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Sample records for estradiol treatment increases

  1. Estradiol increases choice of cocaine over food in male rats.

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    Bagley, Jared R; Adams, Julia; Bozadjian, Rachel V; Bubalo, Lana; Ploense, Kyle L; Kippin, Tod E

    2017-10-19

    Estradiol modulates the rewarding and reinforcing properties of cocaine in females, including an increase in selection of cocaine over alternative reinforcers. However, the effects of estradiol on male cocaine self-administration behavior are less studied despite equivalent levels of estradiol in the brains of adult males and females, estradiol effects on motivated behaviors in males that share underlying neural substrates with cocaine reinforcement as well as expression of estrogen receptors in the male brain. Therefore, we sought to characterize the effects of estradiol in males on choice between concurrently-available cocaine and food reinforcement as well as responding for cocaine or food in isolation. Male castrated rats (n=46) were treated daily with estradiol benzoate (EB) (5μg/0.1, S.C.) or vehicle (peanut oil) throughout operant acquisition of cocaine (1mg/kg, IV; FI20 sec) and food (3×45mg; FI20 sec) responding, choice during concurrent access and cocaine and food reinforcement under progressive ratio (PR) schedules. EB increased cocaine choice, both in terms of percent of trials on which cocaine was selected and the proportion of rats exhibiting a cocaine preference as well as increased cocaine, but not food, intake under PR. Additionally, within the EB treated group, cocaine-preferring rats exhibited enhanced acquisition of cocaine, but not food, reinforcement whereas no acquisition differences were observed across preferences in the vehicle treated group. These findings demonstrate that estradiol increases cocaine choice in males similarly to what is observed in females. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Effects of chronic estradiol treatment on the thyroid gland structure and function of ovariectomized rats

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    Elgendy Mohamed S

    2009-08-01

    Full Text Available Abstract Background Estrogen therapy is widely used nowadays in women to treat many postmenopausal symptoms but it may have some undesirable effects due to multiple organs affection. So, the aim of this study was to determine the effects of chronic estradiol treatment on the structure and function of the thyroid gland in ovarictomized rats as a model simulating menopause. Findings Thirty adult female Wistar rats divided into three groups were used in this study; the first group was sham-operated, while the second and third groups were ovariectomized. The first and second groups were injected with olive oil while the third group was injected with estradiol dipropionate daily for three months, after that; hormonal assay for T3, T4, TSH and specimens of the thyroid were taken and processed to be examined by light and electron microscopy. The results of this study revealed that serum levels of T3 and T4 decreased in ovariectomized animals and significantly increased after estradiol treatment, while TSH increased in ovariectomized animals and decreased with estradiol treatment. Histological and morphometric study in ovariectomized group revealed marked accumulation of colloid in follicular lumens with decreased epithelial height in addition to increased connective tissue amount. After estradiol treatment the follicles became smaller in size, having small amount of colloid with increased epithelial height in addition to decreased connective tissue content. Ultrastructural study supported these results in addition to the presence of large amount of intracytoplasmic colloid vesicles after estradiol treatment. Conclusion Low estrogen level may lead to mild thyroidal hypofunction while estradiol treatment may lead to hyperactivity so it should be used very cautiously in the treatment of postmenopausal symptoms to avoid its undesirable stimulatory effect on the thyroid.

  3. Acute treatment with 17beta-estradiol attenuates astrocyte-astrocyte and astrocyte-neuron communication.

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    Rao, Shilpa P; Sikdar, Sujit Kumar

    2007-12-01

    Astrocytes are now recognized as dynamic signaling elements in the brain. Bidirectional communication between neurons and astrocytes involves integration of neuronal inputs by astrocytes and release of gliotransmitters that modulate neuronal excitability and synaptic transmission. The ovarian steroid hormone, 17beta-estradiol, in addition to its rapid actions on neuronal electrical activity can rapidly alter astrocyte intracellular calcium concentration ([Ca2+]i) through a membrane-associated estrogen receptor. Using calcium imaging and electrophysiological techniques, we investigated the functional consequences of acute treatment with estradiol on astrocyte-astrocyte and astrocyte-neuron communication in mixed hippocampal cultures. Mechanical stimulation of an astrocyte evoked a [Ca2+]i rise in the stimulated astrocyte, which propagated to the surrounding astrocytes as a [Ca2+]i wave. Following acute treatment with estradiol, the amplitude of the [Ca2+]i elevation in astrocytes around the stimulated astrocyte was attenuated. Further, estradiol inhibited the [Ca2+]i rise in individual astrocytes in response to the metabotropic glutamate receptor agonist, trans-(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid. Mechanical stimulation of astrocytes induced [Ca2+]i elevations and electrophysiological responses in adjacent neurons. Estradiol rapidly attenuated the astrocyte-evoked glutamate-mediated [Ca2+]i rise and slow inward current in neurons. Also, the incidence of astrocyte-induced increase in spontaneous postsynaptic current frequency was reduced in the presence of estradiol. The effects of estradiol were stereo-specific and reversible following washout. These findings may indicate that the regulation of neuronal excitability and synaptic transmission by astrocytes is sensitive to rapid estradiol-mediated hormonal control. (c) 2007 Wiley-Liss, Inc.

