initial concentration of the parent compound. 2,3,4,5,6-CBP produced 2,3,5,6-, 2,4,6-, and 2,6-CBPs. At 15 months the sum of all congeners accounted for only about 50% of the initial amount of the parent congener. On the other hand, 2,4,5,2[prime],4[prime],5[prime]-CBP yielded six daughter products, including 2,2[prime]-CBP, and did not show any decrease in total molar concentration even at 20 months. 2,4,2[prime],4[prime]-CBP did not show any change at 15 months. These results indicate that anaerobic PCB biotransformation may include mechanisms other than dechlorination and that the mechanisms are congener dependent. Biphenyl was detected with 3,4,3[prime],4[prime]-CBP, indicating complete dechlorination; however, it accounted for <10% of the total molar loss. [sup 14]C-labeled tracer of this congener showed that all radioactivity was in the hexane fraction, suggesting that transformation products were hydrophobic.

  2. The Effects of Individual PCB Congeners on the Soil Bacterial Community Structure and the Abundance of Biphenyl Dioxygenase Genes

    PubMed Central

    Correa, Paola A.; Lin, LianShin; Just, Craig L.; Hu, Dingfei; Hornbuckle, Keri C.; Schnoor, Jerald L.; Van Aken, Benoit

    2009-01-01

    Polychlorinated biphenyls (PCBs) are toxic environmental contaminants that represent a class of 209 congeners characterized by different degree of chlorination and substitution patterns. Most of experimental studies about microbial degradation of PCBs have been conducted on PCB mixtures, even though evidence accumulated in bacteria and other organisms shows that exposure to different congeners may have different biological effects. Microcosm experiments were conducted using aerobic agitated soil slurries individually exposed to PCB congeners with different degrees of chlorination: PCB-3, 15, 28, and 77, and the commercial mixture Aroclor 1242. After four weeks of incubation, PCBs were analyzed by gas chromatography/mass spectrometry (GC/MS) showing different transformation extents: With the exception of PCB-15 that was not significantly transformed (7%), biodegradation rates decreased with the degree of chlorination, from 75% for PCB-3 to 22% for PCB-77 and Aroclor 1242. The bacterial abundance, as measured by colony counting and 16S rDNA quantification by real-time PCR, was lower (of about 40%) in soil microcosms exposed to the higher-chlorinated congeners, PCB-28, PCB-77, and Aroclor 1242, as compared to non-exposed soils and soils exposed to the lower-chlorinated congeners, PCB-3 and PCB-15. The relative abundance of different taxonomic groups, as determined by real-time PCR, revealed an increase of β-Proteobacteria and Actinobacteria in all microcosms exposed to PCBs, as compared with non-exposed soil. In addition, exposure to PCB-77 and Aroclor 1242 resulted in a higher abundance of α-Proteobacteria and Acidobacteria. Globally, these results suggest that exposure to PCBs (and especially to higher-chlorinated congeners and Aroclor 1242) selected bacterial groups involving most known PCB degraders, i.e., β-Proteobacteria and Acidobacteria. The quantification of biphenyl dioxygenase (BPH) genes - involved in the aerobic degradation of PCBs - using real

  3. Comparing biological effects of estrone (E1) and 17ß-estradiol (E2) in mature fathead minnows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of endocrine active compounds such as estrogens in treated wastewater effluent and their effects on aquatic life are causing concern among aquatic resource managers. Among the natural estrogens are 17ß-estradiol, 17a-estradiol, and estrone. Although 17ß-estradiol has received significa...

  4. An overview of the development of combined oral contraceptives containing estradiol: focus on estradiol valerate/dienogest

    PubMed Central

    Fruzzetti, Franca; Trémollieres, Florence; Bitzer, Johannes

    2012-01-01

    Natural estrogens such as estradiol (E2) or its valerate ester (E2V) offer an alternative to ethinyl estradiol (EE). E2-containing combined oral contraceptives (COCs) have demonstrated sufficient ovulation inhibition and acceptable contraceptive efficacy. However, earlier formulations were generally associated with unacceptable bleeding profiles. Two E2V-containing preparations have been approved to date for contraceptive use: E2V/cypro-terone acetate (CPA) (Femilar®; only approved in Finland and only in women >40 years or women aged 35–40 years in whom a COC containing EE is not appropriate) and E2V/dienogest (DNG; Qlaira®/Natazia®). The objective of the current review is to provide an overview of the development of COCs containing natural estrogen, highlighting past issues and challenges faced by earlier formulations, as well as the current status and future directions. The majority of information to date pertains to the development of E2V/DNG. PMID:22468839

  5. Time-Trends and Congener Profiles of PBDEs and PCBs in California Peregrine Falcons (Falco peregrinus)

    PubMed Central

    Park, June-Soo; Holden, Arthur; Chu, Vivian; Kim, Michele; Rhee, Alexandra; Patel, Puja; Shi, Yating; Linthicum, Janet; Walton, Brian J.; Mckeown, Karen; Jewell, Nicholas P.; Hooper, Kim

    2010-01-01

    High levels (µg/g lw) of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured in peregrine falcon eggs from California (n = 90 eggs from 52 birds, 38 nest sites, collected 1986–2007, ΣPBDEs median = 4.53, range = 0.08–53.1). Over the past 22 years, PBDE levels more than tripled each decade in the eggs, whereas PCB levels had no significant changes. PBDE levels were highest in eggs from major California cities (“Big Cities”), whereas PCBs showed no difference across the regions. For PBDEs, Big City eggs had markedly different patterns from Coastal eggs:BDE-209 and the higher brominated PBDEs (hexa–nona) were dominant congeners in Big City eggs, while BDE-47 and -99 were dominant in Coastal eggs. In many of the birds that gave multiple eggs over time (“time series”), PBDE patterns changed over time: the high proportions of BDE-209 and higher brominated PBDEs (short half-lives) in young birds contrasted with increasingly higher proportions of BDE-153 (long half-life) and other lower brominated PBDEs as the birds aged. These data are consistent with metabolic debromination of BDE-209 (t1/2 = 1–2 weeks) to the lower brominated PBDEs, with accumulation over time of BDE-153 (t1/2 = 3–4 years). In contrast, PCB patterns showed no differences by locations, and did not change over time. Diet (prey birds) may explain the urban PBDE pattern, as the patterns in urban pigeons and peregrines were similar, with high proportions of BDE-209 and the higher-brominated PBDEs. Also, our prey data (feathers from peregrine nests) showed urban peregrines having a higher proportion (>2 fold) of granivorous/opportunistic birds (e.g., “introduced feral” pigeons, mourning doves, starlings) in their diet than coastal peregrines. In summary, these data indicate that BDE-209 exits consumer products as an environmental contaminant to be taken up by wildlife (particularly in urban locations), and undergoes metabolic debromination to the

  6. Lymphoid reconstitution after transplantation of congenic hematopoietic cells in busulfan-treated mice.

    PubMed

    Yeager, A M; Shinn, C; Pardoll, D M

    1991-12-15

    The effects of pretransplant conditioning with high-dose busulfan, a myeloablative but nonimmunosuppressive alkylating agent, on reconstitution of lymphoid tissues by donor cells after bone marrow transplantation (BMT) has not been extensively examined. We used flow cytometric analyses to study the kinetics and extent of lymphocyte repopulation in C57BL/6 mice (immunophenotype Ly-5.2) given graded doses of busulfan (10 to 100 mg/kg) or total body irradiation (TBI; 900 rad) and hematopoietic cell transplantation (HCT; transplantation of bone marrow and spleen cells) from congenic Ly-5.1 donors. Mice transplanted after 10 mg/kg of busulfan had slow and incomplete lymphoid engraftment; only 6% to 11% of lymphocytes in the peripheral blood, lymph nodes, and spleen were positive for Ly-5.1 at 30 days after transplant, slightly increased to 13% to 20% at 60 days, and stabilized at 40% to 46% by 180 days after HCT. Higher doses of busulfan (20 to 100 mg/kg) provided dose-dependent congenic lymphoid reconstitution. Thirty days after HCT, the range of Ly-5.1 cells in blood, lymph nodes, and spleen of Ly-5.2 recipient mice was 43% to 54% after 20 mg/kg of busulfan, 66% to 71% after 50 to 80 mg/kg, and 77% to 85% after 100 mg/kg. Sixty days after transplant, lymphoid chimerism increased to 57% to 68% in 20 mg/kg recipients, 72% to 79% after 35 mg/kg, and 75% to 90% in animals given 50 mg/kg or greater, as seen in radiation chimeras. Despite slower early reconstitution after lower doses of busulfan, donor lymphocytes exceeded 90% to 95% by 90 to 120 days after HCT in all mice given at least 20 mg/kg. Even though busulfan lacks directly immunosuppressive properties, virtually complete sustained lymphoid reconstitution by transplanted congenic donor stem cells occurs after its administration. These observations suggest that pretreatment with busulfan may be effective in gene therapy strategies that involve infusion of autologous marrow cells into which functional genes have been

  7. Time-trends and congener profiles of PBDEs and PCBs in California peregrine falcons (Falco peregrinus).

    PubMed

    Park, June-Soo; Holden, Arthur; Chu, Vivian; Kim, Michele; Rhee, Alexandra; Patel, Puja; Shi, Yating; Linthicum, Janet; Walton, Brian J; McKeown, Karen; Jewell, Nicholas P; Hooper, Kim

    2009-12-01

    High levels (microg/g lw) of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) were measured in peregrine falcon eggs from California (n = 90 eggs from 52 birds, 38 nest sites, collected 1986-2007, SigmaPBDEs median = 4.53, range = 0.08-53.1). Over the past 22 years, PBDE levels more than tripled each decade in the eggs, whereas PCB levels had no significant changes. PBDE levels were highest in eggs from major California cities ("Big Cities"), whereas PCBs showed no difference across the regions. For PBDEs, Big City eggs had markedly different patterns from Coastal eggs: BDE-209 and the higher brominated PBDEs (hexa-nona) were dominant congeners in Big City eggs, while BDE-47 and -99 were dominant in Coastal eggs. In many of the birds that gave multiple eggs over time ("time series"), PBDE patterns changed over time: the high proportions of BDE-209 and higher brominated PBDEs (short half-lives) in young birds contrasted with increasingly higher proportions of BDE-153 (long half-life) and other lower brominated PBDEs as the birds aged. These data are consistent with metabolic debromination of BDE-209 (t(1/2) = 1-2 weeks) to the lower brominated PBDEs, with accumulation over time of BDE-153 (t(1/2) = 3-4 years). In contrast, PCB patterns showed no differences by locations, and did not change over time. Diet (prey birds) may explain the urban PBDE pattern, as the patterns in urban pigeons and peregrines were similar, with high proportions of BDE-209 and the higher-brominated PBDEs. Also, our prey data (feathers from peregrine nests) showed urban peregrines having a higher proportion (>2 fold) of granivorous/opportunistic birds (e.g., "introduced feral" pigeons, mourning doves, starlings) in their diet than coastal peregrines. In summary, these data indicate that BDE-209 exits consumer products as an environmental contaminant to be taken up by wildlife (particularly in urban locations), and undergoes metabolic debromination to the banned lower

  8. Influence of colloids on sediment-water partition coefficients of polychlorobiphenyl congeners in natural waters

    SciTech Connect

    Baker, J.E.; Capel, P.D.; Eisenreich, S.J.

    1986-11-01

    Measurements of sediment-water partitioning of polychlorobiphenyl (PCB) congeners in Lake Superior provide some of the first field evidence demonstrating the importance of colloids to the fates of highly hydrophobic organic pollutants. Laboratory-derived correlations between sediment-water distribution coefficients and properties of both the contaminant (octanol-water partition coefficient) and the suspended solids (organic carbon content, concentration) do not accurately predict PCB speciation in Lake Superior. This failure can be explained by the presence of colloidal matter with which contaminants may associate and the very low solids concentrations in oligotrophic surface waters. A surprising consequence of such colloid associations is that the observed sediment-water distribution coefficients are independent of properties of highly hydrophobic compounds. A three-phase model including nonfilterable microparticles and macromolecular organic matter shows that colloidal-associated contaminants may be the dominant species in most surface waters. Colloidal associations are therefore likely to significantly impact the geochemistry of hydrophobic pollutants.

  9. Antifouling bastadin congeners target mussel phenoloxidase and complex copper(II) ions.

    PubMed

    Bayer, Mirko; Hellio, Claire; Maréchal, Jean-Philippe; Frank, Walter; Lin, Wenhan; Weber, Horst; Proksch, Peter

    2011-12-01

    Synthetically prepared congeners of sponge-derived bastadin derivatives such as 5,5'-dibromohemibastadin-1 (DBHB) that suppress the settling of barnacle larvae were identified in this study as strong inhibitors of blue mussel phenoloxidase that is involved in the firm attachment of mussels to a given substrate. The IC₅₀ value of DBHB as the most active enzyme inhibitor encountered in this study amounts to 0.84 μM. Inhibition of phenoloxidase by DBHB is likely due to complexation of copper(II) ions from the catalytic centre of the enzyme by the α-oxo-oxime moiety of the compound as shown here for the first time by structure activity studies and by X-ray structure determination of a copper(II) complex of DBHB. PMID:21547349

  10. Polychlorinated biphenyl congeners in sediment cores from the Upper Mississippi River.

    PubMed

    Martinez, Andres; Schnoebelen, Douglas J; Hornbuckle, Keri C

    2016-02-01

    We determined polychlorinated biphenyls (PCBs) and radionuclide (137)Cs in sediment cores from the Upper Mississippi River (UMR) and the Iowa River, Iowa, at their confluence. Vertical distribution of (137)Cs indicated negligible mixing in the UMR core, while the Iowa River core showed signs of mixing. A clear (137)Cs peak was found in the UMR core, which was correlated to 1963. The PCB vertical distribution in UMR core was similar to the historical trend in Aroclor production observed in Great Lakes cores, with a peak close to the (137)Cs peak, suggesting a date near 1960. In general, PCB congener profiles in both cores resembled the Iowa soil background signal. We concluded that despite evidence of mixing in the Iowa River core, both cores retain the PCB signature of historical and regional environmental exposure. Further, our results indicate that this iconic waterway has a long history of PCBs that reflects national production and use. PMID:26547030

  11. Alkali Metal Carbenoids: A Case of Higher Stability of the Heavier Congeners.

    PubMed

    Molitor, Sebastian; Gessner, Viktoria H

    2016-06-27

    As a result of the increased polarity of the metal-carbon bond when going down the group of the periodic table, the heavier alkali metal organyl compounds are generally more reactive and less stable than their lithium congeners. We now report a reverse trend for alkali metal carbenoids. Simple substitution of lithium by the heavier metals (Na, K) results in a significant stabilization of these usually highly reactive compounds. This allows their isolation and handling at room temperature and the first structure elucidation of sodium and potassium carbenoids. The control of stability was used to control reactivity and selectivity. Hence, the Na and K carbenoids act as selective carbene-transfer reagents, whereas the more labile lithium systems give rise to product mixtures. Additional fine tuning of the M-C interaction by means of crown ether addition further allows for control of the stability and reactivity. PMID:27100278

  12. Gateway synthesis of daphnane congeners and their protein kinase C affinities and cell-growth activities

    NASA Astrophysics Data System (ADS)

    Wender, Paul A.; Buschmann, Nicole; Cardin, Nathan B.; Jones, Lisa R.; Kan, Cindy; Kee, Jung-Min; Kowalski, John A.; Longcore, Kate E.

    2011-08-01

    The daphnane diterpene orthoesters constitute a structurally fascinating family of natural products that exhibit a remarkable range of potent biological activities. Although partial activity information is available for some natural daphnanes, little information exists for non-natural congeners or on how changes in structure affect mode of action, function, potency or selectivity. A gateway strategy designed to provide general synthetic access to natural and non-natural daphnanes is described and utilized in the synthesis of two novel members of this class. In this study, a commercially available tartrate derivative was elaborated through a key late-stage diversification intermediate into B-ring yuanhuapin analogues to initiate exploration of the structure-function relationships of this class. Protein kinase C was identified as a cellular target for these agents, and their activity against human lung and leukaemia cell lines was evaluated. The natural product and a novel non-natural analogue exhibited significant potency, but the epimeric epoxide was essentially inactive.

  13. Displacement of Tetropium cinnamopterum (Coleoptera: Cerambycidae) by Its Invasive Congener Tetropium fuscum.

    PubMed

    Dearborn, Kenneth W; Heard, Stephen B; Sweeney, Jon; Pureswaran, Deepa S

    2016-08-01

    We examined the native community of insects interacting with an invasive species, Tetropium fuscum (F.) (Coleoptera: Cerambycidae), in its new range to explore reasons for the invader's relatively slow spread. Tetropium fuscum is a European spruce borer established in Nova Scotia since at least 1990, but it has spread only about 125 km from its site of introduction. We compared the densities of Tetropium spp., their known parasitoids, and the community of wood-boring insects at sites located within the invasion zone in Nova Scotia versus well outside this zone, in New Brunswick, Canada. Using red spruce trees stressed by girdling or felling, we tested whether: 1) T. fuscum had altered the native wood-boring community; 2) T. fuscum displaced a native congener, Tetropium cinnamopterum (Kirby); and 3) parasitism rates of Tetropium spp. differed between the invaded and noninvaded zones. Both Tetropium spp. and their parasitoid wasps emerged exclusively from felled trees as opposed to girdled trees. We found no difference in community diversity inside versus outside the invasion zone. The combined densities of both Tetropium spp. and their overall parasitism rates also did not differ between zones, but T. cinnamopterum density was significantly greater outside the invasion zone, suggesting T. fuscum may displace the native congener where they are sympatric. Our results suggest that the native and invasive Tetropium spp. act as a single functional species in the invasion zone. We speculate that natural control agents (predators, parasitoids, and competitors) might be limiting the rate of spread of T. fuscum. PMID:27247305

  14. Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation

    PubMed Central

    Cui, Yue; Franciszkiewicz, Katarzyna; Mburu, Yvonne K.; Mondot, Stanislas; Le Bourhis, Lionel; Premel, Virginie; Martin, Emmanuel; Kachaner, Alexandra; Duban, Livine; Ingersoll, Molly A.; Rabot, Sylvie; Jaubert, Jean; De Villartay, Jean-Pierre; Soudais, Claire; Lantz, Olivier

    2015-01-01

    Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%–10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-α locus and led to higher usage of the distal Vα segments, including Vα19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4–CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7–). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18Rα, and IL-12Rβ and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor γ (RORγt). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease. PMID:26524590

  15. Accumulation of polychlorinated biphenyl congeners from Lake Champlain sediments by Mysis relicta

    SciTech Connect

    Lester, D.C.; McIntosh, A. . Vermont Water Resources and Lake Studies Center)

    1994-11-01

    Polychlorinated biphenyl (PCB) levels in lake trout (Salvelinus namaycush) from Lake Champlain often exceed the F.D.A. tolerance level of 2 [mu]g/g (wet weight). Of added concern are recent studies that suggest a relationship between the dioxin-like properties of non-ortho-substituted PCB congeners and impaired lake trout egg hatchability. Dietary accumulation of PCBs is thought to be an important exposure route for fish. The epibenthic freshwater shrimp Mysis relicta is an integral part of the benthic and pelagic food web in lake Champlain and may act as a link between PCBs in sediments and lake trout. Previous investigations have shown that diurnal migrations of mysids enhance the movement and distribution of toxic contaminants, effectively coupling the benthic and pelagic zones. The objective of this research was to examine the role contaminated sediments play in the transfer of PCBs to mysids. Bioaccumulation was assessed by exposing mysids to such sediments in two ways: (a) with organisms screened from sediments; and (b) with organisms in direct contact with sediments. Accumulation of PCBs over the course of the 24-day exposure period was examined on the following days: 0, 3, 6, 12, 21, and 24. Eighty-nine individual PCB congeners were measured in tissue and sediment. Mysids in direct contact with sediments accumulated significantly higher levels of PCBs than did organisms screened from sediments. Mysids accumulated substantial levels of PCBs, suggesting they may play an important part in the transfer of PCBs from sediments into the Lake Champlain food web. It is clear from this research that sediments can play a critical role in the accumulation of PCBs by mysids.

  16. Partitioning and removal of dioxin-like congeners in flue gases treated with activated carbon adsorption.

    PubMed

    Chi, Kai Hsien; Chang, Shu Hao; Huang, Chia Hua; Huang, Hung Chi; Chang, Moo Been

    2006-08-01

    Activated carbon adsorption is commonly used to control dioxin-like congener (PCDD/Fs and PCBs) emissions. Partitioning of PCDD/Fs and PCBs between vapor and solid phases and their removal efficiencies achieved with existing air pollution control devices (APCDs) at a large-scale municipal waste incinerator (MWI) and an industrial waste incinerator (IWI) are evaluated via intensive stack sampling and analysis. Those two facilities investigated are equipped with activated carbon injection (ACI) with bag filter (BF) and fixed activated carbon bed (FACB) as major PCDD/F control devices, respectively. Average PCDD/F and PCB concentrations of stack gas with ACI+BF as APCDs are 0.031 and 0.006ng-TEQ/Nm(3), and that achieved with FACB are 1.74 and 0.19ng-TEQ/Nm(3) in MWI and IWI, respectively. The results show that FACB could reduce vapor-phase PCDD/Fs and PCBs concentrations in flue gas, while the ACI+BF can effectively adsorb the vapor-phase dioxin-like congener and collect the solid-phase PCDD/Fs and PCBs in the meantime. Additionally, the results of the pilot-scale adsorption system (PAS) experimentation indicate that each gram activated carbon adsorbs 105-115ng-PCDD/Fs and each surface area (m(2)) of activated carbon adsorbs 10-25ng-PCDD/Fs. Based on the results of PAS experimentation, this study confirms that the surface area of mesopore+macropore (20-200A) of the activated carbon is a critical factor affecting PCDD/F adsorption capacity. PMID:16488462

  17. Feasibility of Trace Alcohol Congener Detection and Identification Using Laser-Induced Breakdown Spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Jialiang; Wang, Shangmin; Zhao, Lixian; Liu, Liying; Wang, Dezhen

    2014-12-01

    In this paper, a feasible scheme is reported for the detection and identification of trace alcohol congeners that have identical elemental composition using laser-induced breakdown spectroscopy (LIBS). In the scheme, an intensive pulsed laser is used to break down trace alcohol samples and the optical emission spectra of the induced plasma are collected for the detection and identification of alcohol molecules. In order to prepare trace alcohol samples, pure ethanol or methanol is bubbled by argon carrier gas and then mixed into matrix gases. The key issue for the scheme is to constitute indices from the LIBS data of the alcohol samples. Two indices are found to be suitable for alcohol detection and identification. One is the emission intensity ratio (denoted as H/C) of the hydrogen line (653.3 nm) to the carbon line (247.9 nm) for identification and the other is the ratio of the carbon line (as C/Ar) or the hydrogen line (as H/Ar) to the argon lines (866.7 nm) for quantitative detection. The calibration experiment result shows that the index H/C is specific for alcohol congeners while almost being independent of alcohol concentration. In detail, the H/C keeps a specific constant of 34 and 23 respectively for ethanol and methanol. In the meanwhile, the C/Ar and H/Ar indices respond almost linearly to the alcohol concentration below 1300 ppm, and are therefore competent for concentration measurement. With the indices, trace alcohol concentration measurement achieves a limit of 140 ppm using a laser pulse energy of 300 mJ.

  18. Polychlorinated biphenyl congener patterns in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed, western Massachusetts, USA, using a novel statistical approach.

    PubMed

    Custer, Christine M; Read, Lorraine B

    2006-07-01

    A novel application of a commonly used statistical approach was used to examine differences in polychlorinated biphenyl (PCB) congener patterns among locations and sample matrices in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed in western Massachusetts, USA. The most prevalent PCB congeners in tree swallow tissue samples from the Housatonic River watershed were Ballsmitter Zell numbers 153, 138, 180, 187, 149, 101, and 170. These congeners were seven of the eight most prevalent congeners in Aroclor 1260, the PCB mixture that was the primary source of contamination in the Housatonic River system. Using paired-Euclidean distances and tolerance limits, it was demonstrated that congener patterns in swallow tissues from sites on the main stem of the Housatonic River were more similar to one another than to two sites upstream of the contamination or from a nearby reference area. The congener patterns also differed between the reference area and the two upstream tributaries and between the two tributaries. These pattern differences were the same in both pipper (eggs or just hatched nestlings) and 12-day-old nestling samples. Lower-chlorinated congeners appeared to be metabolized in nestlings and pippers compared to diet, and metabolized more in pippers compared to nestlings. Euclidean distances and tolerance limits provide a simple and statistically valid method to compare PCB congener patterns among groups. PMID:16377044

  19. Relationship between Carotenoids, Retinol, and Estradiol Levels in Older Women

    PubMed Central

    Maggio, Marcello; de Vita, Francesca; Lauretani, Fulvio; Bandinelli, Stefania; Semba, Richard D.; Bartali, Benedetta; Cherubini, Antonio; Cappola, Anne R.; Ceda, Gian Paolo; Ferrucci, Luigi

    2015-01-01

    Background. In vitro evidence suggests anti-estrogenic properties for retinol and carotenoids, supporting a chemo-preventive role of these phytochemicals in estrogen-dependent cancers. During aging there are significant reductions in retinol and carotenoid concentrations, whereas estradiol levels decline during menopause and progressively increase from the age of 65. We aimed to investigate the hypothesis of a potential relationship between circulating levels of retinol, carotenoids, and estradiol (E2) in a cohort of late post-menopausal women. Methods. We examined 512 women ≥ 65 years from the InCHIANTI study. Retinol, α-caroten, β-caroten, β-criptoxantin, lutein, zeaxanthin, and lycopene levels were assayed at enrollment (1998–2000) by High-Performance Liquid Chromatography. Estradiol and testosterone (T) levels were assessed by Radioimmunometry (RIA) and testosterone-to-estradiol ratio (T/E2), as a proxy of aromatase activity, was also calculated. General linear models adjusted for age (Model 1) and further adjusted for other confounders including Body Mass Index (BMI) BMI, smoking, intake of energy, lipids, and vitamin A; C-Reactive Protein, insulin, total cholesterol, liver function, and testosterone (Model 2) were used to investigate the relationship between retinol, carotenoids, and E2 levels. To address the independent relationship between carotenoids and E2 levels, factors significantly associated with E2 in Model 2 were also included in a fully adjusted Model 3. Results. After adjustment for age, α-carotene (β ± SE = −0.01 ± 0.004, p = 0.02) and β-carotene (β ± SE = −0.07 ± 0.02, p = 0.0007) were significantly and inversely associated with E2 levels. α-Carotene was also significantly and positively associated with T/E2 ratio (β ± SE = 0.07 ± 0.03, p = 0.01). After adjustment for other confounders (Model 2), the inverse relationship between α-carotene (β ± SE = −1.59 ± 0.61, p = 0.01), β-carotene (β ± SE = −0.29 ± 0.08, p

  20. Seizure facilitating activity of the oral contraceptive ethinyl estradiol.

    PubMed

    Younus, Iyan; Reddy, Doodipala Samba

    2016-03-01

    Contraceptive management is critical in women with epilepsy. Although oral contraceptives (OCs) are widely used by many women with epilepsy, little is known about their impact on epileptic seizures and epileptogenesis. Ethinyl estradiol (EE) is the primary component of OC pills. In this study, we investigated the pharmacological effect of EE on epileptogenesis and kindled seizures in female mice using the hippocampus kindling model. Animals were stimulated daily with or without EE until generalized stage 5 seizures were elicited. EE treatment significantly accelerated the rate of epileptogenesis. In acute studies, EE caused a significant decrease in the afterdischarge threshold and increased the incidence and severity of seizures in fully-kindled mice. In chronic studies, EE treatment caused a greater susceptibility to kindled seizures. Collectively, these results are consistent with moderate proconvulsant-like activity of EE. Such excitatory effects may affect seizure risk in women with epilepsy taking OC pills. PMID:26874323

  1. Laccase mediated transformation of 17β-estradiol in soil.

    PubMed

    Singh, Rashmi; Cabrera, Miguel L; Radcliffe, David E; Zhang, Hao; Huang, Qingguo

    2015-02-01

    It is known that 17β-estradiol (E2) can be transformed by reactions mediated by some oxidoreductases such as laccase in water. Whether or how such reactions can happen in soil is however unknown although they may significantly impact the environmental fate of E2 that is introduced to soil by land application of animal wastes. We herein studied the reaction of E2 in a model soil mediated by laccase, and found that the reaction behaviors differ significantly from those in water partly because of the dramatic difference in laccase stability. We also examined E2 transformation in soil using (14)C-labeling in combination with soil organic matter extraction and size exclusion chromatography, which indicated that applied (14)C radioactivity was preferably bound to humic acids. The study provides useful information for understanding the environmental fate of E2 and for developing a novel soil remediation strategy via enzyme-enhanced humification reactions. PMID:25489747

  2. Detection of estradiol-17β during a mass coral spawn

    NASA Astrophysics Data System (ADS)

    Atkinson, S.; Atkinson, M. J.

    1992-04-01

    The steroid estradiol-17β (E2) is associated with female gametogenesis in all vertebrates and many invertebrates. This is the first report of estrogens in scleractinian corals. Seawater and egg slicks were collected during a mass coral spawn at Ningaloo reef, Western Australia for the measurement of total phosphate (TP) and E2. Total P in the water column increased 600 times, from 0.5μM to 300μM. Concentrations of E2 increased nearly 8 fold during the spawn, from 55 to 420 pg/100 ml seawater. Coral eggs collected from egg slicks contained 368±40 pg E2/g dry wt of eggs. Estrogen may be a key hormone in a simple endocrine system of scleractinian corals that synchronizes growth and development of coral oocytes. Its potential role in triggering spawning via chemical messengers in the water column warrants further research.

  3. Effects of estradiol and progesterone on the reproduction of the freshwater crayfish Cherax albidus.

    PubMed

    Coccia, E; De Lisa, E; Di Cristo, C; Di Cosmo, A; Paolucci, M

    2010-02-01

    In this study we have investigated the role of 17beta-estradiol and progesterone in the reproduction of the crayfish Cherax albidus by using vitellogenin (VTG) as a biomarker. Early-vitellogenic (EV), full-vitellogenic (FV), and non-vitellogenic (NV) females of Cherax albidus were treated with 17beta-estradiol, progesterone, or both for 4 weeks. Levels of VTG mRNA in the hepatopancreas were detected by RT-PCR. The PCR product was sequenced and showed 97% homology with Cherax quadricarinatus VTG. 17beta-estradiol was more effective than progesterone and 17beta-estradiol plus progesterone in increasing the vitellogenin transcript in the hepatopancreas of EV and FV females. On the contrary, progesterone was more effective than 17beta-estradiol and 17beta-estradiol plus progesterone in increasing the vitellogenin concentration in the hemolymph of EV and FV females. Hepatopancreas histology and fatty acid composition of females injected with hormones showed major modifications. No effects were registered in NV females. In conclusion, 17beta-estradiol and progesterone influence VTG synthesis, although our data indicate that they act through different pathways and are not effective until the proper hormonal environment is established, as demonstrated by their inefficacy in NV females. PMID:20203252

  4. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole

    PubMed Central

    Beery, Annaliese K.; Loo, Theresa J.; Zucker, Irving

    2008-01-01

    Non-sexual social bonding between adult mammals remains poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 hour partner preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior. PMID:18387611

  5. High estradiol levels improve false memory rates and meta-memory in highly schizotypal women.

    PubMed

    Hodgetts, Sophie; Hausmann, Markus; Weis, Susanne

    2015-10-30

    Overconfidence in false memories is often found in patients with schizophrenia and healthy participants with high levels of schizotypy, indicating an impairment of meta-cognition within the memory domain. In general, cognitive control is suggested to be modulated by natural fluctuations in oestrogen. However, whether oestrogen exerts beneficial effects on meta-memory has not yet been investigated. The present study sought to provide evidence that high levels of schizotypy are associated with increased false memory rates and overconfidence in false memories, and that these processes may be modulated by natural differences in estradiol levels. Using the Deese-Roediger-McDermott paradigm, it was found that highly schizotypal participants with high estradiol produced significantly fewer false memories than those with low estradiol. No such difference was found within the low schizotypy participants. Highly schizotypal participants with high estradiol were also less confident in their false memories than those with low estradiol; low schizotypy participants with high estradiol were more confident. However, these differences only approached significance. These findings suggest that the beneficial effect of estradiol on memory and meta-memory observed in healthy participants is specific to highly schizotypal individuals and might be related to individual differences in baseline dopaminergic activity. PMID:26292620

  6. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule

    PubMed Central

    Pickar, J. H.; Amadio, J. M.; Bernick, B. A.; Mirkin, S.

    2016-01-01

    Abstract Objective To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17β-estradiol for vulvar and vaginal atrophy and compare its pharmacokinetics with that of an approved vaginal estradiol tablet in healthy postmenopausal women. Methods Two randomized, single-dose, two-way cross-over, relative bioavailability trials compared the pharmacokinetics of a solubilized vaginal estradiol softgel capsule (TX-004HR, test) with that of a vaginal estradiol tablet (Vagifem®, reference) in postmenopausal women (aged 40–65 years) at 10-μg and 25-μg doses. In each study, women were randomly assigned to receive a single dose of the test capsule or reference tablet, followed by a single dose of the alternate drug after a 14-day washout. Results Thirty-five women completed the 10-μg study and 36 completed the 25-μg study. Significantly lower systemic levels of estradiol, estrone, and estrone sulfate at both doses of the test product were observed compared with equivalent doses of the reference product, with lower AUC0-24 and C max and earlier t max. No adverse events were reported in either trial. Conclusion TX-004HR, a novel estradiol vaginal softgel capsule, exhibited significantly lower systemic exposure than equivalent doses of an approved vaginal estradiol tablet at both 10-μg and 25-μg doses. Both doses of each product were safe and well-tolerated. PMID:26857443

  7. Regulation of the mouse medial prefrontal cortical synapses by endogenous estradiol.

    PubMed

    Galvin, Christopher; Ninan, Ipe

    2014-08-01

    Recent studies suggest that low endogenous estradiol might be a susceptibility factor for anxiety and trauma-related disorders in women. Consistently, fear extinction, a form of inhibitory learning critical for the management of anxiety symptoms, is positively correlated with endogenous estradiol levels. To understand the synaptic basis of the effect of endogenous estradiol on fear extinction, we studied glutamatergic transmission and plasticity in the infralimbic medial prefrontal cortex (IL-mPFC), a brain region crucial for the regulation of fear extinction. Diestrus mice (low estradiol) exhibited a higher basal glutamatergic transmission compared with proestrus mice (high estradiol). Synaptic plasticity was also regulated by endogenous estradiol, which favored synaptic potentiation in a GluN2B-dependent manner. Activation of estrogen receptor β (ERβ) but not ERα rescued synaptic potentiation in diestrus mice by enhancing GluN2B-mediated NMDA receptor transmission. Our results suggest that both endogenous estradiol and ERβ activation facilitate the ability of the IL-mPFC synapses to undergo potentiation, a mechanism necessary for the regulation of fear extinction. PMID:24608267

  8. Context-Specific Effects of Estradiol on Spatial Learning and Memory in the Zebra Finch

    PubMed Central

    Rensel, M.A.; Salwiczek, L.; Roth, J.; Schlinger, B.A.

    2012-01-01

    Estradiol is known to impact cognitive function including spatial learning and memory, with studies focused largely on rodent models. Estrogens can be produced peripherally or centrally as neuroestrogens, and the specific role for neuroestrogens in memory processes remains unresolved. Many songbirds possess remarkable spatial memory capabilities and also express the estrogen synthetic enzyme aromatase abundantly in the hippocampus, suggesting that locally-produced estrogens may promote the acquisition or retrieval of spatial memories in these birds. We examined the effect of estradiol on spatial memory in three contexts in the zebra finch: retrieval after discrimination training, retrieval after familiarization but without discrimination training, and memory acquisition, using a combination of estradiol implants and oral dosing with the aromatase inhibitor fadrozole (FAD). Retrieval of spatial memory in both contexts was impaired when estradiol production was blocked. However, spatial memory acquisition was enhanced when estradiol production was inhibited whereas estradiol replacement impaired acquisition. These results provide evidence for a context-specific role of estradiol in songbird spatial memory, results that finds accord with some mammalian studies but have not yet been observed in birds. PMID:23257279

  9. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule.

    PubMed

    Pickar, J H; Amadio, J M; Bernick, B A; Mirkin, S

    2016-04-01

    Objective To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17β-estradiol for vulvar and vaginal atrophy and compare its pharmacokinetics with that of an approved vaginal estradiol tablet in healthy postmenopausal women. Methods Two randomized, single-dose, two-way cross-over, relative bioavailability trials compared the pharmacokinetics of a solubilized vaginal estradiol softgel capsule (TX-004HR, test) with that of a vaginal estradiol tablet (Vagifem®, reference) in postmenopausal women (aged 40-65 years) at 10-μg and 25-μg doses. In each study, women were randomly assigned to receive a single dose of the test capsule or reference tablet, followed by a single dose of the alternate drug after a 14-day washout. Results Thirty-five women completed the 10-μg study and 36 completed the 25-μg study. Significantly lower systemic levels of estradiol, estrone, and estrone sulfate at both doses of the test product were observed compared with equivalent doses of the reference product, with lower AUC0-24 and Cmax and earlier tmax. No adverse events were reported in either trial. Conclusion TX-004HR, a novel estradiol vaginal softgel capsule, exhibited significantly lower systemic exposure than equivalent doses of an approved vaginal estradiol tablet at both 10-μg and 25-μg doses. Both doses of each product were safe and well-tolerated. PMID:26857443

  10. Day length and estradiol affect same-sex affiliative behavior in the female meadow vole.

    PubMed

    Beery, Annaliese K; Loo, Theresa J; Zucker, Irving

    2008-06-01

    Non-sexual social bonding between adult mammals is poorly understood, despite its importance in many species. Female meadow voles are territorial and nest alone in long summer day lengths when circulating estradiol concentrations are high, but cohabit in groups in short winter photoperiods when estradiol secretion is low. The influence of day length and estradiol on same-sex huddling behavior was assessed in adult female pairs housed together in long day lengths (LDs) or short day lengths (SDs) from weaning. The behavior of intact, ovariectomized, and estradiol-treated ovariectomized females from each photoperiod was assessed during 3 h partner-preference tests. Intact SD voles, unlike intact LD voles, spent the majority of the test in proximity to their cage-mates. Estradiol treatment of SD voles significantly reduced time spent huddling with the partner. Neither ovariectomy nor estradiol treatment significantly affected the amount of time LD females spent in contact with their partners. Low estradiol availability is therefore a necessary but not sufficient condition for maintenance of high levels of huddling. These results establish that ovarian hormones interact with photoperiod to affect same-sex social behavior. PMID:18387611

  11. TISSUE DISTRIBUTION OF PCBS AND ORGANOCHLORINE PESTICIDES IN ALASKAN NORTHERN FUR SEALS: COMPARISON OF VARIOUS CONGENER CLASSIFICATION SCHEMES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) are believed to adversely affect reproduction and cause health problems in Pinnipeds 1-4. In this study, 145 PCB congeners and OCPs were analyzed in 10 juvenile male northern fur seals, Callorhinus ursinus, collected from Alaskan...

  12. Phenotypic plasticity of invasive Alternanthera philoxeroides in relation to different water availability, compared to its native congener

    NASA Astrophysics Data System (ADS)

    Geng, Yu-Peng; Pan, Xiao-Yun; Xu, Cheng-Yuan; Zhang, Wen-Ju; Li, Bo; Chen, Jia-Kuan

    2006-11-01

    Phenotypic plasticity and genetic differentiation are two possible mechanisms that plants use to cope with varying environments. Although alligator weed ( Alternanthera philoxeroides) possesses very low genetic diversity, this alien weed has successfully invaded diverse habitats with considerably varying water availability (from swamps to dry lands) in China. In contrast, its native congener ( Alternanthera sessilis) has a much narrower ecological breadth, and is usually found in moist habitats. To understand the mechanisms underlying the contrasting pattern, we performed a greenhouse experiment to compare the reaction norms of alligator weed with those of its native congener, in which water availability was manipulated. Our results revealed that the two congeners had similar direction of phenotypic plasticity. However, A. philoxeroides showed greater plasticity in amount than did A. sessilis in many traits examined during the switch from wet to drought treatment. Nearly all of the phenotypic variance in A. philoxeroides could be ascribed to plasticity, while A. sessilis had a much higher fraction of phenotypic variance that could be explained by genotypic variation. These interspecific differences in plastic responses to variable water availability partially explained the difference in spatial distribution of the two congeners.

  13. PCB CONGENERS AND HEXACHLOROBENZENE BIOTA SEDIMENT ACCUMULATING FACTORS FOR MACOMA NASUTA EXPOSED TO SEDIMENTS WITH DIFFERENT TOTAL ORGANIC CARBON CONTENTS

    EPA Science Inventory

    Deposit-feeding marine clams (Macoma nasuta) were exposed for 119d to three sediment types that varied in total organic carbon (TOC) from 0.8 to 2.5%. ediments were spiked with equal concentrations of 13 polychlorinated biphenyl congeners and hexachlorobenzene. issue residues wer...

  14. GC/MS ANALYSIS OF PCB CONGENERS IN BLOOD OF THE HARBOR SEAL PHOCA VITULINA FROM SAN FRANCISCO BAY

    EPA Science Inventory

    Here we report a validated technique for quantifying up to 20 specific PCB congeners in 1-2 g samples of whole blood with a detection limit below 1 ng/g (ppb) wet weight. Specimens were analyzed from 14 harbor seals sampled in south San Francisco Bay, California during 1991-1992....

  15. HIGH RESOLUTION MODELLING OF PCB CONGENERS IN LAKE MICHIGAN USING THE LAKE MICHIGAN (LM3) CONTAMINANT MODEL

    EPA Science Inventory

    The Lake Michigan Level 3 (LM3) Model is a numerical model of Lake Michigan used to predict the fate and transport of 54 PCB congeners. The LM3 model segments Lake Michigan horizontally with a 5 x 5 km grid and vertically with 19 sigma layers for a total of 44,042 water column se...

  16. Response to Ecological Risk Assessment Forum Request for Information on the Benefits of PCB Congener-Specific Analyses

    EPA Science Inventory

    In August, 2001, the Ecological Risk Assessment Forum (ERAF) submitted a formal question to the Ecological Risk Assessment Support Center (ERASC) on the benefits of evaluating PCB congeners in environmental samples. This question was developed by ERAF members Bruce Duncan and Cla...

  17. Subchronic inhalation exposure study of an airborne polychlorinated biphenyl mixture resembling the Chicago ambient air congener profile.

    PubMed

    Hu, Xin; Adamcakova-Dodd, Andrea; Lehmler, Hans-Joachim; Hu, Dingfei; Hornbuckle, Keri; Thorne, Peter S

    2012-09-01

    Although inhalation of atmospheric polychlorinated biphenyls (PCBs) is the most universal exposure route and has become a substantial concern in urban areas, research is lacking to determine the body burden of inhaled PCBs and consequent health effects. To reflect the Chicago airshed environment and mimic the PCB profile in Chicago air, we generated vapors from a Chicago air mixture (CAM). Sprague-Dawley rats were exposed to the CAM vapor for 1.6 h/day via nose-only inhalation for 4 weeks, 520 ± 10 μg/m(3). Congener-specific quantification in tissue and air samples was performed by gas chromatography-tandem mass spectrometry (GC/MS/MS). In contrast to the lower-chlorinated congener-enriched vapor, body tissues mainly contained tri- to hexachlorobiphenyls. Congener profiles varied between vapor and tissues and among different organs. The toxic equivalence (TEQ) and neurotoxic equivalence (NEQ) were also investigated for tissue distribution. We evaluated a variety of end points to catalogue the effects of long-term inhalation exposure, including immune responses, enzyme induction, cellular toxicity, and histopathologic abnormalities. Glutathione oxidized/reduced ratio (GSSG/GSH) was increased in the blood of exposed animals, accompanied by elevation of hematocrit. This study demonstrated that inhalation contributed to the body burden of mostly tri- to hexachlorobiphenyls and produced a distinct profile of congeners in tissue, yet minimal toxicity was found at this exposure dose, estimated at 134 μg/rat. PMID:22846166

  18. WASTES FROM MANUFACTURE OF DYES AND PIGMENTS: VOLUME 1. AZO DYES AND PIGMENTS (BENZIDINE AND ITS CONGENERS SUBSECTOR)

    EPA Science Inventory

    In a study of the manufacture of dyes and pigments based on benzidine and its congeners, several solid waste streams that could contain hazardous material were identified. The solid residues included filter cake from clarifying operations, intermediates on discarded shipping cont...