  4. Increased serum estrone and estradiol following spironolactone administration in hypertensive men

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    Miyatake, A; Noma, K; Nakao, K; Morimoto, Y; Yamamura, Y [Osaka Univ. (Japan). Faculty of Medicine

    1978-12-01

    This study was undertaken to evaluate long-term effects of spironolactone on basal serum estrone, estradiol, testosterone, LH and prolactin concentrations in hypertensive male patients. Serum prolactin response to TRH was also evaluated. There were two groups, (a) six males with essential hypertension given 75 - 150 mg spironolactone daily for 12 weeks, and (b) two males with idiopathic hyperaldosteronism given 300 mg daily for over 40 weeks. In the conventional-dosage group, serum estrone concentrations significantly increased (P < 0.01) at 12 weeks serum estradiol gradually increased but not statistically significantly (P < 0,2). Basal serum testosterone, LH and prolactin concentrations did not show significant changes. There was no increase in serum prolactin response to TRH. In the high-dosage group, serum estrone levels remained high, and serum estradiol increased with the development of gynaecomastia. Serum testosterone, LH and prolactin concentrations showed no marked changes. The elevations in circulating oestrogens could well explain the oestrogenic side-effects of spironolactone treatment.

  5. Estradiol increases the Bax/Bcl-2 ratio and induces apoptosis in the anterior pituitary gland.

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    Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

    2009-01-01

    Estrogens are recognized as acting as modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals, thus participating in anterior pituitary homeostasis during the estrous cycle. The balance of pro- and antiapoptotic proteins of the Bcl-2 family is known to regulate cell survival and apoptosis. In order to understand the mechanisms underlying apoptosis during the estrous cycle, we evaluated the expression of the proapoptotic protein Bax and the antiapoptotic proteins Bcl-2 and Bcl-xL in the anterior pituitary gland in cycling female rats as well as the influence of estradiol on the expression of these proteins in anterior pituitary cells of ovariectomized rats. As determined by Western blot, the expression of Bax was higher in anterior pituitary glands from rats at proestrus than at diestrus I, Bcl-2 protein levels showed no difference and Bcl-xL expression was lower, thus increasing the Bax/Bcl-2 ratio at proestrus. Assessed by annexin V binding and flow cytometry, the percentage of apoptotic anterior pituitary cells was higher in rats at proestrus than at diestrus I. Chronic estrogen treatment in ovariectomized rats enhanced the Bax/Bcl-2 ratio and induced apoptosis. Moreover, incubation of cultured anterior pituitary cells from ovariectomized rats with 17beta-estradiol for 24 h increased the Bax/Bcl-2 ratio, decreased Bcl-xL expression and induced apoptosis. Our results demonstrate that estradiol increases the ratio between proapoptotic and antiapoptotic proteins of the Bcl-2 family. This effect could participate in the sensitizing action of estrogens to proapoptotic stimuli and therefore be involved in the high apoptotic rate observed at proestrus in the anterior pituitary gland.

  6. Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

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    Menon, M.; Peegel, H.; Katta, V.

    1985-01-01

    In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction

  7. Estradiol-induced alopecia in five dogs after contact with a transdermal gel used for the treatment of postmenopausal symptoms in women.

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    Wiener, Dominique J; Rüfenacht, Silvia; Koch, Hans J; Mauldin, Elizabeth A; Mayer, Ursula; Welle, Monika M

    2015-10-01

    Noninflammatory alopecia is a frequent problem in dogs. Estrogen-induced alopecia is well described in dogs, with estrogen producing testicular tumors and canine female hyperestrogenism. To increase awareness that extensive alopecia in dogs can be caused by exposure to estradiol gel used by owners to treat their postmenopausal symptoms. Skin biopsies from five dogs with extensive alopecia were examined. Owners were asked for a thorough case history, including possible exposure to an estradiol gel. Complete blood work and serum chemistry panel analysis were performed to investigate possible underlying causes. Formalin-fixed skin biopsy samples were obtained from lesional skin and histopathology was performed. All owners confirmed the use of a transdermal estradiol gel and close contact with the affected dogs before development of alopecia. Histopathologic examination showed a similar picture in all five dogs. Most hair follicles were predominantly either in kenogen or telogen and hair follicle infundibula showed mild to moderate dilation. Hair regrowth was present in all five dogs after the exposure to the estradiol gel was stopped or minimized. Blood work and serum chemistry panel were within normal limits in all cases. One dog had elevated estradiol concentrations, whereas in another dog estradiol concentrations were within normal limits. Alopecia can occur after contact with a transdermal gel used as treatment for postmenopausal symptoms in women. Estradiol gel used by female owners therefore represents a possible cause for noninflammatory alopecia in dogs. Estradiol concentrations are not necessarily elevated in affected dogs. © 2015 ESVD and ACVD.