  19. Estradiol enhances the acquisition of lithium chloride-induced conditioned taste aversion in castrated male rats

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Fan; Tsai, Yuan-Feen; Tai, Mei-Yun; Yeh, Kuei-Ying

    2015-10-01

    The present study examined the effects of short-term treatment with ovarian hormones on the acquisition of conditioned taste aversion (CTA). Adult male rats were castrated and randomly divided into LiCl- and saline-treated groups. Nineteen days after castration, all of the animals were subjected to 23.5-h daily water deprivation for seven successive days (day 1 to day 7). On the conditioning day (day 8), the rats received either a 4 ml/kg of 0.15 M LiCl or the same dose of saline injection immediately after administration of a 2 % sucrose solution during the 30-min water session. Starting from day 6, rats in both groups received one of the following treatments: daily subcutaneous injection of (1) estradiol alone (30 μg/kg; estradiol benzoate (E) group), (2) estradiol plus progesterone (500 μg; E + progesterone (P) group), or (3) olive oil. From day 9 to day 11, all of the rats were given daily two-bottle preference tests during the 30-min fluid session. The estradiol and estradiol plus progesterone treatments in the LiCl groups resulted in significantly lower preference scores for the sucrose solution compared with the olive oil treatment groups, but no difference in preference score was seen between these two groups. These results indicate that both the estradiol and estradiol plus progesterone treatments in the LiCl groups enhanced the acquisition of CTA learning and suggest that estradiol affects the acquisition of CTA mediated by an activational effect in male rats, whereas progesterone treatment does not influence the effects of estradiol on the acquisition of CTA.

  20. Increased Estradiol and Improved Sleep, But Not Hot Flashes, Predict Enhanced Mood during the Menopausal Transition

    PubMed Central

    Petrillo, Laura Fagioli; Koukopoulos, Alexia; Viguera, Adele C.; Hirschberg, April; Nonacs, Ruta; Somley, Brittny; Pasciullo, Erica; White, David P.; Hall, Janet E.; Cohen, Lee S.

    2011-01-01

    Background: The antidepressant effect of estrogen in women undergoing the menopause transition is hypothesized to be mediated by central nervous system effects of increasing estradiol on mood or through a pathway involving suppression of hot flashes and associated sleep disturbance. Estrogen therapy (ET) and the hypnotic agent zolpidem were selected as interventions in a three-arm, double-blind, placebo-controlled trial to distinguish the effects of estradiol, sleep, and hot flashes on depression. Methods: Women with depressive disorders, hot flashes, and sleep disturbance were randomly assigned to transdermal 17β-estradiol 0.05 mg/d, zolpidem 10 mg/d, or placebo for 8 wk. Changes in serum estradiol, perceived sleep quality, objectively measured sleep, and hot flashes were examined as predictors of depression improvement [Montgomery-Åsberg Depression Rating Scale (MADRS)] using multivariate linear regression. Results: Seventy-two peri/postmenopausal women with depression disorders were randomized to 17β-estradiol (n = 27), zolpidem (n = 31), or placebo (n = 14). There was no significant difference between groups in depression improvement (overall MADRS decrease 11.8 ± 8.6). Increasing estradiol (P = 0.009) and improved sleep quality (P < 0.001) predicted improved mood in adjusted models but reduced hot flashes (P = 0.99) did not. Post hoc subgroup analyses revealed that the therapeutic effect of increasing estradiol levels on mood was seen in perimenopausal (P = 0.009), but not postmenopausal, women. Conclusions: For women with menopause-associated depression, improvement in depression is predicted by improved sleep, and among perimenopausal women, by increasing estradiol levels. These results suggest that changes in estradiol and sleep quality, rather than hot flashes, mediate depression during the menopause transition. Therapies targeting insomnia may be valuable in treating menopause-associated depression. PMID:21525161

  1. Low doses of estradiol partly inhibit release of GH in sheep without affecting basal levels.

    PubMed

    Hudmon, A; Davenport, G; Coleman, E S; Sartin, J L

    2009-10-01

    Estradiol increases basal growth hormone (GH) concentrations in sheep and cattle. This study sought to determine the effects of estradiol on GH-releasing hormone (GRH)-stimulated GH release in sheep. Growth hormone secretory characteristics, the GH response to GRH, and steady-state GH mRNA concentrations were determined in castrated male lambs treated with 2 different doses of estradiol 17-beta for a 28-d experimental period. Although no differences between treatments in mean GH, basal GH, or GH pulse number were observed after 28 d of estradiol treatment, GH pulse amplitude was greater (P < 0.05) in the 2.00-cm implant-treated animals than in the control and 0.75-cm implant group. The effect of estradiol treatment on GRH-stimulated GH release revealed differences between the control and estradiol-treated animals (P < 0.05). The 15-min GH responses to 0.075 microg/kg hGRH in the control, 0.75-cm, and 2.00-cm implant groups, respectively, were 76 +/- 10, 22.6 +/- 2.1, and 43.6 +/- 15.0 ng/mL. Growth hormone mRNA content was determined for pituitary glands from the different treatment groups, and no differences in steady-state GH mRNA levels were observed. There were no differences in the mean plasma concentrations of IGF-I, cortisol, T(3), or T(4) from weekly samples. Growth hormone release from cultured ovine pituitary cells from control sheep was not affected by estradiol after 72 h or in a subsequent 3-h incubation with estradiol combined with GRH. These data suggest that estradiol has differing actions on basal and GRH-stimulated GH concentrations in plasma, but the increase in pulse amplitude does not represent an increased pituitary sensitivity to GRH. PMID:19616401

  2. Nuclear estradiol binding in rat adipocytes. Regional variations and regulatory influences of hormones.

    PubMed

    Pedersen, S B; Børglum, J D; Eriksen, E F; Richelsen, B

    1991-06-01

    The nuclear estrogen receptor was characterised in isolated rat adipocytes. The binding reaction with [3H]estradiol was performed with intact isolated rat adipocytes and the radioactivity associated with the nucleus was subsequently determined after cell lysis. The nuclear uptake of [3H]estrogen in rat adipocytes was temperature dependent and steroid specific. The steady-state binding was achieved after 30 min at 37 degrees C and was constant for several hours. Estradiol was found to bind to a homogeneous class of nuclear receptors in epididymal adipocytes with an apparent Kd of 3.1 +/- 0.76 nM and a Bmax of 7.98 +/- 1.11 fmol/10(6) cells corresponding to about 4800 receptors per nucleus. The estradiol binding exhibited regional variations in isolated adipocytes. In lean rats the highest receptor number was found in epididymal adipocytes, whereas there was a significantly lower number of nuclear binding sites in perirenal and subcutaneous adipocytes (P less than 0.05), unlike in older and more obese rats where the nuclear estradiol binding was greatest in adipocytes from the perirenal fat depot. Incubations with isoproterenol (10 microM) and dibutyryl-cAMP (2.5 mM) both reduced estradiol binding by 56% (P less than 0.005), while insulin (1 nM) enhanced the estradiol binding by 37% (P less than 0.01). In conclusion, a specific and high affinity nuclear estradiol receptor was demonstrated in rat adipocytes and regional differences in nuclear estradiol binding were detected. Furthermore, it was demonstrated that nuclear estradiol binding could be modulated by other agents known to affect adipocyte metabolism. PMID:1646650

  3. Low-dosage micronized 17 beta-estradiol prevents bone loss in postmenopausal women

    NASA Technical Reports Server (NTRS)

    Ettinger, B.; Genant, H. K.; Steiger, P.; Madvig, P.

    1992-01-01

    With the use of a double-blind, randomized, dose-ranging design, we tested during an 18-month period the degree of protection against postmenopausal bone loss afforded by micronized 17 beta-estradiol in dosages of 0.5, 1.0, and 2.0 mg. All subjects received supplementation to ensure a minimum of 1500 mg calcium daily. Fifty-one subjects completed at least 1 year of follow-up bone density measurements by quantitative computed tomography and by single- and dual-photon absorptiometry. In the placebo group spinal trabecular bone density decreased 4.9% annually (p less than 0.001), whereas in those taking micronized 17 beta-estradiol bone density tended to increase (annual increases of 0.3% in the 0.5 mg micronized 17 beta-estradiol group, 1.8% in the 1.0 mg micronized 17 beta-estradiol group, and 2.5% in the 2.0 mg micronized 17 beta-estradiol group). After completing the double-blind phase, 41 subjects completed an additional 18 months of follow-up while taking 1.0 mg micronized 17 beta-estradiol. During this time one third of the subjects were randomly assigned to discontinue calcium supplements. Among those who previously received placebo, trabecular bone density increased 4.3% annually, whereas among those who had used micronized 17 beta-estradiol, trabecular bone density response was inversely related to the dosage previously used. Additionally and independently, the level of calcium intake showed a statistically significant correlation with the change in spinal trabecular bone density (r = 0.37, p = 0.02). We conclude that micronized 17 beta-estradiol has a continuous skeletal dose-response effect in the range of 0.5 to 2.0 mg and that calcium intake positively modifies the skeletal response to 1.0 mg micronized 17 beta-estradiol.

  4. Steady-state pharmacokinetics following application of a novel transdermal estradiol spray in healthy postmenopausal women.

    PubMed

    Morton, Terri L; Gattermeir, David J; Petersen, Craig A; Day, Wesley W; Schumacher, Robert J

    2009-09-01

    This study was designed to evaluate the steady-state pharmacokinetics (PK) of estradiol and its metabolites, estrone and estrone sulfate, following application of a novel estradiol transdermal spray to healthy postmenopausal women. Participants were randomly assigned in parallel to receive 1-, 2-, or 3-spray doses (24 participants/dose level) of a 1.7% estradiol metered-dose transdermal spray (1.53 mg/spray) once daily for 14 days. Blood was collected predose on days 1 to 14 and over 7 days after the last dose. Serum concentrations for all 3 analytes reached steady state by day 7 or 8 and were still slightly above baseline on day 21. Estradiol, estrone, and estrone sulfate serum concentrations generally increased with increasing dose. Mean estradiol and estrone maximum serum concentration (C(max)) following 1, 2, or 3 sprays for 14 days were 36 and 50, 57 and 60, and 54 and 71 pg/mL, respectively. Estradiol time when maximum concentration occurred (t(max)) was 18 to 20 hours. The area under the serum concentration-time curve over 24 hours following the last dose of study drug (AUC(0-24 h)) on day 14 for the 1-, 2-, and 3-spray groups, respectively, was 471, 736, and 742 pg.h/mL for estradiol; 886, 1208, and 1367 pg x h/mL for estrone; and 16,501, 26,515, and 27,971 pg x h/mL for estrone sulfate. The metered-dose estradiol transdermal spray delivers estradiol at therapeutic levels and produces low serum estrone concentrations. PMID:19628730

  5. A metabolomics study of the inhibitory effect of 17-beta-estradiol on osteoclast proliferation and differentiation.

    PubMed

    Liu, Xiaoyan; Liu, Yanqiu; Cheng, Mengchun; Zhang, Xiaozhe; Xiao, Hongbin

    2015-02-01

    Estradiol is a major drug used clinically to alleviate osteoporosis, partly through inhibition of the activity of osteoclasts, which play a crucial role in bone resorption. So far, little is known about the effects of estradiol on osteoclast metabolism. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC/MS)-based metabolomics strategy was used to investigate the metabolite response to 17β-estradiol in mouse osteoclast RAW264.7, a commonly used cell model for studying osteoporosis. Our results showed that the application of estradiol altered the levels of 27 intracellular metabolites, including lysophosphatidylcholines (LysoPCs), other lipids and amino acid derivants. The changes of all the 27 metabolites were observed in the study of estradiol induced osteoclast proliferation inhibition (1 μM estradiol applied), while the changes of only 18 metabolites were observed in the study of differentiation inhibition (0.1 μM estradiol applied). Further pathway impact analysis determined glycerophospholipid metabolism as the main potential target pathway of estradiol, which was further confirmed by LCAT (phosphatidylcholine-sterol acyltransferase) activity changes and lipid peroxidative product (MDA, methane dicarboxylic aldehyde) changes caused by estradiol. Additionally, we found that estradiol significantly decreased intracellular oxidative stress during cell proliferation but not during cell differentiation. Our study suggested that estradiol generated a highly condition-dependent influence on osteoclast metabolism. PMID:25474166

  6. Mechanism of the Rapid Effect of 17β -Estradiol on Medial Amygdala Neurons

    NASA Astrophysics Data System (ADS)

    Nabekura, Junichi; Oomura, Yutaka; Minami, Taketsugu; Mizuno, Yuji; Fukuda, Atsuo

    1986-07-01

    The mechanism by which sex steroids rapidly modulate the excitability of neurons was investigated by intracellular recording of neurons in rat medial amygdala brain slices. Brief hyperpolarization and increased potassium conductance were produced by 17β - estradiol. This effect persisted after elimination of synaptic input and after suppression of protein synthesis. Thus, 17β -estradiol directly changes the ionic conductance of the postsynaptic membrane of medial amygdala neurons. In addition, a greater proportion of the neurons from females than from males responded to 17β -estradiol.

  7. Evidence of elevated levels of polychlorinated biphenyl congeners in commonly consumed fish from Eleyele Reservoir, Southwestern Nigeria.

    PubMed

    Adeogun, Aina O; Adedara, Isaac A; Farombi, Ebenezer O

    2016-01-01

    Environmental pollution of water, which is a source of cheap and affordable protein in the form of fish on which the population depends on, is of great concern globally. The present study assesses the levels of polychlorinated biphenyls (PCBs) congeners in sediments and six commonly consumed cichlid species from Eleyele Reservoir, Southwestern Nigeria. The results indicate that the concentrations of heavier PCB congeners are higher than the lighter congeners in both sediment and fish tissue. The predominant PCB congeners in the sediment samples from this site were PCBs 8, 44, 114, 101, 189, 196, 206 and 209. The concentration of PCB congeners increased with increasing molecular weight from hepta-PCB to deca-PCB in all fish species. The trend in accumulation of total PCBs in fish was as follows: Tilapia guineensis (2,531.1 ± 74.6 ng/g) > Sarotherodon galilaeus (1178.7 ± 68.5 ng/g) > Oreochromis niloticus > (891.8 ± 49.6 ng/g) > Tilapia zillii (832.8 ± 38.2 ng/g) > Hemichromis fasciatus (475.7 ± 28.5 ng/g) > Sarotherodon melanotheron (333.2 ± 26.1 ng/g). In summary, data from this study shows that the levels of PCBs in cichlid species from Eleyele Reservoir are higher than the threshold level of 0.023-0.047 ng g(-1) recommended by United States Environmental Protection Agency. Such elevated PCB levels present significant health implications for human consumers and a threat to the resident fish communities. PMID:23859942

  8. Distribution and uptake of key polychlorinated biphenyl and polybrominated diphenyl ether congeners in benthic infauna relative to sediment organic enrichment.

    PubMed

    Burd, Brenda J; Macdonald, Tara A; Macdonald, Robie W; Ross, Peter S

    2014-10-01

    As part of a broader study of budgets, transport, and bioaccumulation of persistent organic contaminants in the Strait of Georgia, Canada, matching samples of sediment and bulk benthos were collected near two marine sewage outfalls, two large urban harbours, and background areas. Samples were analyzed for polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) congeners. We present data for those congeners that fell within the top six rankings by concentration (23 PCBs and 10 PBDEs) within at least one of the environmental media measured in other studies (air, water, sediments, benthos, pelagic biota). Multifactor regression analyses incorporating sediment characteristics (total organic carbon, fines) predicted uptake (r (2) = 0.74 to 0.98, p < 0.04) over the range of congeners and habitats examined. PBDEs were taken up by biota more readily than PCBs, suggesting a large, potentially available biological reservoir of PBDEs in sediments. Dominant congeners in benthos comprised PBDEs 47, 99, 209, and 100 and PCBs 138/163, 153, 101, 118, and 110. PBDE uptake was anomalously high near one wastewater outfall, likely due to selective feeding on PBDE-enriched particulates from that source. Conversely, outfalls supply food and sediments with PCB concentrations similar to ambient sediments. However, organic enrichment of sediments near outfalls clearly enhanced PCB uptake by benthos, probably due to greatly increased biomass turnover near these sources. Data suggest there to be an initial reservoir of PCBs in newly settled juvenile benthos, which is much less evident for PBDEs. This is likely a consequence of the ecosystem-wide distribution of legacy PCBs but not the more current-use PBDEs. Congener-uptake patterns were dependent on source and input dynamics, feeding methods, and contaminant metabolism or debromination, particularly of deca-BDE. PMID:24699838

  9. Comparison of cytochrome P-450 species which catalyze the hydroxylations of the aromatic ring of estradiol and estradiol 17-sulfate.

    PubMed

    Watanabe, K; Takanashi, K; Imaoka, S; Funae, Y; Kawano, S; Inoue, K; Kamataki, T; Takagi, H; Yoshizawa, I

    1991-06-01

    For identification of microsomal cytochrome P-450 (P-450) enzymes which catalyze 2- or 4-hydroxylations of estrogens in the rat liver, estradiol (E2) and estradiol 17-sulfate (E2-17-S) were selected as the substrates and incubated with various kinds of purified P-450 enzymes: PB-1, PB-2, PB-4 and PB-5 obtained from phenobarbital-treated male rats (Sprague-Dawley); MC-1 and MC-5 from 3-methylcholanthrene-treated male rats; and UT-1, UT-2, UT-4 and UT-5 from untreated animals. The reactions were carried out under the P-450-reconstructed system, and the resulting products were determined by HPLC using electrochemical detection. All the enzymes tested were shown to have varying degrees of catalytic activities for 2-hydroxylation of the two substrates; UT-1 and UT-2 had the highest activity. Of the induced P-450 enzymes, PB-2 and MC-1 showed fairly high catalytic activity for 4-hydroxylation of E2. The P-450 enzymes obtained from the untreated male rats, especially UT-4, showed the highest catalytic activity for 4-hydroxylation of the two substrates. From these results and also from kinetic experiments, the P-450 enzymes which catalyze 2- and 4-hydroxylations of estrogen were considered to be different species. A part of E2 was converted to such metabolites as estrone and those having a hydroxyl group at positions 6 beta, 15 alpha or 16 alpha, each production of which was estimated to be catalyzed by single or multiple P-450s. PMID:2064989

  10. OOCYTE ENVELOPE PROTEINS AND VITELLOGENIN IN MALE SHEEPHEAD MINNOW EXPOSED TO ESTRADIOL

    EPA Science Inventory

    Oocyte Envelope Proteins and Vitellogenin Expression in Male Sheepshead Minnows Exposed to Estradiol (Abstract). To be presented at the 22nd Annual Meeting of the Society of Environmental Toxicology and Chemistry: Changing Environmental Awareness: Societal Concerns and Scientifi...

  11. Estradiol: Mediator of memories, spine density and cognitive resilience to stress in female rodents.

    PubMed

    Luine, Victoria

    2016-06-01

    Estradiol rapidly activates, within minutes, various physiological functions and behaviors including cognition in rodents. This review describes rapid effects of estradiol on hippocampal dependent learning and memory tasks in rodents. Mechanisms underlying the memory enhancements including the activation of signaling molecules and the enhancement of dendritic spinogenesis are briefly reviewed. In addition, the role of estradiol in the cognitive resilience to chronic stress exhibited only in females is discussed including contributions of ovarian as well as intra-hippocampally derived estrogens to this sex difference. Finally, speculations on possible physiologic functions for rapid mnemonic changes mediated by estrogens are made. Overall, the emergence of a novel and powerful mechanism for regulation of cognition by estradiol is described. PMID:26241030

  12. COULD ETHINYL ESTRADIOL AFFECT THE POPULATION BIOLOGY OF CUNNER, TAUTOGOLABRUS ADSPERSUS

    EPA Science Inventory

    Endocrine disrupting chemicals in the environment may disturb the population dynamics of wildlife by affecting reproductive output and embryonic development of organisms. This study used a population model to evaluate whether ethinyl estradiol (EE2 could affect cunner Tautogolabr...

  13. Proplatelet formation of megakaryocytes is triggered by autocrine-synthesized estradiol

    PubMed Central

    Nagata, Yuka; Yoshikawa, Jun; Hashimoto, Atsushi; Yamamoto, Masayuki; Payne, Anita H.; Todokoro, Kazuo

    2003-01-01

    A matured megakaryocyte releases thousands of platelets through a drastic morphological change, proplatelet formation (PPF). The megakaryocyte/erythrocyte-specific transcription factor, p45 NF-E2, is essential for initiating PPF, but the factor regulating PPF has not been identified. Here we report that estradiol synthesized in megakaryocytes triggers PPF. We demonstrate that a key enzyme for steroid hormone biosynthesis, 3β-hydroxysteroid dehydrogenase (3β-HSD), is a target of p45 NF-E2, and rescues PPF of p45 NF-E2-deficient megakaryocytes. We also show that estradiol is synthesized within megakaryocytes, and that extracellular estradiol stimulates PPF, inhibition of 3β-HSD activity blocks PPF, and estrogen receptor antagonists inhibit platelet production in vivo. We conclude that autocrine estradiol action regulates platelet production by triggering PPF. PMID:14665668

  14. Testosterone and estradiol produce different effects on cognitive performance in male rats

    PubMed Central

    Gibbs, Robert B.

    2008-01-01

    The effects of castration and hormone treatment on cognitive performance were evaluated in male rats. Castrated animals received either testosterone or estradiol and were compared with gonadally intact animals and with castrated controls. Results revealed a dissociation between the effects of testosterone and estradiol on cognitive performance in male rats. Specifically, estradiol enhanced acquisition of a delayed matching-to-position spatial task, similar to previously published observations in females. In contrast, neither castration nor testosterone treatment had any significant effect on acquisition of the delayed matching-to-position task, but did appear to affect delay-dependent working memory. None of the treatments had any significant effect on acquisition of a configural association negative patterning task, suggesting that effects on the delayed matching-to-position task were not due to effects on motivational factors. These data demonstrate that, as in females, gonadal hormones influence cognitive performance in males and suggest that estradiol and testosterone affect distinct cognitive domains. PMID:15890350

  15. Tyrosinase-like activity and estradiol binding in rat uterine nuclear extracts.

    PubMed

    Garai, J; Clark, J H

    1992-05-01

    Nuclear extracts from the uteri of estradiol-implanted rats contain a tyrosinase-like enzyme that has three activities: monophenolase or cresolase, diphenolase or catecholase, and estrogen binding. When [3H]estradiol was used as a substrate, 3H2O was released from the A ring in the presence of copper and ascorbic acid. The optimal concentrations of these cofactors for the cresolase activity were established. The cresolase activity was lost on attempts at further purification. Estradiol binding was observed in conjunction with the enzymatic activity and was dependent on the presence of ascorbic acid and copper. The most potent inhibitors of 3H2O release from [3H]estradiol were those with a dihydroxyphenol moiety. The reaction was also sensitive to sulfhydryl reagents. These features of the enzyme are distinctive from other oxidases capable of attacking the aromatic ring of estrogens. PMID:1488787

  16. [Effectiveness of transdermal administration of 17-beta-estradiol in the management of menopause].

    PubMed

    Grio, R; Piacentino, R; Abbondanza, M; Cirnigliaro, C; Fusi, D; Corsello, F P; Arrichiello, G; Canestrelli, M; Marchino, G L

    1992-01-01

    Seventeen-beta-estradiol administered via a transdermic route was used to treat menopausal symptoms. The results obtained demonstrate the drug's good level of tolerability and considerable efficacy. PMID:1508379

  17. Functionalized Congeners of 1,4-Dihydropyridines as Antagonist Molecular Probes for A3 Adenosine Receptors

    PubMed Central

    Li, An-Hu; Chang, Louis; Ji, Xiao-duo; Melman, Neli; Jacobson, Kenneth A.

    2012-01-01

    4-Phenylethynyl-6-phenyl-1,4-dihydropyridine derivatives are selective antagonists at human A3 adenosine receptors, with Ki values in a radioligand binding assay vs [125I]AB-MECA [N6-(4-amino-3-iodobenzyl)-5′-N-methylcarbamoyl-adenosine] in the submicromolar range. In this study, functionalized congeners of 1,4-dihydropyridines were designed as chemically reactive adenosine A3 antagonists, for the purpose of synthesizing molecular probes for this receptor subtype. Selectivity of the new analogues for cloned human A3 adenosine receptors was determined in radioligand binding in comparison to binding at rat brain A1 and A2A receptors. Benzyl ester groups at the 3- and/or 5-positions and phenyl groups at the 2- and/or 6-positions were introduced as potential sites for chain attachment. Structure–activity analysis at A3 adenosine receptors indicated that 3,5-dibenzyl esters, but not 2,6-diphenyl groups, are tolerated in binding. Ring substitution of the 5-benzyl ester with a 4-fluorosulfonyl group provided enhanced A3 receptor affinity resulting in a Ki value of 2.42 nM; however, a long-chain derivative containing terminal amine functionalization at the 4-position of the 5-benzyl ester showed only moderate affinity. This sulfonyl fluoride derivative appeared to bind irreversibly to the human A3 receptor (1 h incubation at 100 nM resulting in the loss of 56% of the specific radioligand binding sites), while the binding of other potent dihydropyridines and other antagonists was generally reversible. At the 3-position of the dihydropyridine ring, an amine-functionalized chain attached at the 4-position of a benzyl ester provided higher A3 receptor affinity than the corresponding 5-position isomer. This amine congener was also used as an intermediate in the synthesis of a biotin conjugate, which bound to A3 receptors with a Ki value of 0.60 μM. PMID:10411465

  18. Abnormal proinsulin congeners as autoantigens that initiate the pathogenesis of Type 1 diabetes.

    PubMed

    Csorba, Thomas R; Lyon, Andrew W

    2005-01-01

    Exposure of concentrated and purified monomeric insulin solutions to inorganic oxidants as iodine and chlorine lead to the appearance of a minor peak on gel chromatography that was disulfide cross-linked. It exhibited a 20-fold reduction in bioactivity, a markedly decreased immunoreactivity and a different electrophoretic pattern as compared to the starting material. The covalent dimer was formed by way of aggregation. These findings were reproduced by incubating monomeric insulin in normal blood spiked to hyperglycemic levels. In contrast, normoglycemic blood used as incubating medium failed to induce dimerization. Since the conformation of proinsulin is similar to that of insulin, involving the exposure of the anterior A7-B7 disulfide bridge, the authors hypothesize that proinsulin dimers rather than insulin dimers might be formed in Type 1 diabetes (TD1), leading to the autoimmune destruction of pancreatic B-cells. Proinsulin is present in a soluble aggregate state in the coated granule and may further accumulate allowing disulfide exchange due to abnormalities of the processing enzymes. This might be caused by inborn errors in genetically susceptible children or perhaps secondary to viral infection, whereas crystallization of insulin in mature granules is unlikely to be conducive to dimerization. Dimeric proinsulin would then migrate to pancreatic B-cell membranes to be taken up by surface immunoglobulins on B-lymphocytes that would in turn present it to cytotoxic T lymphocytes. The abnormal configuration of this congener would not be recognized as self by the immune system, triggering a selective destruction of pancreatic B-cells in the early pre-clinical development of TD1, resulting eventually in clinical disease. Since proinsulin is continuously converted to insulin in the coated granules of Type 2 diabetics, dimerization is unlikely in this condition. As pointed out by earlier investigators, TD1 is not a homogeneous disease, since several of its clinical

  19. Combination of automatic HPLC-RIA method for determination of estrone and estradiol in serum.

    PubMed

    Yasui, T; Yamada, M; Kinoshita, H; Uemura, H; Yoneda, N; Irahara, M; Aono, T; Sunahara, S; Mito, Y; Kurimoto, F; Hata, K

    1999-01-01

    We developed a highly sensitive assay for estrone and 17 beta-estradiol in serum. Estrone and 17 beta-estradiol, obtained by solid-phase extraction using a Sep pak tC18 cartridge, were purified by high-performance liquid chromatography (HPLC). Quantitation of estrone and 17 beta-estradiol were carried out by radioimmunoassay. Not insignificantly, this automatic system of extraction and HPLC succeeded in analyzing 80 samples a week. Intra-assay coefficients of variation (CV) for estrone and 17 beta-estradiol ranged from 19.5 to 28.7%, and from 8.5 to 13.7%, respectively. The minimum detectable dose for estrone and 17 beta-estradiol were 1.04 pg/ml and 0.64 pg/ml, respectively. The serum levels of 17 beta-estradiol using our method strongly correlated with those by Gas chromatography mass spectrometry (GC-MS). The serum levels of estrone and 17 beta-estradiol in 154 peri- and postmenopausal women were estimated to be between 15 and 27 pg/ml and between 3.5 and 24.0 pg/ml, respectively, while the serum level of 17 beta-estradiol in postmenopausal women, in particular, was estimated to be from 3.5 to 6.3 pg/ml. For postmenopausal women who suffered from vasomotor symptoms, the mean levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with daily 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) were 135.0 and 21.3 pg/ml at 12 months, respectively. On the other hand, levels of estrone and 17 beta-estradiol at 12 to 18 hours after treatment with CEE and MPA every other day, were 73.4 and 15.3 pg/ml, respectively. These highly sensitive assays for estrone and 17 beta-estradiol are useful in measuring low levels of estrogen in postmenopausal women, and monitoring estrogen levels in women receiving CEE as hormone replacement therapy. PMID:10633293

  20. Estradiol influences the mechanical properties of human fetal osteoblasts through cytoskeletal changes

    SciTech Connect

    Muthukumaran, Padmalosini; Lim, Chwee Teck; Lee, Taeyong

    2012-07-06

    Highlights: Black-Right-Pointing-Pointer Estradiol induced stiffness changes of osteoblasts were quantified using AFM. Black-Right-Pointing-Pointer Estradiol causes significant decrease in the stiffness of osteoblasts. Black-Right-Pointing-Pointer Decreased stiffness was caused by decreased density of f-actin network. Black-Right-Pointing-Pointer Stiffness changes were not associated with mineralized matrix of osteoblasts. Black-Right-Pointing-Pointer Estradiol increases inherent alkaline phosphatase activity of osteoblasts. -- Abstract: Estrogen is known to have a direct effect on bone forming osteoblasts and bone resorbing osteoclasts. The cellular and molecular effects of estrogen on osteoblasts and osteoblasts-like cells have been extensively studied. However, the effect of estrogen on the mechanical property of osteoblasts has not been studied yet. It is important since mechanical property of the mechanosensory osteoblasts could be pivotal to its functionality in bone remodeling. This is the first study aimed to assess the direct effect of estradiol on the apparent elastic modulus (E{sup Asterisk-Operator }) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with {beta}-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E{sup Asterisk-Operator }. The underlying changes in cytoskeleton were studied by staining the cells with TRITC-Phalloidin. Following estradiol treatment, the cells were also tested for proliferation, alkaline phosphatase activity and mineralization. With estradiol treatment, E{sup Asterisk-Operator} of osteoblasts significantly decreased by 43-46%. The confocal images showed that the changes in f-actin network observed in estradiol treated cells can give rise to the changes in the stiffness of the cells. Estradiol also increases the inherent alkaline phosphatase activity of the cells. Estradiol induced stiffness

  1. Estradiol and mental rotation: relation to dimensionality, difficulty, or angular disparity?

    PubMed

    Hampson, Elizabeth; Levy-Cooperman, Na'ama; Korman, Jennifer M

    2014-03-01

    Several studies have reported that performance on spatial rotation tests is better at menses than at high estradiol phases of the menstrual cycle in women. These effects are debated because nearly all reports of menstrual cycle variability have relied on a single test, the Mental Rotations Test (MRT, Vandenberg and Kuse, 1978). In the present study, we investigated key features of the MRT that might be responsible for its association with estradiol levels. We hypothesized that associations could be demonstrated for other tasks that share the same characteristics. Forty-four women ages 20-38 years, matched on education and general ability, were assessed at low (n=24) or high (n=20) estradiol stages of the menstrual cycle on a set of spatial tests that varied in dimensionality, plane of rotation, angular disparity, and effortfulness. Saliva was used to quantify estradiol and progesterone. Low estradiol was found to be associated with significantly better accuracy on the MRT and also on a mental rotation task that required large angles of rotation but employed only two-dimensional object representations and rotations limited to the picture plane. In contrast, a task using identical stimuli that required only small angles of rotation did not show an estradiol effect. A group difference also was seen on a test of perceptual closure. The results confirm that the estradiol effect is not limited to the MRT, and identify the rotational element, but also aspects of figural perception, as possible processes that may be responsive to estrogens. These findings advance our understanding by showing an association between estradiol and discrete spatial processes. Implications for understanding the origins of the robust sex difference commonly observed on the MRT are discussed. PMID:24394702

  2. Estradiol Stimulates Vasodilatory and Metabolic Pathways in Cultured Human Endothelial Cells

    PubMed Central

    Sobrino, Agua; Mata, Manuel; Laguna-Fernandez, Andrés; Novella, Susana; Oviedo, Pilar J.; García-Pérez, Miguel Angel; Tarín, Juan J.; Cano, Antonio; Hermenegildo, Carlos

    2009-01-01

    Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cytoskeleton signaling, pentose phosphate pathway, axonal guidance signaling and integrin signaling were the top-five canonical pathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxigenase (COX)1, dimethylarginine dimethylaminohydrolase (DDAH)2, phospholipase A2 group IV (PLA2G4) B, and 7-dehydrocholesterol reductase were up-regulated by estradiol in a dose-dependent and estrogen receptor-dependent way, whereas COX2, DDAH1 and PLA2G4A remained unaltered. Moreover, estradiol-induced COX1 gene expression resulted in increased COX1 protein content and enhanced prostacyclin production. DDAH2 protein content was also increased, which in turn decreased asymmetric dimethylarginine concentration and increased NO release. All stimulated effects of estradiol on gene and protein expression were estrogen receptor-dependent, since were abolished in the presence of the estrogen receptor antagonist ICI 182780. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes. PMID:20011585

  3. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  4. Stereological study of the effects of letrozole and estradiol valerate treatment on the ovary of rats

    PubMed Central

    Noorafshan, Ali; Ahmadi, Maryam; Mesbah, Seyed-Fakhroddin

    2013-01-01

    Objective Letrozole and estradiol valerate are used to treat some hormonally-responsive symptoms and also in modeling of the polycystic ovary syndrome. However, the stereological analysis of the ovary has received less attention. Estimation of the whole ovary volume using the Cavalieri method can be applied in any orientation desired, but estimation of the mean volume of the oocytes requires isotropic uniform random sectioning. Here, a combined method was developed for estimating the parameters. To our knowledge, no comparison has been made of the effects of letrozole and estradiol on the ovary. Methods Sixty rats were divided into 4 groups receiving estradiol (4 mg/kg), olive oil, letrozole (1 mg/kg), or normal saline. After 21 days, their ovaries were studied. Results Relative to the control group, the total volume of the ovary and the cortex increased in the letrozole-treated and estradiol-treated rats. In addition, the number of the preantral, antral, and granulosa cells decreased by 43% to 56% in the letrozole- and estradiol-treated rats. On average, a 19% increase was observed in the atretic oocytes of the letrozole-treated and estradiol-treated rats, but the mean oocyte volume decreased by 29% to 44% in letrozole- and estradiol-treated rats. Furthermore, the letrozole-treated rats showed a 5-fold and 7-fold increase in the volume of the cysts and corpus luteum, respectively. A 3-fold increase was found in the volume of both the cysts and corpus luteum in the estradiol group. Conclusion The structural changes of the ovary were most pronounced in the letrozole-treated animals. PMID:24179868

  5. Methods for long-term 17β-estradiol administration to mice.

    PubMed

    Ingberg, E; Theodorsson, A; Theodorsson, E; Strom, J O

    2012-01-01

    Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17β-estradiol. However, a thorough assessment of the methods for long-term administration of 17β-estradiol to mice is lacking. The fact that 17β-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17β-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 μg 17β-estradiol/mL sesame oil), or a novel peroral method (56 μg 17β-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17β-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within--except on one occasion--the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17β-estradiol, superior to the widely used commercial pellets. PMID:22137913

  6. Galanthamine Plus Estradiol Treatment Enhances Cognitive Performance in Aged Ovariectomized Rats

    PubMed Central

    Gibbs, R.B.; Chipman, A.M.; Hammond, R.; Nelson, D.

    2011-01-01

    We hypothesize that beneficial effects of estradiol on cognitive performance diminish with age and time following menopause due to a progressive decline in basal forebrain cholinergic function. This study tested whether galanthamine, a cholinesterase inhibitor used to treat memory impairment associated with Alzheimer’s disease, could enhance or restore estradiol effects on cognitive performance in aged rats that had been ovariectomized in middle-age. Rats were ovariectomized at 16–17 months of age. At 21–22 months of age rats began receiving daily injections of galanthamine (5 mg/day) or vehicle. After one week, half of each group also received 17ß-estradiol administered subcutaneously. Rats were then trained on a delayed matching to position (DMP) T-maze task, followed by an operant stimulus discrimination/reversal learning task. Treatment with galanthamine + estradiol significantly enhanced the rate of DMP acquisition and improved short-term delay-dependent spatial memory performance. Treatment with galanthamine or estradiol alone were without significant effect. Effects were task-specific in that galanthamine + estradiol treatment did not significantly improve performance on the stimulus discrimination/reversal learning task. In fact, estradiol was associated with a significant increase in incorrect responses on this task after reversal of the stimulus contingency. In addition, treatments did not significantly affect hippocampal choline acetyltransferase activity or acetylcholine release. This may be an effect of age, or possibly is related to compensatory changes associated with long-term cholinesterase inhibitor treatment. The data suggest that treating with a cholinesterase inhibitor can enhance the effects of estradiol on acquisition of a DMP task by old rats following a long period of hormone deprivation. This could be of particular benefit to older women who have not used hormone therapy for many years and are beginning to show signs of mild

  7. Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis.

    PubMed

    Esteller-Vico, A; Liu, I K M; Vaughan, B; Steffey, E P; Brosnan, R J

    2016-01-01

    Uterine vascular elastosis in mares is characterized by degeneration of uterine vasculature through thickening of the elastin layers. Factors commonly associated with this degeneration include age, parity, and chronic uterine endometritis. Affected mares have also been shown to exhibit decreases in uterine blood flow and perfusion of the uterus. Due to the increased thickness of the elastin layers, we hypothesize that vasodilatation of the uterine vasculature is also impaired. To test the functionality of these vessels, we evaluated the vasodilatory effects of estradiol on the uterine vascular bed in mares with normal vasculature and mares with severe elastosis. Both groups were tested in estrus and diestrus. Fluorescent microspheres were used to determine basal blood perfusion, followed by the intravenous administration of 1.0 μg/kg of 17β-estradiol. After 90 min, perfusion was measured once again to determine the vascular response to estradiol. Control mares in estrus displayed a significant increase in total uterine blood flow after the administration of estradiol when compared to baseline levels. No other group had a significant increase in total blood flow and perfusion after estradiol administration. The administration of estradiol in control mares induced regional increases in perfusion in the uterine horns and uterine body during estrus and only in the uterine horns during diestrus. Mares affected by elastosis exhibited no regional differences in perfusion levels post-estradiol administration. The difference in the vasodilatory response induced by estradiol between reproductively healthy mares and mares affected with elastosis indicates that the functionality of the affected vessels is compromised. PMID:26642749

  8. Signaling mechanisms involved in the acute effects of estradiol on 5-HT clearance.

    PubMed

    Benmansour, Saloua; Privratsky, Anthony A; Adeniji, Opeyemi S; Frazer, Alan

    2014-05-01

    Estradiol was found previously to have an antidepressant-like effect and to block the ability of selective serotonin reuptake inhibitors (SSRIs) to have an antidepressant-like effect. The antidepressant-like effect of estradiol was due to estrogen receptor β (ERβ) and/or GPR30 activation, whereas estradiol's blockade of the effect of an SSRI was mediated by ERα. This study focuses on investigating signaling pathways as well as interacting receptors associated with these two effects of estradiol. In vivo chronoamperometry was used to measure serotonin transporter (SERT) function. The effect of local application of estradiol or selective agonists for ERα (PPT) or ERβ (DPN) into the CA3 region of the hippocampus of ovariectomized (OVX) rats on 5-hydroxytryptamine (5-HT) clearance as well as on the ability of fluvoxamine to slow 5-HT clearance was examined after selective blockade of signaling pathways or that of interacting receptors. Estradiol- or DPN-induced slowing of 5-HT clearance mediated by ERβ was blocked after inhibition of MAPK/ERK1/2 but not of PI3K/Akt signaling pathways. This effect also involved interactions with TrkB, and IGF-1 receptors. Estradiol's or PPT's inhibition of the fluvoxamine-induced slowing of 5-HT clearance mediated by ERα, was blocked after inhibition of either MAPK/ERK1/2 or PI3K/Akt signaling pathways. This effect involved interactions with the IGF-1 receptor and with the metabotropic glutamate receptor 1, but not with TrkB. This study illustrates some of the signaling pathways required for the effects of estradiol on SERT function, and particularly shows that ER subtypes elicit different as well as common signaling pathways for their actions. PMID:24423185

  9. Sorption and transport of 17beta-estradiol and testosterone in undisturbed soil columns.

    PubMed

    Sangsupan, H A; Radcliffe, D E; Hartel, P G; Jenkins, M B; Vencill, W K; Cabrera, M L

    2006-01-01

    Land-applied domestic animal wastes contain appreciable amounts of 17beta-estradiol (henceforth, estradiol) and testosterone. These sex hormones may be transported through soil to groundwater and streams, where they may adversely affect the environment. Previous column transport studies with these hormones used repacked soil and did not consider preferential flow. We, therefore, determined the sorption and transport characteristics of estradiol and testosterone in undisturbed soil columns (15-cm i.d. by 32-cm height). In the sorption experiment, isotherms for estradiol and testosterone were nonlinear with Freundlich exponents (n) less than one. Sorption of both hormones decreased with soil depth, and estradiol sorbed more strongly than testosterone. Average estradiol Freundlich sorption coefficients (K(f)) values were 36.9 microg(1 - n) mL(n) g(-1) for the 0- to 10-cm soil depth and 25.7 microg(1 - n) mL(n) g(-1) for the 20- to 30-cm soil depth. Average testosterone K(f) values were 26.7 microg(1 - n) mL(n) g(-1) for the 0- to 10-cm soil depth and 14.0 microg(1 - n) mL(n) g(-1) for the 20- to 30-cm soil depth. In the transport experiment, 27% of the estradiol and 42% of the testosterone leached through the soil columns. Approximately 50% of the remaining soil-bound hormones were sorbed in the top 10 cm of soil. In almost all instances, breakthrough concentrations of estradiol, testosterone, and a chloride tracer peaked simultaneously. Simultaneous breakthrough and HYDRUS-1D transport parameters indicated both chemical and physical nonequilibrium processes affected hormone transport. This suggests hormones placed on soil surfaces may contaminate groundwater under conditions of preferential flow. PMID:17071897

  10. Polychlorinated biphenyl congener patterns in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed, western Massachusetts, USA, using a novel statistical approach

    USGS Publications Warehouse

    Custer, Christine M.; Read, L.B.

    2006-01-01

    A novel application of a commonly used statistical approach was used to examine differences in polychlorinated biphenyl (PCB) congener Patterns among locations and sample matrices in tree swallows (Tachycineta bicolor) nesting in the Housatonic River watershed in western Massachusetts. USA. The most prevalent PCB congeners in tree swallow tissue samples from the Housatonic River watershed were Ballsmitter Zell numbers 153. 138 180, 187 149, 101, and 170. These congeners were seven of the eight most prevalent congeners in Aroclor (R) 1260, the PCB mixture that was the primary source of contamination in the Housatonic River system. Using paired-Euclidean distances and tolerance limits, it was demonstrated that conuener patterns in swallow tissues from sites on the main stem of the Housatonic River were more similar to one another than to two sites upstream of the contamination or from a nearby reference area. The congener patterns also differed between the reference area and the two upstream tributaries and between the two tributaries. These pattern differences were the same in both pipper (eggs or just hatched nestlings) and 12-day-old nestling samples. Lower-chlorinated congeners appeared to be metabolized in nestlings and pippers compared to diet. and metabolized more in pippers compared to nestlings. Euclidean distances and tolerance limits provide a simple and statistically valid method to compare PCB congener patterns among groups. Published by Elsevier Ltd.

  11. Estimation of uptake rate constants for PCB congeners accumulated by semipermeable membrane devices and brown treat (Salmo trutta)

    USGS Publications Warehouse

    Meadows, J.C.; Echols, K.R.; Huckins, J.N.; Borsuk, F.A.; Carline, R.F.; Tillitt, D.E.

    1998-01-01

    The triolein-filled semipermeable membrane device (SPMD) is a simple and effective method of assessing the presence of waterborne hydrophobic chemicals. Uptake rate constants for individual chemicals are needed to accurately relate the amounts of chemicals accumulated by the SPMD to dissolved water concentrations. Brown trout and SPMDs were exposed to PCB- contaminated groundwater in a spring for 28 days to calculate and compare uptake rates of specific PCB congeners by the two matrixes. Total PCB congener concentrations in water samples from the spring were assessed and corrected for estimated total organic carbon (TOC) sorption to estimate total dissolved concentrations. Whole and dissolved concentrations averaged 4.9 and 3.7 ??g/L, respectively, during the exposure. Total concentrations of PCBs in fish rose from 0.06 to 118.3 ??g/g during the 28-day exposure, while concentrations in the SPMD rose from 0.03 to 203.4 ??g/ g. Uptake rate constants (k1) estimated for SPMDs and brown trout were very similar, with k1 values for SPMDs ranging from one to two times those of the fish. The pattern of congener uptake by the fish and SPMDs was also similar. The rates of uptake generally increased or decreased with increasing K(ow), depending on the assumption of presence or absence of TOC.The triolein-filled semipermeable membrane device (SPMD) is a simple and effective method of assessing the presence of waterborne hydrophobic chemicals. Uptake rate constants for individual chemicals are needed to accurately relate the amounts of chemicals accumulated by the SPMB to dissolved water concentrations. Brown trout and SPMDs were exposed to PCB-contaminated groundwater in a spring for 28 days to calculate and compare uptake rates of specific PCB congeners by the two matrixes. Total PCB congener concentrations in water samples from the spring were assessed and corrected for estimated total organic carbon (TOC) sorption to estimate total dissolved concentrations. Whole and

  12. [Analysis of toxaphene and its eight congeners in sediment and fish tissue by gas chromatography-negative ion mass spectrometry].

    PubMed

    Lao, Wenjian

    2013-07-01

    Toxaphene quantification incorporating gas chromatography/negative chemical ionization mass spectrometry (GC/NCI-MS) offers improved sensitivity and specificity. The U. S. Environmental Protection Agency (USEPA) recently released a GC/NCI-MS method (Method 8276) for the measurement of technical toxaphene and eight specific congeners (Hx-Sed, Hp-Sed, P26, P41, P40, P44, P50 and P62). However, there is still lack of a practical and complete analytical method including sample extraction, clean up, instrumental analysis, and data analysis. The goal of this work was to develop a ready-to-use method for the quantification of total toxaphene and the eight congeners. Sediment and salmon fish tissue were selected as sample matrices and extracted with methylene chloride using an accelerated solvent extraction system. The sample extracts were cleaned up with active copper powder or gel permeation chromatography, and finally silica/alumina combination column. Separation was performed on a DB-XLB column. GC/NCI-MS was operated under selected ion monitoring mode with an identical set of confirmation and quantitation ions for total toxaphene and the eight congeners. Oxygen reaction of polychlorinated biphenyls (PCB) was monitored by PCB204, an internal calibration standard, and the reaction level was kept below 1%. Average relative response factors were used in quantitation. Quantitation of total toxaphene employed the sum of all detectable (S/N > or = 3) 6-C1 to 10-Cl homolog peak areas, while the individual congeners were quantified followed the standard procedures for single analytes. Multi-point calibration solutions ranged from 0. 5 (5 for P62) to 500 microg/L for the individual congeners, and 50 to 500 microg/L for technical toxaphene, with the lowest calibration levels as lower limits of quantitation. Average congener recovery was (90.8 +/- 17.4)% (n =10) in spiked sediment with relative standard deviations of 5.4% - 12.8% (n =10), underscoring an excellently accurate and

  13. Consequences of nongenomic actions of estradiol on pathogenic genital tract response

    PubMed Central

    2013-01-01

    Estradiol is a steroid hormone that regulates the structure and function of the female reproductive system. In addition to its genomic effects, which are mediated by activated nuclear receptors, estradiol elicits a variety of rapid signaling events independently of transcriptional or genomic regulation. These nongenomic actions influence the milieu of the genital tract, which changes the ability of pathogens to infect the genital tract. This review discusses our current knowledge regarding the mechanisms and relevance of nongenomic estradiol signaling in the genital tract that could change the ability of pathogens to invade epithelial cells. PubMed was searched through January 1980 for papers related to estradiol actions in the ovary, fallopian tube, uterus and cervix. The mechanisms conveying these rapid effects consist of a multitude of signaling molecules and include cross-talk with slower transcriptional actions. The nongenomic actions of estradiol that influence the infectious abilities of pathogens occur either directly on the genital tract cells or indirectly by modulating the local and systemic immune systems. Additional in-depth characterization of the response is required before the normal and pathological reproductive functions of the nongenomic estradiol pathway can be targeted for pharmacological intervention. PMID:23351368

  14. Estradiol attenuates directed migration of vascular smooth muscle cells in vitro.

    PubMed Central

    Kolodgie, F. D.; Jacob, A.; Wilson, P. S.; Carlson, G. C.; Farb, A.; Verma, A.; Virmani, R.

    1996-01-01

    Although the cardiovascular benefits of the hormone estrogen are at least, in part, mediated by its antiproliferative effect on vascular smooth muscle, its action on the migration of these cells is unknown. To explore this relationship, female rat aortic smooth muscle cells were grown in hormone-free medium, and the effect of various concentrations of beta-estradiol on directed cellular migration was measured in vitro using a microwell Boyden chamber apparatus. Migration of smooth muscle cells to the known chemoattractants platelet-derived growth factor, insulin-like growth factor-1, and fibronectin (all at peak doses for migratory activity) was attenuated by beta-estradiol (0.5 to 10 ng/ml) in a concentration-dependent manner relative to control cells treated with vehicle (0.01% ethanol). This response was insensitive to pretreatment with indomethacin and was stereospecific (17 alpha-estradiol lacked response). Like beta-estradiol, the synthetic estrogen diethylstilbestrol attenuated directed smooth muscle cell migration whereas the male hormone testosterone was ineffective. Additional studies showed that beta-estradiol-mediated suppression of migration was inhibited by the anti-estrogen ICI 164,384 and the gene transcription inhibitor actinomycin D. These are the first results demonstrating a reduction in directed smooth muscle cell migration by beta-estradiol. The mechanism of this estrogen-mediated response appears to involve conventional estrogen receptors. PMID:8774151

  15. Modulatory Effects of Sex Steroids Progesterone and Estradiol on Odorant Evoked Responses in Olfactory Receptor Neurons

    PubMed Central

    Scholz, Paul; Mohrhardt, Julia; Gisselmann, Günter; Hatt, Hanns

    2016-01-01

    The influence of the sex steroid hormones progesterone and estradiol on physiology and behavior during menstrual cycles and pregnancy is well known. Several studies indicate that olfactory performance changes with cyclically fluctuating steroid hormone levels in females. Knowledge of the exact mechanisms behind how female sex steroids modulate olfactory signaling is limited. A number of different known genomic and non-genomic actions that are mediated by progesterone and estradiol via interactions with different receptors may be responsible for this modulation. Next generation sequencing-based RNA-Seq transcriptome data from the murine olfactory epithelium (OE) and olfactory receptor neurons (ORNs) revealed the expression of several membrane progestin receptors and the estradiol receptor Gpr30. These receptors are known to mediate rapid non-genomic effects through interactions with G proteins. RT-PCR and immunohistochemical staining results provide evidence for progestin and estradiol receptors in the ORNs. These data support the hypothesis that steroid hormones are capable of modulating the odorant-evoked activity of ORNs. Here, we validated this hypothesis through the investigation of steroid hormone effects by submerged electro-olfactogram and whole cell patch-clamp recordings of ORNs. For the first time, we demonstrate that the sex steroid hormones progesterone and estradiol decrease odorant-evoked signals in the OE and ORNs of mice at low nanomolar concentrations. Thus, both of these sex steroids can rapidly modulate the odor responsiveness of ORNs through membrane progestin receptors and the estradiol receptor Gpr30. PMID:27494699

  16. Sex, estradiol, and spatial memory in a food-caching corvid.

    PubMed

    Rensel, Michelle A; Ellis, Jesse M S; Harvey, Brigit; Schlinger, Barney A

    2015-09-01

    Estrogens significantly impact spatial memory function in mammalian species. Songbirds express the estrogen synthetic enzyme aromatase at relatively high levels in the hippocampus and there is evidence from zebra finches that estrogens facilitate performance on spatial learning and/or memory tasks. It is unknown, however, whether estrogens influence hippocampal function in songbirds that naturally exhibit memory-intensive behaviors, such as cache recovery observed in many corvid species. To address this question, we examined the impact of estradiol on spatial memory in non-breeding Western scrub-jays, a species that routinely participates in food caching and retrieval in nature and in captivity. We also asked if there were sex differences in performance or responses to estradiol. Utilizing a combination of an aromatase inhibitor, fadrozole, with estradiol implants, we found that while overall cache recovery rates were unaffected by estradiol, several other indices of spatial memory, including searching efficiency and efficiency to retrieve the first item, were impaired in the presence of estradiol. In addition, males and females differed in some performance measures, although these differences appeared to be a consequence of the nature of the task as neither sex consistently out-performed the other. Overall, our data suggest that a sustained estradiol elevation in a food-caching bird impairs some, but not all, aspects of spatial memory on an innate behavioral task, at times in a sex-specific manner. PMID:26232613

  17. Promotion of human adipocyte precursor replication by 17beta-estradiol in culture.

    PubMed Central

    Roncari, D A; Van, R L

    1978-01-01

    The influence of 17beta-estradiol and 17alpha-estradiol on adult human omental adipocyte precursors grown in a propagating culture system was studied. Cells were grown in subculture in the presence or absence of hormone. 17beta-estradiol resulted in significant promotion of adipocyte precursor replication, as determined by cell counting and incorporation of radioactive thymidine into DNA. The hormone stimulated cell multiplication in the concentration range 0.5--500 ng/ml growth medium. The highest level tested was 500 ng/ml. The maximal effects were obtained at 50 ng/ml (P less than 0.001 by paired t test, 48 h after hormone addition). All 10 cell strains (five were derived from men and five from women) that were tested responded similarly to the hormone. 17beta-estradiol did not affect cell size. 17alpha-estradiol did not promote the replication of adipocyte precursors, nor did it influence cell size. Thus, 17beta-estradiol, which is the active isomer in known target tissues, stimulates the multiplication of human adipocyte precursors in culture. Images PMID:690182

  18. Estradiol receptor: phosphorylation on tyrosine in uterus and interaction with anti-phosphotyrosine antibody.

    PubMed Central

    Migliaccio, A; Rotondi, A; Auricchio, F

    1986-01-01

    Estradiol receptor from rat uteri incubated with [32P] orthophosphate has been purified by diethylstilbestrol--Sepharose followed by heparin--Sepharose chromatography. The purified receptor, analyzed by centrifugation through sucrose gradients after incubation with monoclonal antibodies against purified estradiol receptor, appears to be labeled with 32P. The receptor preparation has been further purified by immunoaffinity chromatography and submitted to SDS--poly-acrylamide gel electrophoresis. A heavily 32P-labeled 68 kd protein and a very lightly 32P-labeled 48 kd protein, probably a proteolytic product of the 68 kd protein, were detected. Phosphoamino acid analysis of the receptor eluted from the immunoaffinity column shows that its 32P-labeling occurs exclusively on tyrosine. This is the first report on phosphorylation on tyrosine of a steroid receptor in tissue. It is consistent with our previous finding that a uterus estradiol receptor-kinase, which confers hormone binding ability to the estradiol receptor, in vitro phosphorylates this receptor exclusively on tyrosine. Calf uterus receptor binds with high specificity and affinity to monoclonal anti-phosphotyrosine antibodies covalently bound to Sepharose (Kd = 0.28 nM). Dephosphorylation of the receptor by nuclei containing the calf uterus nuclear phosphatase abolishes the interaction with antibodies. These results suggest that also in calf uterus, estradiol receptor is phosphorylated on tyrosine. Anti-phosphotyrosine antibodies bound to Sepharose have been used to partially purify the estradiol receptor from calf uterus. Images Fig. 2. Fig. 3. PMID:2431901

  19. Analyses of synovial tissues from arthritic and protected congenic rat strains reveal a new core set of genes associated with disease severity

    PubMed Central

    Brenner, Max; Laragione, Teresina

    2013-01-01

    Little is known about the genes regulating disease severity and joint damage in rheumatoid arthritis (RA). In the present study we analyzed the gene expression characteristics of synovial tissues from four different strains congenic for non-MHC loci that develop mild and nonerosive arthritis compared with severe and erosive DA rats. DA.F344(Cia3d), DA.F344(Cia5a), DA.ACI(Cia10), and DA.ACI(Cia25) rats developed mild arthritis compared with DA. We found 685 genes with significantly different expression between congenics and DA, independent of the specific congenic interval, suggesting that these genes represent a new nongenetic core group of mediators of arthritis severity. This core group includes genes not previously implicated or with unclear role in arthritis severity, such as Tnn, Clec4m, and Spond1 among others, increased in DA. The core genes also included Scd1, Selenbp1, and Slc7a10, increased in congenics. Genes implicated in nuclear receptor activity, xenobiotic and lipid metabolism were also increased in the congenics, correlating with protection. Several disease mediators were among the core genes reduced in congenics, including IL-6, IL-17, and Ccl2. Analyses of upstream regulators (genes, pathways, or chemicals) suggested reduced activation of Stat3 and TLR-related genes and chemicals in congenics. Additionally, cigarette smoking was among the upstream regulators activated in DA, while p53 was an upstream regulator activated in congenics. We observed congenic-specific differential expression and detection in each individual strain. In conclusion, this new nongenetically regulated core genes of disease severity or protection in arthritis should provide new insight into critical pathways and potential new environmental risk factor for arthritis. PMID:24046282

  20. Quantitative structure-activity relationship models for prediction of the toxicity of polybrominated diphenyl ether congeners.

    PubMed

    Wang, Yawei; Liu, Huanxiang; Zhao, Chunyan; Liu, Hanxia; Cai, Zongwei; Jiang, Guibin

    2005-07-01

    Levels of polybrominated diphenyl ethers (PBDEs) are increasing in the environment and may cause long-term health problems in humans. The similarity in the chemical structures of PBDEs and other halogenated aromatic pollutants hints on the possibility that they might share similar toxicological effects. In this work, three-dimensional quantitative structure activity relationships (3-D-QSAR) models, using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA), were built based on calculated structural indices and a reported experimental toxicology index (aryl hydrocarbon receptor relative binding affinities, RBA) of 18 PBDEs congeners, to determine the factors required for the RBA of these PBDEs. After performing leave-one-out cross-validation, satisfactory results were obtained with cross-validation O2 and R2 values of 0.580 and 0.995 by the CoMFA model and 0.680 and 0.982 by the CoMSIA model, respectively. The results showed clearly that the nonplanar conformations of PBDEs result in the lowest energy level and that the electrostatic index was the main factor reflecting the RBA of PBDEs. The two QSAR models were then used to predict the RBA value of 46 PBDEs for which experimental values are unavailable at present. PMID:16053097

  1. Continuous coculture degradation of selected polychlorinated biphenyl congeners by Acinetobacter spp. in an aerobic reactor system

    SciTech Connect

    Adriaens, P.; Focht, D.D. )

    1990-07-01

    A coculture of two Acinetobacter spp. was applied to degrade polychlorinated biphenyls during a 42-day incubation study in a continuous aerobic fixed-bed reactor system, filled with polyurethane foam boards as support for bacterial biofilm development. The reactor was supplied with mineral medium containing 500 ppm sodium benzoate as a growth (primary) substrate, while the incoming airstream was saturated with biphenyl vapors to induce for PCB cometabolism in Acinetobacter sp. strain P6. The chlorobenzoates thus generated from 4,4{prime}-dichlorobiphenyl (4,4{prime}-DCBP), 3,4-dichlorobiphenyl (3,4-DCBP), and 3,3{prime},4,4{prime}-tetrachlorobiphenyl were further metabolized by Acinetobacter sp. strain 4-CB1. The chlorobenzoate metabolites, as well as ring-fission product ({lambda}{sub max} = 442 nm) from the PCB congeners, accounted for the degradation of 63% (2.8 mM) of the 4,4{prime}-DCBP, 100% (0.5 mM) of the 3,4-DCBP, and 32% (0.12 mM) of the 3,3{prime},4,4{prime}-TCBP, the biofilm responded with a concurrent higher release of chlorobenzoates and chloride through cosubstrate utilization.

  2. Introduced and native congeners use different resource allocation strategies to maintain performance during infection.

    PubMed

    Coon, Courtney A C; Brace, Amber J; McWilliams, Scott R; McCue, Marshall D; Martin, Lynn B

    2014-01-01

    Abstract Hosts can manage parasitic infections using an array of tactics, which are likely to vary contingent on coevolutionary history between the host and the parasite. Here we asked whether coping ability of congeners that differ in host-parasite coevolutionary history differed in response to experimental infections with a coccidian parasite. House sparrows (Passer domesticus) and gray-headed sparrows (Passer griseus) are sympatric and ecologically similar, but house sparrows are recent colonizers of Kenya, the site of our comparison, whereas gray-headed sparrows are native. We evaluated three variables as barometers of infection coping ability: vertical flight, pectoral muscle size, and fat score. We also measured routing of a dose of (13)C-labeled leucine, an essential amino acid, among tissues to compare resource allocation strategies in response to infection. We found that burden effects on performance were minimal in both species, but house sparrows maintained considerably higher burdens than gray-headed sparrows regardless of exposure. House sparrows also had more exogeneous leucine tracer in all tissues after 24 h, demonstrating a difference in the way the two species allocate or distribute resources. We argue that house sparrows may be maintaining larger resource reserves to mitigate costs associated with exposure and infection. Additionally, in response to increased parasite exposure, gray-headed sparrows had less leucine tracer in their spleens and more in their gonads, whereas house sparrows did not change allocation, perhaps indicating a trade-off that is not experienced by the introduced species. PMID:24940920

  3. Atmospheric pressure ionization LC-MS-MS determination of urushiol congeners.

    PubMed

    Draper, William M; Wijekoon, Donald; McKinney, Michael; Behniwal, Paramjit; Perera, S Kusum; Flessel, C Peter

    2002-03-27

    This paper describes atmospheric pressure ionization (API) LC-MS-MS determination of urushiols, 3-n-alkenyl- and -alkyl-substituted catechols responsible for poison oak dermatitis. Urushiol was isolated from Western poison oak according to the method of Elsohly et al. (1) (J. Nat. Prod. 1982, 45, 532-538)-the purified preparation contained C(17)- and C(15)-substituted urushiols with zero, one, two, and three double bonds as determined from GC-MS analysis of trimethylsilyl derivatives. Urushiol mixtures were separated on a C(18) reversed phase HPLC column with a methanol-water gradient with urushiols eluting in 100% methanol. Atmospheric pressure chemical ionization (APCI) produced primarily [M - H](-) and MH(+) molecule ions. Electrospray ionization (ESI) yielded [M - H](-) and adduct ions including [M + Cl](-). Daughter ions of [M - H](-) included quinoid radical anions ([M - H - H(2)](-) and m/z 122(-)) and a benzofuran phenate (m/z 135(-)). A suite of hydrocarbon fragments were produced by collision-induced dissociation of MH(+) directly or via an intermediate [MH - H(2)O](+) daughter ion. Six urushiol congeners, one not previously reported in poison oak, were determined by negative ion API-LC-MS-MS with detection limits of approximately 8 pg/microL (ESI) and approximately 800 pg/microL (APCI). API-LC-MS-MS was used to determine urushiol in surface wipes, air samples, and plant materials. PMID:11902923

  4. Sorption behaviors of a persistent toxaphene congener on marine sediments under different physicochemical conditions.

    PubMed

    Soubaneh, Youssouf Djibril; Gagné, Jean-Pierre; Lebeuf, Michel; Gouteux, Bruno; Nikiforov, Vladimir; Awaleh, Mohamed Osman

    2014-11-01

    Sorptive processes are important parameters affecting the mobility, availability and fate of persistent organic pollutants (POPs), such as toxaphene, in aquatic systems. The sorption and desorption behaviors of the B7-1450, a stable toxaphene congener in environment, on marine sediment was studied under different temperature and salinity conditions to better understand the B-1450 distribution in estuarine systems. The data were fitted to different sorption models to characterize sorption behaviors by evaluating sorption coefficients and sequestrated fraction of B7-1450 on sediments. High carbon-normalized sorption coefficients (Koc) of the B7-1450 were observed with values ranging from 3.2×104 to 6.0×104 mL g(-1) under experimental conditions. The data showed an increase of B7-1450 sorption coefficients with the salinity and a decrease with temperature. These investigations indicate that B7-1450 is three times more sequestred on sediments in cold (2°C, 30 psu) than in warm marine conditions (20°C, 30 psu). These results suggest that the mobility and bioavailable of B7-1450 or other POPs from the sediments could be less important in cold marine comparatively in warm marine and warm freshwater media. As a result of climate changes, the warming of mid and high latitudes coastal waters could enhance the mobility of POPs. PMID:25113217

  5. Mapping drug interactions at the covalent topoisomerase II-DNA complex by bisantrene/amsacrine congeners.

    PubMed

    Capranico, G; Guano, F; Moro, S; Zagotto, G; Sissi, C; Gatto, B; Zunino, F; Menta, E; Palumbo, M

    1998-05-22

    To identify structural determinants for the sequence-specific recognition of covalent topoisomerase II-DNA complexes by anti-cancer drugs, we investigated a number of bisantrene congeners, including a 10-azabioisoster, bearing one or two 4, 5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1, 4, or 9 of the anthracene ring system. The studied bisantrene/amsacrine (m-AMSA) hybrid and bisantrene isomers were able to poison DNA topoisomerase II with an intermediate activity between those of bisantrene and m-AMSA. Moving the side chain from the central to a lateral ring (from C-9 to C-1/C-4) only slightly modified the drug DNA affinity, whereas it dramatically affected local base preferences of poison-stimulated DNA cleavage. In contrast, switching the planar aromatic systems of bisantrene and m-AMSA did not substantially alter the sequence specificity of drug action. A computer-assisted steric and electrostatic alignment analysis of the test compounds was in agreement with the experimental data, since a common pharmacophore was shared by bisantrene, m-AMSA, and 9-substituted analogs, whereas the 1-substituted isomer showed a radically changed pharmacophoric structure. Thus, the relative space occupancy and electron distribution of putative DNA binding (aromatic rings) and enzyme binding (side chains) moieties are fundamental in directing the specific action of topoisomerase II poisons and in determining the poison pharmacophore. PMID:9582297

  6. Synthesis, liquid chromatographic fractionation and partial characterization of polybrominated dibenzofuran congeners.

    PubMed

    Gallistl, Christoph; Vetter, Walter

    2016-04-15

    Polybrominated dibenzofurans (PBDFs) are a class of highly toxic environmental contaminants which comprises 135 structurally different congeners. While the gas chromatographic separation and analysis of the most polychlorinated dibenzofurans (PCDFs) are well-documented, comparably little data is currently available in the case of PBDFs. In this study dibenzofuran was brominated to give a mixture of ∼40 PBDFs with one to seven bromine atoms. This synthesis mixture was fractionated by both countercurrent chromatography (CCC) with the solvent system n-hexane/toluene/acetonitrile and non-aqueous reversed-phase high performance liquid chromatography (RP-HPLC) with acetonitrile as the mobile phase. All together 80 consecutive CCC fractions and 40 HPLC fractions were taken and analyzed for PBDFs by gas chromatography coupled to mass spectrometry (GC/MS). CCC and RP-HPLC offered orthogonal separation of the PBDF mixture. As a consequence, selected CCC fractions were further fractionated by RP-HPLC. In this way, eight PBDFs could be isolated and the structures of twelve PBDFs were elucidated by proton magnetic resonance spectroscopy ((1)H NMR). PMID:26993783

  7. Congenic Mice Confirm That Collagen X Is Required for Proper Hematopoietic Development

    PubMed Central

    Sweeney, Elizabeth; Roberts, Douglas; Corbo, Tina; Jacenko, Olena

    2010-01-01

    The link between endochondral skeletal development and hematopoiesis in the marrow was established in the collagen X transgenic (Tg) and null (KO) mice. Disrupted function of collagen X, a major hypertrophic cartilage matrix protein, resulted in skeletal and hematopoietic defects in endochondrally derived tissues. Manifestation of the disease phenotype was variable, ranging from perinatal lethality in a subset of mice, to altered lymphopoiesis and impaired immunity in the surviving mice. To exclude contribution of strain specific modifiers to this variable manifestation of the skeleto-hematopoietic phenotype, C57Bl/6 and DBA/2J collagen X congenic lines were established. Comparable disease manifestations confirmed that the skeleto-hematopoietic alterations are an inherent outcome of disrupted collagen X function. Further, colony forming cell assays, complete blood count analysis, serum antibody ELISA, and organ outgrowth studies established altered lymphopoiesis in all collagen X Tg and KO mice and implicated opportunistic infection as a contributor to the severe disease phenotype. These data support a model where endochondral ossification-specific collagen X contributes to the establishment of a hematopoietic niche at the chondro-osseous junction. PMID:20209091

  8. Neuroactive Multifunctional Tacrine Congeners with Cholinesterase, Anti-Amyloid Aggregation and Neuroprotective Properties

    PubMed Central

    Kozurkova, Maria; Hamulakova, Slavka; Gazova, Zuzana; Paulikova, Helena; Kristian, Pavol

    2011-01-01

    The review summarizes research into the highly relevant topics of cholinesterase and amyloid aggregation inhibitors connected to tacrine congeners, both of which are associated with neurogenerative diseases. Various opinions will be discussed regarding the dual binding site inhibitors which are characterized by increased inhibitor potency against acetylcholin/butyrylcholine esterase and amyloid formation. It is suggested that these compounds can both raise levels of acetylcholine by binding to the active site, and also prevent amyloid aggregation. In connection with this problem, the mono/dual binding of the multifunctional derivatives of tacrine, their mode of action and their neuroprotective activities are reported. The influence of low molecular compounds on protein amyloid aggregation, which might be considered as a potential therapeutic strategy in the treatment of Alzheimer's disease is also reported. Finally, attention is paid to some physico-chemical factors, such as desolvation energies describing the transfer of the substrate solvated by water, the metal-chelating properties of biometals reacting with amyloid precursor protein, amyloid beta peptide and tau protein.

  9. Foodchain bioaccumulation patterns of pesticides, PCB isomers and dioxin/furan congeners in the Great Lakes

    SciTech Connect

    Whittle, D.M.; Kiriluk, R.M.; Carswell, A.; Keir, M.J.

    1994-12-31

    Lake Ontario is one of the most contaminated Great Lakes. A detailed analysis of whole body concentrations of organic contaminants was conducted on a simple 4 compartment coldwater foodchain consisting of 7 species including several invertebrate diet items, prey fish species and the top predator lake trout. Sediment samples from the same site were analyzed for a similar suite of contaminants. Analyses were performed using a combination of HRMS/MS and GC/MS. All concentrations were reported on a whole animal wet weight basis and lipid weight concentrations. Total Toxic Equivalent Factors (TEFS) were calculated for both dioxin and furan isomers and coplanar PCBs. PCB 110 (pentachlorobiphenyl) was the dominant congener in sediment samples as well as samples of benthic invertebrates. On the other hand, PCB 138 and 153 (hexachlorobiphenyls) were found at the highest concentration in the top predator lake trout and a prey species that feeds primarily in the water column. Mysis relicta, a zooplankton species that migrates diurnally through the water column, had similar levels of both PCB 110 and PCB 138/153. PCB 77 was consistently the highest coplanar PCB found in all samples. In all biological samples analyzed 2,3,7,8 substituted tetrachlorodioxin and furan isomers were consistently found at the highest levels. Lipid normalization of all whole body data did not significantly change the bioaccumulation factors calculated using wet weight concentrations.

  10. Chlorinated paraffins in indoor air and dust: concentrations, congener patterns, and human exposure.

    PubMed

    Fridén, Ulrika E; McLachlan, Michael S; Berger, Urs

    2011-10-01

    Chlorinated paraffins (CPs) are large production volume chemicals used in a wide variety of commercial applications. They are ubiquitous in the environment and humans. Human exposure via the indoor environment has, however, been barely investigated. In the present study 44 indoor air and six dust samples from apartments in Stockholm, Sweden, were analyzed for CPs, and indoor air concentrations are reported for the first time. The sumCP concentration (short chain CPs (SCCPs) and medium chain CPs (MCCPs)) in air ranged from <5-210 ng m(-3) as quantified by gas chromatography coupled to electron ionization tandem mass spectrometry (GC/EI-MS/MS). Congener group patterns were studied using GC with electron capture negative ionization MS (GC/ECNI-MS). The air samples were dominated by the more volatile SCCPs compared to MCCPs. SumCPs were quantified by GC/EI-MS/MS in the dust samples at low μg g(-1) levels, with a chromatographic pattern suggesting the prevalence of longer chain CPs compared to air. The median exposure to sumCPs via the indoor environment was estimated to be ~1 μg day(-1) for both adults and toddlers. Adult exposure was dominated by inhalation, while dust ingestion was suggested to be more important for toddlers. Comparing these results to literature data on dietary intake indicates that human exposure to CPs from the indoor environment is not negligible. PMID:21612825

  11. Concentrations of polychlorinated biphenyl congeners in cultivated oysters (Crassostrea gigas) in western Taiwan.

    PubMed

    Fang, M D; Fang, H-T; Lee, C-L; Ko, F-C; Baker, J E

    2006-08-01

    Spatial and temporal variations of polychlorinated biphenyl (PCB) concentrations in cultivated oysters from five aquaculture areas along the western coast of Taiwan were investigated. Poor correlations between total PCB concentrations (ng/g dry weight [dw]) and physiologic parameters of oysters (shell length, width, thickness, and lipid content) were found. Total PCB concentrations ranged from 3.4 to 94 cng/g dw. The highest value was found in oysters from the Lu'ermen aquaculture area, which receives wastewater from a sodium hydroxide and pentachlorophenol factory. Furthermore, principal component analysis confirmed that the PCB congener pattern in this area was distinct from others and that two additional pollution sources might exist in the Tainan and Hsinchu areas. Oysters with PCB concentrations > 1 SD above the geometric mean were found mainly in Tainan (stations TN5 to TN9) with only one increased concentration in the Yunlin (station YL2) and Hsinchu (station HC4) aquaculture areas. Except for four confined stations, TN3 to TN6, where total PCB concentrations were higher (p = 0.028) in the warmer (May and July) than in the colder season (November and March), seasonal variation of total PCB concentrations in oysters was not significant. Geometric mean and geometric mean plus 1 SD of total PCB concentrations in this study are lower than those in South Korea and the United States (Mussel Watch). PMID:16583259

  12. Dioxins and congener-specific polychlorinated biphenyls in three avian species from the Wisconsin River, Wisconsin

    USGS Publications Warehouse

    Custer, T.W.; Custer, Christine M.; Hines, Randy K.

    2002-01-01

    Sediments from the Wisconsin River, WI, USA are contaminated with 2,3,7,8-tetrachloro-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs). Wet weight concentrations of TCDD and PCBs in eggs were at background levels and highest in the piscivorous hooded merganser (Lophodytes cucullatus; geometric MEAN=7 pg/g TCDD and 0.92 I?g/g PCBs) and lowest in the omnivorous wood duck (Aix sponsa) (<1 pg/g and 0.07 I?g/g); concentrations in eggs of the insectivorous tree swallow (Tachycineta bicolor) were intermediate (<1 pg/g and 0.33 I?g/g). Positive accumulation rates of TCDD (8a??19 pg/day) and PCBs (0.4a??0.7 I?g/day) in tree swallow nestlings suggest that the Wisconsin River is the source of these contaminants for tree swallow nestlings. The lower representation of trichlorobiphenyls and tetrachorobiphenyls in hooded merganser eggs compared to wood duck or tree swallow eggs suggests that the hooded merganser or its diet has a greater ability to metabolize lower-numbered PCB congeners than wood ducks or tree swallows.

  13. Dioxins and congener-specific polychlorinated biphenyls in three avian species from the Wisconsin River, Wisconsin.

    PubMed

    Custer, T W; Custer, C M; Hines, R K

    2002-01-01

    Sediments from the Wisconsin River. WI. USA are contaminated with 2,3,7,8-tetrachloro-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs). Wet weight concentrations of TCDD and PCBs in eggs were at background levels and highest in the piscivorous = 7 pg/g TCDD a hooded merganser (Lophodytes cucullatus; geometric m ean nd 0.92 microg/g PCBs) a nd lowest in the omnivorous wood duck (Aix sponsa) (< 1 pg/g and 0.07 microg/g); concentrations in eggs of the insectivorous tree swallow (Tachycineta bicolor) were intermediate (< 1 pg/g and 0.33 pg/g). Positive accumulation rates of TCDD (8-19 pg/day) and PCBs (0.4-0.7 microg/day) in tree swallow nestlings suggest that the Wisconsin River is the source of these contaminants for tree swallow nestlings. The lower representation of trichlorobiphenyls and tetrachorobiphenyls in hooded merganser eggs compared to wood duck or tree swallow eggs suggests that the hooded merganser or its diet has a greater ability to metabolize lower-numbered PCB congeners than wood ducks or tree swallows. PMID:12166666

  14. Hydrocortisone-induced embryotoxicity and embryonic drug disposition in H-2 congenic mice

    SciTech Connect

    Roberts, L.S.G.

    1986-01-01

    Congenic mouse strains C57BL/10Sn (B10) and B10.A/SgSn(B10A), genetically different only at the H-2 complex, were compared for sensitivity to glucocorticoid-induced embryotoxicity and embryonic drug disposition. B10A mice dosed intramuscularly with 0, 100, 150 and 200 mg hydrocortisone/kg body weight on gestational day twelve, and B10 mice injected with 0, 200, 400, 600, and 800 mg/kg, were evaluated at dissection on gestational day eighteen for signs of toxicity. In both strains, probit analysis of cleft palate production demonstrated a linear dose response. The ED50 for cleft palate production demonstrates a linear dose response. The ED50 for cleft palate production in B10A mice was 143.6 mg/kg and 512.0 mg/kg for the B10 strain. Embryonic exposure was evaluated by administration of /sup 3/H-hydrocortisone (5 uCi/mouse) to pregnant mice on day twelve of gestation, at the ED50 for cleft palate production in B10A strain. The purposes of the experiment were to quantify the difference in susceptibility to steroid-induced cleft palate, determine if a milder manifestation of embryotoxicity, fetal growth retardation, occurred at sub-clefting dosages, and determine if the difference in sensitivity to hydrocortisone-induced embryotoxicity was the result of an underlying difference in embryonic exposure to the teratogen.

  15. [Membrane receptors for estradiol--new way of biological action].

    PubMed

    Lachowicz-Ochedalska, Agnieszka

    2005-01-01

    Classical action of steroid hormones, called genomic, includes binding to their intracellular receptor, require hours or days to occur and require transcriptional effects with subsequent modulation of protein expression. Some of the biological effects induced by steroids, and mainly by sex steroids, take place within seconds or few minutes, time far too fast to be due to the genomic changes. The rapid, nongenomic action of estradiol are attributed to membrane action, probably through variety of proteins present in cell membrane. The rapid effects of steroid hormones are manifold, ranging from activation of protein and tyrosine kinases, G proteins, and modulation of ion channels. The nongenomic way of action includes also non-direct control of processes of transcription and gene expression. There are at least three different way to interact with cell membrane. Steroids may change membrane fluidity, without binding to any known protein or receptor. Another way is allosteric modulation of non-specific for steroid hormones receptors, or structural and enzymatic protein present in cell membrane. Evidence suggests that the classical steroid receptors can be localized at the plasma membrane, triggering signals typical for G-proteins coupled receptors. Physiological significance of nongenomic action of steroids needs to be elucidated. PMID:16350726

  16. Differences in oocyte development and estradiol sensitivity among mouse strains.

    PubMed

    Pepling, Melissa E; Sundman, Emily A; Patterson, Nicole L; Gephardt, Grant W; Medico, Leonard; Wilson, Krystal I

    2010-02-01

    Mouse oocytes develop in clusters of interconnected cells called germline cysts. Shortly after birth, the majority of cysts break apart and primordial follicles form, consisting of one oocyte surrounded by granulosa cells. Concurrently, oocyte number is reduced by two-thirds. Exposure of neonatal females to estrogenic compounds causes multiple oocyte follicles that are likely germline cysts that did not break down. Supporting this idea, estrogen disrupts cyst breakdown and may regulate normal oocyte development. Previously, the CD-1 strain was used to study cyst breakdown and oocyte survival, but it is unknown if there are differences in these processes in other mouse strains. It is also unknown if there are variations in estrogen sensitivity during oocyte development. Here, we examined neonatal oocyte development in FVB, C57BL/6, and F2 hybrid (Oct4-GFP) strains, and compared them with the CD-1 strain. We found variability in oocyte development among the four strains. We also investigated estrogen sensitivity differences, and found that C57BL/6 ovaries are more sensitive to estradiol than CD-1, FVB, or Oct4-GFP ovaries. Insight into differences in oocyte development will facilitate comparison of mice generated on different genetic backgrounds. Understanding variations in estrogen sensitivity will lead to better understanding of the risks of environmental estrogen exposure in humans. PMID:19846484

  17. Estradiol protective role in atherogenesis through LDL structure modification

    NASA Astrophysics Data System (ADS)

    Papi, Massimiliano; Brunelli, Roberto; Ciasca, Gabriele; Maiorana, Alessandro; Maulucci, Giuseppe; Palmieri, Valentina; Parasassi, Tiziana; De Spirito, Marco

    2016-07-01

    Relevant physiological functions are exerted by circulating low density lipoprotein (LDL) as well as eventual pathological processes triggering atherogenesis. Modulation of these functions can well be founded on modifications of LDL structure. Given its large dimension, multicomponent organization and strong interactions between the protein apoB-100 and lipids, determining LDL 3D structure remains a challenge. We propose a novel quantitative physical approach to this complex biological problem. We introduce a three-component model, fitted to small angle x-ray scattering data on LDL maintained in physiological conditions, able to achieve a consistent 3D structure. Unexpected features include three distinct protein domains protruding out of a sphere, quite rough in its surface, where several core lipid areas are exposed. All LDL components are affected by 17-β-estradiol (E2) binding to apoB-100. Mostly one of the three protruding protein domains, dramatically reducing its presence on the surface and with a consequent increase of core lipids’ exposure. This result suggests a structural basis for some E2 protecting roles and LDL physiological modifications.

  18. Estradiol promotes the rewarding effects of nicotine in female rats.

    PubMed

    Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

    2016-07-01

    It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2. PMID:27059334

  19. Estradiol regulates MICA expression in human endometrial cells

    PubMed Central

    Basu, Satarupa; Pioli, Patricia A.; Conejo-Garcia, Jose; Wira, Charles R.; Sentman, Charles L.

    2008-01-01

    The human endometrium undergoes cyclical changes regulated by sex hormones. Evidence suggests sex hormones regulate NK cell recruitment into the uterus in large numbers. NKG2D is an activating receptor expressed on human NK cells, γδ and CD8 T cells. NKG2D ligands are known to be sensors of cellular “stress”. In this study, we investigated whether sex hormones directly regulate expression of NKG2D ligands in the human uterus. Estradiol increased MICA expression on uterine epithelial cells; regulation was estrogen receptor-dependent. Real-time PCR analysis showed that NKG2D ligands MICA and MICB were expressed in the human endometrium. MICA protein was detected primarily on epithelial cells, and greater expression was observed in immunohistochemical analysis of tissues from patients in the secretory phase of the menstrual cycle. Thus, estrogens regulate expression of MICA. These data suggest hormonal regulation of innate immunity and NKG2D-mediated recognition in other tissues and diseases where estrogen may be involved. PMID:18728002

  20. Estradiol replacement extends the window of opportunity for hippocampal function

    PubMed Central

    Vedder, LC; Bredemann, TM; McMahon, LL

    2014-01-01

    We previously reported that treating aged female rats, ovariectomized (OVX) as young adults, with acute proestrous levels of 17β estradiol (E2) increases CA1 spine density, NMDAR/AMPAR ratio, GluN2B-mediated NMDAR current, and LTP at CA3-CA1 synapses if administered by 15, but not at 19, months post-OVX, defining the critical window of opportunity. Importantly, when rats are aged with ovaries intact until OVX at 20 months, hippocampal E2 responsiveness is maintained, indicating the deficit at 19 months post-OVX is a consequence of the duration of hormone deprivation and not chronological age. Here, we find the beneficial effect of E2 on novel object recognition in OVX rats was constrained by the same critical window. Furthermore, chronic low level E2 replacement, commenced by 11 months post-OVX using subcutaneous capsules removed 2 weeks prior to acute proestrous E2 treatment, prevents the loss of hippocampal responsiveness at 19 months post-OVX. These data define the dynamic nature of the critical window showing that chronic replacement with physiological E2 levels within a certain period post-OVX can lengthen the window. PMID:24813636

  1. Estradiol replacement extends the window of opportunity for hippocampal function.

    PubMed

    Vedder, Lindsey C; Bredemann, Teruko M; McMahon, Lori L

    2014-10-01

    We previously reported that treating aged female rats, ovariectomized (OVX) as young adults, with acute proestrous levels of 17β estradiol (E2) increases CA1 spine density, NMDAR to AMPAR ratio, GluN2B-mediated NMDAR current, and long-term potentiation at CA3-CA1 synapses if administered by 15, but not at 19-month post-OVX, defining the critical window of opportunity. Importantly, when rats are aged with ovaries intact until OVX at 20 months, hippocampal E2 responsiveness is maintained, indicating the deficit at 19-month post-OVX is a consequence of the duration of hormone deprivation and not chronological age. Here, we find the beneficial effect of E2 on novel object recognition in OVX rats was constrained by the same critical window. Furthermore, chronic low-level E2 replacement, commenced by 11-month post-OVX using subcutaneous capsules removed 2 weeks before acute proestrous E2 treatment, prevents the loss of hippocampal responsiveness at 19-month post-OVX. These data define the dynamic nature of the critical window showing that chronic replacement with physiological E2 levels within a certain period post-OVX can lengthen the window. PMID:24813636

  2. Laboratory estimation of net trophic transfer efficiencies of PCB congeners to lake trout (Salvelinus namaycush) from its prey

    USGS Publications Warehouse

    Madenjian, Charles P.; Rediske, Richard R.; O'Keefe, James P.; David, Solomon R.

    2014-01-01

    A technique for laboratory estimation of net trophic transfer efficiency (γ) of polychlorinated biphenyl (PCB) congeners to piscivorous fish from their prey is described herein. During a 135-day laboratory experiment, we fed bloater (Coregonus hoyi) that had been caught in Lake Michigan to lake trout (Salvelinus namaycush) kept in eight laboratory tanks. Bloater is a natural prey for lake trout. In four of the tanks, a relatively high flow rate was used to ensure relatively high activity by the lake trout, whereas a low flow rate was used in the other four tanks, allowing for low lake trout activity. On a tank-by-tank basis, the amount of food eaten by the lake trout on each day of the experiment was recorded. Each lake trout was weighed at the start and end of the experiment. Four to nine lake trout from each of the eight tanks were sacrificed at the start of the experiment, and all 10 lake trout remaining in each of the tanks were euthanized at the end of the experiment. We determined concentrations of 75 PCB congeners in the lake trout at the start of the experiment, in the lake trout at the end of the experiment, and in bloaters fed to the lake trout during the experiment. Based on these measurements, γ was calculated for each of 75 PCB congeners in each of the eight tanks. Mean γ was calculated for each of the 75 PCB congeners for both active and inactive lake trout. Because the experiment was replicated in eight tanks, the standard error about mean γ could be estimated. Results from this type of experiment are useful in risk assessment models to predict future risk to humans and wildlife eating contaminated fish under various scenarios of environmental contamination.

  3. Determining indicator toxaphene congeners in soil using comprehensive two-dimensional gas chromatography-tandem mass spectrometry.