  8. Estradiol increases the expression of TNF-α and TNF receptor 1 in lactotropes.

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    Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

    2011-01-01

    Estrogens are recognized modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that plays an important role in tissue homeostasis modulating cell proliferation, differentiation and death. We previously demonstrated that TNF-α-induced apoptosis of anterior pituitary cells from female rats is estrogen-dependent and predominant in cells from rats at proestrus when estradiol levels are the highest. Considering that one of the mechanisms involved in the apoptotic action of estrogens can result from increased expression of cytokines and/or their receptors, the aim of the present study was to evaluate the effect of estrogens on the expression of TNF-α and its receptor, TNF receptor 1 (TNFR1), in anterior pituitary cells. TNFR1 expression, determined by Western blot, was higher in anterior pituitary glands from rats at proestrus than at diestrus. Incubation of anterior pituitary cells from ovariectomized rats with 17β-estradiol enhanced TNFR1 protein expression. As determined by double immunocytochemistry, the expression of TNF-α and TNFR1 was detected in prolactin-, GH-, LH- and ACTH-bearing cells. 17β-estradiol increased the percentage of TNF-α and TNFR1-immunoreactive lactotropes but did not modify the number of GH-bearing cells expressing TNF-α or TNFR1. Our results demonstrate that estradiol increases the expression of TNF-α and TNFR1 in anterior pituitary cells, especially in lactotropes. The sensitizing action of estrogens to proapoptotic stimuli at proestrus in the anterior pituitary gland may involve changes in the expression of the TNF-α/TNFR1 system. Copyright © 2011 S. Karger AG, Basel.

  9. Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF, TrkB receptor and synaptic factors in ovariectomized rats

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    Li Zhuoneng

    2010-09-01

    Full Text Available Abstract Background Estrogen or phytoestrogens treatment has been suggested to improve cognitive function of the brain in postmenopausal women. However, there is lack of information on the mechanism of such treatment on the central nervous system. The present study aimed to determine the effects of estradiol and soy germ phytoestrogens on spatial memory performance in ovariectomized rats and to explore the underlying mechanisms affecting the central nervous system. Methods Ovariectomized Sprague-Dawley rats were fed a basic diet supplemented with soy germ phytoestrogens (0.4 g/kg or 1.6 g/kg or 17β-estradiol (0.15 g/kg for 12 weeks. At the end of the experiment, animals were evaluated for their spatial learning and memory performance by the Morris Water Maze task. The expressions of brain-derived neurotrophic factor (BDNF and synaptic formation proteins in the hippocampal tissue were estimated using RT-PCR and ELISA. Results It was found that rats supplemented with soy germ phytoestrogens or estradiol performed significantly better in spatial memory acquisition and retention when compared to the rats fed on the control diet. Estradiol or the high dose of phytoestrogens treatment significantly increased BDNF concentration and the mRNA levels for BDNF and its TrkB receptors as well as the synaptic formation proteins, synaptophysin, spinophilin, synapsin 1 and PSD-95, in the hippocampal tissue of the experimental animals. It was also found that phytoestrogens, in contrast to estradiol, did not show any significant effect on the vaginal and uteri. Conclusion Soy germ phytoestrogens, which may be a substitute of estradiol, improved spatial memory performance in ovariectomized rats without significant side-effects on the vaginal and uteri. The memory enhancement effect may relate to the increase in BDNF and the synaptic formation proteins expression in the hippocampus of the brain.

  10. Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol.

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    Bertha J Vandegrift

    Full Text Available Gender differences in psychiatric disorders such as addiction may be modulated by the steroid hormone estrogen. For instance, 17β-estradiol (E2, the predominant form of circulating estrogen in pre-menopausal females, increases ethanol consumption, suggesting that E2 may affect the rewarding properties of ethanol and thus the development of alcohol use disorder in females. The ventral tegmental area (VTA is critically involved in the rewarding and reinforcing effects of ethanol. In order to determine the role of E2 in VTA physiology, gonadally intact female mice were sacrificed during diestrus II (high E2 or estrus (low E2 for electrophysiology recordings. We measured the excitation by ethanol and inhibition by dopamine (DA of VTA DA neurons and found that both excitation by ethanol and inhibition by dopamine were greater in diestrus II compared with estrus. Treatment of VTA slices from mice in diestrus II with an estrogen receptor antagonist (ICI 182,780 reduced ethanol-stimulated neuronal firing, but had no effect on ethanol-stimulated firing of neurons in slices from mice in estrus. Surprisingly, ICI 182,780 did not affect the inhibition by DA, indicating different mechanisms of action of estrogen receptors in altering ethanol and DA responses. We also examined the responses of VTA DA neurons to ethanol and DA in ovariectomized mice treated with E2 and found that E2 treatment enhanced the responses to ethanol and DA in a manner similar to what we observed in mice in diestrus II. Our data indicate that E2 modulates VTA neuron physiology, which may contribute to both the enhanced reinforcing and rewarding effects of alcohol and the development of other psychiatric disorders in females that involve alterations in DA neurotransmission.

  11. Long-term estradiol treatment improves VIP-mediated vasodilation in atherosclerotic proximal coronary arteries

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    Dalsgaard, T.; Mortensen, Alicja; Larsen, C. R.