    PubMed

    Zhu, Shuai; Gao, Lirong; Zheng, Minghui; Liu, Huimin; Zhang, Bing; Liu, Lidan; Wang, Yiwen

    2014-01-01

    Toxaphene, which is a broad spectrum chlorinated pesticide, is a complex mixture of several hundred congeners, mainly polychlorinated bornanes. Quantifying toxaphene in environmental samples is difficult because of its complexity, and because each congener has a different response factor. Toxaphene chromatograms acquired using one-dimensional gas chromatography (1DGC) show that this technique cannot be used to separate all of the toxaphene congeners. We developed and validated a sensitive and quantitative method for determining three indicator toxaphene congeners in soil using an isotope dilution/comprehensive two-dimensional gas chromatography-tandem mass spectrometry (GC × GC-MS). The samples were extracted using accelerated solvent extraction, and then the extracts were purified using silica gel columns. (13)C₁₀-labeled Parlar 26 and 50 were used as internal standards and (13)C₁₀-labeled Parlar 62 was used as an injection standard. The sample extraction and purification treatments and the GC × GC-MS parameters were optimized. Subsequently the samples were determined by GC × GC-MS. The limits of detection for Parlar 26, 50, and 62 were 0.6 pg/g, 0.4 pg/g, and 1.0 pg/g (S/N=3), respectively, and the calibration curves had good linear correlations between 50 and 1000 μg/L (r(2)>0.99). Comprehensive two-dimensional GC gave substantial improvements over one-dimensional GC in the toxaphene analysis. We analyzed soil samples containing trace quantities of toxaphene to demonstrate that the developed method could be used to analyze toxaphene in environmental samples. PMID:24274290

  4. Temporal and spatial trends in total PCB and PCB congeners in biota in a river-reservoir system

    SciTech Connect

    Horwitz, R.J.; McNair, J.N.; Hermanson, M.H.

    1995-12-31

    Since 1984, biennial studies of PCBs have been conducted in fishes, crayfish and insects in the Housatonic River, CT., and additional data are available from earlier studies. PCB data quantitated from presumptive Aroclor concentrations overestimated total PCB concentrations ([TPCB]) by about 13%, although the estimates by the 2 methods were very highly correlated. Ages of all fish specimens were determined. Spatial and temporal trends in [TPCB] were analyzed using ANCOVA to adjust for relationships between [TPCB] and age, lipid content, location and sex. Adjusted [TPCB] consistently decreased in the downstream direction. [TPCB] decreased within the years after cessation of direct inputs (around 1978). However, in the 1984--1992 period [TPCB] trends were weak and variable. Concentrations in 1994 were lower than previous years (statistical comparisons showing 1994 to be the lowest year or among a group of years with the lowest concentrations). Between year differences were probably related to temperature, storm flows and other factors affecting availability and accumulation. These variations were greater in riverine sites than in reservoirs. In brown trout, [TPCB] increased rapidly within 1--2 months after stocking. Over longer periods, [TPCB] were more closely related to seasonal cycles in lipid content rather than to time in river. Increases in [TPCB] with age were most evident for long-lived species in reservoirs. Several congeners which are abundant in Aroclors 1254 and 1260 predominated the samples. However, spatial and temporal differences in accumulation of different congeners were evident. Spatial differences in the concentration of some marker congeners reflected enrichment of these congeners from original Aroclor 1254 and 1260 sources, as well as supplemental inputs of Aroclor 1242.

  5. The effects of an environmentally relevant 58-congener polychlorinated biphenyl (PCB) mixture on cardiac development in the chick embryo.

    PubMed

    Carro, Tiffany; Taneyhill, Lisa A; Ann Ottinger, Mary

    2013-06-01

    Chicken (Gallus domesticus) embryonic exposure in ovo to a 58-congener polychlorinated biphenyl (PCB) mixture resulted in teratogenic heart defects in chick embryos at critical heart developmental stages Hamburger-Hamilton (HH) stages 10, 16, and 20. The 58-congener mixture contained relative proportions of primary congeners measured in belted sandpiper (Megaceryle alcyon) and spotted sandpiper (Actitis macularia) eggs collected along the upper Hudson River, New York, USA, and chicken doses were well below observed environmental exposure levels. Embryos were injected with 0.08 µg PCBs/g egg weight and 0.50 µg PCBs/g egg weight (0.01 and 0.064 ng toxic equivalent/g, respectively) at embryonic day 0, prior to incubation. Mortality of exposed embryos was increased at all developmental stages, with a marked rise in cardiomyopathies at HH16 and HH20 (p < 0.05). Heart abnormalities occurred across all treatments, including abnormal elongation and expansion of the heart tube at HH10, improper looping and orientation, indentations in the emerging ventricular wall (HH16 and HH20), and irregularities in overall heart shape (HH10, HH16, and HH20). Histology was conducted on 2 cardiac proteins critical to embryonic heart development, ventricular myosin heavy chain and titin, to investigate potential mechanistic effects of PCBs on heart development, but no difference was observed in spatiotemporal expression. Similarly, cellular apoptosis in the developing heart was not affected by exposure to the PCB mixture. Conversely, cardiomyocyte proliferation rates dramatically declined (p < 0.01) at HH16 and HH20 as PCB exposure concentrations increased. Early embryonic cardiomyocyte proliferation contributes to proper formation of the morphology and overall thickness of the ventricular wall. Therefore, in ovo exposure to this 58-congener PCB mixture at critical stages adversely affects embryonic heart development. PMID:23417652

  6. Molecular phylogeography of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae) and genetic relationships with congeners using cytochrome b gene marker.

    PubMed

    Yong, Hoi-Sen; Eamsobhana, Praphathip; Song, Sze-Looi; Prasartvit, Anchana; Lim, Phaik-Eem

    2015-08-01

    Angiostrongylus cantonensis is an important emerging zoonotic parasite causing human eosinophilic meningitis (or meningoencephalitis) in many parts of the world. To-date there is only a single study using mitochondrial cytochrome b (CYTB) gene to determine its genetic structure in eight geographical localities in Thailand. The present study examined the molecular phylogeography of this rat lungworm and its phylogenetic relationship with congeners using CYTB gene marker. A total of 15 CYTB haplotypes was found in 37 sequences from 14 geographical localities (covering north, west, east, central and south regions) in Thailand. These CYTB haplotypes were distinct from those of A. cantonensis for China and Hawaii. In Thailand, some CYTB haplotypes appeared to be confined to specific geographical localities. The partial CYTB DNA nucleotide sequences separated unequivocally the A. cantonensis isolates of Thailand, China and Hawaii as well as the congeners Angiostrongylus malaysiensis, A. costaricensis and Angiostrongylus vasorum, with A. malaysiensis grouped with A. cantonensis and A. costaricensis grouped with A. vasorum. Likewise the congeners of Metastrongylus and Onchocerca genera could also be clearly differentiated. The present study added two new definitive hosts (Bandicota savilei and Rattus losea) and three new localities (Mae Hong Son in the north, Tak in the west, and Phang Nga in the south) for A. malaysiensis in Thailand, indicating its wide occurrence in the country. Three CYTB haplotypes were found in the Thailand samples of A. malaysiensis. In addition to differentiation of congeners, CYTB gene marker could be used for determining the genetic diversity of a given population/taxon. PMID:25930187

  7. Laboratory Estimation of Net Trophic Transfer Efficiencies of PCB Congeners to Lake Trout (Salvelinus namaycush) from Its Prey

    PubMed Central

    Madenjian, Charles P.; Rediske, Richard R.; O'Keefe, James P.; David, Solomon R.

    2014-01-01

    A technique for laboratory estimation of net trophic transfer efficiency (γ) of polychlorinated biphenyl (PCB) congeners to piscivorous fish from their prey is described herein. During a 135-day laboratory experiment, we fed bloater (Coregonus hoyi) that had been caught in Lake Michigan to lake trout (Salvelinus namaycush) kept in eight laboratory tanks. Bloater is a natural prey for lake trout. In four of the tanks, a relatively high flow rate was used to ensure relatively high activity by the lake trout, whereas a low flow rate was used in the other four tanks, allowing for low lake trout activity. On a tank-by-tank basis, the amount of food eaten by the lake trout on each day of the experiment was recorded. Each lake trout was weighed at the start and end of the experiment. Four to nine lake trout from each of the eight tanks were sacrificed at the start of the experiment, and all 10 lake trout remaining in each of the tanks were euthanized at the end of the experiment. We determined concentrations of 75 PCB congeners in the lake trout at the start of the experiment, in the lake trout at the end of the experiment, and in bloaters fed to the lake trout during the experiment. Based on these measurements, γ was calculated for each of 75 PCB congeners in each of the eight tanks. Mean γ was calculated for each of the 75 PCB congeners for both active and inactive lake trout. Because the experiment was replicated in eight tanks, the standard error about mean γ could be estimated. Results from this type of experiment are useful in risk assessment models to predict future risk to humans and wildlife eating contaminated fish under various scenarios of environmental contamination. PMID:25226430

  8. Estradiol-induced vaginal mucus inhibits antigen penetration and CD8+ T cell priming in response to intravaginal immunization

    PubMed Central

    Seavey, Matthew M.; Mosmann, Tim R.

    2010-01-01

    Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8+ T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APC) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8+ T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8+ T cell priming after insemination or vaginal vaccination. PMID:19428849

  9. Maternal-to-fetal transfer and concentration profiles of PCB congeners for Steller sea lions (Eumetopias jubatus) from Hokkaido, Japan.

    PubMed

    Kubo, Keiko; Yamaguchi, Katsuyuki; Ishinazaka, Tsuyoshi; Yamada, Wakana; Hattori, Kaoru; Tanaka, Shunitz

    2014-01-15

    The concentrations of PCB congeners in the blubber and liver of mother Steller sea lions (Eumetopias jubatus; SSLs) and their fetuses from the coast of Hokkaido, Japan in 2008, 2010 and 2012 were analyzed by HRGC-HRMS, in order to elucidate PCB congener profiles and maternal-to-fetal transfer of PCBs in SSLs. ΣPCBs in the fetuses were 1400 ± 660 (the mean ± SD) ng/g-fat in the blubber and 570 ± 320 ng/g-fat in the liver, respectively. There was a concern that SSLs had been contaminated by PCBs during the fetal period. The concentrations of the major congeners in the blubber and liver were a correlation between the fetus and mother (blubber: r=0.9934, liver: r=0.9160; P ≦ 0.05). The results indicated that PCBs in the fetuses came from the mothers. #177 and #199 showed no correlations between the fetus and the mother in the blubber and liver. This indicated a selective capture by some natural protector such as the placenta. PMID:24269191

  10. Polychlorinated biphenyl source attribution in Green Bay, Wisconsin, USA, using multivariate similarity among congener profiles in sediment samples.

    PubMed

    Cacela, Dave; Beltman, Douglas J; Lipton, Joshua

    2002-08-01

    Polychlorinated biphenyl (PCB) congener concentrations measured in 1,189 sediment samples from Green Bay (MI/WI, USA), Lake Michigan (MI/WI, USA), and the Fox River (WI, USA) were analyzed statistically to evaluate whether PCB congener profiles in outer Green Bay are more similar to those observed in inner Green Bay or Lake Michigan. Similarities among PCB profiles were assessed with complementary multivariate analysis techniques: Principal component analysis (PCA), cluster analysis, and classification trees. The PCA indicated that profiles in outer Green Bay are distinct from those of inner Green Bay or Lake Michigan but are more similar to those of inner Green Bay. The outer bay profiles are dissimilar to profiles that would result from a simple process of mixing contaminated sediments from the inner bay with Lake Michigan sediments and, therefore, support the conclusion that contaminants in outer Green Bay come from discharges of the Fox River. Several classification trees based on small sets of congener proportions defined simple rules that consistently distinguished the regional profiles. Application of these rules to classify the outer bay samples suggests that the profiles of less than 7% of outer bay samples are similar to Lake Michigan profiles. These results are interpreted with respect to physical transport and chemical weathering processes that may account for the observed differences. PMID:12152758

  11. Congener specific determination and enantiomeric ratios of chiral polychlorinated biphenyls in striped dolphins (Stenella coeruleoalba) from the Mediterranean Sea

    SciTech Connect

    Reich, S.; Schurig, V.; Jimenez, B.; Hernandez, L.M.; Gonzalez, M.J.; Marsili, L.

    1999-06-01

    Blubber and liver samples from six striped dolphins (Stenella coeruleoalba) found dead in the Mediterranean Sea in 1989--1990 were tested for 37 coplanar and chiral polychlorinated biphenyls (PCBs), including the enantiomeric ratios of 9 chiral PCBs. The method includes a fractionation step using HPLC (PYE column) for separating the PCBs according to the number of chlorine atoms in the ortho positions. HRGC/ECD and HRGC/LRMS with an a chiral column (DB-5) were used to determine the PCB congeners. The enantiomeric ratios of nine chiral PCBs were determined by HRGC/LRMS (SIM) with a chiral column (Chirasil-Dex) and by MDGC as the confirmatory technique. The total PCB concentration (sum of 37 congeners) ranged from 7.2 to 89.6 {micro}g/g (wet weight) and from 0.52 to 29.2 {micro}g/g (wet weight) for blubber and liver samples, respectively. PCB profiles were dominated by congeners 138, 153, 170, and 180. The toxic equivalent values (TEQ) ranged from 0.17 to 3.93 ng/g (wet weight) and from 0.02 to 0.73 ng/g (wet weight) for blubber and liver samples, respectively. PCBs 95, 132, 135, 149, and 176 revealed an enantiomeric excess of the second eluted enantiomer in almost all of the samples, whereas PCBs 136 and 174 were racemic or almost racemic. PCBs 88 and 91 were under the detection limits of the methodology used.

  12. Cytochrome P450 responses and PCB congeners in pipping heron embryos from Virginia, the Great Lakes and San Francisco Bay

    USGS Publications Warehouse

    Rattner, B.A.; Melancon, M.J.; Custer, T.W.; Tillett, D.E.; Woodin, Bruce R.; Stegeman, John J.

    1992-01-01

    Pipping black-crowned night-heron (Nvcticorax nvcticorax) embryos were collected from undisturbed (Chincoteague National Wildlife Refuge VA; CNWR) and industrialized (Cat Island, Green Bay WI and San Francisco Bay, CA; SFB) locations. Hepatic monooxygenases (AHH, EROD, BROD, ECOD) were induced up to 100-fold, and were correlated (r=0.50 to 0.72) with total PCB burdens (N =61 embryos). A subset of 30 embryos have now been analyzed by GC/MS for 12 AHH-active PCB congeners and by Western blot for cytochromes P450lA and P450llB. At Cat Island, concentrations of 8 congeners were greater (P <0.05) than at CNWR. P450lA and P450llB were detected in 44% and 100% of the Cat Island embryos compared to 8% and 33% of the CNWR + SFB embryos. Cytochrome P450 parameters were correlated with the total PCBs (r =0.44 to 0.67) and with at least 9 PCB congeners (r =0.39 to 0.77). Since P450 responses might be affected by other contaminants, sample extract potency in the H411E rat hepatoma bioassay is being determined to study relationships among dioxin equivalents and cytochrome P450 parameters.

  13. Levels and distribution patterns of polychlorinated biphenyl congeners in surface sediments from Galicia coast (Northwestern, Spain) according to granulometric characteristics.

    PubMed

    Carro, N; García, I; Ignacio, M; Moureira, A

    2002-08-01

    In order to know distribution patterns of polychlorinated biphenyl congeners in the marine environment from Galida, PCBs n degrees 31, 28, 52, 101, 118, 153, 105, 138, 156 and 180 were isolated by Soxhlet extraction from three fractions of different particle size (<0.063 mm, 0.063-0.2 mm and >0.2 mm) in surface marine sediments; the quantification was performed using GC-MS and GC-ECD. Distribution of PCB congeners was shifted in favour of higher chlorinated compounds (CBs 138,153 and 180) and highly correlated to TOC content. In general, the finest fractions (<0.063 mm) of sediment presented the highest loadings of PCBs, only the sediment from As Pías zone exhibited the highest concentration of chlorinated congeners in the coarsest fraction. CB 52 concentration, slightly volatile compound, was related to water temperature. By means of multivariate techniques of data exploration as hierarchical duster analysis and principal components analysis, sediment samples from un-contaminated and slightly contaminated areas were clearly separated; groupings between samples from nearby zones appeared. PMID:12211452

  14. Seasonal variability of polychlorinated biphenyls (PCBs) and polychlorinated diphenyl ethers (PBDEs) congener profiles in butter in Poland: dietary risk evaluation.

    PubMed

    Roszko, Marek; Szymczyk, Krystyna; Rzepkowska, Małgorzata; Jędrzejczak, Renata

    2014-01-01

    Various statistical methods have been employed to analyse in details seasonal diversification of polychlorinated biphenyl (PCB)/polybrominated diphenyl ether (PBDE) congener profiles found in butter fat. The variability of the PCB/PBDE congener profiles indicates the presence of various sources of the milk fat contamination. The obtained results suggest that the environmental chemical background has the highest share in the contamination sources pattern. Ion trap mass spectrometry coupled to high-resolution gas chromatography with semi-permeable membrane dialysis sample cleanup was used for determination of PCBs and PBDEs in milk fat. Determined butter fat PCB profiles were similar to the profiles characteristic for Aroclor 1254 technical mixture. Our data indicate that dietary intake of PCB/PBDE with milk and milk products may be estimated to be about 717.5 pg kg b.w.(-1) day(-1) for six-indicator PCBs, 0.329 (equivalent toxicity, TEQ) pg kg b.w.(-1) day(-1) for 12 DL PCBs and 50 pg kg b.w.(-1) day(-1) for PBDEs (sum of 14 congeners). PMID:24380619

  15. PCB congener analysis of water and caddisfly larvae (Insecta:Trichoptera) in the upper Hudson River by glass capillary chromatography

    SciTech Connect

    Bush, B.; Simpson, K.W.; Shane, L.; Koblintz, R.R.

    1985-01-01

    The separation and analysis of the constituents of industrially produced polychlorinated biphenyls (PCBs) has been almost exclusively performed using techniques involving packed gas chromatographic columns. However, the packed column chromatograms proved to be inadequate with regard to the separation of the many congeners which compose the complex PCB mixtures. Unlike the packed column methods, a separation technique based upon gas capillary technology produces chromatograms with sharp peaks, and hence accurate analysis is possible according to individual congener concentrations. This capability permitted more precise analysis of macroinvertebrates - specifically aquatic insects in the polluted water of the upper Hudson River. This study examines the presence and relative concentration of 74 congeners in water and caddisfly larvae collected from 3 sites in the Hudson River. Caddisfly larvae (Insecta:Trichoptera) usually dominate the macroinvertebrate communities in riffle habitats of the study area. Their relatively large size and abundance facilitated the acquisition of sufficient biomass for analysis (200 mg wet weight). The sampling was carried out on July 6, 1983 and August 15, 1983.

  16. COMPARISON OF THE EFFECTS OF ESTRADIOL AND PROGESTERONE ON SEROTONERGIC FUNCTION

    PubMed Central

    Benmansour, Saloua; Weaver, Rami S.; Barton, Amanda K.; Adeniji, Opeyemi S.; Frazer, Alan

    2011-01-01

    Background Ovarian hormones may contribute to the vulnerability to depression as well as to the response to antidepressants (ADs). Previously we reported that acute systemic treatment with estradiol or progesterone blocked the ability of the selective serotonin reuptake inhibitor (SSRI), fluvoxamine, to inhibit serotonin transporter (SERT) function in ovariectomized (OVX) rats. In this study, behavioral consequences as well as receptor mechanisms underlying these hormonal effects were investigated. Methods Using the forced swimming test (FST), the acute effect of estradiol and/or progesterone on fluvoxamine’s AD-like effects was investigated. Using in vivo chronoamperometry, the effect of local application of estradiol or progesterone into the CA3 region of the hippocampus of OVX rats on 5-HT clearance as well as on the ability of fluvoxamine to slow 5-HT clearance was investigated. Results The decreased immobility and increased swimming caused by fluvoxamine in the FST was blocked in rats treated with estradiol and/or progesterone. Local application of estradiol, but not progesterone, slowed 5-HT clearance and both hormones blocked the ability of fluvoxamine to slow 5-HT clearance. Use of hormone receptor agonists, antagonists and hormone-BSA complexes revealed that the effects of estradiol are mediated by activation of membrane as well as nuclear estrogen receptors (ER). The AD-like effect of estradiol involved ERβ and GPR30 whereas its blockade of fluvoxamine’s effects was ERα-mediated. The effects of progesterone occurred solely by activation of intracellular progesterone receptors. Conclusion Targeting of ERβ or GPR30 might reveal a strategy to permit beneficial effects of estrogen without its deleterious effect on SSRI-efficacy. PMID:22225849

  17. Effects of endocrine disruptors on genes associated with 17beta-estradiol metabolism and excretion.

    PubMed

    Hanet, Nathalie; Lancon, Allan; Delmas, Dominique; Jannin, Brigitte; Chagnon, Marie-Christine; Cherkaoui-Malki, Moustapha; Latruffe, Norbert; Artur, Yves; Heydel, Jean-Marie

    2008-11-01

    In order to provide a global analysis of the effects of endocrine disruptors on the hormone cellular bioavailability, we combined 17beta-estradiol (E2) cellular flow studies with real-time PCR and Western blot expression measurements of genes involved in the hormone metabolism and excretion. Three endocrine disruptors commonly found in food were chosen for this study, which was conducted in the estrogen receptor (ER) negative hepatoblastoma HepG2 cell line: bisphenol A (BPA), genistein (GEN) and resveratrol (RES). We showed that 24 h after a single dose treatment with genistein, resveratrol or bisphenol A, the expression of ATP-binding cassette transporters (the multidrug resistance or MDR, and the multidrug resistance associated proteins or MRP) uridine diphosphate-glucuronosyltransferases (UGT) and/or sulfotransferases (ST) involved in 17beta-estradiol elimination process were significantly modulated and that 17beta-estradiol cellular flow was modified. Resveratrol induced MDR1 and MRP3 expressions, bisphenol A induced MRP2 and MRP3 expressions, and both enhanced 17beta-estradiol efflux. Genistein, on the other hand, inhibited ST1E1 and UGT1A1 expressions, and led to 17beta-estradiol cellular retention. Thus, we demonstrate that bisphenol A, genistein and resveratrol modulate 17beta-estradiol cellular bioavailability in HepG2 and that these modulations most probably involve regulations of 17beta-estradiol phase II and III metabolism proteins. Up to now, the estrogenicity of environmental estrogenic pollutants has been based on the property of these compounds to bind to ERs. Our results obtained with ER negative cells provide strong evidence for the existence of ER-independent pathways leading to endocrine disruption. PMID:18634814

  18. VITAMIN D–BINDING PROTEIN IN HEALTHY PRE- AND POSTMENOPAUSAL WOMEN: RELATIONSHIP WITH ESTRADIOL CONCENTRATIONS

    PubMed Central

    Pop, L. Claudia; Shapses, Sue A.; Chang, Brian; Sun, Wei; Wang, Xiangbing

    2016-01-01

    Objective To examine the relationship between endogenous serum estradiol and vitamin D–binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women. Methods In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels. Results Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in pre- than postmenopausal women (P<.05). Serum estradiol correlated with DBP (r = 0.22; P<.01) and total 25OHD (r = 0.27; P<.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P<.05). Conclusion Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration. PMID:26121448

  19. Estradiol protects female rats against sepsis induced by Enterococcus faecalis improving leukocyte bactericidal activity.

    PubMed

    Saia, Rafael Simone; Garcia, Fabíola Morales; Cárnio, Evelin Capellari

    2015-10-01

    Enterococcus faecalis is a Gram-positive bacteria described as an important causative agent of sepsis. The contact between host leukocytes and bacteria activates the innate immunity, participating as the first defense mechanism against infection. Pro-inflammatory cytokines [including tumor necrosis factor (TNF)-α and interleukin-1β] and nitric oxide (NO) are essential to recruitment of leukocytes into the infectious focus as well as their activation for phagocytosis. Beyond the bacteria species, gender has been considered another factor to predict outcome in septic patients. Studies suggest that females exhibit a protective advantage during sepsis models, being gonadal hormones possible modulators of functions of immune cells. Nevertheless, the role of estradiol during Gram-positive infection remains a literature gap. Our aims were to investigate whether estradiol protects rats against bacterial dissemination during E. faecalis-induced sepsis. We determined whether estradiol modulates the local and systemic inflammatory response, as well as the cell migration into the infectious focus and the bactericidal capacity of leukocytes. Our findings demonstrated that estradiol pre-treated rats showed a dose-dependent reduction in bacterial counts in peritoneal lavage fluid (PLF) and in liver. Moreover, TNF-α and nitrate levels were increased in plasma, while only TNF-α was increased in the PLF in estradiol-treated rats. The prevention of bacterial dissemination may be related to the enhanced neutrophil and macrophage migration into the peritoneal cavity. Furthermore, estradiol improved the phagocytic and bactericidal ability of these both inflammatory cells. Taken together, the present study clearly demonstrates an important protective role of estradiol against sepsis induced by E. faecalis in female rats. PMID:26143494

  20. Detection of estradiol at an electrochemical immunosensor with a Cu UPD|DTBP-Protein G scaffold.

    PubMed

    Liu, Xiaoqiang; Wang, Xinhai; Zhang, Jiamei; Feng, Heqing; Liu, Xiuhua; Wong, Danny K Y

    2012-05-15

    A copper monolayer was formed on a gold electrode surface via underpotential deposition (UPD) method to construct a Cu UPD|DTBP-Protein G immunosensor for the sensitive detection of 17β-estradiol. Copper UPD monolayer can minimize the non-specific adsorption of biological molecules on the immunosensor surface and enhance the binding efficiency between immunosensor surface and thiolated Protein G. The crosslinker DTBP (Dimethyl 3,3'-dithiobispropionimidate · 2HCl) has strong ability to immobilize Protein G molecules on the electrode surface and the immobilized Protein G provides an orientation-controlled binding of antibodies. A monolayer of propanethiol was firstly self-assembled on the gold electrode surface, and a copper monolayer was deposited via UPD on the propanethiol modified electrode. Propanethiol monolayer helps to stabilize the copper monolayer by pushing the formation and stripping potentials of the copper UPD monolayer outside the potential range in which copper monolayer can be damaged easily by oxygen in air. A droplet DTBP-Protein G was then applied on the modified electrode surface followed by the immobilization of estradiol antibody. Finally, a competitive immunoassay was conducted between estradiol-BSA (bovine serum albumin) conjugate and free estradiol for the limited binding sites of estradiol antibody. Square wave voltammetry (SWV) was employed to monitor the electrochemical reduction current of ferrocenemethanol and the SWV current decreased with the increase of estradiol-BSA conjugate concentration at the immunosensor surface. Calibration of immunosensors in waste water samples spiked with 17β-estradiol yielded a linear response up to ≈ 2200 pg mL(-1), a sensitivity of 3.20 μA/pg mL(-1) and a detection limit of 12 pg mL(-1). The favorable characteristics of the immunosensors such as high selectivity, sensitivity and low detection limit can be attributed to the Cu UPD|DTBP-Protein G scaffold. PMID:22405841

  1. Peripheral microvascular vasodilatory response to estradiol and genistein in women with insulin resistance

    PubMed Central

    Wenner, Megan M.; Taylor, Hugh S.; Stachenfeld, Nina S.

    2015-01-01

    Objective Estradiol enhances vasodilation in healthy women, but vascular effects of the phytoestrogen genistein are still under investigation. Insulin resistance (IR) compromises microvascular function. We therefore examined the interaction of estradiol, genistein, and IR on microvascular vasodilatory responsiveness. Methods We hypothesized that estradiol and genistein increase microvascular vasodilation in healthy women (control, n=8, 23±2 yr, BMI 25.9±2.9 kg/m2) but not in women with IR (n=7, 20±1 yr, BMI 27.3±3.0 kg/m2). We used the cutaneous circulation as a model of microvascular vasodilatory function. We determined cutaneous vascular conductance (CVC) with laser Doppler flowmetry and beat-to-beat blood pressure during local cutaneous heating (42°C) with estradiol or genistein microdialysis perfusions. Because heat induced vasodilation is primarily an NO mediated response, we examined microvascular vasodilation with and without L-NMMA. Results In control women, estradiol enhanced CVC (94.4±2.6 % vs. saline 81.6±4.2 % CVCmax, P<0.05), which was reversed with L-NMMA (80.9±7.8 % CVCmax, P<0.05), but genistein did not affect vasodilation. Neither estradiol nor genistein altered CVC in IR, although L-NMMA attenuated CVC during genistein. Conclusions Our study does not support improved microvascular responsiveness during genistein exposure in healthy young women, and demonstrates that neither estradiol nor genistein improve microvascular vasodilatory responsiveness in women with IR. PMID:25996650

  2. Comparison of Two Methods of Estradiol Replacement: their Physiological and Behavioral Outcomes

    PubMed Central

    Mosquera, Laurivette; Shepherd, Luz; Torrado, Aranza I; Torres-Diaz, Yvonne M; Miranda, Jorge D; Segarra, Annabell C

    2016-01-01

    Fluctuating sex steroids during the estrous or menstrual cycle of mammalian females make it difficult to determine their role on behaviors and physiology. To avoid this, many investigators ovariectomize their animals and administer progesterone, estradiol or a combination of both. Several different strategies are used to administer estradiol, which confounds interpretation of results. This study compared two methods of estradiol replacement implants: Silastic tubes filled with crystalline estradiol benzoate (E2) and commercially available estradiol benzoate pellets. Implants were placed subcutaneously in adult ovariectomized (OVX) rats and blood samples obtained weekly. Control OVX rats received empty Silastic tubes or placebo pellets. Our data shows that E2 plasma levels from rats with Silastic implants peaked after one week and decreased slowly thereafter. In contrast, plasma E2 from commercial pellets peaked after two weeks, increasing and decreasing over time. To validate hormone release, body weight was monitored. All E2 treated animals maintained a similar body weight over the four weeks period whereas an increase in body weight over time was observed in the OVX group that received empty implants, confirming E2 release and supporting the role of E2 in the regulation of body weight. Furthermore, the effects of E2 on basal locomotor activity were assessed using animal activity cages. Results showed no difference between E2 and control group in several locomotor activities. These results indicate that Silastic implants achieve more stable plasma estradiol levels than pellets and thus are a better alternative for studies of estradiol on brain function and behavior. PMID:26962471

  3. Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle.

    PubMed

    Albert, Kimberly; Pruessner, Jens; Newhouse, Paul

    2015-09-01

    Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle-related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women. PMID:26123902

  4. Estradiol regulation of nucleotidases in female reproductive tract epithelial cells and fibroblasts.

    PubMed

    Shen, Zheng; Fahey, John V; Bodwell, Jack E; Rodriguez-Garcia, Marta; Rossoll, Richard M; Crist, Sarah G; Patel, Mickey V; Wira, Charles R

    2013-01-01

    The use of topical and oral adenosine derivatives in HIV prevention that need to be maintained in tissues and cells at effective levels to prevent transmission prompted us to ask whether estradiol could influence the regulation of catabolic nucleotidase enzymes in epithelial cells and fibroblasts from the upper and lower female reproductive tract (FRT) as these might affect cellular TFV-DP levels. Epithelial cells and fibroblasts were isolated from endometrium (EM), endocervix (CX) and ectocervix (ECX) tissues from hysterectomy patients, grown to confluence and treated with or without estradiol prior to RNA isolation. The expression of nucleotidase (NT) genes was measurable by RT-PCR in epithelial cells and fibroblasts from all FRT tissues. To determine if sex hormones have the potential to regulate NT, we evaluated NT gene expression and NT biological activity in FRT cells following hormone treatment. Estradiol increased expression of Cytosolic 5'-nucleotidase after 2 or 4 h in endometrial epithelial cells but not epithelial cells or fibroblasts from other sites. In studies using a modified 5'-Nucleotidase biological assay for nucleotidases, estradiol increased NT activity in epithelial cells and fibroblasts from the EM, CX and ECX at 24 and 48 h. In related studies, HUVEC primary cells and a HUVEC cell line were unresponsive to estradiol in terms of nucleotidase expression or biological activity. Our findings of an increase in nucleotidase expression and biological activity induced by estradiol do not directly assess changes in microbicide metabolism. However, they do suggest that when estradiol levels are elevated during the menstrual cycle, FRT epithelial cells and fibroblasts from the EM, CX and ECX have the potential to influence microbicide levels that could enhance protection of HIV-target cells (CD4+T cells, macrophages and dendritic cells) throughout the FRT. PMID:23936114

  5. Acaricidal effects of quinone and its congeners and color alteration of Dermatophagoides spp. with quinone.

    PubMed

    Lee, Hoi-Seon

    2007-08-01

    Acaricidal activity of the active constituent derived from Pyrus ussuriensis fruits against Dermatophagoides farinae and D. pteronyssinus was examined and compared with that of the commercial benzyl benzoate. The LD50 value of the ethyl acetate fraction obtained from the aqueous extract of P ussuriensis fruits was 9.51 and 8.59 microg/cm3 against D. farinae and D. pteronyssinus, respectively. The active constituent was identified as quinone by spectroscopic analyses. On the basis of LD50 values with quinone and its congeners, the compound most toxic against D. farinae was quinone (1.19 microg/cm3), followed by quinaldine (1.46), benzyl benzoate (9.32), 4-quinolinol (86.55), quinine (89.16), and 2-quinolinol (91.13). Against D. pteronyssinus, these were quinone (1.02 microg/ cm3), followed by quinaldine (1.29), benzyl benzoate (8.54), 4-quinolinol (78.63), quinine (82.33), and 2-quinolinol (86.24). These results indicate that the acaricidal activity of the aqueous extracts can be mostly attributed to quinone. Quinone was about 7.8 and 8.4 times more toxic than benzyl benzoate against D. farinae and D. pteronyssinus. Additionally, quinaldine was about 6.4 and 6.6 times more toxic than benzyl benzoate against D. farinae and D. pteronyssinus, respectively. Furthermore, the skin color of the dust mites was changed from colorless-transparent to dark brown-black by the treatment of quinone. These results indicate that quinone can be very useful as potential control agents, lead compounds, or the indicator of house dust mites. PMID:18051611

  6. Comparative developmental toxicity of planar polychlorinated biphenyl congeners in chickens, American kestrels, and common terns

    SciTech Connect

    Hoffman, D.J.; Melancon, M.J.; Klein, P.N.; Eisemann, J.D.; Spann, J.W.

    1998-04-01

    The effects of polychlorinated biphenyl (PCB) congeners, PCB 126 (3,3{prime},4,4{prime},5-pentaCB) and PCB 77 (3,3{prime},4,4{prime}-tetraCB), were examined in chicken (Gallus gallus), American kestrel (Falco sparverius), and common tern (Sterna hirundo) embryos through hatching, following air cell injections on day 4. PCB 126 caused malformations and edema in chickens starting at 0.3 ppb, in kestrels at 2.3 to 23 ppb, but in terns only at levels affecting hatching success (44 ppb). Extent of edema was most severe in chickens and least in terns. Defects of the beak were common in all species but with crossed beak most prevalent in terns. Effects on embryo growth were most apparent for PCB 126 in chickens and kestrels. The approximate 50% lethal dose (LD50) for PCB 126 in chickens was 0.4 ppb, in kestrels was 65 ppb, and in terns was 104 ppb. The approximate LD50 for PCB 77 in chickens was 2.6 ppb and in kestrels was 316 ppb. Induction of cytochrome P450 associated monooxygenase activity (ethoxyresorufin-O-dealkylase activity) by PCB 126 in chick embryo liver was about 800 times more responsive than in tern and at least 1,000 times more responsive than in kestrel. High concentrations of PCB 126 found in bald eagle eggs are nearly 20-fold higher than the lowest toxic concentration tested in kestrels. Concentrations of PCB 126 causing low-level toxic effects in common tern eggs are comparable to highest levels in common terns and Forster`s terns in the field, suggesting additional involvement of other compounds in the Great Lakes.

  7. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

    PubMed

    Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs. PMID:26694966

  8. Supervised pattern recognition procedures for discrimination of whiskeys from gas chromatography/mass spectrometry congener analysis.

    PubMed

    González-Arjona, Domingo; López-Pérez, Germán; González-Gallero, Víctor; González, A Gustavo

    2006-03-22

    The volatile congener analysis of 52 commercialized whiskeys (24 samples of single malt Scotch whiskey, 18 samples of bourbon whiskey, and 10 samples of Irish whiskey) was carried out by gas chromatography/mass spectrometry after liquid-liquid extraction with dichloromethane. Pattern recognition procedures were applied for discrimination of different whiskey categories. Multivariate data analysis includes linear discriminant analysis (LDA), k nearest neighbors (KNN), soft independent modeling of class analogy (SIMCA), procrustes discriminant analysis (PDA), and artificial neural networks techniques involving multilayer perceptrons (MLP) and probabilistic neural networks (PNN). Classification rules were validated by considering the number of false positives (FPs) and false negatives (FNs) of each class associated to the prediction set. Artificial neural networks led to the best results because of their intrinsic nonlinear features. Both techniques, MLP and PNN, gave zero FPs and zero FNs for all of the categories. KNN is a nonparametric method that also provides zero FPs and FNs for every class but only when selecting K = 3 neighbors. PDA produced good results also (zero FPs and FNs always) but only by selecting nine principal components for class modeling. LDA shows a lesser classification performance, because of the building of linear frontiers between classes that does not apply in many real situations. LDA led to one FP for bourbons and one FN for scotches. The worse results were obtained with SIMCA, which gave a higher number of FPs (five for both scotches and bourbons) and FNs (six for scotchs and two for bourbons). The possible cause of these findings is the strong influence of class inhomogeneities on the SIMCA performance. It is remarkable that in any case, all of the methodologies lead to zero FPs and FNs for the Irish whiskeys. PMID:16536565

  9. Comparative developmental toxicity of planar polychlorinated biphenyl congeners in chickens, American kestrels, and common terns

    USGS Publications Warehouse

    Hoffman, D.J.; Melancon, M.J.; Klein, P.N.; Eisemann, J.D.; Spann, J.W.

    1998-01-01

    The effects of PCB congeners, PCB 126 (3,3',4,4',5-pentaCB) and PCB 77 (3,3'4,4'-tetraCB), were examined in chicken (Gallus gallus), American kestrel (Falco sparverius), and common tern (Sterna hirundo) embryos through hatching, following air cell injections on day 4. PCB 126 caused malformations and edema in chickens starting at 0.3 ppb, in kestrels at 2.3 ppb, but in terns only at levels affecting hatching success (44 ppb). Extent of edema was most severe in chickens and least in terns. Defects of the beak were common in all species, but with crossed beak most prevalent in terns. Effects on embryo growth were most apparent for PCB 126 in chickens and kestrels. The approximate LD50 for PCB 126 in chickens was 0.4 ppb, in kestrels was 65 ppb, and in terns was 104 ppb. The approximate LD50 for PCB 77 in chickens was 2.6 ppb and in kestrels was 316 ppb. Induction of cytochrome P450 associated monooxygenase activity (EROD activity) by PCB 126 in chick embryo liver was about 800 times more responsive than in tern and at least 1000 times more responsive than in kestrel. High concentrations of PCB 126 found in bald eagle eggs are nearly 20-fold higher than the lowest toxic concentration tested in kestrels. Concentrations of PCB 126 causing low level toxic effects in common tern eggs are comparable to highest levels in common terns and Forster's terns in the field, suggesting additional involvement of other compounds in the Great Lakes.

  10. Synthesis and aryl hydrocarbon receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners

    SciTech Connect

    Farrell, K.; Safe, L.; Safe, S.

    1987-11-15

    Microchlorination of 1,4,9(/sup 3/H)dibenzofuran gave several polychlorinated dibenzofuran (PCDF) products and 2,3,7,8-(/sup 3/H)tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-(/sup 3/H)pentachlorodibenzofuran (PeCDF), and 1,2,3,6,7,8-/1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) of high specific activity (57, 34, and 32.5 Ci/mmol, respectively) were purified by preparative high-pressure liquid chromatography. These compounds were investigated as radioligands for the rat liver cytosolic aryl hydrocarbon (Ah) receptor protein. Like 2,3,7,8-(/sup 3/H)tetrachlorodibenzo-p-dioxin (TCDD), the radiolabeled PCDF congeners exhibited saturable binding with the receptor protein and sucrose density gradient analysis of the radiolabeled ligand-receptor complexes gave specific binding peaks with comparable sedimentation profiles. The rank order of radioligand binding affinities (Kd values) was 2,3,7,8-TCDD greater than 2,3,7,8-TCDF greater than 1,2,3,6,7,8-HCDF greater than 1,2,3,7,8-PeCDF and the maximum difference in Kd values for the four radioligands was less than 13-fold (0.44-5.9 nM). The interactions of the PCDF radioligands with the cytosolic receptor all exhibited saturable binding curves and linear Scatchard plots and the slopes of their Hill plots were in the range 1.0-1.1, thus indicating that cooperativity was not a factor in these binding interactions. The relative stabilities and dissociation kinetics of the radioligand-receptor complexes were highly dependent on the structure of the radioligand. The dissociation curves of the 2,3,7,8-(/sup 3/H)TCDD and PCDF receptor complexes were biphasic and this suggests that there may be a temporal shift in ligand binding affinities. However, the rates of dissociation did not correlate with the rank order of ligand binding affinities.

  11. The potential for estradiol and ethinylestradiol degradation in English rivers.

    PubMed

    Jürgens, Monika D; Holthaus, Karlijn I E; Johnson, Andrew C; Smith, JenniferJ L; Hetheridge, Malcom; Williams, Richard J

    2002-03-01

    Water samples were collected in spring, summer, and winter from English rivers in urban/industrial (River Aire and River Calder, Yorkshire, UK) and rural environments (River Thames, Oxfordshire, UK) to study the biodegradation potential of the key steroid estrogen 17beta-estradiol (E2) and its synthetic derivate ethinylestradiol (EE2). Microorganisms in the river water samples were capable of transforming E2 to estrone (E1) with half-lives of 0.2 to 9 d when incubated at 20 degrees C. The E1 was then further degraded at similar rates. The most rapid biodegradation rates were associated with the downstream summer samples of the River Aire and River Calder. E2 degradation rates were similar for spiking concentrations throughout the range of 20 ng/L to 500 microg/L. Microbial cleavage of the steroid ring system was demonstrated by release of radiolabeled CO2 from the aromatic ring of E2 (position 4). When E2 was degraded, the loss of estrogenicity, measured by the yeast estrogen screen (YES) assay, closely followed the loss of the parent molecule. Thus, apart from the transient formation of E1, the degradation of E2 does not form other significantly estrogenic intermediates. The E2 could also be degraded when incubated with anaerobic bed sediments. Compared to E2, EE2 was much more resistant to biodegradation, but both E2 and EE2 were susceptible to photodegradation, with half-lives in the order of 10 d under ideal conditions. PMID:11883412

  12. Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

    PubMed Central

    Krumenacker, Joshua S.; Hyder, Salman M.; Murad, Ferid

    2001-01-01

    Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17β-estradiol (E2) regulates the α1 and β1 subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC α1 10% and sGC β1 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression. PMID:11209068

  13. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

    PubMed

    Wisner, Katherine L; Sit, Dorothy K Y; Moses-Kolko, Eydie L; Driscoll, Kara E; Prairie, Beth A; Stika, Catherine S; Eng, Heather F; Dills, John L; Luther, James F; Wisniewski, Stephen R

    2015-08-01

    Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 μg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  14. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot Randomized Trial

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Moses-Kolko, Eydie L.; Driscoll, Kara E.; Prairie, Beth; Stika, Catherine S.; Eng, Heather F.; Dills, John L; Luther, James F.; Wisniewski, Stephen R.

    2015-01-01

    Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  15. Estradiol rapidly inhibits soluble guanylyl cyclase expression in rat uterus

    NASA Technical Reports Server (NTRS)

    Krumenacker, J. S.; Hyder, S. M.; Murad, F.

    2001-01-01

    Previous reports that investigated the regulation of the NO/soluble guanylyl cyclase (sGC)/cGMP pathway by estrogenic compounds have focused primarily on the levels of NO, NO-producing enzymes, and cGMP in various tissues. In this study, we demonstrate that 17beta-estradiol (E2) regulates the alpha(1) and beta(1) subunits of the NO receptor, sGC, at the mRNA and protein levels in rat uterus. Using real-time quantitative PCR, we found that within 1 h of in vivo E2 administration to rats, sGC mRNA levels begin to diminish. After 3 h, there is a maximal diminution of sGC mRNA expression (sGC alpha(1) 10% and sGC beta(1) 33% of untreated). This effect was blocked by the estrogen receptor antagonist, ICI 182,780, indicating that estrogen receptor is required. The effect of E2 also was observed in vitro with incubations of uterine tissue, indicating that the response does not depend on the secondary release of other hormones or factors from other tissues. Puromycin did not block the effect, suggesting the effects occur because of preexisting factors in uterine tissues and do not require new protein synthesis. Using immunoblot analysis, we found that sGC protein levels also were reduced by E2 over a similar time course as the sGC mRNA. We conclude that sGC plays a vital role in the NO/sGC/cGMP regulatory pathway during conditions of elevated estrogen levels in the rat uterus as a result of the reduction of sGC expression.

  16. Estradiol-induced gene expression in largemouth bass (Micropterus salmoides)

    USGS Publications Warehouse

    Bowman, C.J.; Kroll, K.J.; Gross, T.G.; Denslow, N.D.

    2002-01-01

    Vitellogenin (Vtg) and estrogen receptor (ER) gene expression levels were measured in largemouth bass to evaluate the activation of the ER-mediated pathway by estradiol (E2). Single injections of E2 ranging from 0.0005 to 5 mg/kg up-regulated plasma Vtg in a dose-dependent manner. Vtg and ER mRNAs were measured using partial cDNA sequences corresponding to the C-terminal domain for Vtg and the ligand-binding domain of ER?? sequences. After acute E2-exposures (2 mg/kg), Vtg and ER mRNAs and plasma Vtg levels peaked after 2 days. The rate of ER mRNA accumulation peaked 36-42 h earlier than Vtg mRNA. The expression window for ER defines the primary response to E2 in largemouth bass and that for Vtg a delayed primary response. The specific effect of E2 on other estrogen-regulated genes was tested during these same time windows using differential display RT-PCR. Specific up-regulated genes that are expressed in the same time window as Vtg were ERp72 (a membrane-bound disulfide isomerase) and a gene with homology to an expressed gene identified in zebrafish. Genes that were expressed in a pattern that mimics the ER include the gene for zona radiata protein ZP2, and a gene with homology to an expressed gene found in winter flounder. One gene for fibrinogen ?? was down-regulated and an unidentified gene was transiently up-regulated after 12 h of exposure and returned to basal levels by 48 h. Taken together these studies indicate that the acute molecular response to E2 involves a complex network of responses over time. ?? 2002 Elsevier Science Ireland Ltd. All rights reserved.

  17. Tracking polychlorinated biphenyls (PCBs) congener patterns in Newark Bay surface sediment using principal component analysis (PCA) and positive matrix factorization (PMF).

    PubMed

    Saba, Tarek; Su, Steave

    2013-09-15

    PCB congener data for Newark Bay surface sediments were analyzed using PCA and PMF, and relationships between the outcomes from these two techniques were explored. The PCA scores plot separated the Lower Passaic River Mouth samples from North Newark Bay, thus indicating dissimilarity. Although PCA was able to identify subareas in the Bay system with specific PCB congener patterns (e.g., higher chlorinated congeners in Elizabeth River), further conclusions reading potential PCB source profiles or potential upland source areas were not clear for the PCA scores plot. PMF identified five source factors, and explained the Bay sample congener profiles as a mix of these Factors. This PMF solution was equivalent to (1) defining an envelope that encompasses all samples on the PCA scores plot, (2) defining source factors that plot on that envelope, and (3) explaining the congener profile for each Bay sediment sample (inside the scores plot envelope) as a mix of factors. PMF analysis allowed identifying characteristic features in the source factor congener distributions that allowed tracking of source factors to shoreline areas where PCB inputs to the Bay may have originated. The combined analysis from PCA and PMF showed that direct discharges to the Bay are likely the dominant sources of PCBs to the sediment. Review of historical upland activities and regulatory files will be needed, in addition to the PCA and PMF analysis, to fully reconstruct the history of operations and PCB releases around the Newark Bay area that impacted the Bay sediment. PMID:23831929

  18. Comparison of three enzyme immunoassays for measuring 17beta-estradiol in flushed dairy manure wastewater.

    PubMed

    Hanselman, Travis A; Graetz, Donald A; Wilkie, Ann C

    2004-01-01

    Natural steroidal estrogens are an environmental concern because low nanogram per liter concentrations in water can adversely affect aquatic vertebrate species by disrupting the normal function of their endocrine systems. There is a critical need to accurately measure estrogens in dairy wastes, a potential source of estrogens such as 17beta-estradiol, to assess the risk of estrogen contamination of agricultural drainage waters resulting from land application. Commercially available enzyme immunoassay (EIA) kits have been used for measuring 17beta-estradiol in livestock manure, but it is not known if different EIAs provide similar results. We compared three EIAs by measuring 17beta-estradiol in two samples of flushed dairy manure wastewater (FDMW). The measured concentrations of 17beta-estradiol in FDMW differed according to the immunoassay used. The differences were attributed to a matrix interference associated with coextracted humic substances. Future research should develop methods that enable routine measurement of 17beta-estradiol in livestock wastes by more conclusive analytical techniques such as gas chromatography-mass spectrometry. PMID:15356254

  19. Estradiol receptor of calf uterus: interactions with heparin-agarose and purification.

    PubMed Central

    Molinari, A M; Medici, N; Moncharmont, B; Puca, G A

    1977-01-01

    Heparin attached covalently to agarose beads binds the "native" form of the estradiol receptor with very high affinity. Chondroitin sulfate does not bind to the receptor. When the receptor is complexed with hormone, the affinity is at least 10 times higher. Only the "native" and not the "nuclear" or the "derived" (i.e., after activation by a calcium-dependent enzyme) forms of the estradiol receptor interact with heparin. The "native" estradiol-receptor complex is purified to homogeneity after chromatography on columns of heparin-agarose, Sephadex G-200, and DEAE-cellulose, followed by two more Sephadex G-200 columns. The purified molecule is a single polypeptide of molecular weight 69,000 by polyacrylamide gel electrophoresis in sodium dodecyl sulphate. The sedimentation coefficient on sucrose gradients is 4.3 S, the Stokes radius from gel filtration is 36.5 A, and the isoelectric point is 6.4. The purified [3H]estradiol-receptor complex exchanges the radioactive hormone with estradiol or other estrogenic steroids, but not with testosterone, 5alpha-dihydrotestosterone, or progesterone. Images PMID:270721

  20. Differing transcriptional responses to pulsed or continuous estradiol exposure in human umbilical vein endothelial cells.

    PubMed

    Li, Jin; Wang, Hongliang; Johnson, Suzanne M; Horner-Glister, Emma; Thompson, John; White, Ian N H; Al-Azzawi, Farook

    2008-07-01

    This study used human umbilical vein endothelial cells (HUVECs) that were treated with 17beta-estradiol for 5 days as 1h pulse or 24h continuous treatment at concentrations such that the 24h exposure (concentration x time) was identical in both conditions. Cell proliferation was studied and gene expression profiling was carried out using the Affymetrix GeneChip microarray analysis. Changes in morphology and apoptosis in HUVECs were examined with electron microscopy. Time-course studies of expression of genes vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were performed by quantitative PCR. We observed that cell proliferation was significantly decreased over days 3-5 with pulsed estradiol treatment relative to constant exposure. Microarray results showed that after 5 days, 801 genes differed (P<0.05) between continuous versus pulsed estradiol treatment. Functional analysis showed a significant number of genes to be associated with apoptosis and cell cycle pathways. We did not find any evidence of apoptosis from flow cytometry or electron microscopy examination. Our study highlights a large number of significantly different molecular responses to estradiol depending upon the mode of administration of estradiol. Significant changes were observed in genes involved in apoptosis and proliferation including VEGF, IGF receptors, and tumor protein p53. PMID:18562193

  1. Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

    PubMed

    Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures. PMID:22710371

  2. Ovariectomy and 17β-estradiol Replacement in Rats and Mice: A Visual Demonstration

    PubMed Central

    Ström, Jakob O.; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

    2012-01-01

    Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results1-3. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol4-6. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration7, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures. PMID:22710371

  3. Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment

    PubMed Central

    Aenlle, Kristina K.; Foster, Thomas C.

    2009-01-01

    This study used microarray analysis to examine age-related changes in gene expression 6 and 12 hr following a single estradiol injection in ovariectomized mice. Estradiol-responsive gene expression at the 6 hr time point was reduced in aged (18 mo) animals compared to young (4 mo) and middle-aged (MA, 12 mo) mice. Examination of gene clustering within biological and functional pathways indicated that young and MA mice exhibited increased expression of genes for cellular components of the synapse and decreased expression of genes related to oxidative phosphorylation and mitochondrial dysfunction. At the 12 hr time point, estradiol-responsive gene expression increased in aged animals and decreased in young and MA mice compared to the 6 hr time point. Gene clustering analysis indicated that aged mice exhibited increased expression of genes for signaling pathways that are rapidly influenced by estradiol. The age differences in gene expression for rapid signaling pathways may relate to disparity in basal pathway activity and estradiol mediated activation of rapid signaling cascades. PMID:19790252

  4. Testosterone metabolism in human skin cells in vitro and its interaction with estradiol and dutasteride.

    PubMed

    Münster, U; Hammer, S; Blume-Peytavi, U; Schäfer-Korting, M

    2003-01-01

    Since the limited knowledge of cutaneous drug metabolism can impair the development of specifically acting topical dermatics and transdermal application systems, the cell-type-specific androgen metabolism in human skin and its inhibition by drugs were investigated. Cultured human foreskin and scalp skin keratinocytes and fibroblasts as well as occipital scalp dermal papilla cells (DPC) were incubated with testosterone 10(-6) and 10(-8)M alone and in the presence of 17alpha-estradiol, 17beta-estradiol or dutasteride for 24 h. Androgens extracted from culture supernatants were subjected to thin-layer chromatography and quantified by beta-counting. In keratinocytes and DPC, dihydrotestosterone (DHT) was only formed to a low extent while androstenedione was the main metabolite. In fibroblasts, DHT formation was pronounced following 10(-8)M testosterone. Dutasteride 10(-8)M completely suppressed 5alpha-dihydro metabolite formation. 17alpha-Estradiol and 17beta-estradiol at nontoxic concentrations decreased 17-ketometabolites. Human skin regulates testosterone action by cell-type-specific activation or deactivation. Effects of 17alpha-estradiol in androgenetic alopecia are not due to 5alpha-reductase inhibition. Dutasteride may be useful in acne and androgenetic alopecia. PMID:14528059

  5. Testosterone reduces cumulative burying in female Wistar rats with minimal participation of estradiol.

    PubMed

    Gutiérrez-García, Ana G; Contreras, Carlos M; Vásquez-Hernández, Diana I; Molina-Jiménez, Tania; Jacome-Jacome, Emma

    2009-10-01

    Testosterone exerts anxiolytic effects, but the participation of its aromatase metabolic product estradiol is controversial. Therefore, we used the defensive burying paradigm in female Wistar rats to explore testosterone's (1.0 mg/rat, s.c.) interactions with picrotoxin (a noncompetitive gamma-aminobutyric acid-A receptor [GABA(A)] antagonist; 1.0 mg/kg, i.p.), formestane (an aromatase inhibitor; 3.0 mg/rat, s.c.), and tamoxifen (an estrogen receptor-beta antagonist; 1.0 mg/kg, s.c.). Serum levels of testosterone, estradiol, and progesterone were determined in the same rats. Burying latency and locomotion did not significantly change. Systemic testosterone administration enhanced serum testosterone and estradiol levels and reduced defensive burying. This reduction in total burying was blocked by pretreatment with picrotoxin and tamoxifen, but not formestane. We conclude that testosterone produced anxiolytic-like effects in female rats that were mediated by actions at the GABA(A) receptor, with participation of the estradiol receptor-beta, rather than estradiol aromatization. PMID:19520107

  6. Estradiol in the Preoptic Area Regulates the Dopaminergic Response to Cocaine in the Nucleus Accumbens.

    PubMed

    Tobiansky, Daniel J; Will, Ryan G; Lominac, Kevin D; Turner, Jonathan M; Hattori, Tomoko; Krishnan, Krittika; Martz, Julia R; Nutsch, Victoria L; Dominguez, Juan M

    2016-06-01

    The sex-steroid hormone estradiol (E2) enhances the psychoactive effects of cocaine, as evidenced by clinical and preclinical studies. The medial preoptic area (mPOA), a region in the hypothalamus, is a primary neural locus for neuroendocrine integration, containing one of the richest concentrations of estrogen receptors in the CNS and also has a key role in the regulation of naturally rewarding behaviors. However, whether estradiol enhances the neurochemical response to cocaine by acting in the mPOA is still unclear. Using neurotoxic lesions and microdialysis, we examined whether the mPOA modulates cocaine-induced neurochemical activity in the nucleus accumbens. Tract tracing and immunohistochemical staining were used to determine whether projections from the mPOA to the ventral tegmental area (VTA) are sensitive to estrogen signaling. Finally, estradiol microinjections followed by microdialysis were used to determine whether estrogenic signaling in the mPOA modulates cocaine-induced changes of dopamine in the nucleus accumbens. Results showed that lesions of the mPOA or microinjections of estradiol directly into the mPOA increased cocaine-induced release of dopamine in the nucleus accumbens. Immunohistochemical analyses revealed that the mPOA modulates cocaine responsiveness via projections to both dopaminergic and GABAergic neurons in the VTA, and that these projections are sensitive to estrogenic stimulation. Taken together, these findings point to a novel estradiol-dependent pathway that modulates cocaine-induced neurochemical activity in the mesolimbic system. PMID:26647972

  7. Estradiol receptor has proteolytic activity that is responsible for its own transformation.

    PubMed Central

    Puca, G A; Abbondanza, C; Nigro, V; Armetta, I; Medici, N; Molinari, A M

    1986-01-01

    We have investigated the effect of various protease inhibitors and substrates on the hormone- and temperature-dependent binding of partially purified estradiol-receptor complex to isolated nuclei. Only serine protease substrates and inhibitors significantly depressed estradiol receptor transformation. At 20 degrees C, we observed 50% inhibition with about 3 microM aprotinin or with 1.4 mM diisopropyl fluorophosphate. Aprotinin also blocked those size and charge modifications of receptor that are characteristic of the transformation process. The estradiol receptor was able to bind to aprotinin-agarose only under transforming conditions; i.e., the interaction was hormone- and temperature-dependent and inhibited by molybdate. Diisopropyl fluorophosphate, a covalent reagent for serine esterases, competitively inhibited the binding and specifically eluted the estradiol-receptor complex that had been bound to aprotinin-agarose. These results indicate that estradiol receptor transformation is due to the effect of a serine protease and that the receptor itself is endowed with this catalytic activity, which is triggered by the steroid. PMID:2426695

  8. Estradiol receptor has proteolytic activity that is responsible for its own transformation.

    PubMed

    Puca, G A; Abbondanza, C; Nigro, V; Armetta, I; Medici, N; Molinari, A M

    1986-08-01

    We have investigated the effect of various protease inhibitors and substrates on the hormone- and temperature-dependent binding of partially purified estradiol-receptor complex to isolated nuclei. Only serine protease substrates and inhibitors significantly depressed estradiol receptor transformation. At 20 degrees C, we observed 50% inhibition with about 3 microM aprotinin or with 1.4 mM diisopropyl fluorophosphate. Aprotinin also blocked those size and charge modifications of receptor that are characteristic of the transformation process. The estradiol receptor was able to bind to aprotinin-agarose only under transforming conditions; i.e., the interaction was hormone- and temperature-dependent and inhibited by molybdate. Diisopropyl fluorophosphate, a covalent reagent for serine esterases, competitively inhibited the binding and specifically eluted the estradiol-receptor complex that had been bound to aprotinin-agarose. These results indicate that estradiol receptor transformation is due to the effect of a serine protease and that the receptor itself is endowed with this catalytic activity, which is triggered by the steroid. PMID:2426695

  9. Final report on key comparison CCQM-K55.a (estradiol): An international comparison of mass fraction purity assignment of estradiol

    NASA Astrophysics Data System (ADS)

    Westwood, Steven; Josephs, Ralf; Daireaux, Adeline; Wielgosz, Robert; Davies, Stephen; Wang, Hongjie; Rodrigues, Jainana; Wollinger, Wagner; Windust, Anthony; Kang, Ma; Fuhai, Su; Philipp, Rosemarie; Kuhlich, Paul; Wong, Siu-kay; Shimizu, Yoshitaka; Pérez, Melina; Avila, Marco; Fernandes-Whaley, Maria; Prevoo, D.; de Vos, J.; Visser, R.; Archer, M.; LeGoff, Thierry; Wood, Steve; Bearden, Dan; Bedner, Mary; Boroujerdi, Arezue; Duewer, David; Hancock, Diane; Lang, Brian; Porter, Barbara; Schantz, Michele; Sieber, John; White, Edward; Wise, Stephen A.

    2012-01-01

    Under the auspices of the Organic Analysis Working Group (OAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a key comparison, CCQM K55.a, was coordinated by the Bureau International des Poids et Mesures (BIPM) in 2009/2010. Eleven national measurement institutes and the BIPM participated. Participants were required to assign the mass fraction of estradiol present as the main component in the comparison sample (CCQM-K55.a) which consisted of a bulk estradiol hemihydrate material obtained from a commercial supplier that had been extensively but not exhaustively dried prior to sub-division into the units supplied for the comparison. Estradiol was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of organic compounds of medium structural complexity [molar mass range 300-500 Da] and low polarity (pKOW < -2) for which related structure impurities can be quantified by capillary gas phase chromatography (GC) or by high performance liquid chromatography (LC). The majority of participants used a mass balance approach to determine the estradiol content. The key comparison reference value (KCRV) for estradiol in CCQM-K55.a was assigned by combination of KCRVs assigned by consensus from participant results for each orthogonal impurity class. This allowed participants to demonstrate the efficacy (or otherwise) of their implementation of the mass balance approach and to demonstrate that their assigned value for the main component agreed with the KCRV through use of internally consistent contributing methods. The KCRV for the estradiol content of the material was 984.3 mg/g with a combined standard uncertainty of 0.42 mg/g. The individual participant results showed that a relative expanded uncertainty for the purity assignment of 0.2% is a reasonable estimate of the best achievable result by an individual laboratory for a material of this complexity available in this amount at this level of

  10. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells.

    PubMed Central

    Migliaccio, A; Di Domenico, M; Castoria, G; de Falco, A; Bontempo, P; Nola, E; Auricchio, F

    1996-01-01

    The mechanism by which estradiol acts on cell multiplication is still unclear. Under conditions of estradiol-dependent growth, estradiol treatment of human mammary cancer MCF-7 cells triggers rapid and transient activation of the mitogen-activated (MAP) kinases, erk-1 and erk-2, increases the active form of p21ras, tyrosine phosphorylation of Shc and p190 protein and induces association of p190 to p21ras-GAP. Both Shc and p190 are substrates of activated src and once phosphorylated, they interact with other proteins and upregulate p21ras. Estradiol activates the tyrosine kinase/p21ras/MAP-kinase pathway in MCF-7 cells with kinetics which are similar to those of peptide mitogens. It is only after introduction of the human wild-type 67 kDa estradiol receptor cDNA that Cos cells become estradiol-responsive in terms of erk-2 activity. This finding, together with the inhibition by the pure anti-estrogen ICI 182 780 of the stimulatory effect of estradiol on each step of the pathway in MCF-7 cells proves that the classic estradiol receptor is responsible for the transduction pathway activation. Transfection experiments of Cos cells with the estradiol receptor cDNA and in vitro experiments with c-src show that the estradiol receptor activates c-src and this activation requires occupancy of the receptor by hormone. Our experiments suggest that c-src is an initial and integral part of the signaling events mediated by the estradiol receptor. Images PMID:8635462

  11. Relationship between modulation by estradiol, progesterone and calcium upon the pharmacological reactivity of uteri of dogs.

    PubMed

    Calixto, J B; Aucélio, J G; Jurkiewicz, A

    1979-09-01

    The influence of treatment with estradiol and progesterone, was studied on the contractions induced in immature dog uteri by histamine, acetylcholine, oxytocin and barium chloride, in vitro. Two parameters were measured from dose-response curves: rho and pD2. It was observed that although pD2 values were slightly affected by hormonal treatment, the values of rho for oxytocin and acetylcholine receptors were greatly reduced by estradiol treatment and further decreased by association of estradiol plus progesterone; the effects for histamine and barium chloride were less affected. Increasing Ca2+ concentration in the nutrient solution completely reverted the variations for rho values. The results indicate tat the effect of drugs on the dog uterus depends on the balance between the modulating actions of ovarian hormones and calcium. PMID:504784

  12. What if the Women's Health Initiative had used transdermal estradiol and oral progesterone instead?

    PubMed

    Simon, James A

    2014-07-01

    The author considers hypothetical comparisons between oral conjugated equine estrogens and transdermal estradiol and between oral medroxyprogesterone acetate and oral micronized progesterone for their effects on four primary outcomes of the Women's Health Initiative (WHI): cardiovascular disease risk, cerebrovascular disease risk, venous thromboembolism risk, and breast cancer risk. Although the discussion in this article focuses on transdermal estradiol delivered through patches, gels, or lotions, it could be broadened to include all forms of nonoral estrogen administration. After a brief review of the WHI and a survey of the relevant literature in which the safety of these various hormone therapies is assessed or compared, the author uses statistical methods to ascertain the attributable risk of venous thromboembolism for transdermal estradiol versus oral hormone therapy and imputes those risks into the WHI primary outcomes. PMID:24398406

  13. Bioavailability of phthalate congeners to earthworms (Eisenia fetida) in artificially contaminated soils.

    PubMed

    Hu, Xiao-yu; Wen, Bei; Zhang, Shuzhen; Shan, Xiao-quan

    2005-09-01

    Bioavailability of phthalate congeners, dimethyl phthalate, diethyl phthalate, di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and dioctyl phthalate, to earthworms (Eisenia fetida) were studied when earthworms were exposed to two artificially contaminated agricultural and forest soils. Only DBP and DEHP were detected in earthworms. The uptake kinetics of DBP and DEHP in earthworms was fast within the initial 10 days followed by a nearly steady state for the subsequent 20 days. An equilibrium partitioning model could be used to describe the uptake kinetics of DBP and DEHP by earthworm in two types of soils (r = 0.709-0.864). The average biota-to-soil accumulation factors (BSAFs) of DBP and DEHP at 5 mg kg(-1) in soil were 0.27 +/- 0.07 and 0.17 +/- 0.03, respectively, in agricultural soil, while the BSAFs were 0.21 +/- 0.06 and 0.07 +/- 0.02, respectively, in forest soil. The concentrations of phthalates in earthworms increased with increasing concentrations of phthalates in soil. There was a significant correlation between logC(soil) and logC(worm), with r = 0.999-0.993, demonstrating a single linear partitioning of phthalates between soil and earthworms. The bioavailability of DBP and DEHP was assessed by Soxhlet, methanol, and methanol-water (1:1) extraction methods. Our results indicated that the extractable amounts of freshly added DBP and DEHP in soils by these extraction methods were significantly correlated with those in earthworms. It was observed that the extractable DBP and DEHP by the methanol and methanol-water (1:1) extraction methods decreased with their increasing residence time in soil. In contrast, the amount extracted by the Soxhlet extraction method did not show a similar decline. Therefore, Soxhlet extraction was a poor indicator of the bioavailability of DBP and DEHP to earthworms in soil, which could lead to overestimation of the risk of soil-associated DBP and DEHP. The extractable DBP and DEHP by methanol and methanol

  14. SIGNALING MECHANISMS INVOLVED IN THE ACUTE EFFECTS OF ESTRADIOL ON 5-HT CLEARANCE

    PubMed Central

    Benmansour, Saloua; Privratsky, Anthony A.; Adeniji, Opeyemi S.; Frazer, Alan

    2014-01-01

    Estradiol was found previously to have an antidepressant-like effect and to block the ability of selective serotonin reuptake inhibitors (SSRIs) to have an antidepressant-like effect. The antidepressant-like effect of estradiol was due to estrogen receptor β (ERβ) and/or GPR30 activation whereas estradiol’s blockade of the effect of an SSRI was mediated by ERα. This study focuses on investigating signaling pathways as well as interacting receptors associated with these two effects of estradiol. In vivo chronoamperometry was used to measure serotonin transporter (SERT) function. The effect of local application of estradiol or selective agonists for ERα (PPT) or ERβ (DPN) into the CA3 region of the hippocampus of ovariectomized (OVX) rats on 5-hydroxytryptamine (5-HT, serotonin) clearance as well as on the ability of fluvoxamine to slow 5-HT clearance was examined after selective blockade of signaling pathways or that of interacting receptors. Estradiol- or DPN-induced slowing of 5-HT clearance mediated by ERβ was blocked after inhibition of MAPK/ERK1/2 but not of PI3K/Akt signaling pathways. This effect also involved interactions with TrkB, and IGF-1 receptors. Estradiol’s or PPT’s inhibition of the fluvoxamine-induced slowing of 5-HT clearance mediated by ERα, was blocked after inhibition of either MAPK/ERK1/2 or PI3K/Akt signaling pathways. This effect involved interactions with the IGF-1 receptor and with the metabotropic glutamate receptor 1 but not with TrkB. This study illustrates some of the signaling pathways required for the effects of estradiol on SERT function and particularly shows that ER subtypes elicit different as well as common signaling pathways for their actions. PMID:24423185

  15. Polymorphism of 17-beta estradiol in a transdermal drug delivery system.

    PubMed

    Variankaval, N E; Jacob, K I; Dinh, S M

    2002-03-01

    The inclusions in a typical transdermal drug delivery system (TDS) containing estradiol drug were characterized using microscopic, spectroscopic and thermal analytical techniques. Optical and scanning electron microscopy were used to determine the locations and morphologies of the crystals in the matrix. Two different types of crystals randomly distributed laterally inside the patch were observed. Solid aggregates were found surrounding needle-like inclusions. Optical imaging through the thickness of the patch and SEM sections of the patch revealed that these inclusions were found to occupy a single layer inside the adhesive matrix. No inclusions were observed either in the backing-matrix interface or the matrix-liner interface. The inclusions exhibited a wide range of sizes. The thickness of the crystals as determined by SEM ranged from 10-14 microm. Out of the four crystal forms of estradiol, two of which are solvates (EA and EM) and the other two are anhydrous (EC and ED). Forms EC and ED did not exhibit significant differences in the spectra. Thermal analysis revealed that this was due to the highly unstable nature of ED and its tendency to either convert spontaneously to EC or occur in mixtures with it. The Raman spectrum of the aggregates in the patch showed peaks that seemed characteristic of at least two different forms of estradiol. Only one of these forms is a completely hydrogen bonded system and therefore, was concluded to be estradiol hemihydrate. A splitting of the C17-O peak at 1284 cm(-1) and 1294 cm(-1) was attributed to the existence of at least two types of crystal forms - one that exhibits hydrogen bonding and one that does not. DSC on different concentrations of estradiol in acrylic adhesive showed a clear endotherm for 14 wt % estradiol and apparent endotherms for lower concentrations. The absence of crystallization exotherms is due to the extremely slow kinetics of crystals growth in the polymeric patch. PMID:15348624

  16. Relationships of serum estradiol levels, menopausal duration, and mood during hormonal replacement therapy.

    PubMed

    Klaiber, E L; Broverman, D M; Vogel, W; Peterson, L G; Snyder, M B

    1997-10-01

    A study was undertaken in 38 menopausal women on-cyclic HRT (estropipate) and estropipate + nor-ethindrone). Serum estradiol levels during treatment were related to mood changes and platelet MAO activity. The relationship between serum estradiol levels and mood changes was found to be a function of the duration of menopause. Women with a short duration of menopause (12.9 months +/- 6.1) were compared to women with a long duration of menopause (76.6 months +/- 52.3). Women with a short duration of menopause had significantly lower mean serum estradiol levels during HRT compared to women with a long duration of menopause (216.9 +/- 62.3 vs. 291.13 +/- 118.12, respectively, p < .02). It had previously been reported that estrogen treatment in menopausal women had a positive effect on mood, whereas the combination of estrogen plus a progestin had a negative effect on mood. We found that the women with a long duration of menopause and higher treatment serum estradiol levels had significantly more dysphoria when receiving a combination of estrogen plus progestin than did the women with a short duration of menopause and lower serum estradiol levels. However, both short and long duration menopausal groups showed improvement in mood when estrogen was administered alone. Platelet MAO levels, a marker of adrenergic and serotonergic function thought to relate to mood, were negatively correlated with serum estradiol levels during HRT. We suggest that these paradoxical findings may be secondary to a prolonged estrogen deficiency state in women with a long duration of menopause. PMID:9373888

  17. Effect of estradiol and bisphenol A on human hepatoblastoma cell viability and telomerase activity.

    PubMed

    Xu, B L; Zhao, Q Z; Gao, X Y; Hou, G J

    2015-11-01

    Sex hormones from environmental and physiological sources might play a major role in the pathogenesis of hepatoblastoma in children. This study investigated the effects of estradiol and bisphenol A on the proliferation and telomerase activity of human hepatoblastoma HepG2 cells. The cells were divided into 6 treatment groups: control, bisphenol A, estradiol, anti-estrogen ICI 182,780 (hereinafter ICI), bisphenol A+ICI, and estradiol+ICI. Cell proliferation was measured based on average absorbance using the Cell Counting-8 assay. The cell cycle distribution and apoptotic index were determined by flow cytometry. Telomerase activity was detected by polymerase chain reaction and a telomeric repeat amplification protocol assay. A higher cell density was observed in bisphenol A (P<0.01) and estradiol (P<0.05) groups compared with the control group. Cell numbers in S and G2/M phases after treatment for 48 h were higher (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h (P<0.05) were higher in these groups than in the control group. The cell density was also higher in bisphenol A+ICI (P<0.01) and estradiol+ICI (P<0.05) groups compared with the ICI group. Furthermore, cell numbers were increased in S and G2/M phases (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h were higher (P<0.05) in these groups than in the ICI group. Therefore, bisphenol A and estradiol promote HepG2 cell proliferation in vitro by inhibition of apoptosis and stimulation of telomerase activity via an estrogen receptor-dependent pathway. PMID:26397976

  18. 17β-estradiol protects the lung against acute injury: possible mediation by vasoactive intestinal polypeptide.

    PubMed

    Hamidi, Sayyed A; Dickman, Kathleen G; Berisha, Hasan; Said, Sami I

    2011-12-01

    Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60-90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen. PMID:22009726

  19. 17β-Estradiol Protects the Lung against Acute Injury: Possible Mediation by Vasoactive Intestinal Polypeptide

    PubMed Central

    Hamidi, Sayyed A.; Dickman, Kathleen G.; Berisha, Hasan

    2011-01-01

    Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ERα and ERβ and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60–90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen. PMID:22009726

  20. Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

    PubMed

    Fteita, Dareen; Könönen, Eija; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2014-06-01

    Alterations in the quantity and quality of biofilms at gingival margin are considered to play a role in the initiation and development of pregnancy-related gingivitis. Prevotella intermedia sensu lato is able to consume estradiol, the major sex hormone secreted during pregnancy, in the absence of vitamin K. The aim of the study was to examine the effect of estradiol on the planktonic growth, coaggregation, polysaccharide production, and biofilm formation of the P. intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, and Prevotella pallens. In all experiments, the type strain (ATCC) and a clinical strain (AHN) of P. intermedia, P. nigrescens, and P. pallens were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol. Planktonic growth was assessed by means of the colony forming unit method, while coaggregation and biofilm formation were assessed by spectrophotometric methods. In the determination of protein and polysaccharide levels, the Bradford and phenol-sulfuric acid methods were used, respectively. P. pallens AHN 9283 and P. nigrescens ATCC 33563 increased their numbers at planktonic stage with increasing estradiol concentrations. In 48-h biofilm tests, elevated protein levels were found for both strains of P. intermedia, and the strains P. nigrescens ATCC 33563 and P. pallens AHN 9283 in the presence of estradiol. The P. intermedia strains also increased the levels of polysaccharide formation in the biofilm. Coaggregation of the P. intermedia group organisms with Fusobacterium nucleatum was enhanced only in P. intermedia AHN 8290. In conclusion, our in vitro experiments indicate that estradiol regulates planktonic growth, coaggregation, polysaccharide production, and biofilm formation characteristics of P. intermedia, P. nigrescens, and P. pallens differently. These results may, at least partly, explain the differences seen in their contribution to the pathogenesis of pregnancy-related gingivitis. PMID

  1. A Pilot Study on BMI, Serum Testosterone and Estradiol Levels in Allergic Male Patients

    PubMed Central

    Lokaj-Berisha, Violeta; Gacaferri-Lumezi, Besa; Berisha, Naser; Gashi-Hoxha, Sanije

    2015-01-01

    BACKGROUND: The dramatic increase in the prevalence of high body mass index (BMI) increases the prevalence of allergic diseases, both in adults and children and obesity is associated with hypogonadism in adult males. AIM: We aimed to evaluate the effect of high body mass index on plasma concentrations of testosterone and estradiol in young pubertal and adult males with allergic diseases. MATERIAL AND METHODS: Morning fasting blood samples were obtained form 51 allergic patients and 6 healthy volunteer males between the ages 11-57 years (Mean 26.9, DS ± 11.9 years). Total testosterone, estradiol, FSH and LH concentrations were measured by radioimmunoassay. All participants were subjected to skin prick tests with test kit G aeroallergens, and BMI was calculated according to the body weight divided by the square of height (kg/m2). RESULTS: Low levels of testosterone and high levels of estradiol were associated with high BMI only in patients with asthma/rhinitis, but not in asthma patients. Allergic dermatitis/urticaria group along with healthy controls were overweight but within normal ranges for total testosterone and estradiol concentrations. Patients with allergic rhinitis were within normal ranges for BMI, total testosterone and estradiol concentrations. CONCLUSION: High BMI is not always associated with low levels of testosterone and high levels of estradiol in our patients with allergic diseases, but low levels of testosterone are present in patients with asthma and asthma/rhinitis although not among patients with rhinitis only. Our results should be confirmed in a larger group of participants.

  2. Estradiol modulates medial prefrontal cortex and amygdala activity during fear extinction in women and female rats

    PubMed Central

    Zeidan, Mohamed A.; Igoe, Sarah A.; Linnman, Clas; Vitalo, Antonia; Levine, John B.; Klibanski, Anne; Goldstein, Jill M.; Milad, Mohammed R.

    2011-01-01

    Background Men and women differ in their ability to extinguish fear. Fear extinction requires the activation of brain regions including the ventromedial prefrontal cortex (vmPFC) and amygdala. Could estradiol modulate the activity of these brain regions during fear extinction? Methods All rat experiments were conducted in naturally cycling females. Rats underwent fear conditioning on day 1. On day 2, they underwent extinction training during the metestrus phase of the cycle (low estrogen and progesterone). Extinction recall was assessed on day 3. Systemic injections of estrogen-receptor beta and alpha agonists, and estradiol were administered at different time points to assess their influence on extinction consolidation and c-fos expression in the vmPFC and amygdala. In parallel, healthy naturally cycling women underwent an analogous fear conditioning extinction training while in a 3T fMRI scanner. Measurement of their estradiol levels and skin conductance responses were obtained throughout the experiment. Results In female rats, administration of the estrogen-receptor beta (but not alpha) agonist facilitated extinction recall. Immediate (but not delayed) post-extinction training administration of estradiol facilitated extinction memory consolidation and increased c-fos expression in the vmPFC while reducing it in the amygdala. In parallel, natural variance in estradiol in pre-menopausal cycling women modulated vmPFC and amygdala reactivity and facilitated extinction recall. Conclusion We provide translational evidence that demonstrates the influence of endogenous and exogenous estradiol on the fear extinction network. Our data suggest that women’s endogenous hormonal status should be considered in future neurobiological research related to anxiety and mood disorders. PMID:21762880

  3. Changes in ovarian function associated with circulating concentrations of estradiol before a GnRH-induced ovulation in beef cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    These studies were conducted to evaluate causes for differences in circulating concentrations of estradiol prior to a GnRH-induced ovulation and to determine if exogenous GnRH administration could alter LH secretion and subsequent follicular estradiol production. Beef cows (Experiment 1; n = 32, Ex...

  4. Mammary gland morphology and gene expression signature of prepubertal male and female rats following exposure to exogenous estradiol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to characterize the actions of xenoestrogens, it is essential to possess a solid portrait of the physiological effects of exogenous estradiol. We assessed effects of three doses of exogenous estradiol (E2) (0.1, 1.0 and 10 micrograms/kg/day) on the mammary gland morphology and gene expressi...

  5. Reproductive performance in sows treated with estradiol benzoate/human chorionic gonadotrophin combination at weaning.

    PubMed Central

    Friendship, R M; Bosu, W T; King, G J

    1982-01-01

    The effects of estradiol benzoate plus human chorionic gonadotrophin administered on the day of weaning on the reproductive performance in sows was studied. The treatment advanced the onset of estrus but the duration of estrus was slightly prolonged. Breeding on the post-weaning estrus was associated with poor pregnancy rate and smaller litters. The treatment did not cause permanent damage to the reproductive tract as the reproductive performance of the treated sows after subsequent breedings were unaffected. The possible causes of the poor fertility in the estradiol benzoate plus human chorionic gonadotrophin treated sows are discussed. PMID:6890868

  6. [Zoely, a combined oral contraceptive, monophasic pill containing estradiol and nomegestrol acetate].

    PubMed

    Pintiaux, A; Gaspard, U; Nisolle, M

    2012-03-01

    A new combined oral contraceptive called Zoely has just been marketed in Belgium. It contains nomegestrol acetate, a progestin known for its high contraceptive reliability based on its antigonadotropic power and long half-life. This progestin is associated with estradiol and Zoely is devoid of ethinyl estradiol, which is the usual component of the majority of combined oral contraceptives and is primarily responsible for thrombotic side effects of the pill. The compositon and type of regimen of this new oral contraceptive contribute to its efficacy and excellent clinical tolerance. PMID:22611833

  7. Effects of Estradiol and Venlafaxine on Insomnia Symptoms and Sleep Quality in Women with Hot Flashes

    PubMed Central

    Ensrud, Kristine E.; Guthrie, Katherine A.; Hohensee, Chancellor; Caan, Bette; Carpenter, Janet S.; Freeman, Ellen W.; LaCroix, Andrea Z.; Landis, Carol A.; Manson, JoAnn; Newton, Katherine M.; Otte, Julie; Reed, Susan D.; Shifren, Jan L.; Sternfeld, Barbara; Woods, Nancy F.; Joffe, Hadine

    2015-01-01

    Study Objectives: Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. Design: 3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks. Setting: Academic research centers. Participants: 339 community-dwelling perimenopausal and postmenopausal women with ≥ 2 bothersome hot flashes per day. Measurements and Results: Insomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was −4.1 points (−5.3 to −3.0) with estradiol, −5.0 points (−6.1 to −3.9) with venlafaxine, and −3.0 points (−3.8 to −2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was −2.2 points (−2.8 to −1.6) with estradiol, −2.3 points (−2.9 to −1.6) with venlafaxine, and −1.2 points (−1.7 to −0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine). Conclusions: Among perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality. Clinical Trial Registration: NCT01418209 at www.clinicaltrials.gov Citation: Ensrud KE, Guthrie KA, Hohensee C, Caan B, Carpenter JS, Freeman EW, LaCroix AZ, Landis CA, Manson J, Newton KM, Otte J, Reed SD, Shifren JL, Sternfeld B, Woods NF, Joffe H. Effects of estradiol and venlafaxine on insomnia symptoms

  8. Congener-specific determination of polychlorinated biphenyls and organochlorine pesticides in human milk from Norwegian mothers living in Oslo

    SciTech Connect

    Johansen, H.R.; Becher, G.; Polder, A.; Skaare, J.U.

    1994-12-31

    Human milk samples from 28 mothers at Oslo City Hospital, Norway, were collected in 1991 and analyzed for individual polychlorinated biphenyl (PCB) congeners, IUPAC numbers 28, 74, 99, 101, 105, 114, 118, 128, 138, 141, 153, 156, 157, 170, 180, 194, and 206, plus selected non-ortho-substituted compounds, IUPAC numbers 77, 126, and 169. Sum DDTs (sum of concentrations of DDT and related compounds), hexachlorobenzene (HCB), oxychlordane, transnonachlor, and sum hexachlorocyclohexanes (HCHs) (sum of concentrations of {alpha}-HCH, {beta}-HCH, and {gamma}-HCH) were also determined. The mean levels of sum DDTs, HCB, oxychlordane, transnonachlor, and sum HCHs were 338, 41, 9, 19, and 36 ng/g, respectively, in human milk fat. p,p{prime}-DDE and {beta}-HCH accounted for 81 and 93% of sum DDTs and sum HCHs, respectively. The mean level of sum PCBs (sum of mean concentrations of 20 individual congeners) was 372 ng/g milk fat. A very good correlation was found between sum PCBs and PCB-153 (r = .97). Sum PCBs determined on a capillary column was found to account for 62-79% of total PCBs calculated by using the packed column method used in previous human milk surveys in Norway. Comparison with previous results revealed that the mean sum PCB, HCB and sum DDT levels were decreased by 70, 65, and 75%, respectively during the past 9 yr. The contribution of individual PCDD/PCDF (earlier Norwegian study) and non- and mono-ortho-substituted PCB congeners to the total calculated toxic equivalent values was assessed, and the PCBs were found to constitute a major part of the TCDD equivalents in human milk, with PCB-126 as the main contributor. 40 refs., 6 figs., 2 tabs.

  9. OXIDATION OF POLYCHLORINATED BIPHENYLS BY LIVER TISSUE SLICES FROM PHENOBARBITAL-PRETREATED MICE IS CONGENER-SPECIFIC AND ATROPSELECTIVE

    PubMed Central

    Wu, Xianai; Duffel, Michael; Lehmler, Hans-Joachim

    2013-01-01

    Mouse models are powerful tools to study the developmental neurotoxicity of polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice have not been reported. Here we investigate the atropselective oxidation of chiral PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) and PCB 149 (2,2',3,4',5',6-hexachlorobiphenyl) to OH-PCBs in liver tissue slices prepared from female mice. The metabolite profile of PCB 136 typically followed the rank order 5-OH-PCB > 4-OH-PCB > 4,5-OH-PCB, and metabolite levels increased with PCB concentration and incubation time. A similar OH-PCB profile was observed with the other PCB congeners, with 5-OH-PCB:4-OH-PCB ratios ranging from 2 to 12. More 5-OH-PCB 136 was formed in liver tissue slices obtained from animals pretreated with phenobarbital (P450 2B inducer) or, to a lesser extent, dexamethasone (P450 2B and 3A enzyme inducer) compared to tissue slices prepared from vehicle-pretreated animals. The apparent rate of 5-OH-PCBs formation followed the approximate rank order PCB 149 > PCB 91 > PCB 132 ~ PCB 136 > PCB 95. Atropselective gas chromatography revealed a congener-specific atropisomeric enrichment of major OH-PCB metabolites. Comparison of our results with published OH-PCB patterns and chiral signatures (i.e., the direction and extent of the atropisomeric enrichment) from rat liver microsomal revealed drastic differences between both species, especially following induction of P450 2B enzymes. These species differences in the metabolism of chiral PCBs should be considered in developmental neurotoxicity studies of PCBs. PMID:24107130

  10. Linkage of the Fv-2 gene to a newly reinserted ecotropic retrovirus in Fv-2 congenic mice.

    PubMed Central

    Mowat, M; Bernstein, A

    1983-01-01

    Restriction enzyme and Southern gel analyses were used to determine the number and location of endogenous ecotropic retroviruses in the germ line of several mouse strains congenic at the Fv-2 gene locus. A new endogenous ecotropic provirus was observed in the germ line of B6.S (Fv-2ss) mice, in addition to the resident provirus found in its congenic partner C57BL/6 (Fv-2rr). This new provirus was similar in structure to the C57BL provirus. The SIM strain of mice, the donors of the Fv-2s allele in B6.S mice, does not contain ecotropic proviruses, suggesting that the new provirus in the B6.S mouse strain arose by germ-line reintegration during the construction of this strain. Mendelian segregation analysis indicated that this new provirus was linked to the Fv-2 gene locus on chromosome 9. In three other Fv-2s congenic mouse strains--B10.C (47N), B6.C (H-7b), and C57BL/6J Trfa, Bgsd--no additional ecotropic endogenous viruses were detected, suggesting that the reinsertion event that occurred during the construction of B6.S is not essential for the acquisition of the Fv-2s phenotype in the C57BL genetic background. Although numerous reports of germ-line reinsertions of ecotropic virus in high-virus mouse strains have been received, the present results provide definitive evidence that similar germ-line amplifications of endogenous ecotropic virus can occur in a low-virus mouse strain. Images PMID:6620461

  11. Coronaridine congeners inhibit human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites.

    PubMed

    Arias, Hugo R; Targowska-Duda, Katarzyna M; Feuerbach, Dominik; Jozwiak, Krzysztof

    2015-08-01

    To characterize the interaction of coronaridine congeners with human (h) α3β4 nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The Ca(2+) influx results established that coronaridine congeners noncompetitively inhibit hα3β4 AChRs with the following potency (IC50's in μM) sequence: (-)-ibogamine (0.62±0.23)∼(+)-catharanthine (0.68±0.10)>(-)-ibogaine (0.95±0.10)>(±)-18-methoxycoronaridine [(±)-18-MC] (1.47±0.21)>(-)-voacangine (2.28±0.33)>(±)-18-methylaminocoronaridine (2.62±0.57 μM)∼(±)-18-hydroxycoronaridine (2.81±0.54)>(-)-noribogaine (6.82±0.78). A good linear correlation (r(2)=0.771) between the calculated IC50 values and their polar surface area was found, suggesting that this is an important structural feature for its activity. The radioligand competition results indicate that (±)-18-MC and (-)-ibogaine partially inhibit [(3)H]imipramine binding by an allosteric mechanism. Molecular docking, molecular dynamics, and in silico mutation results suggest that protonated (-)-18-MC binds to luminal [i.e., β4-Phe255 (phenylalanine/valine ring; position 13'), and α3-Leu250 and β4-Leu251 (leucine ring; position 9')], non-luminal, and intersubunit sites. The pharmacophore model suggests that nitrogens from the ibogamine core as well as methylamino, hydroxyl, and methoxyl moieties at position 18 form hydrogen bonds. Collectively our data indicate that coronaridine congeners inhibit hα3β4 AChRs by blocking the ion channel's lumen and probably by additional negative allosteric mechanisms by interacting with a series of non-luminal sites. PMID:26022277

  12. Chlorinated dibenzo-p-dioxin and dibenzofuran congener and homologue distributions in tree bark from Sauget, Illinois, U.S.