    2003-01-01

    arteries. Female ovariectomized homozygous Watanabe heritable hyperlipidemic rabbits were randomized to 16 weeks treatment with 17beta-estradiol or placebo. The diet was semisynthetic, thereby avoiding the influence of phytoestrogens. Artery ring segments were mounted for isometric tension recordings...... in myographs. Following precontraction, the dose-response relationships for VIP and PACAP were evaluated. Treatment with 17beta-estradiol significantly improved the maximum VIP-mediated vasodilation (E-max, percentage of precontraction) in proximal coronary arteries (45.8 +/- 9.6% vs. 24.1 +/- 3.7%, p ....05). In the same artery segment, 17β-estradiol induced a significant decrease in the relative ratio between the repeated contractile response to potassium 30 and 120 mM (100 +/- 7% vs. 132 +/- 11%, p

  12. Treatment of labial adhesion with topical estrogen and correlation with serum estradiol level

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    Safaian B

    2013-05-01

    Full Text Available Background: Serum estradiol level is a controversial prognostic factor in the outcome of labial adhesion. The aim of this study was to evaluate serum estradiol levels and topical estrogen response in patients with labial adhesion.Methods: A prospective interventional study was conducted among girls with labial adhesion that referred to Pediatrics clinic in Taleghani University Hospital, Gorgan city, Iran in 2011. One hundred patients entered the study. The diagnosis was conducted by clinical examination of vestibule area. Inclusion criteria were, three months to eight years old prepuberty girls, no ambiguous genitalia, lack of vulvovaginitis symptoms, labial adhesion more than twenty five percent, no history of previous topical estrogen treatment since two weeks ago and previous incomplete treatment. The patients who did not use proper amount and duration of drug and also with adverse drug reactions during treatment period were excluded from the study. Results: The maximum frequency of labial adhesion was in the group of less than one year old. The minimum frequency of labial adhesion was in the 7-8 years old group. Eighty six patients had complete or partial remission. No evidence of an improvement was observed in fourteen children. Severity of adhesions did not worsen in our patients. Serum estradiol levels were lower in patients who had a positive response to treatment. There were significant differences in serum estradiol levels between full or relative improvement with no improvement groups (P=0.044.Conclusion: Findings of this study showed that the labial adhesion patients with low serum estradiol level had better treatment response after using topical estrogen.

  13. Estradiol treatment in preadolescent females enhances adolescent spatial memory and differentially modulates hippocampal region-specific phosphorylated ERK labeling.

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    Wartman, Brianne C; Keeley, Robin J; Holahan, Matthew R

    2012-10-24

    Estrogen levels in rats are positively correlated with enhanced memory function and hippocampal dendritic spine density. There is much less work on the long-term effects of estradiol manipulation in preadolescent rats. The present work examined how injections of estradiol during postnatal days 19-22 (p19-22; preadolescence) affected water maze performance and hippocampal phosphorylated ERK labeling. To investigate this, half of the estradiol- and vehicle-treated female rats were trained on a water maze task 24h after the end of estradiol treatment (p23-27) while the other half was not trained. All female rats were tested on the water maze from p40 to p44 (adolescence) and hippocampal pERK1/2 labeling was assessed as a putative marker of neuronal plasticity. During adolescence, preadolescent-trained groups showed lower latencies than groups without preadolescent training. Retention data revealed lower latencies in both estradiol groups, whether preadolescent trained or not. Immunohistochemical detection of hippocampal pERK1/2 revealed elevations in granule cell labeling associated with the preadolescent trained groups and reductions in CA1 labeling associated with estradiol treatment. These results show a latent beneficial effect of preadolescent estradiol treatment on adolescent spatial performance and suggest an organizational effect of prepubescent exogenously applied estradiol. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Ethinyl estradiol-drospirenone vs ethinyl estradiol-drospirenone plus metformin in the treatment of lean women with polycystic ovary syndrome.

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    Cinar, Nese; Harmanci, Ayla; Bayraktar, Miyase; Yildiz, Bulent O

    2013-03-01

    Oral contraceptive use might be associated with cardiometabolic risk in PCOS. We aimed to compare the effects of ethinyl estradiol-drospirenone (EE/DRSP) alone vs EE/DRSP plus metformin on clinical and cardiometabolic parameters in PCOS. Prospective observational study. Forty-five lean patients with PCOS who received EE/DRSP (30 μg/3 mg) (n = 25) or EE/DRSP plus metformin (1700 mg/day) (n = 20) and 45 BMI-matched healthy controls. BMI, waist-to-hip ratio (WHR), hirsutism scores, androgens, lipids, glucose and insulin levels during an OGTT were measured before and after 6 months of treatment in patients and compared to controls. At baseline, patients with PCOS showed similar glucose, insulin and lipids but increased 2 h glucose values compared to controls. Hirsutism scores and free androgen index decreased in both treatment groups. BMI and WHR did not show any change in the EE/DRSP group, while metformin addition resulted in a decrease in BMI. Lipid levels increased in both groups. Glucose and insulin parameters did not change in any group, but metformin addition compared to EE/DRSP alone significantly decreased waist circumference, fasting insulin and HOMA-IR. After-treatment values for both EE/DRSP alone and in combination with metformin compared to the control group showed increased 2 h glucose and increased lipids in patients with PCOS. EE/DRSP alone or in combination with metformin improves clinical and biochemical hyperandrogenism in lean PCOS. Both treatments similarly alter lipid profile. EE/DRSP alone does not affect insulin sensitivity, whereas combining EE/DRSP with metformin might improve it. © 2012 Blackwell Publishing Ltd.