    PubMed

    Hermanson, Mark H; Johnson, Glenn W

    2015-01-20

    Polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) are ubiquitous urban/industrial contaminants found in tree bark, which acts as a long-term passive atmospheric sampler. Twenty seven bark samples (tree age 8–92 years) were collected from residential and industrial areas near Sauget, IL to identify the trends of 2,3,7,8-Cl PCDD & PCDF congener distributions, toxic equivalents (TEQ), and PCDD & PCDF homologue distributions. The Sauget area is heavily industrialized, with a long history of chlorine production, and is the largest single contributor to air pollution exposure risk in St. Louis. Analysis of seven 2,3,7,8 Cl-substituted PCDD and 10 PCDF congeners showed ∑PCDD7 ranging from 2214 to 71821 pg g(–1) lipid and ∑PCDF10 from 355 to 13707 pg g(–1) lipid, the highest in trees <20 years old in both cases. OctaCCD and octaCDF respectively dominated ∑PCDD7 (89% average) and ∑PCDF10 (57% average). The 2,3,7,8-Cl congener profiles showed slight differences among samples showing that all were affected by similar sources but at different magnitudes. ∑TEQ ranged from 35 to 624 pg g(–1) lipid, dominated by 1,2,3,7,8-PeCDD (average = 41.3% of total TEQ). Tetra-Cl through hepta-Cl homologues were dominated by non-2,3,7,8-Cl compounds for both CDD and CDF. Homologue profiles for 26 samples had a “sink” profile dominated by octaCDD, whereas one sample showed effects of a local source. PMID:25496230

  13. 17beta-estradiol-induced activation of ERK1/2 through endogenous androgen receptor-estradiol receptor alpha-Src complex in human prostate cells.

    PubMed

    Chieffi, Paolo; Kisslinger, Annamaria; Sinisi, Antonio A; Abbondanza, Ciro; Tramontano, Donatella

    2003-09-01

    We examined the effect of estrogens on mitogen-activated protein kinase (MAPK) in EPN cells, a line of epithelial cells derived from human normal prostate. 17beta-estradiol (E2) caused a rapid and transient activation of MAPK (ERK1/2) within 5 min. This effect was counteracted by the anti-estrogen ICI 182-780 and by MEK inhibitor PD098059. The activation of ERK1/2 through 17beta-estradiol triggered simultaneous association of endogenous androgen receptor, estrogen receptor alpha and Src. In addition, E2 stimulated the proliferation of EPN cells, suggesting that the formation of the ternary complex and the consequent activation of ERKs are implicated in the mechanism regulating proliferation of epithelial prostate cells. PMID:12888920

  14. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model

    PubMed Central

    Šedová, Lucie; Pravenec, Michal; Křenová, Drahomíra; Kazdová, Ludmila; Zídek, Václav; Krupková, Michaela; Liška, František; Křen, Vladimír; Šeda, Ondřej

    2016-01-01

    Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16) and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx) into the genomic background of the spontaneously hypertensive rat (SHR) strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18–28 mmHg difference) and diastolic (10–15 mmHg difference) blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001). The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes) are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1). Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic syndrome

  15. Linear free energy relationship based estimates for the congener specific relative reductive defluorination rates of perfluorinated alkyl compounds.

    PubMed

    Rayne, Sierra; Forest, Kaya; Friesen, Ken J

    2009-07-15

    Linear free energy relationships (LFERs) were developed to estimate the congener specific relative rates of reductive defluorination for a suite of perfluorinated compound (PFC) classes. The LFERs were based on the semiempirically calculated lowest unoccupied molecular orbital energy (ELUMO) using gas and aqueous phase computations with the PM6 and RM1 methods. PFC classes in the modeling effort included the C1 through C8 perfluoroalkyl sulfonates (PFSAs), carboxylates (PFCAs), sulfonyl fluorides (PFSFs), sulfonamides and their derivatives (SAs), and the perfluorotelomer alcohols (PFTAls), olefins (PFTOls), and acids (PFTAcs). Gas and aqueous phase calculations using the PM6 method predict that branched PFSA, PFCA, and PFSF congeners will have more rapid reductive defluorination kinetics than their linear counterparts. The RM1 method predicts that only PFSFs will display intrahomologue dependent branching effects. For the PFSAs and PFSFs, both the PM6 and RM1 methods predict no significant difference in mean rates of reductive defluorination between the homologue groups. For the PFCAs, the PM6 method suggests no significant difference in inter-homologue mean rates of reductive defluorination, whereas the RM1 method predicts a significant increase with a lengthening perfluoroalkyl chain. All approaches used suggest that the intrahomologue variability in reduction rates increases with increasing chain length for PFSAs, PFCAs, and PFSFs, implying that the larger homologue groups in these classes will see a more rapid linearization of the congener profiles under reducing conditions than their lower homologue counterparts. Chain length has a negligible effect on the estimated rates of SA reductive defluorination, but a significant role for the fluorotelomer derivatives. Ratios of rates between the C8:C1 straight chain telomeric congeners are expected to range up to 200-fold depending on the computational combination. The kinetics for reductively defluorinating PFC

  16. Striatal transcriptome analysis of a congenic mouse line (chromosome 11: 50-60Mb) exhibiting reduced methamphetamine sensitivity.

    PubMed

    Yazdani, Neema; Shen, Ying; Johnson, W Evan; Bryant, Camron D

    2016-06-01

    Addiction to psychostimulants such as Methamphetamine (MA) is a significant public health issue in the United States and currently, there are no FDA approved pharmacological interventions. Previously, using short term-selected mouse lines for high and low MA sensitivity that were derived from an F2 cross between C57BL/6J (B6) and DBA/2J (D2) strains, we identified a quantitative trait locus (QTL) on chromosome (chr) 11 that influenced sensitivity to MA-induced locomotor activity (D2 < B6). Using interval-specific murine congenic lines containing various D2 allelic segments on a B6 background, we fine mapped the QTL to a 206 kb critical interval on chromosome 11. To investigate the neurobiological mechanism by which this QTL decreases MA sensitivity, we conducted transcriptome analysis in a 10 Mb congenic mouse (chromosome 11: 50-60 Mb) on whole-striatum brain tissue punches compared to wild-type B6 littermate controls [1]. The data from this study can be found in the NCBI Gene Expression Omnibus (GSE66366). PMID:27222804

  17. Organochlorine pesticides and polychlorinated biphenyl congeners in lanner Falco biarmicus feldeggli Schlegel chicks and lanner prey in Sicily, Italy.

    PubMed

    Movalli, Paola; Lo Valvo, Mario; Pereira, M Glória; Osborn, Daniel

    2008-09-01

    This paper reports on research conducted to elucidate the risk posed to the Sicilian population of the endangered lanner falcon Falco biarmicus feldeggii Schlegel by organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs), as part of a wider study on contaminant risk to the lanner. Seventeen lanner nest sites were studied in northern and central Sicily. Sampling (in 2005) and analysis were carried out for selected OC pesticides and PCB congeners in lanner chick blood (15 chicks from 6 nest sites) and in two of the main lanner prey species, magpie Pica pica (36 individuals from 6 lanner nest sites) and rock dove Columba livia (10 individuals from 2 lanner nest sites). No OC and PCB residues were found in lanner chick blood above the detection limits, except for one solitary congener PCB153 (21.8 ng g(-1) wet weight), suggesting that these contaminants do not pose a significant risk to lanner chicks in the study area. Magpie and dove appeared mostly free of contamination with OC pesticides, though contamination levels were significantly higher in magpie than in dove. The presence of exceptional DDE and HEOD values in approximately 8% of the P. pica sample, and one P. pica sample showing recent DDT contamination, may indicate a local OC pesticide hazard to some lanner. Future research to further elucidate the contaminant risk to lanner in Sicily is suggested. PMID:18833798

  18. Investigations on the sorption of a toxaphene model congener, the B7-1450, on marine sediments.

    PubMed

    Soubaneh, Youssouf Djibril; Lebeuf, Michel; Gouteux, Bruno; Xie, Huixiang; Nikiforov, Vladimir; Gagné, Jean-Pierre

    2008-04-01

    Sorption is a natural process that takes place in sediments or soils and changes the mobility and availability of hydrophobic organic compounds, such as toxaphene pesticide in the environment. The sorption of the 2-exo,3-endo,5-exo,8,9,10,10-heptachlorobornane (B7-1450), used as a model compound of the toxaphene heptachlorobornane congeners found in sediments, was investigated for the first time through a series of batch sorption experiments. The losses of B7-1450 due to adsorption onto glass walls and to evaporation occurring during analytical treatment steps were corrected. The study showed that these specific losses ranged from 2% to 3.5% for the glass walls adsorption and can be as high as 15% for the evaporation treatment. The sorption coefficients, K(d) and K(oc), of B7-1450 could be overestimated by >30%, particularly for low-concentration samples, if the losses were not corrected. Loss correction equations were established, validated and applied to determine sorption coefficients for the B7-1450 congener. The K(oc) values for B7-1450 determined over a gradient of concentrations ranged from 3.5x10(4) to 6.5x10(4)mlg(-1), revealing a strong affinity of B7-1450 for marine sediments. PMID:18295821

  19. Reductive dechlorination of octachlorodibenzo-p-dioxin by nanosized zero-valent zinc: modeling of rate kinetics and congener profile.

    PubMed

    Bokare, Varima; Jung, Ju-Lim; Chang, Yoon-Young; Chang, Yoon-Seok

    2013-04-15

    Polychlorinated dibenzo-p-dioxins (PCDDs), a group of recalcitrant toxic compounds, are ubiquitous in nature. Amongst them, octachlorodibenzo-p-dioxin (OCDD) is not only prevalent in soil and sediment due to its high lipophilicity and hydrophobicity, but also detected in ground water and surface water. The present study examined the degradation of OCDD in aqueous solutions using four different zero-valent metal nanoparticles; zero-valent aluminum (nZVAL), zero-valent zinc (nZVZ), zero-valent iron (nZVI) and zero-valent nickel (nZVN). Only nZVZ was found to efficiently degrade OCDD into lower chlorinated congeners [OCDD → 1,2,3,4,6,7,9-HxCDD (63%)→ 1,2,3,6,8,9-HpCDD (21%) → 1,2,4,7,8-PeCDD (46%) → 1,2,4,7-TeCDD (19%)] under ambient conditions. Simulations were also performed to predict the OCDD dechlorination pathway using a linear free energy relationship (LFER) model. Additionally, toxic equivalent quantity (TEQ) and homologue patterns were calculated by LFER modeling. The experimentally observed congener profiles were in excellent agreement with the model-predicted results, especially considering the complexity of the OCDD dechlorination pathway (256 theoretically possible reactions). This study proposes nZVZ as a suitable candidate for OCDD dechlorination and constitutes the first report on OCDD degradation using zero-valent metal nanoparticles under ambient conditions. PMID:23500419

  20. Ratio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties

    PubMed Central

    Lancz, Kinga; Palkovičová, L’ubica; Patayová, Henrieta; Drobná, Beata; Wimmerová, Soňa; Šovčíková, Eva; Kováč, Ján; Farkašová, Dana; Hertz-Picciotto, Irva; Jusko, Todd A.; Trnovec, Tomáš

    2014-01-01

    The aim was to characterize placental transfer of some congeners of polychlorinated biphenyls (PCBs) and to relate human in utero exposure to these pollutants to their physicochemical properties. We included into the study 1134 births during the period 2002–2003 from two highly PCB contaminated districts in eastern Slovakia. Concentrations of 15 PCB congeners (IUPAC No. 28, 52, 101, 123+149, 118, 114, 153, 105, 138+163, 167, 156+171, 157, 180, 170, and 189) in umbilical cord (C) and maternal serum (M) were determined. The C/M ratios were significantly related, either positively or inversely depending on parameter, to the logarithm of partition coefficient octanol-water (KOW), to fusion enthalpy at the melting point, molecular weight, water solubility, total surface area of the molecule, solvent accessible surface area, melting point, molar volume, and molecular electronegativity distance vector. We found an inverse association between log KOW and lipid adjusted log C/M (const= 1.078, b1 = −0.179, p < 0.001, R2 = 0.039). Parameters evaluated were interrelated except fusion enthalpy at the melting point and electron affinity vs. solubility. We discuss the possible role of cholesterol as a transplacental transporter of PCBs. PMID:25277764

  1. Multiparameter analyses of spontaneous nonthymic lymphomas occurring in NFS/N mice congenic for ecotropic murine leukemia viruses.

    PubMed Central

    Fredrickson, T. N.; Morse, H. C.; Yetter, R. A.; Rowe, W. P.; Hartley, J. W.; Pattengale, P. K.

    1985-01-01

    Mouse strains congenic for ecotropic retrovirus genes have a much higher frequency of spontaneous lymphomas than the background NFS/N strain. In this study, most of these lymphomas have been identified as B-cell in origin by morphologic features, identification of immunoglobulin class, and cell-surface antigens. The classification suggested by Pattengale and Taylor proved to be applicable to the lymphomas studied. Most were of large follicular center cells and are considered typical of the type formerly designated as "reticulum cell sarcoma, type B." Many lymphomas contained a large proportion of nonneoplastic cells which partially obscured their neoplastic component. The role of ecotropic murine leukemia viruses as etiologic agents for B-cell lymphomas remains equivocal. However, because the only difference between the NFS/N and congenic mice is the expression of viruses in the latter, it appears that these viruses are somehow involved in induction of B-cell lymphomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 9 Figure 10 PMID:2998195

  2. Ratio of cord to maternal serum PCB concentrations in relation to their congener-specific physicochemical properties.

    PubMed

    Lancz, Kinga; Murínová, Lubica; Patayová, Henrieta; Drobná, Beata; Wimmerová, Soňa; Sovčíková, Eva; Kováč, Ján; Farkašová, Dana; Hertz-Picciotto, Irva; Jusko, Todd A; Trnovec, Tomáš

    2015-01-01

    The aim was to characterize placental transfer of some congeners of polychlorinated biphenyls (PCBs) and to relate human in utero exposure to these pollutants to their physicochemical properties. We included into the study 1134 births during the period 2002-2003 from two highly PCB contaminated districts in eastern Slovakia. Concentrations of 15 PCB congeners (IUPAC No. 28, 52, 101, 123(+149), 118, 114, 153, 105, 138(+163), 167, 156(+171), 157, 180, 170, and 189) in umbilical cord (C) and maternal serum (M) were determined. The C/M ratios were significantly related, either positively or inversely depending on parameter, to the logarithm of partition coefficient octanol-water (KOW), to fusion enthalpy at the melting point, molecular weight, water solubility, total surface area of the molecule, solvent accessible surface area, melting point, molar volume, and molecular electronegativity distance vector. We found an inverse association between logKOW and lipid adjusted logC/M (const=1.078, b1=-0.179, p<0.001, R(2)=0.039). Parameters evaluated were interrelated except fusion enthalpy at the melting point and electron affinity vs. solubility. We discuss the possible role of cholesterol as a transplacental transporter of PCBs. PMID:25277764

  3. Dioxins, furans and AHH-active PCB congeners in eggs of two gull species from the western Mediterranean.

    PubMed

    Pastor, D; Ruiz, X; Barceló, D; Albaigés, J

    1995-09-01

    Polychlorinated biphenyls, dibenzodioxins and dibenzofurans were analysed in eggs of a protected gull species, the Audouin's Gull (Larus audouinii) and compared to those of the Yellow-legged Gull (Larus cachinnans), both breeding in the Western Mediterranean (Ebro Delta and Medes Islands, respectively). Differences in concentrations as well as in congener profiles reflected differences in both habitat and diet of the two species. Levels of AHH-active PCB congeners were lower in Yellow-legged Gull (0.4-1.6 micrograms/g d.w) than in Audouin's Gull eggs (1.2-33.9 micrograms/g d.w.). These concentrations, expressed in international toxic equivalence factors (i-TEQ/g d.w.), were on average 24 times higher in the Audouin's gull. I-TEQ levels due to dioxins were also higher in this species by a factor of ca. 7. I-TEQ levels related to PCBs resulted 90-230 times higher than those of dioxins and furans. Thus, AHH-inducing PCBs might represent even higher toxicological hazards than dioxins and furans to some populations of seabirds. The necessity of assessing the impact of these compounds in rare and protected species is pointed out. PMID:8528648

  4. Pregnancy rates after ewes were treated with estradiol-17beta and oxytocin.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cervical dilation may improve transcervical sheep embryo-transfer procedures, if the cervical dilation method does not reduce pregnancy rates. This experiment was conducted to determine whether estradiol-17beta-oxytocin treatment, which dilates the cervix in luteal-phase ewes, affects pregnancy rat...

  5. Effects of liquid swine manure on dissipation of 17ß-estradiol in soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2), an estrogenic hormone, degrades within hours and bind strongly to soils and sediments; however, estrogens are frequently detected in the environment at concentrations that impact water quality. Colloidal (COC) and dissolved (DOC) organic carbon may enhance the persistence and mob...

  6. An On-Farm Survey of Spatial and Temporal Stratifications of 17ß-Estradiol Concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2), a natural estrogenic hormone, may cause endocrine disruption in sensitive organisms. It has been reported to dissipate rapidly in soil laboratory studies, but is frequently detected in the environment leading to question about possible sources and processes that explain the mobil...

  7. Sorption and degradation of 17ß-estradiol-17sulfate in agricultural soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2) can induce endocrine disruptions at low concentrations. Laboratory studies have indicated low potential for persistence and mobility of E2 in the environment, and yet field studies measure estrogens at concentrations of concern. Humans and animals eliminate E2 primarily as a conju...

  8. Changes in salivary estradiol predict changes in women's preferences for vocal masculinity.

    PubMed

    Pisanski, Katarzyna; Hahn, Amanda C; Fisher, Claire I; DeBruine, Lisa M; Feinberg, David R; Jones, Benedict C

    2014-08-01

    Although many studies have reported that women's preferences for masculine physical characteristics in men change systematically during the menstrual cycle, the hormonal mechanisms underpinning these changes are currently poorly understood. Previous studies investigating the relationships between measured hormone levels and women's masculinity preferences tested only judgments of men's facial attractiveness. Results of these studies suggested that preferences for masculine characteristics in men's faces were related to either women's estradiol or testosterone levels. To investigate the hormonal correlates of within-woman variation in masculinity preferences further, here we measured 62 women's salivary estradiol, progesterone, and testosterone levels and their preferences for masculine characteristics in men's voices in five weekly test sessions. Multilevel modeling of these data showed that changes in salivary estradiol were the best predictor of changes in women's preferences for vocal masculinity. These results complement other recent research implicating estradiol in women's mate preferences, attention to courtship signals, sexual motivation, and sexual strategies, and are the first to link women's voice preferences directly to measured hormone levels. PMID:25051294

  9. EFFECTS OF ETHYNYL ESTRADIOL EXPOSURE ON REPRODUCTIVE PARAMETERS IN AN ESTUARINE FISH

    EPA Science Inventory

    This study investigated the impact of ethynyl estradiol (EE2) on reproductive success of cunner, Tautogolabrus adspersus. EE2 is the estrogen used in human contraceptives and is released into the aquatic environment in sewage treatment effluent. Reproductively active male and fem...

  10. Objective Habitual Physical Activity and Estradiol Levels in Obese Latina Adolescents

    PubMed Central

    Gyllenhammer, Lauren E.; Vanni, Amanda K.; Byrd-Williams, Courtney E.; Kalan, Marc; Bernstein, Leslie; Davis, Jaimie N.

    2013-01-01

    Background Lifetime physical activity (PA) is associated with decreased breast cancer (BC) risk; reports suggest that PA during adolescence contributes strongly to this relationship. PA lowers production of sex hormones, specifically estradiol, or decreases insulin resistance (IR), thereby lowering risk. Overweight Latina adolescents are insulin resistant and exhibit low levels of PA, potentially increasing their future BC risk. Methods 37 obese Latina adolescents (15.7 ±1.1 yrs) provided measures of PA using accelerometry; plasma follicular phase estradiol, sex-hormone binding globulin, total and free testosterone, dehydroepiandrosterone-sulfate (DHEAS); IR using HOMA-IR; body composition via DEXA. Partial correlations and stepwise linear regressions assessed cross-sectional relationships between sex hormones, IR and PA. Body composition, and age were included a priori as covariates. Results Estradiol was negatively associated with accelerometer counts per minute (CPM) (r= −0.4; p=0.02), percent time spent in moderate PA (%MPA) (r= −0.5; p=0.006), and percent time in moderate or vigorous PA (%MVPA) (r= −0.5; p=0.007). DHEAS was positively associated with CPM (r=0.4, p=0.009), %MPA (r=0.3, p=0.04), and %MVPA (r=0.3, p=0.04). Other sex hormones and IR were not associated with PA measures. Conclusion This study is the first to show that higher habitual PA was inversely associated with estradiol in obese adolescents. PMID:23038707

  11. Dynamics of estradiol and testosterone and seminal fluid indexes in smokers and nonsmokers.

    PubMed

    Klaiber, E L; Broverman, D M

    1988-10-01

    The serum levels of estradiol (E2) and testosterone (T), the metabolic clearance rates of estradiol (MCRE2) and testosterone (MCRT), and the production rates of estradiol and testosterone (PRE2) and (PRT) were examined in 22 male smokers and 21 male nonsmokers. Seminal fluid indexes (sperm count, % motility, grade of motility, and % of sperm with abnormal morphology) were also assessed. The mean E2 level and the mean PRE2 were significantly greater in smokers than in nonsmokers (P less than 0.001 and P less than 0.01, respectively); however, the means of MCRE2, MCRT, PRT, and T did not differ significantly in smokers compared to nonsmokers. No significant product-moment correlations were found between the various hormonal measures and the seminal fluid indexes in the overall sample. However, the smokers with sperm counts below the median sperm count of the sample had significantly higher mean levels of E2 and PRE2 than did the smokers with sperm counts above that median. Mechanisms that might mediate the greater PRE2 of smokers and a negative relationship between estradiol and sperm count are discussed. PMID:3169284

  12. [Medication of the month. A new combined oral contraceptive containing estradiol valerate and dienogest (Qlaira)].

    PubMed

    Gaspard, U; Pintiaux, A; Kridelka, F

    2010-12-01

    In combined oral contraception (OC), a drastic reduction of both ethinylestradiol and androgenic progestins mostly derived from 19 NOR testosterone, allowed to moderately reduce the adverse impact of classical combined pills on metabolism and circulation (both arterial and venous). However, the marked hepatic action of ethinylestradiol, even in small dosages, lessens the expected risk reduction. For the first time, an OC has been developed, which contains estradiol valerate (with reduced hepatic action because of lack of a 17alpha ethinyl group) with dienogest, a 19 NOR testosterone-derived nonandrogenic progestin, which powerfully inhibits endometrial proliferation. Thanks to a dynamic modulation of estrogen and progestin doses (26 active days + 2 placebo days), an adequate contraceptive effectiveness, a good cycle control and drug tolerance are achieved, similar to those obtained with a classical low-dose OC. Recent data indicate that this new combination reduces the usually observed metabolic impact. An adequate cycle control (with 20% amenorrhea) is achieved for the first time with estradiol valerate + progestin,, in opposition with prior catastrophic results with other formulations containing 17beta-estradiol. A second combination containing estradiol + nomegestrol acetate (monophasic, 24 active days + 4 placebo days) is under study and seems also to yield promising results. Of course, in-depth study of metabolic and vascular effects of these new combinations is mandatory - and ongoing. PMID:21287768

  13. 17ß-Estradiol Is Necessary for Extinction of Cocaine Seeking in Female Rats

    ERIC Educational Resources Information Center

    Twining, Robert C.; Tuscher, Jennifer J.; Doncheck, Elizabeth M.; Frick, Karyn M.; Mueller, Devin

    2013-01-01

    Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17ß-estradiol (E[subscript 2]) affects expression and extinction of cocaine seeking in female rats. Using a…

  14. EFFECTS OF ETHINYL ESTRADIOL ON GONDAL DEVELOPMENT AND PATHOLOGY IN CUNNER, TAUTOGOLABRUS ADSPERSUS

    EPA Science Inventory

    The intent of this study was to determine histopathologically the effect of ethinyl estradiol (EE2) on gonadal development, liver and kidney condition in reproductively active cunner, Tautogolabrus adspersus. Reproductively active cunner were treated by implanting EE2 in a slow r...

  15. Effects of bromocriptine on (/sup 3/H)estradiol binding in cytosol of anterior pituitary

    SciTech Connect

    De Nicola, A.F.; Weisenberg, L.S.; Arakelian, M.C.; Libertun, C.

    1981-07-01

    The hypothalamus may control hormone receptors in the anterior pituitary either by a direct trophic effect or indirectly by regulation of serum pituitary hormone levels. Rats whose medial basal hypothalamus had been destroyed in order to suppress neural control of the gland showed a reduction in (/sup 3/H)estradiol binding in the anterior pituitary and high serum PRL levels; both changes were reversed by treatment of the lesioned rats with daily injections of bromocriptine, a dopamine agonist. In nonlesioned animals, the same treatment did not modify significantly those parameters. In another hyperprolactinemic model (rats with anterior pituitaries transplanted under the kidney capsule), (/sup 3/H)estradiol binding by the in situ pituitaries of the host rats was similar to that in the nongrafted controls. These results suggest that changes due to median eminence lesion are reversible and that bromocriptine is able to act as a substitutive therapy which restores binding of estradiol in glands whose receptors have been decreased by the effect of the lesion. High PRL levels due to pituitary transplant do not account for the observed changes in the pituitary estradiol binding.

  16. Effects of field-manure applications on stratified 17B-estradiol concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The estrogenic hormone, 17'-estradiol (E2), is a potent endocrine disrupting compound found in animal manures. The objective of this study was to assess the occurrence of manure-borne E2 stratified through soil in fields that receive swine (Sus scrofa domestica) manure slurry as fertilizer. Soil cor...

  17. Transport of 17beta-estradiol and testosterone in a field lysimeter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2) and testosterone (T) are present in sources such as waste treatment effluent and manures, and can potentially disrupt aquatic organisms at low concentrations. Laboratory studies consistently indicate limited mobility and rapid attenuation of E2 and T in soils; however, these hormo...

  18. Sorption and degradation of 17ß-estradiol-17-sulfate in sterilized soil-water systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify abiotic processes that govern the fate of a sulfate conjugated estrogen, 17ß-estradiol-17-sulfate (E2-17S), soil batch experiments were conducted to investigate the dissipation, sorption, and degradation of radiolabeled E2-17S under sterilized conditions. The aqueous dissipation half-liv...

  19. Transport of 17ß-Estradiol and Testosterone in a Field Lysimeter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    17ß-estradiol (E2) and testosterone (T) are naturally present in manures and have the potential to disrupt aquatic organisms at low concentrations. Laboratory studies have indicated that E2 and T would have limited mobility and would attenuate rapidly in soils; however, these hormones are consistent...

  20. Persistence and Fate of 17beta-estradiol and testosterone in agricultural soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Steroidal hormones are constantly released into the environment by man-made and natural sources. The goal of this study was to examine the persistence and fate of 17beta-estradiol and testosterone, the two primary natural hormones. Incubation experiments were conducted under aerobic and anaerobic co...

  1. Effects of liquid swine manure on sorption of 17ß-estradiol to soil

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogens are potent endocrine disrupting chemicals and can be found in the environment. Animal manure can contain estrogenic hormones, specifically 17'-estradiol (E2). A common manure management practice is to contain liquid manure in a manure storage ponds or lagoons, which is then applied on or i...

  2. Isolation and Bioaugmentation of an Estradiol-Degrading Bacterium and Its Integration into a Mature Biofilm▿

    PubMed Central

    Iasur-Kruh, Lilach; Hadar, Yitzhak; Minz, Dror

    2011-01-01

    Bioaugmentation can alter the potential activity as well as the composition of the naturally occurring microbial biota during bioremediation of a contaminated site. The focus of the current study is the pollutant 17β-estradiol (E2), which can cause endocrine effects and is potentially harmful to aquatic biota and to public health. The community composition and function of biofilms, originating from a wetland system, as affected by augmentation of an estradiol-degrading bacterium (EDB-LI1) under different conditions, were investigated. EDB-LI1 inoculation into biofilm from two wetland ponds representing early and advanced water treatment stages, respectively, yielded three significant observations, as follows: (i) EDB-LI1, enriched from a biofilm of a constructed wetland wastewater treatment system, was detected (by quantitative PCR [qPCR] analysis) in this environment in the augmented biofilm only; (ii) the augmented biofilm acquired the ability to remove estradiol; and (iii) the bacterial community composition (analyzed by PCR-denaturing gradient gel electrophoresis [DGGE]) of the augmented biofilm differed from that of the control biofilm. Furthermore, EDB-LI1 bioaugmentation showed a higher level of removal of estradiol with biofilms that originated from the advanced-treatment-stage wetland pond than those from the early-treatment-stage pond. Hence, the bioaugmentation efficiency of EDB-LI1 depends on both the quality of the feed water and the microbial community composition in the pond. PMID:21478310

  3. Estradiol and song affect female zebra finch behavior independent of dopamine in the striatum

    PubMed Central

    Svec, Lace A.; Lookingland, Keith J.; Wade, Juli

    2009-01-01

    Female songbirds display preferences for certain song characteristics, but the neural and hormonal mechanisms mediating these preferences are not fully clear. The present study sought to further explore the role of estradiol, as well as assess potential roles of dopaminergic systems, on behavioral responses to song. Adult female zebra finches were treated with estradiol and exposed to tutored or untutored song or silence. Behavior was quantified and neurochemistry of the nucleus accumbens and striatum was examined with high performance liquid chromatography. As a control, the responses of these two systems to treatment with raclopride, a specific D2 receptor antagonist, were also evaluated. This manipulation did not affect dopamine (DA), but did increase DOPAC and the DOPAC/DA ratio. Estradiol reduced the display of two behaviors, distance calls and visual scanning, but had no effect on dopaminergic responses. Auditory stimulus exposure affected other vocalizations, but song presentation did not modulate the levels of DA or its metabolite, DOPAC in the nucleus accumbens or striatum. Collectively, the results suggest that both estradiol and auditory stimuli can modify the behavioral responses of adult zebra finches, but they may not change DA concentration or turnover in striatal dopamine neurons. PMID:19615392

  4. The anorectic effect of fenfluramine is increased by estradiol treatment in ovariectomized rats.

    PubMed

    Rivera, Heidi M; Eckel, Lisa A

    2005-10-15

    The emergence of sex- and estrous cycle-related differences in the anorectic effect of fenfluramine, a serotonin (5-HT) agonist, prompted us to investigate whether these behavioral changes are mediated by estradiol. Rats were ovariectomized and housed in cages that permitted the analysis of feeding and locomotor activity via an automated, computerized system. Using a within-subjects design, we investigated the effects of 1 mg/kg d-fenfluramine and saline vehicle on food intake and wheel running in ovariectomized rats following estradiol benzoate (EB) and oil vehicle treatment. A cyclic regimen of EB treatment was used to mimic the changes in endogenous estradiol secretion over the rat's 4-day estrous cycle. The decrease in food intake following fenfluramine treatment was greater in EB-treated rats, relative to oil-treated rats. Fenfluramine also produced a small but significant decrease in wheel running in ovariectomized rats that was not modulated by EB treatment. Thus, EB's ability to increase the anorectic effect of this dose of fenfluramine appears behaviorally specific. Although the inhibition of food intake by fenfluramine is largely attributed to its ability to increase synaptic levels of 5-HT, additional research involving selective 5-HT receptor agonists and antagonists is necessary to determine whether estradiol interacts with the endogenous 5-HT system to control food intake in the female rat. PMID:16139852

  5. Sensitive determination of 17β-estradiol in river water using a graphene based electrochemical sensor.

    PubMed

    Moraes, Fernando C; Rossi, Bruno; Donatoni, Maria C; de Oliveira, Kleber T; Pereira, Ernesto C

    2015-06-30

    In this study, a novel material for the electrochemical determination of 17β-estradiol using an electrode based on reduced graphene oxide and a metal complex porphyrin has been applied to environmental monitoring. The electrochemical profile of the proposed electrode was analyzed by differential pulse voltammetry, which showed a shift of the oxidation peak potential of 17β-estradiol to 150mV in a less positive direction compared to the bare reduced graphene oxide electrode. DPV experiments were performed in PBS at pH 7.0 to determine 17β-estradiol without any previous step of extraction, cleanup, or derivatization, in the range of 0.1-1.0μmolL(-1) with a detection limit archived at 5.3nmolL(-1) (1.4μgL(-1)). The proposed sensor was successfully applied in the determination of 17β-estradiol in a river water sample without any purification step and was successfully analyzed under the standard addition method. All the obtained results were in agreement with those from the HPLC procedure. PMID:26041518

  6. Sorption and Degradation of 17ß-Estradiol-17Sulfate in Agricultural Soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the environment, the natural estrogenic hormone, 17ß-estradiol (E2) can potentially induce endocrine disruptions at low concentrations, i.e. 1-10 ng/L. Laboratory based studies have found low potentials for the persistence and mobility of E2 in the environment due to its high degradation and/or s...

  7. Occurrence and Pathways of Manure-borne 17beta-Estradiol in Vadose Zone Water

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reproductive hormones, such as 17beta-estradiol (E2), can cause physiological and reproductive disorders in numerous species at low part per trillion concentrations. The persistence and transport pathways of manure-borne E2 in agricultural soils were determined by comparing the occurrence of E2 in t...

  8. Triclosan is a potent inhibitor of estradiol and estrone sulfonation in sheep placenta

    PubMed Central

    James, Margaret O.; Li, Wenjun; Summerlot, David P.; Rowland-Faux, Laura; Wood, Charles E.

    2016-01-01

    The personal care product Triclosan, 5-chloro-2(2,4-dichlorophenoxy)-phenol, is widely used in consumer products as an antibacterial agent and is increasingly found in the environment as a contaminant of sewage sludge and wastewater. This compound has been identified in plasma and urine of people in the United States, Sweden and Australia. Triclosan is known to inhibit sulfonation of phenolic xenobiotics and is structurally related to inhibitors of estrogen sulfotransferase, such as polychlorobiphenylols. In pregnancy, the placenta is an important source of estrogen, which is needed for normal fetal development and successful parturition, and estrogen sulfotransferase is thought to play an important role in regulation of estrogen availability. In this study, we examined the effect of Triclosan on sheep placental cytosolic sulfotransferase activity with 17-beta-estradiol and estrone as substrates. For comparison, we studied the effects of 4-hydroxy-3,3′,4′,5-tetrachlorobiphenyl and 2′-hydroxytriclocarban on estradiol sulfonation. The apparent Km for placental cytosolic sulfotransferase activity with estradiol as substrate was 0.27±0.06 nM (mean±S.D., n=3 individuals) and with estrone as substrate was 1.86±0.22 nM. Partial substrate inhibition was observed with estradiol at concentrations higher than 10–20 nM, as is typical of estrogen sulfotransferases (SULT1E1) in other species. Studies of the effect of Triclosan on estrogen sulfotransferase activity were conducted with several concentrations (0.1–6 nM) of estradiol and with 2 nM estrone. Triclosan was a very potent inhibitor of both estradiol and estrone sulfonation. For estradiol the inhibition was shown to be mixed competitive/uncompetitive, with Kic of 0.09±0.01 nM and Kiu of 5.2±2.9 nM. The IC50 for inhibition of estrone sulfonation was 0.60±0.06 nM. At an environmentally relevant concentration of 1 μM, Triclosan was not a substrate for glucuronidation in sheep placental microsomes. Triclosan

  9. Sexual Function in Women on Estradiol or Venlafaxine for Hot Flushes: A Randomized Controlled Trial

    PubMed Central

    Reed, Susan D.; Mitchell, Caroline M.; Joffe, Hadine; Cohen, Lee; Shifren, Jan L.; Newton, Katherine M.; Freeman, Ellen W.; Larson, Joseph C.; Manson, JoAnn E.; LaCroix, Andrea Z.; Guthrie, Katherine A.

    2014-01-01

    Objective To evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes. Methods In an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between oral estradiol 0.5 mg/day or venlafaxine 75 mg/day (both compared with placebo). Measures included composite and 6 domain scores from the Female Sexual Function Index (FSFI) and sexually related personal distress. Results Participants were aged 54.6 (standard deviation [SD] 3.8) years, 59% Caucasian, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline FSFI score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean FSFI change from baseline to week-8 was 1.4 (95% Confidence Interval [CI] -0.4, 3.2) for estradiol, 1.1 (95% CI -0.5, 2.7) for venlafaxine and -0.3 (95% CI -1.6, 1.0) for placebo. Composite FSFI and sexually-related distress change from baseline did not differ between estradiol and placebo (p= 0.38, p=0.30) or venlafaxine and placebo (p=0.79, p=0.48). Among sexually active women, FSFI domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0, 0.6) for estradiol; -0.6 (95% CI -1.2, 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2, 1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction. Conclusions Overall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8-weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although subtle increase in desire (estradiol), and decreases in orgasm and pain (venlafaxine) may exist. PMID:25004335

  10. Naturally-occurring estradiol-17{beta}-fatty acid esters, but not estradiol-17{beta}, preferentially induce mammary tumorigenesis in female rats: Implications for an important role in human breast cancer

    SciTech Connect

    Mills, Laura H.; Yu Jina; Xu Xiaomeng; Lee, Anthony J.; Zhu Baoting

    2008-06-15

    Because mammary glands are surrounded by adipose tissues, we hypothesize that the ultra-lipophilic endogenous estrogen-17{beta}-fatty acid esters may have preferential hormonal and carcinogenic effects in mammary tissues compared to other target organs (such as the uterus and pituitary). This hypothesis is tested in the present study. We found that all 46 rats implanted with an estradiol-17{beta} pellet developed large pituitary tumors (average weight = 251 {+-}103 mg) and had to be terminated early, but only 48% of them developed mammary tumors. In addition, approximately one-fourth of them developed a huge uterus. In the 26 animals implanted with a mixture containing estradiol-17{beta}-stearate and estradiol-17{beta}-palmitate (two representative estradiol-17{beta}-fatty acid esters) or in the 29 animals implanted with estradiol-17{beta}-stearate alone (in the same molar dose as estradiol-17{beta}), 73% and 79%, respectively, of them developed mammary tumors, whereas only 3 or 2 animals, respectively, had to be terminated early due to the presence of a large pituitary tumor. Both tumorous and normal mammary tissues contained much higher levels of estrogen esterase than other tissues, which catalyzes the releases of bioactive estrogens from their fatty acid esters. In conclusion, while estradiol-17{beta} is much stronger in inducing pituitary tumor (100% incidence) than mammary tumor, estradiol-17{beta}-fatty acid esters have a higher efficacy than estradiol-17{beta} in inducing mammary tumor and yet it only has little ability to induce uterine out-growth and pituitary tumorigenesis. This study establishes the endogenous estrogen-17{beta}-fatty acid esters as preferential inducers of mammary tumorigenesis.

  11. Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation

    SciTech Connect

    Zhu, Liangliang; Xiao, Ling; Xia, Yangliu; Zhou, Kun; Wang, Huili; Huang, Minyi; Ge, Guangbo; Wu, Yan; Wu, Ganlin; Yang, Ling

    2015-03-01

    This in vitro study investigates the effects of diethylstilbestrol (DES), a widely used toxic synthetic estrogen, on estradiol-3- and 17-O- (E2-3/17-O) glucuronidation, via culturing human liver microsomes (HLMs) or recombinant UDP-glucuronosyltransferases (UGTs) with DES and E2. DES can potently inhibit E2-3-O-glucuronidation in HLM, a probe reaction for UGT1A1. Kinetic assays indicate that the inhibition follows a competitive inhibition mechanism, with the Ki value of 2.1 ± 0.3 μM, which is less than the possible in vivo level. In contrast to the inhibition on E2-3-O-glucuronidation, the acceleration is observed on E2-17-O-glucuronidation in HLM, in which cholestatic E2-17-O-glucuronide is generated. In the presence of DES (0–6.25 μM), K{sub m} values for E2-17-O-glucuronidation are located in the range of 7.2–7.4 μM, while V{sub max} values range from 0.38 to 1.54 nmol/min/mg. The mechanism behind the activation in HLM is further demonstrated by the fact that DES can efficiently elevate the activity of UGT1A4 in catalyzing E2-17-O-glucuronidation. The presence of DES (2 μM) can elevate V{sub max} from 0.016 to 0.81 nmol/min/mg, while lifting K{sub m} in a much lesser extent from 4.4 to 11 μM. Activation of E2-17-O-glucuronidation is well described by a two binding site model, with K{sub A}, α, and β values of 0.077 ± 0.18 μM, 3.3 ± 1.1 and 104 ± 56, respectively. However, diverse effects of DES towards E2-3/17-O-glucuronidation are not observed in liver microsomes from several common experimental animals. In summary, this study issues new potential toxic mechanisms for DES: potently inhibiting the activity of UGT1A1 and powerfully accelerating the formation of cholestatic E2-17-O-glucuronide by UGT1A4. - Highlights: • E2-3-O-glucuronidation in HLM is inhibited when co-incubated with DES. • E2-17-O-glucuronidation in HLM is stimulated when co-incubated with DES. • Acceleration of E2-17-O-glucuronidationin in HLM by DES is via activating the

  12. DREAM/calsenilin/KChIP3 modulates strategy selection and estradiol-dependent learning and memory.

    PubMed

    Tunur, Tumay; Stelly, Claire E; Schrader, Laura Ann

    2013-12-01

    Downstream regulatory element antagonist modulator (DREAM)/calsenilin(C)/K⁺ channel interacting protein 3 (KChIP3) is a multifunctional Ca²⁺-binding protein highly expressed in the hippocampus that inhibits hippocampus-sensitive memory and synaptic plasticity in male mice. Initial studies in our lab suggested opposing effects of DR/C/K3 expression in female mice. Fluctuating hormones that occur during the estrous cycle may affect these results. In this study, we hypothesized that DR/C/K3 interacts with 17β-estradiol, the primary estrogen produced by the ovaries, to play a role in hippocampus function. We investigated the role of estradiol and DR/C/K3 in learning strategy in ovariectomized (OVX) female mice. OVX WT and DR/C/K3 knockout (KO) mice were given three injections of vehicle (sesame oil) or 17β-estradiol benzoate (0.25 mg in 100 mL sesame oil) 48, 24, and 2 h before training and testing. DR/C/K3 and estradiol had a time-dependent effect on strategy use in the female mice. Male KO mice exhibited enhanced place strategy relative to WT 24 h after pre-exposure. Fear memory formation was significantly reduced in intact female KO mice relative to intact WT mice, and OVX reduced fear memory formation in the WT, but had no effect in the KO mice. Long-term potentiation in hippocampus slices from female mice was enhanced by circulating ovarian hormones in both WT and DR/C/K3 KO mice. Paired-pulse depression was not affected by ovarian hormones but was reduced in DR/C/K3 KO mice. These results provide the first evidence that DR/C/K3 plays a timing-dependent role in estradiol regulation of learning, memory, and plasticity. PMID:24248121

  13. Influence of dynorphin on estradiol- and cervical stimulation-induced prolactin surges in ovariectomized rats.

    PubMed

    Stathopoulos, Andrea M; Helena, Cleyde V; Cristancho-Gordo, Ruth; Gonzalez-Iglesias, Arturo E; Bertram, Richard

    2016-08-01

    Prolactin is an anterior pituitary hormone necessary for fertility, pregnancy maintenance, lactation, and aspects of maternal behavior. In rodents, there is a surge of prolactin on the afternoon of proestrus, and a semi-circadian pattern of prolactin surges during early pregnancy, with a diurnal and nocturnal surge every day. Both of these patterns can be replicated in ovariectomized rats. A prior study demonstrated that central antagonism of κ-opioid receptors, the target of dynorphin, largely abolished the nocturnal prolactin surge in pregnant rats. We build on this to determine whether dynorphin, perhaps from the arcuate population that co-express kisspeptin, neurokinin B, and dynorphin (KNDy neurons), also contributes to the estradiol- or cervical stimulation-induced surges in ovariectomized rats. Ovariectomized rats were treated with either estradiol or cervical stimulation to induce prolactin surge(s). Blood samples were taken around the expected surge time to determine the effect of either acute κ-opioid receptor antagonism or previous chemical ablation of the KNDy population on prolactin levels. Dynorphin antagonism does significantly disrupt the nocturnal prolactin surge, but it does not contribute to the estradiol-induced surge. Chemical ablation of KNDy neurons had opposite effects; ablation of 40 % of the KNDy neurons had no impact on the nocturnal prolactin surge, while a somewhat larger ablation significantly reduced the size of the estradiol-induced surge. We conclude that dynorphin is likely a controlling factor for the nocturnal surge induced by cervical stimulation, and that other KNDy neuron products must play a role in the estradiol-induced surge. PMID:27038317

  14. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    PubMed Central

    Root-Bernstein, Robert; Podufaly, Abigail; Dillon, Patrick F.