  15. Treatment of heavy menstrual bleeding with a new combination of estradiol valerate and dienogest

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    Luis Bahamondes

    2010-11-01

    Full Text Available Luis Bahamondes, Ilza Monteiro, Arlete FernandesHuman Reproduction Unit, Department of Obstetrics and Gynecology, School of Medical Sciences and National Institute of Hormones and Women’s Health, University of Campinas, Campinas, BrazilAbstract: The first combined oral contraceptive (OC was launched in the US 50 years ago and was followed by another formulation introduced in Germany one year later. The most common estrogen component in current formulations is ethinylestradiol; however, many concerns have been raised with respect to this estrogen. Although the natural estrogen produced by the ovary, 17-beta estradiol, is the most potent of the estrogens, it is poorly absorbed orally, and previous attempts to use it in combined OCs have been unsuccessful due to the occurrence of irregular bleeding. Recently, a new combined OC was developed containing a natural estrogen, estradiol valerate, and a new progestin, dienogest, in a dynamic 26-day, four-phasic (estrogen stepdown and progestin stepup scheme of administration. In clinical trials, its contraceptive performance was excellent, with good cycle control and bleeding patterns compared with other combined OCs or with placebo. This review focuses predominantly on the use of an estradiol valerate-dienogest combined OC for the treatment of heavy menstrual bleeding. The findings of two large, randomized, controlled trials have shown that this combined OC constitutes an effective treatment for women with heavy menstrual bleeding, representing a new therapeutic option to reduce menstrual blood loss. Further studies are necessary to confirm these data.Keywords: dienogest, estradiol valerate, heavy menstrual bleeding, menorrhagia, contraception

  16. Efficacy and safety of combined ethinyl estradiol/drospirenone oral contraceptives in the treatment of acne

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    Jerry KL Tan

    2009-11-01

    Full Text Available Jerry KL Tan1, Chemanthi Ediriweera21University of Western Ontario and Windsor Clinical Research Inc., Windsor, Ontario, Canada; 2University of Western Ontario, Southwest Ontario Medical Education Network, Windsor, Ontario, CanadaAbstract: Acne is a common disorder affecting the majority of adolescents and often extends into adulthood. The central pathophysiological feature of acne is increased androgenic stimulation and/or end-organ sensitivity of pilosebaceous units leading to sebum hypersecretion and infundibular hyperkeratinization. These events lead to Propionibacterium acnes proliferation and subsequent inflammation. Hormonal therapy, including combined oral contraceptives (OCs, can attenuate the proximate androgenic trigger of this sequence. For many women, hormonal therapy is a rational option for acne treatment as it may be useful across the spectrum of severity. Drospirenone (DRSP is a unique progestin structurally related to spironolactone with progestogenic, antimineralocorticoid, and antiandrogenic properties. It is available in 2 combined OC preparations (30 µg EE/3 mg DRSP; Yasmin® in a 21/7 regimen; and 20 µg EE/3 mg DRSP; Yaz® in a 24/4 regimen. These preparations are bereft of the fluid retentional side effects typical of other progestins and their safety has been demonstrated in large epidemiological studies in which no increased risk of vascular thromboembolic disease or arrhythmias was observed. In acne, the efficacy of DRSP-containing OCs has been shown in placebo-controlled superiority trials and in active-comparator non-inferiority trials.Keywords: acne vulgaris, combined oral contraceptives, drosperinone, ethinyl estradiol, efficacy, safety, treatment

  17. 17β Estradiol increases resilience and improves hippocampal synaptic function in helpless ovariectomized rats

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    Bredemann, Teruko M.; McMahon, Lori L.

    2014-01-01

    Summary Memory impairment is the most commonly reported cognitive symptom associated with major depressive disorder. Decreased hippocampal volume and neurogenesis in depression link hippocampal dysfunction with deficits in memory. Stress decreases hippocampal dendritic spine density and long-term potentiation (LTP) at glutamate synapses, a cellular correlate of learning and memory. However, elevated plasma levels of 17β estradiol (E2) during proestrus increase hippocampal structure and function, directly opposing the negative consequences of stress. In women, significant fluctuations in ovarian hormones likely increase vulnerability of hippocampal circuits to stress, potentially contributing to the greater incidence of depression compared to men. Using the learned helplessness model of depression and ovariectomized female rats, we investigated whether acquisition of helplessness and hippocampal synaptic dysfunction is differentially impacted by the presence or absence of plasma E2. We find that inescapable shock induces a greater incidence of helplessness in vehicle- versus E2-treated OVX rats. In the vehicle-treated group, LTP was absent at CA3-CA1 synapses in slices only from helpless rats, and CA1 spine density was decreased compared to resilient rats. In contrast, significant LTP was observed in slices from E2-treated helpless rats; importantly, spine density was not different between E2-treated helpless and resilient rats, dissociating spine density from the LTP magnitude. We also find that E2 replacement can reverse previously established helpless behavior. Thus, our results show that E2 replacement in OVX rats increases resilience and improves hippocampal plasticity, suggesting that E2 therapy may increase resilience to stress and preserve hippocampal function in women experiencing large fluctuations in plasma estrogen levels. PMID:24636504

  18. Stress-induced alterations in estradiol sensitivity increase risk for obesity in women.

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    Michopoulos, Vasiliki

    2016-11-01

    The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

  19. 17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib.

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    Girgert, Rainer; Emons, Günter; Gründker, Carsten

    2017-02-01

    Triple-negative breast cancers (TNBCs) are neither susceptible to endocrine therapy due to a lack of estrogen receptor α expression nor trastuzumab. TNBCs frequently overexpress epidermal growth factor receptor (EGFR) and membrane bound estrogen receptor, GPER. To a certain extent the growth of TNBCs is stimulated by 17β-estradiol via GPER. We analyzed whether inhibition of EGFR by gefitinib reduces the expression of GPER and subsequent signal transduction in TNBC cells. Dependence of proliferation on 17β-estradiol was determined using Alamar Blue assay. Expression of GPR30 and activation of c-src, EGFR and cAMP-responsive element binding (CREB) protein by 17β-estradiol was analyzed by western blotting. Expression of c-fos, cyclin D1 and aromatase was determined using RT-PCR. Gefitinib reduced GPER expression concentration‑ and time‑dependently. In HCC70 cells, GPER expression was reduced to 15±11% (p<0.05) after treatment with 200 nM gefitinib for four days, and in HCC1806 cells GPER expression was reduced to 39±5% (p<0.01) of the control. 17β-estradiol significantly increased the percentage of HCC1806 cells within 7 days to 145±29% of the control (HCC70, 110±8%). This increase in cell growth was completely prevented in both TNBC cell lines after GPR30 expression was downregulated by treatment with 200 nM gefitinib. In HCC1806 cells, activation of c-src was increased by 17β-estradiol to 350±50% (p<0.01), and gefitinib reduced src activation to 110%. Similar results were obtained in the HCC70 cells. Phosphorylation of EGFR increased to 240±40% (p<0.05) in the HCC1806 cells treated with 17β-estradiol (HCC70, 147±25%). Gefitinib completely prevented this activation. Phosphorylation of CREB and induction of c-fos, cyclin D1 and aromatase expression by 17β-estradiol were all prevented by gefitinib. These experiments conclusively show that reduction of GPER expression is a promising therapeutic approach for TNBC.

  20. Hyaluronic acid concentration in postmenopausal facial skin after topical estradiol and genistein treatment: a double-blind, randomized clinical trial of efficacy.

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    Patriarca, Marisa Teresinha; Barbosa de Moraes, Andréa Regina; Nader, Helena B; Petri, Valeria; Martins, João Roberto Maciel; Gomes, Regina Célia Teixeira; Soares, José Maria

    2013-03-01

    The aim of this work was to compare the effects of estradiol and genistein treatment on hyaluronic acid (HA) concentration in postmenopausal facial skin. In this study, 30 postmenopausal women were evaluated in a prospective, randomized, double-blind trial. The volunteers were postmenopausal women treated in the Gynecology Department of the Federal University of São Paulo. The participants were divided into two groups: group E, treated with 0.01% 17β-estradiol gel (n = 15), and group G, treated with 4% genistein gel (isoflavones, n = 15). The treatment lasted for 24 consecutive weeks. Preauricular skin biopsies were performed for each participant at baseline (E1 and G1) and after treatment (E2 and G2) to evaluate HA concentration in tissue. The materials were processed using immunohistochemical and biochemical methods. After 24 weeks of treatment, HA concentration increased in both groups, but the effect was greater for estradiol treatment than for genistein treatment. Our data suggest that both treatments may enhance HA concentration in postmenopausal skin but that estrogen produces results that are greater than those produced by isoflavones.

  1. Gradually increasing ethinyl estradiol for Turner syndrome may produce good final height but not ideal BMD.

    Science.gov (United States)

    Hasegawa, Yukihiro; Ariyasu, Daisuke; Izawa, Masako; Igaki-Miyamoto, Junko; Fukuma, Mami; Hatano, Megumi; Yagi, Hiroko; Goto, Masahiro

    2017-02-27

    Estrogen replacement therapy in Turner syndrome should theoretically mimic the physiology of healthy girls. The objective of this study was to describe final height and bone mineral density (BMD) in a group of 17 Turner syndrome patients (group E) who started their ethinyl estradiol therapy with an ultra-low dosage (1-5 ng/kg/day) from 9.8-13.7 years. The subjects in group E had been treated with GH 0.35 mg/kg/week since the average age of 7.4 years. The 30 subjects in group L, one of the historical groups, were given comparable doses of GH, and conjugated estrogen 0.3125 mg/week ∼0.3125 mg/day was initiated at 12.2-18.7 years. The subjects in group S, the other historical group, were 21 patients who experienced breast development and menarche spontaneously. Final height (height gain Turner syndrome. The final height in group L was 148.5 ± 3.0 cm with a SD of 1.30 ± 0.55, which was significantly different from the values for group E. The volumetric BMD of group S (0.290 ± 0.026 g/cm 3 ) was significantly different from that of group L or E (0.262 or 0.262 g/cm 3 as a mean, respectively). This is the first study of patients with Turner syndrome where estrogen was administered initially in an ultra-low dose and then increased gradually. Our estrogen therapy in group E produced good final height but not ideal BMD.

  2. Estradiol-induced increase in the magnitude of long-term potentiation is prevented by blocking NR2B-containing receptors.