    2014-01-01

    Rationale: Insulin (INS) resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome, and obesity. The mechanism by which INS and estrogen interact is unknown. We hypothesize that estrogen binds directly to INS and the insulin receptor (IR) producing INS resistance. Objectives: To determine the binding constants of steroid hormones to INS, the IR, and INS-like peptides derived from the IR; and to investigate the effect of estrogens on the binding of INS to its receptor. Methods: Ultraviolet spectroscopy, capillary electrophoresis, and NMR demonstrated estrogen binding to INS and its receptor. Horse-radish peroxidase-linked INS was used in an ELISA-like procedure to measure the effect of estradiol on binding of INS to its receptor. Measurements: Binding constants for estrogens to INS and the IR were determined by concentration-dependent spectral shifts. The effect of estradiol on INS binding to its receptor was determined by shifts in the INS binding curve. Main Results: Estradiol bound to INS with a Kd of 12 × 10−9 M and to the IR with a Kd of 24 × 10−9 M, while other hormones had significantly less affinity. Twenty-two nanomolars of estradiol shifted the binding curve of INS to its receptor 0.8 log units to the right. Conclusion: Estradiol concentrations in hyperestrogenemic syndromes may interfere with INS binding to its receptor producing significant INS resistance. PMID:25101056

  15. Localization of neuropeptide-Y immunoreactivity in estradiol-concentrating cells in the hypothalamus

    SciTech Connect

    Sar, M.; Sahu, A.; Crowley, W.R.; Kalra, S.P. )

    1990-12-01

    Considerable evidence shows that gonadal steroids exert a facilitatory influence on levels and release of neuropeptide-Y (NPY) from the hypothalamus. However, it is not known whether gonadal steroids act directly on NPY-producing cells in the arcuate nucleus (ARC) of the hypothalamus to produce these facilitatory effects on NPY or whether they act on other cells that have a modulatory influence via synapses on ARC NPY cells. We applied the combined method of steroid autoradiography and immunocytochemistry to assess the localization of (3H)estradiol in relation to NPY-producing cells in the hypothalamus. Rats (n = 6) were bilaterally ovariectomized and injected intracerebroventricularly with colchicine. Twenty-four hours later each rat received an iv injection of 17 beta-(2,4,6,7,16,17(-3)H)estradiol (SA, 166 Ci/mmol) at a dose of 5.0 micrograms/kg BW. One hour after the injection of (3H)estradiol, the rats were perfused with 4% paraformaldehyde; brains were removed, frozen in isopentane precooled in liquid nitrogen (-190 C), sectioned, and processed for autoradiography. The autoradiograms were then incubated with specific antibodies for NPY immunostaining by the avidin-biotin-peroxidase method. The results revealed NPY-immunopositive cells in the ARC, striatum, hippocampus, amygdala, and cerebral cortex and a few cells in the median eminence. NPY-immunoreactive fibers were also detected in the internal layer of the median eminence. The largest number of neurons showing NPY immunoreactivity in the cytoplasm was detected in the ARC, and only in this nucleus did we observed colocalization of (3H)estradiol and NPY immunoreactivity in neurons. A population of NPY-immunopositive cells in the ARC (10-20%) exhibited nuclear (3H)estradiol; the majority of these cells were located in the lateral and ventral portions of the ARC.

  16. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    SciTech Connect

    Cooke, J.B.; Hinton, D.E.

    1995-12-31

    In some laboratory and field studies, female fish have higher prevalences of liver tumors than do males. The authors hypothesize gender and site-specific differences in prevalence are due to variable exposures of previously initiated fish to tumor modulating compounds. Estradiol, a growth promoter, increases incidences of hepatic tumors in carcinogen-treated rainbow trout and medaka (Oryzias latipes). Estradiol also increases incidences of hepatic foci of cellular alteration (FCA) in medaka. FCA are found in subadults of tumor-bearing feral populations. Lack of knowledge about the relationship of various phenotypes of FCA to eventual tumors, however, has prevented use of FCA as a biomarker. The authors examined fate and growth of liver FCA using a 2-step, initiation-promotion protocol. Three week old medaka were exposed to 200 ppm diethylnitrosamine (DEN) for 24 hr. and then fed 0.1 ppm 17-{beta}-estradiol (E2) continuously through sampling at weeks 4--26. Percent volume of FCA and morphometric characteristics of normal and focal hepatocytes, including numerical density and average hepatocyte volume were quantified using computer-assisted stereology. E2 increased percentage of liver occupied by DEN-initiated amphophilic, basophilic and eosinophilic FCA in both sexes. Focal parameters of young, DEN-initiated and estradiol-treated medaka were not reached until much later in fish given only DEN. Non-focal hepatocytes in estradiol-treated medaka were smaller and more numerous than in DEN-only counterparts. Morphometric analysis is quantitatively tracking the fate of specific phenotypes of FCA to determine their role in progression to cancer.

  17. 17Beta-Estradiol Inhibits Calcium-Activated Potassium Channel Expressions in Rat Whole Bladder

    PubMed Central

    2016-01-01

    Purpose: To investigate the effect of estrogen on the expression of calcium-activated potassium (KCa) channels in an overactive bladder rat model. To this end, mRNA and protein levels of KCa channel subtypes in the bladder of ovariectomized rats were measured by reverse transcription polymerase chain reaction and western blotting, respectively. Methods: Ten-week-old female Sprague-Dawley rats were divided randomly into 3 groups: sham-operated control group (n=11), ovariectomy group (n=11), and the group treated with estrogen after ovariectomy (n=12). Rats in the last group were subcutaneously injected with 17β-estradiol (50 μg/kg) every other day for 2 weeks, whereas rats in the other 2 groups received vehicle (soybean oil) alone. Two weeks after treatment, the whole bladder was excised for mRNA and protein measurements. Results: Protein levels of the large-conductance KCa (BK) channels in the ovariectomy group were 1.5 folds higher than those in the sham-operated control group. However, the protein levels of the other KCa channel subtypes did not change significantly upon bilateral ovariectomy. Treatment with 17β-estradiol after ovariectomy restored BK channel protein levels to the control value. In contrast, BK channel mRNA levels were not significantly affected by either ovariectomy alone or 17β-estradiol treatment. The small-conductance KCa type 3 channel (SK3) mRNA and protein levels decreased to 75% of control levels upon 17β-estradiol treatment. Conclusions: These results suggest that 17β-estradiol may influence urinary bladder function by modulating BK and SK3 channel expression. PMID:27032553

  18. Analysis of 19 PCB congeners in catfish tissue using a modified QuEChERS method with GC-MS/MS.

    PubMed

    Chamkasem, Narong; Lee, Sookwang; Harmon, Tiffany

    2016-02-01

    A simple approach to determine 19 PCB congeners in catfish tissue was presented. A modified QuEChERS method employing high solvent to sample ratio 10:1 was used to improve the extraction recovery of 19 PCB congeners. After salting out by shaking with anhydrous magnesium sulfate and sodium chloride, 1 mL of acetonitrile extract was pipetted into a 2-mL centrifuge tube containing anhydrous magnesium sulfate, primary secondary amine sorbent, and C-18 sorbent. The tube was then shaken and centrifuged to absorb fat and fatty acid residue present in the acetonitrile extract. The acetonitrile extract was analyzed by GC-MS/MS. The excellent sensitivity of GC-MS/MS allows for the direct injection of the samples to detect the low level of the PCB congeners. The method therefore is high throughput, uses fewer consumable lab supplies, and provides excellent sensitivity with an LOQ below 1 ng/g. PMID:26304427

  19. Speciation and quantitation of Aroclors based on PCB congener data: Application to California mussels and white croaker. [Mytilus californianus; Genyonemus lineatus

    SciTech Connect

    Draper, W.M. ); Koszdin, S. )

    1991-08-01

    A procedure for speciation and quantitation of Aroclors in capillary gas-liquid chromatography electron capture detector (GC-ECD) chromatograms is described. Four pentachlorobiphenyls (IUPAC no. PCB-87, -110, -118, and -105) and three heptachlorobiphenyls (PCB-183, -180, and -170) are used as markers of Aroclor 1254 and Aroclor 1260, respectively. The Aroclor content of samples is estimated by comparing the cogener composition with USEPA Aroclor reference materials. In this study, the selected congener approach to Aroclor determination is applied to both California marine mussels (Mytilus californianus and M. Edulis) and white croaker (Genyonemus lineatus) muscle. Both Aroclor 1254 and Aroclor 1260 were present in these species, and the congener patterns matched the Aroclor reference materials closely. In cases where reporting Aroclors is not appropriate, e.g., highly weathered samples, the method also provides PCB congener data.

  20. Preparation of 17β-estradiol-imprinted material by surface-initiated atom transfer radical polymerization and its application.

    PubMed

    Gong, Yanru; Niu, Yuling; Gong, Xiaohan; Ma, Meihua; Ren, Xiaowei; Zhu, Weihua; Luo, Ruiming; Gong, Bolin

    2015-04-01

    A novel 17β-estradiol molecularly imprinted polymer was grafted onto the surface of initiator-immobilized silica by surface-initiated atom transfer radical polymerization. The resulting molecularly imprinted polymer was characterized by elemental analysis and thermogravimetric analysis. The binding property of molecularly imprinted polymer for 17β-estradiol was also studied with both static and dynamic methods. The results showed that the molecularly imprinted polymer possessed excellent recognition capacity for 17β-estradiol (180.65 mg/g at 298 K), and also exhibited outstanding selectivity for 17β-estradiol over the other competitive compounds (such as testosterone and progesterone). Then, the determination of trace 17β-estradiol in beef samples was successfully developed by using molecularly imprinted polymer solid-phase extraction coupled with high-performance liquid chromatography. The limit of detection was 0.25 ng/mL, and the amount of 17β-estradiol in beef samples was detected at 2.83 ng/g. This work proposed a sensitive, rapid, reliable, and convenient approach for the determination of trace 17β-estradiol in complicated beef samples. PMID:25619938

  1. Application of stable carbon isotope analysis to the detection of 17beta-estradiol administration to cattle.

    PubMed

    Buisson, C; Hebestreit, M; Weigert, A Preiss; Heinrich, K; Fry, H; Flenker, U; Banneke, S; Prevost, S; Andre, F; Schaenzer, W; Houghton, E; Le Bizec, B

    2005-11-01

    The use of anabolic agents in food producing animals is prohibited within the EU since 1988 (96/22/EC directive). The control of the illegal use of natural steroid hormones in cattle is still an exciting analytical challenge as far as no definitive method and non-ambiguous analytical criteria are available. The ability of gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) to demonstrate the administration of 17beta-estradiol to bovine has been investigated in this paper. By comparison of 13C/12C isotopic ratio of main urinary estradiol metabolite, i.e. 17alpha-estradiol, with two endogenous reference compounds (ERCs), i.e. dehydroepiandrosterone (DHEA) and 5-androstene-3beta,17alpha-diol, the differentiation of estradiol metabolite origin, either endogenous or exogenous, has been proved to be achievable. After treatment, the delta(13)C(VPDB)-values of 17alpha-estradiol reached -27 per thousand to -29 per thousand, whereas delta13CVPDB-values of DHEA remained between -13 per thousand and -20 per thousand depending on the diet, maize and grass, respectively. A significant difference of delta13CVPDB between ERCs and 17alpha-estradiol was measurable over a period of 2 weeks after estradiol ester administration to the animal. PMID:16233872

  2. Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro

    SciTech Connect

    Gupta, Rupesh K.; Singh, Jeffery M.; Leslie, Tracie C.; Meachum, Sharon; Flaws, Jodi A.; Yao, Humphrey H-C

    2010-01-15

    Any insult that affects survival of ovarian antral follicles can cause abnormal estradiol production and fertility problems. Phthalate esters (PEs) are plasticizers used in a wide range of consumer and industrial products. Exposure to these chemicals has been linked to reduced fertility in humans and animal models. Di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) decrease serum estradiol levels and aromatase (Arom) expression, prolong estrous cycles, and cause anovulation in animal and culture models. These observations suggest PEs directly target antral follicles. We therefore tested the hypothesis that DEHP (1-100 mug/ml) and MEHP (0.1-10 mug/ml) directly inhibit antral follicular growth and estradiol production. Antral follicles from adult mice were cultured with DEHP or MEHP, and/or estradiol for 96 h. During culture, follicle size was measured every 24 h as a measurement of follicle growth. After culture, media were collected for measurement of estradiol levels and follicles were subjected to measurement of cylin-D-2 (Ccnd2), cyclin-dependant-kinase-4 (Cdk4), and Arom. We found that DEHP and MEHP inhibited growth of follicles and decreased estradiol production compared to controls at the highest doses. DEHP and MEHP also decreased mRNA expression of Ccnd2, Cdk4, and Arom at the highest dose. Addition of estradiol to the culture medium prevented the follicles from DEHP- and MEHP-induced inhibition of growth, reduction in estradiol levels, and decreased Ccnd2 and Cdk4 expression. Collectively, our results indicate that DEHP and MEHP may directly inhibit antral follicle growth via a mechanism that partially includes reduction in levels of estradiol production and decreased expression of cell cycle regulators.

  3. Transfer rates and pattern of PCB isomers and congeners and p,p'-DDE from mother to egg in Adelie penguin (Pygoscelis adeliae)

    SciTech Connect

    Tanabe, S.; Surbramanian, A.; Hidaka, H.; Tatsukawa, R.

    1986-03-01

    Mother to egg transfer of PCB isomers and congeners and p,p'-DDE was examined in Adelie Penguin (Pygoscelis adeliae) from Antarctica. Transfer rate to a clutch of two eggs was estimated to be small, accounting to about 4.0% for both PCBs and p,p-DDE to the burden in mother. No significant difference was found in the concentration ratios of individual PCB isomers and congeners between mother and egg, which apparently differed from those between mother and fetus of striped dolphin previously reported.

  4. Origin attribution of polychlorinated dibenzo-p-dioxins and dibenzofurans in sediment and soil from a Japanese freshwater lake area through congener-specific data analysis.

    PubMed

    Sakurai, T; Suzuki, N; Masunaga, S; Nakanishi, J

    1998-01-01

    Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) in sediment and soil from a freshwater lake area were congener-specifically determined. The obtained data were examined to estimate the major origins of these compounds, with the aid of principal component analysis (PCA). Four major principal components (PCs) were obtained, and three of them were attributed to PCDDs/PCDFs in the atmosphere, in a diphenyl ether herbicide and in pentachlorophenol, based on congener-specific comparisons with references. One PC remained unattributed. These four were interpreted as the major origins of PCDDs/PCDFs in the area. The relative influence of the origins was also investigated. PMID:9828338

  5. Diabetes Prevalence in Relation to Serum Concentrations of Polychlorinated Biphenyl (PCB) Congener Groups and Three Chlorinated Pesticides in a Native American Population

    PubMed Central

    Aminov, Zafar; Haase, Richard; Rej, Robert; Schymura, Maria J.; Santiago-Rivera, Azara; Morse, Gayle; DeCaprio, Anthony; Carpenter, David O.

    2016-01-01

    Background: Exposure to persistent organic pollutants (POPs) is known to increase risk of diabetes. Objective: To determine which POPs are most associated with prevalence of diabetes in 601 Akwesasne Native Americans. Methods: Multiple logistic regression analysis was used to assess associations between quartiles of concentrations of 101 polychlorinated biphenyl (PCBs) congeners, congener groups and three chlorinated pesticides [dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and mirex] with diabetes. In Model 1, the relationship between quartiles of exposure and diabetes were adjusted only for sex, age, body mass index (BMI), and total serum lipids. Model 2 included additional adjustment for either total PCBs or total pesticides. Results: Total serum PCB and pesticide concentrations were each significantly associated with prevalence of diabetes when adjusted only for covariates (Model 1), but neither showed a significant OR for highest to lowest quartiles after additional adjustment for the other (Model 2). When applying Model 2 to PCB congener groups and individual pesticides, there were significant omnibus differences between the four quartiles (all ps < 0.042) for most groups, with the exception of penta- and hexachlorobiphenyls, DDE and mirex. However, when comparing highest to lowest quartiles only non- and mono-ortho PCBs [OR = 4.55 (95% CI: 1.48, 13.95)], tri- and tetrachloro PCBs [OR = 3.66 (95% CI: 1.37, –9.78)] and HCB [OR = 2.64 (95% CI: 1.05, 6.61)] showed significant associations with diabetes. Among the non- and mono-ortho congeners, highest to lowest quartile of dioxin TEQs was not significant [OR = 1.82 (95% CI: 0.61, 5.40)] but the OR for the non-dioxin-like congeners was [OR = 5.01 (95% CI: 1.76, 14.24)]. Conclusion: The associations with diabetes after adjustment for other POPs were strongest with the more volatile, non-dioxin-like, low-chlorinated PCB congeners and HCB. Because low-chlorinated congeners are more volatile

  6. Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats

    SciTech Connect

    Morio, Lisa A.; Leone, Angelique; Sawant, Sharmilee P.; Nie, Alex Y.; Brandon Parker, J.; Taggart, Peter; Barron, Alfred M.; McMillian, Michael K. . E-mail: mmcmilli@prdus.jnj.com; Lord, Peter

    2006-11-01

    Heme oxygenase-1 (HO-1) is one of several enzymes induced by hepatotoxicants, and is thought to have an important protective role against cellular stress during liver inflammation and injury. The objective of the present study was to evaluate the role of HO-1 in estradiol-induced liver injury. A single dose of ethinyl estradiol (500 mg/kg, po) resulted in mild liver injury. Repeated administration of ethinyl estradiol (500 mg/kg/day for 4 days, po) resulted in no detectable liver injury or dysfunction. Using RT-PCR analysis, we demonstrate that HO-1 gene expression in whole liver tissue is elevated (> 20-fold) after the single dose of ethinyl estradiol. The number and intensity of HO-1 immunoreactive macrophages were increased after the single dose of ethinyl estradiol. HO-1 expression was undetectable in hepatic parenchymal cells from rats receiving Methocel control or a single dose of ethinyl estradiol, however cytosolic HO-1 immunoreactivity in these cells after repeated dosing of ethinyl estradiol was pronounced. The increases in HO-1 mRNA and HO-1 immunoreactivity following administration of a single dose of ethinyl estradiol suggested that this enzyme might be responsible for the observed protection of the liver during repeated dosing. To investigate the effect of HO-1 expression on ethinyl estradiol-induced hepatotoxicity, rats were pretreated with hemin (50 {mu}mol/kg, ip, a substrate and inducer of HO-1), with tin protoporphyrin IX (60 {mu}mol/kg, ip, an HO-1 inhibitor), or with gadolinium chloride (10 mg/kg, iv, an inhibitor/toxin of Kupffer cells) 24 h before ethinyl estradiol treatment. Pretreatment with modulators of HO-1 expression and activity had generally minimal effects on ethinyl estradiol-induced liver injury. These data suggest that HO-1 plays a limited role in antioxidant defense against ethinyl estradiol-induced oxidative stress and hepatotoxicity, and suggests that other coordinately induced enzymes are responsible for protection observed

  7. Estradiol receptors agonists induced effects in rat intestinal microcirculation during sepsis.

    PubMed

    Sharawy, Nivin; Ribback, Silvia; Al-Banna, Nadia; Lehmann, Christian; Kern, Hartmut; Wendt, Michael; Cerny, Vladimir; Dombrowski, Frank; Pavlovic, Dragan

    2013-01-01

    The steroid hormone estradiol is suggested to play a protective role in intestinal injury during systemic inflammation (sepsis). Our aim was to determine the effects of specific estradiol receptor (ER-α and ER-ß) agonists on the intestinal microcirculation during experimental sepsis. Male and sham ovariectomized female rats were subjected to sham colon ascendens stent peritonitis (CASP), and they were compared to male and ovariectomized female rats underwent CASP and either estradiol receptor α (ER-α) agonist propyl pyrazole triol (PPT), estradiol receptor ß (ER-ß) agonist diarylpropiolnitrile (DPN), or vehicle treatment. Intravital microscopy was performed, which is sufficiently sensitive to measure changes in the functional capillary density (FCD) as well as the major steps in leukocyte recruitment (rolling and adhesion). The leukocyte extravasations were also quantified by using histological paraffin sections of formalin fixed intestine. We found that either DPN (ER-β) or PPT (ER-α) significantly reduced (P<0.05) sepsis-induced leukocyte-endothelial interaction (rolling, adherent leukocytes and neutrophil extravasations) and improved the intestinal muscular FCD. [PPT: Female; Leukocyte rolling (n/min): V(3) 3.7±0.7 vs 0.8±0.2, Leukocyte adhesion(n/mm(2)): V(3) 131.3±22.6 vs 57.2±13.5, Neutrophil extravasations (n/10000 μm(2)): 3.1±0.7 vs 6 ±1. Male; Leukocyte adhesion (n/mm(2)): V(1) 154.8±19.2 vs 81.3±11.2, V(3) 115.5±23.1 vs 37.8±12]. [DPN: Female; neutrophil extravasations (n/10000 μm(2)) 3.8±0.6 vs 6 ±1. Male; Leukocyte adhesion (n/mm(2)) V(1) 154.8±19.2 vs 70±10.5, V(3) 115.5±23.1 vs 52.8±9.6].Those results suggest that the observed effects of estradiol receptors on different phases of leukocytes recruitment with the improvement of the functional capillary density could partially explain the previous demonstrated salutary effects of estradiol on the intestinal microcirculation during sepsis. The observed activity of this class of

  8. Redescription of the fish parasite Lernanthropus polynemi Richiardi, 1881 (Copepoda: Siphonostomatoida) and relegation of two congeners to synonymy.

    PubMed

    Piasecki, Wojciech; Hayward, Craig J

    2002-06-01

    Lernanthropus polynemi Richiardi, 1881 is described, for the first time since its original discovery, based on the type-material found in the Museum für Naturkunde in Berlin, Germany. Morphological features of this parasite, which infects the commercially-caught fish Eleutheronema tetradactylum (Shaw), are described and illustrated, including those of the male, which is described for the first time. The types of another species from the same host, L. lappaceus Wilson, 1912, and deposited in the National Museum of Natural History in Washington DC, are also examined based on the type-specimens. The types of a third congener, L. trifoliatus Basset-Smith, 1898, also from the same host, are not available, but the original illustrations are studied. It is considered that the three nominal species described from E. tetradactylum represent a single taxon, and that L. lappaceus and L. trifoliatus be relegated to synonymy with L. polynemi. PMID:12108411

  9. A taxonomic review of the genus Goffartia Hirschmann, 1952 (Rhabditida: Diplogastridae) with a note on the relationship of congeners.

    PubMed

    Tahseen, Qudsia; Mustaqim, Malka

    2015-01-01

    This paper deals with the descriptions and diagnoses of the species of the relatively rare and poorly-understood genus Goffartia Hirschmann, 1952. A comparative account of the salient morphological characters including stoma, amphids, pharynx, and the male accessory sex organs of the six species viz., G. africana (Micoletzky, 1915) Hirschmann, 1952; G. filicaudata (Andrássy, 1968) Sudhaus & Fürst von Lieven, 2003; G. heteroceri Hirschmann, 1952; G. praepilata Shoshin, 1989 and G. variabilis (Micoletzky, 1922) Hirschmann, 1952 and the recently described G. phalacra Singh, Yousuf, Kumar & Ahmad, 2014, has been given. This paper also discusses the variations among and the relationships between these congeners, and provides an identification key. PMID:26624431

  10. Sixteen polymorphic microsatellite markers for a federally threatened species, Hexastylis naniflora (Aristolochiaceae), and co-occurring congeners1

    PubMed Central

    Hamstead, Jacqueline W.; Snider, Brandon L.; Oaks, Robyn; Fitzgerald, Evan; Woodward, Jason; Teat, Alyssa; Hay, Nikolai M.; Estep, Matt C.; Murrell, Zack E.

    2015-01-01

    Premise of the study: Twenty microsatellite loci were developed for the federally threatened species Hexastylis naniflora (Aristolochiaceae) to examine genetic diversity and to distinguish this species from co-occurring congeners, H. heterophylla and H. minor. Methods and Results: Next-generation sequencing approaches were used to identify microsatellite loci and design primers. One hundred fifty-two primer pairs were screened for repeatability, and 20 of these were further characterized for polymorphism. In H. naniflora, the number of alleles identified for polymorphic loci ranged from two to 23 (mean ∼8.8), with a mean heterozygosity of 0.39. Conclusions: These 16 polymorphic primers for H. naniflora will be useful tools in species identification and quantifying genetic diversity within the genus. PMID:26191466

  11. A New Player in Environmentally Induced Oxidative Stress: Polychlorinated Biphenyl Congener, 3,3′-Dichlorobiphenyl (PCB11)

    PubMed Central

    Aykin-Burns, Nukhet

    2013-01-01

    Recent analysis of air samples from Chicago and Lake Michigan areas observed a ubiquitous airborne polychlorinated biphenyl (PCB) congener, 3,3′-dichlorobiphenyl (PCB11). Our analysis of serum samples also revealed the existence of hydroxylated metabolites of PCB11 in human blood. Because PCBs and PCB metabolites have been suggested to induce oxidative stress, this study sought to determine whether environmental exposure to PCB11 and its 4-hydroxyl metabolite could induce alterations in steady-state levels of reactive oxygen species (ROS) and cytotoxicity in immortalized human prostate epithelial cells (RWPE-1). This study also examines if antioxidants could protect the cells from PCB11-induced cytotoxicity. Exponentially growing RWPE-1 cells were exposed to PCB11 and its metabolite, 3,3′-dichlorobiphenyl-4-ol (4-OH-PCB11), as well as an airborne PCB mixture resembling the Chicago ambient air congener profile, every day for 5 days. Results showed that 4-OH-PCB11 could significantly induce cell growth suppression and decrease the viability and plating efficiency of RWPE-1 cells. 4-OH-PCB11 also significantly increased steady-state levels of intracellular superoxide, O2 •−, as well as hydroperoxides. Finally, treatment with the combination of polyethylene glycol–conjugated CuZn superoxide dismutase and catalase added 1h after 4-OH-PCB11 exposures, significantly protected RWPE-1 cells from PCB toxicity. The results strongly support the hypothesis that exposure to a hydroxylated metabolite of PCB11 can inhibit cell proliferation and cause cytotoxicity by increasing steady-state levels of ROS. Furthermore, antioxidant treatments following PCBs exposure could significantly mitigate the PCB-induced cytotoxicity in exponentially growing human prostate epithelial cells. PMID:23997111

  12. Congenic Strains Confirm the Pleiotropic Effect of Chromosome 4 QTL on Mouse Femoral Geometry and Biomechanical Performance

    PubMed Central

    Kristianto, Jasmin; Litscher, Suzanne J.; Johnson, Michael G.; Patel, Forum; Patel, Mital; Fisher, Jacqueline; Zastrow, Ryley K.; Radcliff, Abigail B.; Blank, Robert D.

    2016-01-01

    A pleiotropic quantitative trait locus (QTL) for bone geometry and mechanical performance in mice was mapped to distal chromosome 4 via an intercross of recombinant congenic mice HcB-8 and HcB-23. To study the QTL in isolation, we have generated C3H.B10-(rs6355453-rs13478087) (C.B.4.3) and C3H.B10-(rs6369860-D4Mit170) (C.B.4.2) congenic strains that harbor ~20 Mb and ~3 Mb, respectively, of chromosome 4 overlapping segments from C57BL/10ScSnA (B10) within the locus on a C3H/DiSnA (C3H) background. Using 3-point bend testing and standard beam equations, we phenotyped these mice for femoral mid-diaphyseal geometry and biomechanical performance. We analyzed the results via 2-way ANOVA, using sex and genotype as factors. In the C.B.4.3 strain, we found that homozygous B10/B10 male mice had smaller cross sectional area (CSA) and reduced total displacement than homozygous C3H/C3H mice. Sex by genotype interaction was also observed for maximum load and stiffness for C3H/C3H and B10/B10 mice, respectively. In C.B.4.2 strain, we found that homozygous B10/B10 mice had lower total displacement, post-yield displacement (PYD), stiffness, yield load and maximum load than mice harboring C3H allele. Sex by genotype interaction was observed in B10/B10 mice for perimeter, outer minor axis (OMA) and CSA. There were no significant differences in tissue level mechanical performance, which suggest that the QTL acts primarily on circumferential bone size. These data confirm the prior QTL mapping data and support other work demonstrating the importance of chromosome 4 QTL on bone modeling and bone responses to mechanical loading. PMID:26849124

  13. BALB/c-congenic ANP32B-deficient mice reveal a modifying locus that determines viability

    PubMed Central

    Leo, Vonny I.; Bunte, Ralph M.; Reilly, Patrick T.

    2015-01-01

    We previously found that deletion of the multifunctional factor ANP32B (a.k.a. SSP29, APRIL, PAL31, PHAPI2) resulted in a severe but strain-specific defect resulting in perinatal lethality. The difficulty in generating an adult cohort of ANP32B-deficient animals limited our ability to examine adult phenotypes, particularly cancer-related phenotypes. We bred the Anp32b-null allele into the BALB/c and FVB/N genetic background. The BALB/c, but not the FVB/N, background provided sufficient frequency of adult Anp32b-null (Anp32b−/−) animals. From these, we found no apparent oncogenic role for this protein in mammary tumorigenesis contrary to what was predicted based on human data. We also found runtism, pathologies in various organ systems, and an unusual clinical chemistry signature in the adult Anp32b−/− mice. Intriguingly, genome-wide single-nucleotide polymorphism analysis suggested that our colony retained an unlinked C57BL/6J locus at high frequency. Breeding this locus to homozygosity demonstrated that it had a strong effect on Anp32b−/− viability indicating that this locus contains a modifier gene of Anp32b with respect to development. This suggests a functionally important genetic interaction with one of a limited number of candidate genes, foremost among them being the variant histone gene H2afv. Using congenic breeding strategies, we have generated a viable ANP32B-deficient animal in a mostly pure background. We have used this animal to reliably exclude mouse ANP32B as an important oncogene in mammary tumorigenesis. Our further phenotyping strengthens the evidence that ANP32B is a widespread regulator of gene expression. These studies may also impact the choice of subsequent groups with respect to congenic breeding versus de novo zygote targeting strategies for background analyses in mouse genetics. PMID:26558540

  14. Different Responses of an Invasive Clonal Plant Wedelia trilobata and its Native Congener to Gibberellin: Implications for Biological Invasion.

    PubMed

    Dai, Zhi-Cong; Fu, Wei; Qi, Shan-Shan; Zhai, De-Li; Chen, Si-Chong; Wan, Ling-Yun; Huang, Ping; Du, Dao-Lin

    2016-02-01

    The invasive clonal plant Wedelia trilobata contains higher levels of ent-kaurane diterpenes, which are precursors of gibberellins (GAs), and higher rates of clonal growth than its native congener W. chinensis in invaded habitats. We hypothesized that the higher levels of endogenous GAs facilitate greater ramet growth in W. trilobata compared with W. chinensis. We quantified endogenous levels of GA1+3 in the two species and compared their growth responses to the changes of endogenous and exogenous GA3 by using short-term and long-term hydroponics experiments. After a period of homogeneous cultivation, levels of endogenous GA1+3 were higher in W. trilobata than in W. chinensis. The reduction of endogenous GAs repressed the emergence of adventitious roots and the growth of W. trilobata in the initial cultivation stage, and inhibited its shoot elongation and biomass. Levels of endogenous GA1+3 were positively correlated with the length of shoots and adventitious roots of W. trilobata. Adventitious roots of W. trilobata also emerged earlier and grew faster when treated with exogenous GA3. In contrast, exogenous GA3 treatment inhibited the length of adventitious roots in W. chinensis, and levels of endogenous GA1+3 did not correlate with shoot or adventitious root length. Our study suggests that GAs accelerate the rapid clonal growth of W. trilobata, more than that of its native congener W. chinensis, illustrating the relationship between plant hormones and the clonal growth of invasive plants. These findings are important for understanding the mechanisms associated with the invasiveness of clonal plants and their potential management. PMID:26879680

  15. Organochlorine pesticides and polychlorinated biphenyl congeners in wild terrestrial mammals from Croatia: Interspecies comparison of residue levels and compositions.

    PubMed

    Herceg Romanić, Snježana; Klinčić, Darija; Kljaković-Gašpić, Zorana; Kusak, Josip; Reljić, Slaven; Huber, Đuro

    2015-10-01

    In this pilot study, we investigated levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in the adipose tissues of two free-ranging terrestrial carnivores from Croatia sampled in 2010 and 2011: the brown bear (Ursus arctos; N=32) and the grey wolf (Canis lupus; N=29). Concentrations of ∑OCPs and ΣPCBs ranged from 0.45 to 4.09 ng g(-1) lipid mass (lm) and from 0.93 to 8.52 ng g(-1) lm in brown bear, and from 1.18 to 5.67 ng g(-1) lm and 2.68 to 48.9 ng g(-1) lm in grey wolf adipose tissues, respectively. PCBs were dominant accounting for over 72% of total analyzed persistent organic pollutants (POPs). The sum of six indicator non-dioxin-like PCBs (Σ6IndNDL PCBs) made up 60-93% and 58-85% of the total congener concentrations in brown bears and wolves, respectively. Although the levels of the measured parameters were significantly higher in grey wolves than in bears, the contaminant profiles of the two species were similar, with γ-HCH, HCB, β-HCH and DDE as major OCP contaminants, and PCB-153>PCB-180≈PCB-170>PCB-138 as the dominant congeners. The sum of hexachlorocyclohexanes (ΣHCHs) and 8 toxicologically relevant dioxin-like PCBs (Σ8ToxDL PCBs) was higher in the males than in the females of the brown bear. Concentrations of ΣDDTs, HCB, ΣOCP, ΣPCBs, Σ6IndNDL PCBs, and toxicologically relevant non-dioxin-like PCBs (ΣToxNDL PCBs) were significantly positively correlated with lipid content in the grey wolf. Concentrations of OCPs and PCBs in brown bears and wolves from Croatia were low and normal for large terrestrial mammals. PMID:26002287

  16. (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist

    SciTech Connect

    Burris, K.D.; Breeding, M.; Sanders-Bush, E. )

    1991-09-01

    Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation. (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD.

  17. Removal efficiencies for 136 tetra- through octa-chlorinated dibenzo-p-dioxins and dibenzofuran congeners with activated carbons.

    PubMed

    Zhou, Xu-Jian; Li, Xiao-Dong; Ni, Ming-Jiang; Cen, Ke-Fa

    2015-11-01

    In this study, the removal efficiency of 136 tetra- to octa-chlorinated dibenzo-p-dioxin (CDD)/furan (F) congeners from a nitrogen + oxygen carrier gas was studied using a laboratory-scale, fixed bed adsorption system. Two kinds of activated carbon with dissimilar pore structures were used as adsorbents. The total concentration of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) in the source gas was 541 ng/Nm(3) and that of the 17 toxic 2,3,7,8-substituted PCDD/Fs 96.35 ng/Nm(3), accounting for 17.8% of the total original weight amount. Their toxic equivalent quantity (TEQ) was 8.31 ng I-TEQ/Nm(3). For both activated carbons, the removal efficiencies of the ten PCDD/F homologue groups rise with chlorine substitution number. The removal efficiencies vary approximately as a power function of vapor pressure (correlation coefficients r(2) = 0.93 and 0.81, respectively). Competitive adsorption and desorption occur as adsorption time went on, causing elution of the lower chlorinated homologues, i.e. tetra-CDD/F and Penta-CDD/F congeners. In addition, there are significantly different concentration distributions for isomers in the same homologue groups. However, their removal efficiencies have weak correlation with their initial concentrations. The correlation coefficients are from -0.47 to 0.32 and from -0.57 to 0.46 respectively for the two kinds of activated carbons. PMID:26154037

  18. Record of PCB congeners, sorbents and potential toxicity in core samples in Indiana Harbor and Ship Canal.

    PubMed

    Martinez, Andres; Hornbuckle, Keri C

    2011-10-01

    Indiana Harbor and Ship Canal (IHSC) is an active navigational system that serves a heavily industrial area of southern Lake Michigan. We have determined the amount of polychlorinated biphenyls (PCBs), congener distributions, sorbent types and potential for dioxin-like PCB toxicity from two IHSC sediment cores. Vertical distributions of ΣPCBs (sum of 161 individual or coeluting congeners) ranged from 410 to 91000 and 1800 to 41000 ng g(-1) dry weight (d.w.) for cores 1 and 2, respectively. Core 1 showed its highest accumulation rate for the year ∼1979 and exhibits a strong Aroclor 1248 signal in sediments accumulating over the last 60 years. It appears that from the late 1930s until the beginning of the 1980s there was a large and constant input of PCBs into this system. This pattern differs from lake cores from the Great Lakes region which commonly exhibit a rapid increase, a peak, followed by a sharp decrease in the PCB accumulation rates. Core 2 also has a strong Aroclor 1248 signal in the top layers, but deeper layers show evidence of mixtures of Aroclors and/or weathering processes. High levels of black carbon as a fraction of total organic carbon were found in both cores (median ∼30%), which reflect the long history of local combustion sources. No strong relationship was found between ΣPCB concentration and sorbents. Both cores contain dioxin-like PCBs that are highest in concentration below the surface. The high levels of PCBs in the deep sediments are of concern because of plans to dredge this system. PMID:21899876

  19. Congener-specific polychlorinated biphenyls and the prevalence of diabetes in the Saku Control Obesity Program (SCOP).

    PubMed

    Tanaka, Takahisa; Morita, Akemi; Kato, Masayuki; Hirai, Tetsuya; Mizoue, Tetsuya; Terauchi, Yasuo; Watanabe, Shaw; Noda, Mitsuhiko

    2011-01-01

    The prevalence of diabetes is increasing globally. In addition to established risk factors for diabetes, such as diet, inactivity, overweight and obesity, the involvement of persistent organic pollutants, including dioxins and polychlorinated biphenyls (PCBs), has also been suggested to be a possible, but controversial, cause of this epidemic. The present study investigated the association between blood PCB congener levels and the prevalence of diabetes among middle-aged, overweight and obese Japanese participants in the Saku Control Obesity Program. One hundred seventeen participants had their congener-specific PCB levels measured in addition to undergoing routine blood analyses at the time of a medical checkup. Prevalent diabetes was defined according to two methods: definite diabetes was defined as people with an HbA1c level ≥ 6.9% or who were taking medication for diabetes, and all diabetes was defined as people with an HbA1c level ≥ 6.5%, a fasting plasma glucose level ≥ 126 mg/dL, or a history of doctor-diagnosed diabetes. A multiple logistic regression analysis was performed to analyze the association between the PCB levels and the prevalence of diabetes, with adjustments for sex, age, body mass index and total lipids. As a result, PCB 146 and 180 were positively associated and PCB 163/164 and 170 were negatively associated with the prevalence of definite diabetes. The significance of the association of PCB 180 and 163/164 with the prevalence of diabetes persisted regardless of the definition of diabetes or adjustments for total lipids, suggesting the possibility that these parameters may modify the risk of diabetes. PMID:21551956

  20. The SOD1 transgene expressed in erythroid cells alleviates fatal phenotype in congenic NZB/NZW-F1 mice.

    PubMed

    Otsuki, Noriyuki; Konno, Tasuku; Kurahashi, Toshihiro; Suzuki, Saori; Lee, Jaeyong; Okada, Futoshi; Iuchi, Yoshihito; Homma, Takujiro; Fujii, Junichi

    2016-07-01

    Oxidative stress due to a superoxide dismutase 1 (SOD1) deficiency causes anemia and autoimmune responses, which are phenotypically similar to autoimmune hemolytic anemia (AIHA) and systemic lupus erythematosus (SLE) in C57BL/6 mice and aggravates AIHA pathogenesis in New Zealand black (NZB) mice. We report herein on an evaluation of the role of reactive oxygen species (ROS) in a model mouse with inherited SLE, that is, F1 mice of the NZB × New Zealand white (NZW) strain. The ROS levels within red blood cells (RBCs) of the F1 mice were similar to the NZW mice but lower compared to the NZB mice throughout adult period. Regarding SLE pathogenesis, we examined the effects of an SOD1 deficiency or the overexpression of human SOD1 in erythroid cells by establishing corresponding congenic F1 mice. A SOD1 deficiency caused an elevation in ROS production, methemoglobin content, and hyperoxidation of peroxiredoxin in RBC of the F1 mice, which were all consistent with elevated oxidative stress. However, while the overexpression of human SOD1 in erythroid cells extended the life span of the congenic F1 mice, the SOD1 deficiency had no effect on life span compared to wild-type F1 mice. It is generally recognized that NZW mice possess a larval defect in the immune system and that NZB mice trigger an autoimmune reaction in the F1 mice. Our results suggest that the oxidative insult originated from the NZB mouse background has a functional role in triggering an aberrant immune reaction, leading to fatal responses in F1 mice. PMID:27080108

  1. COMPARISON OF THE ESTROGENIC POTENCIES OF ESTRADIOL, ETHYNYLESTRADIOL, DIETHYLSTILBESTROL, NONYLPHENOL AND METHOXYCHLOR IN VIVO AND IN VITRO

    EPA Science Inventory

    Five natural, pharmaceutical, or xenobiotic chemicals (17b-estradiol, ethynylestradiol, diethystilbestrol, nonylphenol, methoxychlor) were tested in two in vitro (MCF-7 breast tumor cell proliferation [E-screen], yeast estrogen system [YES]), and one in vivo (male sheepshead min...

  2. GABAergic Transmission to Kisspeptin Neurons Is Differentially Regulated by Time of Day and Estradiol in Female Mice

    PubMed Central

    Elias, Carol F.; Moenter, Suzanne M.