    Science.gov (United States)

    Smith, Caroline C; McMahon, Lori L

    2006-08-16

    Estradiol, through activation of genomic estrogen receptors, induces changes in synaptic morphology and function in hippocampus, a brain region important for memory acquisition. Specifically, this hormone increases CA1 pyramidal cell dendritic spine density, NMDA receptor (NMDAR)-mediated transmission, and the magnitude of long-term potentiation (LTP) at CA3-CA1 synapses. We recently reported that the estradiol-induced increase in LTP magnitude occurs only when there is a simultaneous increase in the fractional contribution of NMDAR-mediated transmission relative to AMPA receptor transmission, suggesting a direct role for the increase in NMDAR transmission to the heightened LTP magnitude. Estradiol has been shown to increase expression of the NMDAR subunit NR2B, but whether this translates into an increase in function of NR2B-containing receptors remains to be determined. Here we show that not only is the estradiol-induced increase in NMDAR transmission mediated by NR2B-containing receptors, but blocking these receptors using RO25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol] (0.5 microM), an NR2B selective antagonist, prevents the estradiol-induced increase in LTP magnitude. Thus, our data show a causal link between the estradiol-induced increase in transmission mediated by NR2B-containing NMDARs and the increase in LTP magnitude.

  3. Estradiol-induced increase in novel object recognition requires hippocampal NR2B-containing NMDA receptors.

    Science.gov (United States)

    Vedder, Lindsey C; Smith, Caroline C; Flannigan, Alaina E; McMahon, Lori L

    2013-01-01

    17β-estradiol (E2), at high circulating levels, enhances learning and memory in many women, making it a clinical treatment for hormone-related cognitive decline in aging. However, the mechanisms stimulated by E2, which are responsible for its cognitive enhancing effects, remain incompletely defined. Using an ovariectomized rat model, we previously reported that increasing plasma E2 enhances the magnitude of long-term potentiation (LTP) at hippocampal CA3-CA1 synapses, which is caused by a selective increase in current mediated by NR2B-containing NMDARs, leading to an increase in the NMDAR/AMPAR ratio. Whether the increase in NR2B current is causally related to the ability of E2 to enhance hippocampal dependent learning and memory has yet to be tested. Here, we find that E2 enhances performance in the novel object recognition (NOR) task with the same time course we previously showed E2 enhances the LTP magnitude, temporally linking the increase in LTP to enhanced learning and memory. Furthermore, using the selective NR2B subunit antagonist Ro25-6981, we find that the E2-enhanced NOR, like the enhanced LTP, requires hippocampal NR2B-containing NMDARs, specifically in area CA1. Finally, using whole-cell recordings and the phosphatase inhibitor orthovanadate, we investigated whether the E2-induced increase in NMDAR current is caused by an increase in the density of synaptic NMDARs and/or an increase in NMDAR subunit phosphorylation. We find that both mechanisms are responsible for the enhanced NMDAR current in E2-treated rats. Our results show that the E2-enhanced NOR requires a functional increase in NR2B-containing NMDARs, a requirement shared with the E2-enhanced LTP magnitude at CA3-CA1 synapses, supporting the hypothesis that the increase in LTP likely contributes to the enhanced learning and memory following an increase in plasma E2 levels. Copyright © 2012 Wiley Periodicals, Inc.

  4. Evaluation of estradiol benzoate as a pre-treatment for oocyte recovery in sheep

    Directory of Open Access Journals (Sweden)

    Marilu Constantino Max

    2014-02-01

    Full Text Available The objective of this study was to compare the number of follicles, oocytes and the recovery rate in sheep submitted to the one-shot protocol with or without ovarian priming with estradiol benzoate (EB. Pluriparous non-lactating sheep (n=33 with an average age of five years (range 4-6 and a body condition score of 3.0±0.3 were divided into three groups. The one-shot group (n=10 was treated with a subcutaneous implant containing 1.5 mg of norgestomet from D0 to D10. The animals in this group were administered 0.04 mg of D-cloprostenol, 200 IU of follicle stimulating hormone (FSH and 300 IU of equine chorionic gonadotropin (eCG on D8. Animals in the EB group (n=11 received the same treatment as one-shot plus the administration of 0.6 mg of EB on D0. In the untreated group (n=12, the animals received no hormone stimulation. The collection of the oocytes was performed by laparotomy 36 h after the administration of gonadotropins (D10. Oocytes were searched and classified based on morphology. An increase was observed (p<0.05 in the number of follicles aspirated in the one-shot vs. the EB and untreated groups (16.3±5.6 vs. 9.5±2.4 and 12.1±4.1, respectively. The average number of oocytes and the recovery rate were higher (p<0.05 in the one-shot and EB groups compared to the untreated group, resulting in 14.2±9.0 and 87.1% (142/163, 11.0±6.2 and 91.4% (122/134 vs. 6.8±3.5 and 71.9% (82/114, respectively. It was concluded that the EB did not improve efficiency in the oneshot protocol, but was significantly better than in untreated animals

  5. Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats

    Energy Technology Data Exchange (ETDEWEB)

    Ronis, Martin J., E-mail: mronis@lsuhsc.edu [Department of Pharmacology & Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112 (United States); Gomez-Acevedo, Horacio; Blackburn, Michael L. [Arkansas Children' s Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States); Cleves, Mario A. [Arkansas Children' s Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States); Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States); Singhal, Rohit [Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States); Badger, Thomas M. [Arkansas Children' s Nutrition Center, University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States); Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202 (United States)

    2016-04-15

    There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P < 0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P < 0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P < 0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P < 0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens. - Highlights: • Concerns exist regarding risk of uterine cancer from consumption of soy products. • These concerns are related to potential estrogenicity. • Estradiol and soy protein isolate effects on uterine gene expression were compared. • Soy acts as a selective estrogen

  6. Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats

    International Nuclear Information System (INIS)

    Ronis, Martin J.; Gomez-Acevedo, Horacio; Blackburn, Michael L.; Cleves, Mario A.; Singhal, Rohit; Badger, Thomas M.