    2014-01-01

    Gonadotropin-releasing hormone (GnRH) secretion is regulated by estradiol feedback. This feedback switches from negative to positive in females; this switch depends on time of day in many species. Estradiol feedback is likely conveyed via afferents. Kisspeptin neurons of the arcuate nucleus and anteroventral–periventricular region (AVPV) may differentially regulate GnRH neurons during negative and positive feedback, respectively. We tested estradiol and time of day regulation of GABAergic transmission and postsynaptic response to GABA in these two populations using transgenic mice with GFP-identified kisspeptin neurons. Ovariectomized (OVX) mice treated or not with estradiol (E) were studied in the AM (negative feedback) or PM (positive feedback). GABAA receptor reversal potential was unaffected by time of day or estradiol. GABA depolarized the membrane potential of arcuate neurons from OVX+E mice; this response was blunted in cells from OVX mice. GABA hyperpolarized AVPV kisspeptin neurons, except in the OVX PM group in which GABA did not alter membrane potential attributable to a PM hyperpolarization of baseline membrane potential. In both kisspeptin neuron populations from OVX mice, the frequency of GABAergic spontaneous postsynaptic currents was increased in the PM; this increase was blunted by estradiol. In arcuate, but not AVPV, kisspeptin neurons, estradiol reduced miniature postsynaptic current amplitude independent of time of day. Using nonstationary fluctuation analysis and diazepam to manipulate GABAA receptor apparent affinity, the decrease in arcuate miniature postsynaptic current amplitude was attributed to decreased number of receptors bound by GABA. Time of day and estradiol feedback thus both target presynaptic and postsynaptic mechanisms to differentially regulate kisspeptin neurons via GABAergic transmission. PMID:25471569

  3. Follicle-Stimulating Hormone and Estradiol Interact to Stimulate Glutathione Synthesis in Rat Ovarian Follicles and Granulosa Cells1

    PubMed Central

    Hoang, Yvonne D.; Nakamura, Brooke N.; Luderer, Ulrike

    2009-01-01

    Glutathione (GSH), the most abundant intracellular nonprotein thiol, is critical for many cellular functions. The rate-limiting step in GSH synthesis is catalyzed by glutamate cysteine ligase (GCL), a heterodimer composed of a catalytic (GCLC) and a modifier (GCLM) subunit. The tissue-specific regulation of GSH synthesis is poorly understood. We showed previously that gonadotropin hormones regulate ovarian GSH synthesis. In the present study, we sought to clarify the ovarian cell type-specific effects of follicle-stimulating hormone (FSH) and estradiol on GSH synthesis. Immature female rats were treated with estradiol to stimulate development of small antral follicles. Granulosa cells (GCs) from these follicles or whole follicles were cultured in serum-free media, with or without FSH and 17beta-estradiol. The GSH and GCLC protein and mRNA levels increased in GCs treated with FSH alone. The effects of FSH on GCLC and GCLM protein and mRNA levels, GCL enzymatic activity, and GSH concentrations in GCs were significantly enhanced by the addition of estradiol. Estradiol alone had no effects on GSH. Dibromo-cAMP mimicked and protein kinase A (PKA) inhibitors prevented FSH stimulation of GCL subunit protein levels. In cultured small antral follicles, FSH stimulated estradiol synthesis and robustly increased GCL subunit mRNA and protein levels and GSH concentrations. The GCL subunit mRNA expression increased in both the granulosa cells and theca cells of follicles with FSH stimulation. These data demonstrate that maximal stimulation of GSH synthesis by FSH in granulosa cells and follicles requires estradiol. Without estradiol, FSH causes lesser increases in GCL subunit expression via a PKA-dependent pathway. PMID:19516019

  4. Development and validation of in vitro-in vivo correlation (IVIVC) for estradiol transdermal drug delivery systems.

    PubMed

    Yang, Yang; Manda, Prashanth; Pavurala, Naresh; Khan, Mansoor A; Krishnaiah, Yellela S R

    2015-07-28

    The objective of this study was to develop a level A in vitro-in vivo correlation (IVIVC) for drug-in-adhesive (DIA) type estradiol transdermal drug delivery systems (TDDS). In vitro drug permeation studies across human skin were carried out to obtain the percent of estradiol permeation from marketed products. The in vivo time versus plasma concentration data of three estradiol TDDS at drug loadings of 2.0, 3.8 and 7.6mg (delivery rates of 25, 50 and 100μg/day, respectively) was deconvoluted using Wagner-Nelson method to obtain percent of in vivo drug absorption in postmenopausal women. The IVIVC between the in vitro percent of drug permeation (X) and in vivo percent of drug absorption (Y) for these three estradiol TDDS was constructed using GastroPlus® software. There was a high correlation (R(2)=1.0) with a polynomial regression of Y=-0.227X(2)+0.331X-0.001. These three estradiol TDDS were used for internal validation whereas another two products of the same formulation design (with delivery rates of 60 and 100μg/day) were used for external validation. The predicted estradiol serum concentrations (convoluted from in vitro skin permeation data) were compared with the observed serum concentrations for the respective products. The developed IVIVC model passed both the internal and external validations as the prediction errors (%PE) for Cmax and AUC were less than 15%. When another marketed estradiol TDDS with a delivery rate of 100μg/day but with a slight variation in formulation design was chosen, it did not pass external validation indicating the product-specific nature of IVIVC model. Results suggest that the IVIVC model developed in this study can be used to successfully predict the in vivo performance of the same estradiol TDDS with in vivo delivery rates ranging from 25 to 100μg/day. PMID:25979329

  5. Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus)

    NASA Astrophysics Data System (ADS)

    Saino, N.; Rubolini, D.; Romano, M.; Boncoraglio, G.

    2007-03-01

    The length ratio between individual digits differs between males and females in humans, other mammals, lizards, and one bird species. Sexual dimorphism in digit ratios and variation among individuals of the same sex may depend on differential exposure to androgens and estrogens during embryonic life. Organizational effects of sex hormones could cause the observed correlations between digit ratios and diverse phenotypic traits in humans. However, no study has investigated experimentally the effect of prenatal estrogens on digit ratios. We analyzed the effect of estradiol injection in ring-necked pheasant (Phasianus colchicus) eggs on digit ratios. Males from control eggs had higher ratios between the second or third and the fourth digit of the right foot compared to females. Estradiol-treated eggs produced males with lower (feminized) right foot second to fourth digit ratio. Thus, we provided the first experimental evidence that prenatal exposure to physiologically high estrogen levels affects bird digit ratios.

  6. Matching plasmon resonances to the C=C and C-H bonds in estradiol

    NASA Astrophysics Data System (ADS)

    Mbomson, Ifeoma G.; McMeekin, Scott; De La Rue, Richard; Johnson, Nigel P.

    2015-03-01

    We tune nanoantennas to resonate within mid-infrared wavelengths to match the vibrational resonances of C=C and C-H of the hormone estradiol. Modelling and fabrication of the nanoantennas produce plasmon resonances between 2 μm to 7 μm. The hormone estradiol was dissolved in ethanol and evaporated, leaving thickness of a few hundreds of nanometres on top of gold asymmetric split H-like shaped on a fused silica substrate. The reflectance was measured and a red-shift is recorded from the resonators plasmonic peaks. Fourier transform infrared spectroscopy is use to observe enhanced spectra of the stretching modes for the analyte which belongs to alkenyl biochemical group.

  7. Serum levels of testosterone precursors, testosterone and estradiol in 10 animal species.

    PubMed

    Wichmann, U; Wichmann, G; Krause, W

    1984-05-01

    Blood levels of testosterone precursors, i.e. pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, androstendione, DHEA, and delta 5-androstendiol as well as testosterone and estradiol are measured in 10 animals each of 10 different species. The determination is done by radioimmunoassay with steroidspecific antibodies. Precursors of the delta 5-pathway (DHEA, androstendiol) are low in the red deer, dog, cat, rat and guinea pig. Precursors of the delta 4-pathway (progesterone, 17-hydroxprogesterone, androstendione) are lower in the bull, boar, ram, stallion and rabbit thus indicating a predominance of different pathways in the animal species studied herein. Pregnenolone concentrations are of equal height in all animals, testosterone is lowest in the cat and stallion. In the latter species the estradiol/testosterone ratio is spectacular high. PMID:6540697

  8. Progesterone After Estradiol Modulates Shuttle-Cage Escape by Facilitating Volition

    PubMed Central

    Mayeaux, Darryl J.; Tandle, Sarah M.; Cilano, Sean M.; Fitzharris, Matthew J.

    2015-01-01

    In animal models of depression, depression is defined as performance on a learning task. That task is typically escaping a mild electric shock in a shuttle cage by moving from one side of the cage to the other. Ovarian hormones influence learning in other kinds of tasks, and these hormones are associated with depressive symptoms in humans. The role of these hormones in shuttle-cage escape learning, however, is less clear. This study manipulated estradiol and progesterone in ovariectomized female rats to examine their performance in shuttle-cage escape learning without intentionally inducing a depressive-like state. Progesterone, not estradiol, within four hours of testing affected latencies to escape. The improvement produced by progesterone was in the decision to act, not in the speed of learning or speed of escaping. This parallels depression in humans in that depressed people are slower in volition, in their decisions to take action. PMID:26823653

  9. Increased egg estradiol concentration feminizes digit ratios of male pheasants (Phasianus colchicus).

    PubMed

    Saino, N; Rubolini, D; Romano, M; Boncoraglio, G

    2007-03-01

    The length ratio between individual digits differs between males and females in humans, other mammals, lizards, and one bird species. Sexual dimorphism in digit ratios and variation among individuals of the same sex may depend on differential exposure to androgens and estrogens during embryonic life. Organizational effects of sex hormones could cause the observed correlations between digit ratios and diverse phenotypic traits in humans. However, no study has investigated experimentally the effect of prenatal estrogens on digit ratios. We analyzed the effect of estradiol injection in ring-necked pheasant (Phasianus colchicus) eggs on digit ratios. Males from control eggs had higher ratios between the second or third and the fourth digit of the right foot compared to females. Estradiol-treated eggs produced males with lower (feminized) right foot second to fourth digit ratio. Thus, we provided the first experimental evidence that prenatal exposure to physiologically high estrogen levels affects bird digit ratios. PMID:17136513

  10. Randomized Controlled Trial of Low-Dose Estradiol and the SNRI Venlafaxine for Vasomotor Symptoms

    PubMed Central

    Joffe, Hadine; Guthrie, Katherine A.; LaCroix, Andrea Z.; Reed, Susan D.; Ensrud, Kristine E.; Manson, JoAnn E.; Newton, Katherine M.; Freeman, Ellen W.; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie; Shifren, Jan; Rexrode, Kathryn M.; Caan, Bette; Sternfeld, Barbara; Carpenter, Janet S.; Cohen, Lee

    2014-01-01

    Importance Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine is used widely as a non-hormonal treatment. While clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial. Objective To determine the efficacy and tolerability of low-dose oral 17-beta-estradiol and low-dose venlafaxine XR in alleviating vasomotor symptoms. Design and Participants 339 peri- and postmenopausal women with ≥2 bothersome vasomotor symptoms per day (mean 8.1, SD 5.3/day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites November 2011—October 2012. Interventions Participants were randomized to double-blinded treatment with low-dose oral 17-beta-estradiol 0.5-mg/day (n=97), low-dose venlafaxine XR 75-mg/day (n=96), or placebo (n=146) for 8 weeks. Main Outcomes Primary outcome was the mean daily frequency of vasomotor symptoms after 8 weeks of treatment. Secondary outcomes were vasomotor symptom severity, bother and interference. Intent-to-treat analyses compared change in vasomotor symptom frequency between each active intervention and placebo and between the two active treatments. Results Compared to baseline, mean vasomotor symptom frequency at week 8 decreased by 53% with estradiol, 48% with venlafaxine, and 29% with placebo. Estradiol reduced the frequency of symptoms by 2.3 (95% CI 1.3–3.4) more per day than placebo (p<0.001), and venlafaxine by 1.8 (95% CI 0.8–2.7) more per day than placebo (p=0.005). Results were consistent for VMS severity, bother and interference. Low-dose estradiol reduced symptom frequency by 0.6 more per day than venlafaxine (95% CI, 1.8 more per day to 0.6 fewer per day than

  11. Tissue Distribution of Polychlorinated Biphenyls and Organochlorine Pesticides and Potential Toxicity to Alaskan Northern Fur Seals Assessed Using PCBs Congener Specific Mode of Action Schemes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The concentrations of 145 polychlorinated biphenyl (PCB) congeners were measured using gas chromatography-ion trap mass spectrometry in 8 different tissues (blubber, brain, heart, kidney, liver, lung, muscle, and reproductive tissues) of 10 Alaskan northern fur seals. The mean concentrations of bot...

  12. INCREASED [3H]-PHORBOL ESTER BINDING IN RAT CEREBELLAR GRANULE CELLS BY POLYCHLORINATED BIPHENYL MIXTURES AND CONGENERS: STRUCTURE-ACTIVITY RELATIONSHIPS

    EPA Science Inventory

    Our previous reports indicate that the neuroactivity of polychlorinated biphenyl (PCB) congeners may be associated with perturbations in cellular Ca2-homeostasis, and protein kinase C (PKC) activation/translocation. e have now studied the structure-activity relationship of severa...

  13. Experimental and theoretical studies into the formation of C4-C6 products in partially chlorinated hydrocarbon pyrolysis systems: a probabilistic approach to congener-specific yield predictions.

    PubMed

    McIntosh, Grant J; Russell, Douglas K

    2014-09-25

    This work presents a study of the pyrolytic formation of vinylacetylene and benzene congeners formed from chlorinated hydrocarbon precursors, a complex, multipath polymerization system formed in a monomer-rich environment. (Co-)pyrolyses of dichloro- and trichloroethylene yield a rich array of products, and assuming a single dominant underlying growth mechanism, this (on comparing expected and observed products) allows a number of potentially competing channels to C4 and C6 products to be ruled out. Poor congener/isomer descriptions rule out even-carbon radical routes, and the absence of C3 and C5 products rule out odd-carbon processes. Vinylidenes appear unable to describe the increased reactivity of acetylenes with chlorination noted in our experiments, leaving molecular acetylene dimerization processes and, in C6 systems, the closely related Diels-Alder cyclization as the likely reaction mechanism. The feasibility of these routes is further supported by ab initio calculations. However, some of the most persuasive evidence is provided by congener-specific yield predictions enabled by the construction of a probability tree analogue of kinetic modeling. This approach is relatively quick to construct, provides surprisingly accurate predictions, and may be a very useful tool in screening for important reaction channels in poorly understood congener- or isomer-rich reaction systems. PMID:25225996

  14. USING BASE-SPECIFIC SALMONELLA TESTER STRAINS TO CHARACTERIZE THE TYPES OF MUTATION INDUCED BY BENZIDINE AND BENZIDINE CONGENERS AFTER REDUCTIVE METABOLISM

    EPA Science Inventory

    Abstract
    Benzidine, 4-aminobiphenyl, 3,3'-dichlorobenzidine HCl, 3,3'-dimethylbenzidine, 3,3'- dimethoxybenzidine and benzidine congener-based dye trypan blue were mutagenic in Salmonella typhimurium TAl 00 only with metabolic activation. It was found that a hamster liver 89 ...

  15. Reproductive Characteristics Differed in a Series of B-Congenic Lines of White Leghorns Evidently Indicating Significant Influence of Major Histocompatibility Complex in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reproductive characteristics were compared between a series of seven B-congenic lines of White Leghorns retrospectively using eight year’s reproduction records.The records encompass a total of 33,010 fertile eggs set to hatch under controlled conditions, which were collected accumulatively from 2,1...

  16. Specific congener profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans in blue mussel in Osaka Bay in Japan: Aqueous solubilities of PCDDs and PCDFs

    SciTech Connect

    Miyata, Hideaki; Takayama, Koji; Mimura, Mayumi; Kashimoto, Takashi ); Fukushima, Shigehiko )

    1989-09-01

    The authors have monitored polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in the coastal waters of Japan by using blue mussel (Mytilus edulis) as a biological indicator. The levels of both chemicals were surmised to closely relate to the number of municipal incinerators and the population densities in the cities adjoining the sampling location. The main contamination source in Osaka Bay, which is heavy polluted with PCDDs and PCDFs, was determined to be the fly ash from municipal waste incinerators based upon analytical results of blue mussel from Osaka Bay sediments, sediments from Osaka Bay, and sediments from a river, which is located near a typical urban municipal waste incinerator. However, there was a remarkable difference in congener profiles of PCDDs and PCDFs between the blue mussel and the fly ash, that is, the mussel mainly contained tetraCDDs and tetraCDFs with congener ratios of 56 {plus minus} 9.7% and 62 {plus minus} 6.0%, respectively, whereas the fly ash contained the higher chlorinated PCDDs and PCDFs as major congeners. In this study, the specific congener profiles of PCDDs and PCDFs in blue mussel were investigated from the point of view of their water solubilities.

  17. MONO- TO TRI-CHLORINATED DIBENSODIOXIN (CDD) AND DIBENZOFURAN (CDF) CONGENERS/HOMOLOGUES AS INDICATORS OF CDD AND CDF EMISSIONS FROM MUNICIPAL WASTE AND WASTE/COAL COMBUSTION

    EPA Science Inventory

    Total homologue concentrations and select congener concentrations from amongst the mono- to tri-chlorinated dibenzodioxins (CDDs) and dibenzofurans (CDFs) are used to model both total (mono- to octa-) CDD + CDF emissions and the toxicity equivalent (TEQ) of 2,3,7,8-chlorine-subst...

  18. Phenomenological and Spectroscopic Analysis on the Effects of Sediment Ageing and Organic Carbon on the Fate of a PCB Congener Spiked to Sediment

    EPA Science Inventory

    This study assesses the full cycle transport and fate of a polychlorinated biphenyl (PCB) congener spiked to sediment to empirically and spectroscopically investigate the effects of sediment ageing and organic carbon on the adsorption, desorption, and reaction of the PCB. Caesar ...

  19. DEVELOPMERNT OF A LOW-LEVEL ANALYTICAL METHOD FOR CO-PLANAR PCB CONGENERS IN SOIL/SEDIMENT MATRICES USING GC/ECD.

    EPA Science Inventory

    The method development is on-going in the Region 10 Laboratory. The conditions of the separation technique is complete. The MDLs have been determined to be between 3 to 6 ppt in marine sediment for co-planar PCB congeners #77; #81; #126 and #169. The procedure has been used fo...

  20. Identification of Stmm3 locus Conferring Resistance to Late-stage Chemically Induced Skin Papillomas on Mouse Chromosome 4 by Congenic Mappingand Allele-specific Alteration Analysis

    PubMed Central

    Saito, Megumi; Okumura, Kazuhiro; Miura, Ikuo; Wakana, Shigeharu; Kominami, Ryo; Wakabayashi, Yuichi

    2014-01-01

    Genome-wide association studies have revealed that many low-penetrance cancer susceptibility loci are located throughout the genome; however, a very limited number of genes have been identified so far. Using a forward genetics approach to map such loci in a mouse skin cancer model, we previously identified strong genetic loci conferring resistance to chemically induced skin papillomas on chromosome 4 and 7 with a large number of [(FVB/N × MSM/Ms) F1 × FVB/N] backcross mice. In this report, we describe a combination of congenic mapping and allele-specific alteration analysis of the loci on chromosome 4. We used linkage analysis and a congenic mouse strain, FVB.MSM-Stmm3 to refine the location of Stmm3 (Skin tumor modifier of MSM 3) locus within a physical interval of about 34 Mb on distal chromosome 4. In addition, we used patterns of allele-specific imbalances in tumors from N2 and N10 congenic mice to narrow down further the region of Stmm3 locus to a physical distance of about 25 Mb. Furthermore, immunohistochemical analysis showed papillomas from congenic mice had less proliferative activity. These results suggest that Stmm3 responsible genes may have an influence on papilloma formation in the two-stage skin carcinogenesis by regulating papilloma growth rather than development. PMID:25077764

  1. Evaluation of Comprehensive 2-D Gas Chromatography-Time-Of-Flight Mass Spectrometry for 209 Chlorinated Biphenyl Congeners in Two Chromatographic Runs

    EPA Science Inventory

    This research evaluates a recently developed comprehensive 2-D GC coupled with a time-of-flight (TOF) mass spectrometer for the potential separation of 209 PCB congeners, using a sequence of 1-D and 2-D chromatographic modes. In two consecutive chromatographic runs, using a 40 m,...

  2. Simultaneous Degradation of Estrone, 17β-Estradiol and 17α-Ethinyl Estradiol in an Aqueous UV/H₂O₂ System.

    PubMed

    Ma, Xiaoyan; Zhang, Chao; Deng, Jing; Song, Yali; Li, Qingsong; Guo, Yaping; Li, Cong

    2015-10-01

    UV/H₂O₂, which is an advanced treatment technology used to reduce multiple contaminants, is effective in potable water treatment. Simultaneous degradation effects and kinetics of three types of coexisting micropollutant estrogens (steroid estrogens, SEs), including estrone (E1), 17β-estradiol (E2) and 17α-ethinyl estradiol (EE2), in deionized water were studied. Experiments were carried out with ultraviolet-C (UVC) radiation, together with hydrogen peroxide (H₂O₂), in a cylinder photoreactor. The results demonstrated that the degradation processes of all of the estrogens strongly fit first-order kinetics. Single solutions of E1, E2 and EE2 showed higher degradation rates and removal efficiencies under the same reaction conditions compared with those under mixed conditions. Coexisting combinations of estrogens were put into the UV/H₂O₂ system to estimate their possible competitive influences on each other by examining their removal efficiencies and reaction rate constant, k, values. E1 is predominantly reduced rapidly during the competition, while the presence of other estrogens has negligible impacts on E1; however, the degradation of E2 and EE2 is affected by the competitive background, not in relation to the types but to the existing amounts. In the UV/H₂O₂ system, photocatalysis of the estrogens can stably produce an intermediate X, with the highest quantity coming from E1, while considerably lower quantities are obtained from E2 and EE2. PMID:26404330

  3. Simultaneous Degradation of Estrone, 17β-Estradiol and 17α-Ethinyl Estradiol in an Aqueous UV/H2O2 System

    PubMed Central

    Ma, Xiaoyan; Zhang, Chao; Deng, Jing; Song, Yali; Li, Qingsong; Guo, Yaping; Li, Cong

    2015-01-01

    UV/H2O2, which is an advanced treatment technology used to reduce multiple contaminants, is effective in potable water treatment. Simultaneous degradation effects and kinetics of three types of coexisting micropollutant estrogens (steroid estrogens, SEs), including estrone (E1), 17β-estradiol (E2) and 17α-ethinyl estradiol (EE2), in deionized water were studied. Experiments were carried out with ultraviolet-C (UVC) radiation, together with hydrogen peroxide (H2O2), in a cylinder photoreactor. The results demonstrated that the degradation processes of all of the estrogens strongly fit first-order kinetics. Single solutions of E1, E2 and EE2 showed higher degradation rates and removal efficiencies under the same reaction conditions compared with those under mixed conditions. Coexisting combinations of estrogens were put into the UV/H2O2 system to estimate their possible competitive influences on each other by examining their removal efficiencies and reaction rate constant, k, values. E1 is predominantly reduced rapidly during the competition, while the presence of other estrogens has negligible impacts on E1; however, the degradation of E2 and EE2 is affected by the competitive background, not in relation to the types but to the existing amounts. In the UV/H2O2 system, photocatalysis of the estrogens can stably produce an intermediate X, with the highest quantity coming from E1, while considerably lower quantities are obtained from E2 and EE2. PMID:26404330

  4. Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

    PubMed

    Al Abed, Alice Shaam; Sellami, Azza; Brayda-Bruno, Laurent; Lamothe, Valérie; Noguès, Xavier; Potier, Mylène; Bennetau-Pelissero, Catherine; Marighetto, Aline

    2016-07-01

    Because estrogens have mostly been studied in gonadectomized females, effects of chronic exposure to environmental estrogens in the general population are underestimated. Estrogens can enhance hippocampus-dependent memory through the modulation of information storage. However, declarative memory, the hippocampus-dependent memory of facts and events, demands more than abilities to retain information. Specifically, memory of repetitive events of everyday life such as "where I parked" requires abilities to organize/update memories to prevent proactive interference from similar memories of previous "parking events". Whether such organizational processes are estrogen-sensitive is unknown. We here studied, in intact young and aged adult mice, drinking-water (1μM) estradiol effects on both retention and organizational components of hippocampus-dependent memory, using a radial-maze task of everyday-like memory. Demand on retention vs organization was manipulated by varying the time-interval separating repetitions of similar events. Estradiol increased performance in young and aged mice under minimized organizational demand, but failed to improve the age-associated memory impairment and diminished performance in young mice under high organizational demand. In fact, estradiol prolonged mnemonic retention of successive events without improving organization abilities, hence resulted in more proactive interference from irrelevant memories. c-Fos imaging of testing-induced brain activations showed that the deterioration of young memory was associated with dentate gyrus dysconnectivity, reminiscent of that seen in aged mice. Our findings support the view that estradiol is promnesic but also reveal that such property can paradoxically impair memory. These findings have important outcomes regarding health issues relative to the impact of environmental estrogens in the general population. PMID:27038677

  5. 17β-estradiol differentially regulates stress circuitry activity in healthy and depressed women.

    PubMed

    Jacobs, Emily G; Holsen, Laura M; Lancaster, Katie; Makris, Nikos; Whitfield-Gabrieli, Sue; Remington, Anne; Weiss, Blair; Buka, Stephen; Klibanski, Anne; Goldstein, Jill M

    2015-02-01

    Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17β-estradiol (E₂) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E₂ during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E₂ conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E₂ modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E₂ conditions were attenuated under high E₂ conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced

  6. Association Between Serum Levels of Testosterone and Estradiol With Meibomian Gland Assessments in Postmenopausal Women

    PubMed Central

    Ablamowicz, Anna F.; Nichols, Jason J.; Nichols, Kelly K.

    2016-01-01

    Purpose The aims of this analysis were to determine if there is an association between serum levels of testosterone and estradiol with meibomian gland (MG) morphology and lipid layer thickness. Methods The data used for this analysis were collected from postmenopausal women with and without dry eye disease. Meibography was used to assess MG dropout on the central two-thirds of the eyelid and biomicroscopy was used for assessing MG expressibility and meibum quality. Venous blood samples were drawn for serum hormone level analysis. The Kruskal-Wallis test and Spearman correlations were used for statistical analysis. Results One hundred ninety-eight postmenopausal women with an average age of 61.2 (±9.1) years were included in this analysis. Testosterone levels showed significant differences between MG dropout grades 1 and 4 (P = 0.002) and grades 2 and 4 (P = 0.01), whereas estradiol levels were different based on MG dropout (P = 0.53). No significant correlations were found between testosterone (r = 0.10, P = 0.17) or estradiol (r = 0.05, P = 0.45) and lipid layer thickness. Conclusions Testosterone levels were increased with MG dropout, which was significant between the mild and severe dropout groups, whereas no significant differences were found with estradiol and any MG assessment. Although the literature suggests an association of serum hormone levels and pathogenesis of dry eye disease in postmenopausal women, analysis of active sex steroid precursors and local tissue hormone levels may prove more useful. PMID:26830366

  7. Estradiol-tethered micropatterned surfaces for the study of estrogenic non-genomic pathways.

    PubMed

    Qi, B; Shimizu, Y; Nakanishi, J; Winnik, F M

    2016-08-21

    Besides its well-known hormonal effects initiated in the nucleus, estradiol (E2) also activates non-nuclear pathways through interactions with receptors located on the cell plasma membrane. Micropatterned substrates consisting of gold dots bearing tethered E2 distributed on a cell-adhesive substrate were prepared and shown to trigger specifically E2 non-genomic effects in cells grown on the substrates. PMID:27451960

  8. Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.

    PubMed

    Mello, Nancy K; Negus, S Stevens; Knudson, Inge M; Kelly, Maureen; Mendelson, Jack H

    2008-03-01

    The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E(2)beta) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E(2)beta in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose-effect curve determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17beta-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E(2)beta in cyclodextrin and in sesame oil were studied. Acute administration of E(2)beta did not consistently alter the cocaine self-administration or drug discrimination dose-effect curves in comparison to saline control treatment. Females also did not self-administer E(2)beta (0.00001-0.10 mg/kg, i.v.) above saline levels. Finally, E(2)beta (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys. PMID:17507915

  9. Estradiol modulates myosin regulatory light chain phosphorylation and contractility in skeletal muscle of female mice.

    PubMed

    Lai, Shaojuan; Collins, Brittany C; Colson, Brett A; Kararigas, Georgios; Lowe, Dawn A

    2016-05-01

    Impairment of skeletal muscle function has been associated with changes in ovarian hormones, especially estradiol. To elucidate mechanisms of estradiol on skeletal muscle strength, the hormone's effects on phosphorylation of the myosin regulatory light chain (pRLC) and muscle contractility were investigated, hypothesizing an estradiol-specific beneficial impact. In a skeletal muscle cell line, C2C12, pRLC was increased by 17β-estradiol (E2) in a concentration-dependent manner. In skeletal muscles of C57BL/6 mice that were E2 deficient via ovariectomy (OVX), pRLC was lower than that from ovary-intact, sham-operated mice (Sham). The reduced pRLC in OVX muscle was reversed by in vivo E2 treatment. Posttetanic potentiation (PTP) of muscle from OVX mice was low compared with that from Sham mice, and this decrement was reversed by acute E2 treatment, demonstrating physiological consequence. Western blot of those muscles revealed that low PTP corresponded with low pRLC and higher PTP with greater pRLC. We aimed to elucidate signaling pathways affecting E2-mediated pRLC using a kinase inhibitor library and C2C12 cells as well as a specific myosin light chain kinase inhibitor in muscles. PI3K/Akt, MAPK, and CamKII were identified as candidate kinases sensitive to E2 in terms of phosphorylating RLC. Applying siRNA strategy in C2C12 cells, pRLC triggered by E2 was found to be mediated by estrogen receptor-β and the G protein-coupled estrogen receptor. Together, these results provide evidence that E2 modulates myosin pRLC in skeletal muscle and is one mechanism by which this hormone can affect muscle contractility in females. PMID:26956186

  10. Estradiol and brain serotonin reuptake transporter in long-term ovariectomized parkinsonian monkeys.

    PubMed

    Sánchez, Maria Gabriela; Morissette, Marc; Di Paolo, Thérèse

    2013-08-01

    This study evaluated the effect of a one month 17β-estradiol treatment on brain serotonin (5-HT) reuptake transporter (SERT) in long-term ovariectomized (OVX) female monkeys (Macaca fascicularis) bearing a unilateral lesion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injected directly into the left substantia nigra modeling Parkinson disease (PD). Ovariectomy and MPTP lesion were performed four years before the estrogen treatment to model postmenopausal PD patients. SERT was measured by autoradiography using the radioligand [(3)H]Citalopram. Specific binding to SERT decreased in anterior cerebral cortex, nucleus accumbens, caudate nucleus and putamen on the lesioned side of 17β-estradiol and vehicle-treated monkeys compared to the intact side. In caudate nucleus and putamen the lesioned-induced decrease of [(3)H]Citalopram specific binding was more extensive in anterior and middle than posterior parts. [(3)H]Citalopram specific binding was increased in the cortex anterior cingulate gyrus of monkeys treated with 17β-estradiol in both brain hemispheres and was unchanged in the other brain regions investigated including the raphe nucleus. Positive correlations between [(3)H]Citalopram specific binding and 5-HT as well as 5-HIAA concentrations (reported previously) were obtained in the caudate nucleus and putamen and a negative correlation between SERT binding and 5-HIAA/5-HT concentration ratio suggesting MPTP lesion-induced 5-HT neuronal loss and lower 5-HT neurotransmission controlling and decreasing SERT for homeostasis. 17β-estradiol treatment initiated four years after ovariectomy of monkeys modeling hormonal conditions of post-menopause shows that SERT still displays some responsiveness to estrogens as observed in the anterior cingulate cortex. These results support a role of estrogens in 5-HT activity in PD. PMID:23719069

  11. 17β-Estradiol Differentially Regulates Stress Circuitry Activity in Healthy and Depressed Women

    PubMed Central

    Jacobs, Emily G; Holsen, Laura M; Lancaster, Katie; Makris, Nikos; Whitfield-Gabrieli, Sue; Remington, Anne; Weiss, Blair; Buka, Stephen; Klibanski, Anne; Goldstein, Jill M

    2015-01-01

    Many regions within stress neurocircuitry, including the anterior hypothalamus, amygdala, hippocampus, and medial prefrontal cortex, are densely populated with sex steroid receptors. Substantial evidence from animal studies indicates that the gonadal hormone 17β-estradiol (E2) impacts the structure and function of these regions, but human studies are limited. Characterizing estradiol's role in stress circuitry in vivo in humans may have important clinical implications given the comorbidity between major depressive disorder (MDD), stress circuitry dysfunction and endocrine dysregulation. In this study, we determined estradiol's role in modulating activity within cortical and subcortical stress circuitry regions in healthy and MDD women. Subjects were part of a population-based birth cohort, the New England Family Study. Capitalizing on the endogenous fluctuation in E2 during the menstrual cycle, we conducted a within-person repeated-measures functional neuroimaging study in which 15 women with recurrent MDD, in remission, and 15 healthy control women underwent hormonal evaluations, behavioral testing, and fMRI scanning on two occasions, under low and high E2 conditions. Subjects completed an fMRI scan while undergoing a mild visual stress challenge that reliably activated stress neural circuitry. Results demonstrate that E2 modulates activity across key stress circuitry regions, including bilateral amygdala, hippocampus, and hypothalamus. In healthy women, robust task-evoked BOLD signal changes observed under low E2 conditions were attenuated under high E2 conditions. This hormonal capacity to regulate activity in stress circuitry was not observed in MDD women, despite their remitted status, suggesting that dysregulation of gonadal hormone function may be a characteristic trait of the disease. These findings serve to deepen our understanding of estradiol's actions in the healthy brain and the neurobiological mechanisms that may underlie the pronounced sex

  12. Analyzing the influence of BDNF heterozygosity on spatial memory response to 17β-estradiol

    PubMed Central

    Wu, Y W C; Du, X; van den Buuse, M; Hill, R A

    2015-01-01

    The recent use of estrogen-based therapies as adjunctive treatments for the cognitive impairments of schizophrenia has produced promising results; however the mechanism behind estrogen-based cognitive enhancement is relatively unknown. Brain-derived neurotrophic factor (BDNF) regulates learning and memory and its expression is highly responsive to estradiol. We recently found that estradiol modulates the expression of hippocampal parvalbumin-positive GABAergic interneurons, known to regulate neuronal synchrony and cognitive function. What is unknown is whether disruptions to the aforementioned estradiol–parvalbumin pathway alter learning and memory, and whether BDNF may mediate these events. Wild-type (WT) and BDNF heterozygous (+/−) mice were ovariectomized (OVX) at 5 weeks of age and simultaneously received empty, estradiol- or progesterone-filled implants for 7 weeks. At young adulthood, mice were tested for spatial and recognition memory in the Y-maze and novel-object recognition test, respectively. Hippocampal protein expression of BDNF and GABAergic interneuron markers, including parvalbumin, were assessed. WT OVX mice show impaired performance on Y-maze and novel-object recognition test. Estradiol replacement in OVX mice prevented the Y-maze impairment, a Behavioral abnormality of dorsal hippocampal origin. BDNF and parvalbumin protein expression in the dorsal hippocampus and parvalbumin-positive cell number in the dorsal CA1 were significantly reduced by OVX in WT mice, while E2 replacement prevented these deficits. In contrast, BDNF+/− mice showed either no response or an opposite response to hormone manipulation in both behavioral and molecular indices. Our data suggest that BDNF status is an important biomarker for predicting responsiveness to estrogenic compounds which have emerged as promising adjunctive therapeutics for schizophrenia patients. PMID:25603414

  13. Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse

    SciTech Connect

    Wu, Wenda; He, Kaiyu; Zhou, Hui-Ren; Berthiller, Franz; Adam, Gerhard; Sugita-Konishi, Yoshiko; Watanabe, Maiko; Krantis, Anthony; Durst, Tony; Zhang, Haibin; Pestka, James J.

    2014-07-15

    The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6 h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), the plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528's effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity. - Highlights: • We compared effects of DON congeners on biomarker proinflammatory genes in mice. • Oral DON induced splenic IL-1β, IL-6, TNF-α,CXCL-2, CCL-2 and CCL-7 mRNAs. • 8-Ketotrichothecene ranking for

  14. Estradiol lowers intracranial self-stimulation thresholds and enhances cocaine facilitation of intracranial self-stimulation in rats.

    PubMed

    Galankin, Timofey; Shekunova, Elena; Zvartau, Edwin

    2010-11-01

    Women initiate cocaine use at a younger age and have more complications (e.g., higher rates of major or minor depression) related to cocaine use than men. It has been proposed that estrogens play an important role in these sex differences. The addictive potential of psychoactive drugs can be measured in rats via a rewarding intracranial self-stimulation (ICSS) procedure. The rate-independent method of ICSS allows researchers to assess the "pure" rewarding effect of cocaine without influence of nonspecific motor reactions. The present study aimed to estimate effects of estradiol and a combination of estradiol and cocaine on ICSS in ovariectomized female rats. 17-β-estradiol (5μg/animal/day, 2 days) produced a long-lasting gradual lowering of the thresholds for ICSS. The ability of estradiol to decrease thresholds for ICSS has never been shown previously. Combination of 17-β-estradiol and cocaine (5.0mg/kg, 5 days) produced a greater effect on ICSS thresholds than the effect of either compound alone. No tolerance or sensitization to cocaine developed during the study. Present findings suggest estradiol increases sensitivity of the brain reward system in rats, which may have an important implication in understanding sex differences in cocaine effects. PMID:20736014

  15. The induction of pro-angiogenic processes within a collagen scaffold via exogenous estradiol and endometrial epithelial cells.

    PubMed

    Pence, Jacquelyn C; Clancy, Kathryn B H; Harley, Brendan A C

    2015-10-01

    Nutrient transport remains a major limitation in the design of biomaterials. One approach to overcome this constraint is to incorporate features to induce angiogenesis-mediated microvasculature formation. Angiogenesis requires a temporal presentation of both pro- and anti-angiogenic factors to achieve stable vasculature, leading to increasingly complex biomaterial design scheme. The endometrium, the lining of the uterus and site of embryo implantation, exemplifies a non-pathological model of rapid growth, shedding, and re-growth of dense vascular networks regulated by the dynamic actions of estradiol and progesterone. In this study, we examined the individual and combined response of endometrial epithelial cells and human umbilical vein endothelial cells to exogenous estradiol within a three-dimensional collagen scaffold. While endothelial cells did not respond to exogenous estradiol, estradiol directly stimulated endometrial epithelial cell transduction pathways and resulted in dose-dependent increases in endogenous VEGF production. Co-culture experiments using conditioned media demonstrated estradiol stimulation of endometrial epithelial cells can induce functional changes in endothelial cells within the collagen biomaterial. We also report the effect of direct endometrial epithelial and endothelial co-culture as well as covalent immobilization of estradiol within the collagen biomaterial. These efforts establish the suitability of an endometrial-inspired model for promoting pro-angiogenic events within regenerative medicine applications. These results also suggest the potential for developing biomaterial-based models of the endometrium. PMID:25944769

  16. Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor.

    PubMed

    Stefano, G B; Prevot, V; Beauvillain, J C; Fimiani, C; Welters, I; Cadet, P; Breton, C; Pestel, J; Salzet, M; Bilfinger, T V

    1999-10-01

    We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase (cNOS) activity in human peripheral monocytes by acting on an estrogen surface receptor. NO release was measured in real time with an amperometric probe. 17beta-estradiol exposure to monocytes stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol had no effect. 17beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA, whereas ICI 182,780, a selective inhibitor of the nuclear estrogen receptor, had no effect. We further showed, using a dual emission microfluorometry in a calcium-free medium, that the 17beta-estradiol-stimulated release of monocyte NO was dependent on the initial stimulation of intracellular calcium transients in a tamoxifen-sensitive process. Leeching out the intracellular calcium stores abolished the effect of 17beta-estradiol on NO release. RT-PCR analysis of RNA obtained from the cells revealed a strong estrogen receptor-alpha amplification signal and a weak beta signal. Taken together, a physiological dose of estrogen acutely stimulates NO release from human monocytes via the activation of an estrogen surface receptor that is coupled to increases in intracellular calcium. PMID:10490972

  17. Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

    PubMed

    Fteita, Dareen; Könönen, Eija; Gürsoy, Mervi; Söderling, Eva; Gürsoy, Ulvi Kahraman

    2015-12-01

    Initiation and development of pregnancy-associated gingivitis is seemingly related to the microbial shift towards specific gram-negative anaerobes in subgingival biofilms. It is known that Prevotella intermedia sensu lato is able to use estradiol as an alternative source of growth instead of vitamin K. The aim of the present study was to investigate the impact of estradiol on the bacterial dipeptidyl peptidase IV (DPPIV) enzyme activity in vitro as a virulent factor of the Prevotella intermedia group bacteria, namely P. intermedia, Prevotella nigrescens, Prevotella pallens, and Prevotella aurantiaca. In all experiments, 2 strains of each Prevotella species were used. Bacteria were incubated with the concentrations of 0, 30, 90, and 120 nmol/L of estradiol and were allowed to build biofilms at an air-solid interface. DPPIV activities of biofilms were measured kinetically during 20 min using a fluorometric assay. The enzyme activity was later related to the amount of protein produced by the same biofilm, reflecting the biofilm mass. Estradiol significantly increased DPPIV activities of the 8 Prevotella strains in a strain- and dose-dependent manner. In conclusion, our in vitro experiments indicate that estradiol regulates the DPPIV enzyme activity of P. intermedia, P. nigrescens, P. pallens, and P. aurantiaca strains differently. Our results may, at least partly, explain the role of estradiol to elicit a virulent state which contributes to the pathogenesis of pregnancy-related gingivitis. PMID:26386229

  18. Effect of agricultural antibiotics on the persistence and transformation of 17beta-estradiol in a Sequatchie loam.

    PubMed

    Chun, Soul; Lee, Jaehoon; Geyer, Roland; White, David C; Raman, D Raj

    2005-01-01

    A laboratory incubation study was conducted to investigate the effect of agricultural antibiotics (sulfamethazine, tylosin, and chlortetracycline) on the persistence and transformation of 17beta-estradiol in Sequatchie loam. We measured concentrations of 17beta-estradiol and its primary metabolite (estrone) in soils spiked with antibiotics and 17beta-estradiol. Dehydrogenase activity (DHA) was also measured as an indicator of the total microbial activity of the soils. The presence of antibiotics significantly decreased transformation of 17beta-estradiol to estrone. There was a positive correlation between the DHA and the concentrations of estrone in soil spiked with 17beta-estradiol only, implying that the reaction is mainly catalyzed by dehydrogenases. However, the positive correlation was weakened in soil spiked with 17beta-estradiol and antibiotics together. We recommend that any study evaluating the fate and transport of estrogenic hormones in soil should include the effect of agricultural antibiotics because antibiotics and estrogenic hormones are commonly excreted together in environmental samples. PMID:16190018

  19. Crystallization of beta-estradiol in an acrylic transdermal drug delivery system.

    PubMed

    Variankaval, N E; Jacob, K I; Dinh, S M

    1999-03-15

    Transdermal drug delivery systems are pharmaceutical products that can deliver controlled doses of drugs from polymeric patches applied on the human skin. The long-term stability of these patches is a critical issue relative to their performance in delivering drugs at a constant rate. Where a drug has been dissolved in the polymeric adhesive patch, crystallization has been reported in several systems. This study uses a variety of characterization tools to determine the physical and chemical nature of the precipitates formed in situ in estradiol patches. Optical microscopy revealed that crystals were formed in a single layer inside the adhesive matrix and that there were two distinctly different morphologies: needle-like crystals and aggregates around the needles. From IR measurements it was evident that estradiol probably was present in more than one crystal form in these patches. Raman microscopy showed that the needle-like crystals contain the adhesive component and the aggregates some modified crystal form of estradiol, indicating that in addition to the drug, the polymeric adhesive also crystallizes during storage. PMID:10397943

  20. Localization of /sup 3/H-estradiol in the reproductive organs of male and female baboons

    SciTech Connect

    Weaker, F.J.; Sheridan, P.J.

    1982-05-01

    The uptake and retention of radiolabeled estradiol by both the male and female reproductive organs were examined in the baboon. Two male and two female baboons were injected intracardially with 1 microgram/kg body weight of /sup 3/H-estradiol and two animals, one male and one female, were injected with both labeled and 100 micrograms/kg body weight of unlabeled estradiol. One and a half hours after the injections, the animals were sacrificed and the uterus, cervix, vagina, oviduct, seminal vesicles, and prostate gland were removed and processed for autoradiography. The stratified squamous epithelia of the cervix and vagina demonstrated a light uptake of the label in the germinative, but not in the superficial cell layers. The columnar cells lining the oviduct and uterine glands were labeled, whereas the luminal epithelium of the uterus and the glandular epithelia of the seminal vesicles and prostate gland did not sequester the tritiated steroid. The interstitial cells of all the organs studied demonstrated a moderate to heavy uptake of the radioactivity, whereas the smooth muscle cells were lightly labeled except in the vagina, in which these cells displayed a moderate number of silver grains.