    2016-01-01

    There are concerns regarding reproductive toxicity from consumption of soy foods, including an increased risk of endometriosis and endometrial cancer, as a result of phytoestrogen consumption. In this study, female rats were fed AIN-93G diets made with casein (CAS) or soy protein isolate (SPI) from postnatal day (PND) 30, ovariectomized on PND 50 and infused with 5 μg/kg/d 17β-estradiol (E2) or vehicle. E2 increased uterine wet weight (P < 0.05). RNAseq analysis revealed that E2 significantly altered expression of 1991 uterine genes (P < 0.05). SPI feeding had no effect on uterine weight and altered expression of far fewer genes than E2 at 152 genes (P < 0.05). Overlap between E2 and SPI genes was limited to 67 genes. Functional annotation analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of estrogen receptor (ER)α to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were carcinogenesis and extracellular matrix organization, whereas SPI feeding up-regulated uterine peroxisome proliferator activated receptor (PPAR) signaling and fatty acid metabolism. The combination of E2 and SPI resulted in significant regulation of 504 fewer genes relative to E2 alone. The ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA) as measured by expression of PCNA and Ki67 mRNA was suppressed by feeding SPI (P < 0.05). These data suggest that SPI is a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and is anti-estrogenic in the presence of endogenous estrogens. - Highlights: • Concerns exist regarding risk of uterine cancer from consumption of soy products. • These concerns are related to potential estrogenicity. • Estradiol and soy protein isolate effects on uterine gene expression were compared. • Soy acts as a selective estrogen

  7. Ethinyl Estradiol-Drospirenon Versus Vitex Agnus-Castus Extract in Efficacy of the Treatment of Premenstrual Syndrome

    OpenAIRE

    Mustafa Kaplanoglu

    2016-01-01

    Aim: The premenstrual syndrome (PMS), which causes emotional and physical symptoms, is a common problem in reproductive age women. Several treatment modalities has been used in PMS. But controversial results has been observed in treatment . The present study was performed to compare vitex agnus castus (VAC) and ethinyl estradiol-drospirenone (EE-Drs) in the treatment of PMS. Material ve Method: It was a prospective, randomised, placebo-controlled study carried out in our clinic. A total of 12...

  8. Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: their antioxidant effect and role of estrogen receptor alpha.

    Science.gov (United States)

    Mosquera, Laurivette; Colón, Jennifer M; Santiago, José M; Torrado, Aranza I; Meléndez, Margarita; Segarra, Annabell C; Rodríguez-Orengo, José F; Miranda, Jorge D

    2014-05-02

    17β-Estradiol is a multi-active steroid that imparts neuroprotection via diverse mechanisms of action. However, its role as a neuroprotective agent after spinal cord injury (SCI), or the involvement of the estrogen receptor-alpha (ER-α) in locomotor recovery, is still a subject of much debate. In this study, we evaluated the effects of estradiol and of Tamoxifen (an estrogen receptor mixed agonist/antagonist) on locomotor recovery following SCI. To control estradiol cyclical variability, ovariectomized female rats received empty or estradiol filled implants, prior to a moderate contusion to the spinal cord. Estradiol improved locomotor function at 7, 14, 21, and 28 days post injury (DPI), when compared to control groups (measured with the BBB open field test). This effect was ER-α mediated, because functional recovery was blocked with an ER-α antagonist. We also observed that ER-α was up-regulated after SCI. Long-term treatment (28 DPI) with estradiol and Tamoxifen reduced the extent of the lesion cavity, an effect also mediated by ER-α. The antioxidant effects of estradiol were seen acutely at 2 DPI but not at 28 DPI, and this acute effect was not receptor mediated. Rats treated with Tamoxifen recovered some locomotor activity at 21 and 28 DPI, which could be related to the antioxidant protection seen at these time points. These results show that estradiol improves functional outcome, and these protective effects are mediated by the ER-α dependent and independent-mechanisms. Tamoxifen׳s effects during late stages of SCI support the use of this drug as a long-term alternative treatment for this condition. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Influence of 17β-estradiol treatment on the expression of NF-κB in complete hydatidiform mole culture

    Directory of Open Access Journals (Sweden)

    Tatit Nurseta

    2013-12-01

    Full Text Available Background:  Genetic evidence has established a role of nuclear factor kappa B (NF-κB signaling in oncogenesis. However, activity of NF-κB in complete hydatidiform mole (CHM cell culture under 17β-estradiol (E2 treatment is not yet known. Recently, a positive cross-talk between estrogen receptor (ER and NF-κB to promote survival and progress of cancer cells to a more aggressive phenotype was established. In the present study, we examined the influence of E2 treatment on the NF-κB expression in CHM’s culture.Methods:  This experimental study measured the expression of NF-κB in CHM culture treated with E2: 10, 100, 300, 600, and 1000 pg/mL and without E2. Imunohistochemistry staining was used to assess the expression of NF-κB. Microphotographs were taken using 400x magnification. Adobe photoshop CS2 was used to assess the NF-κB expression in cell nucleus. The lower the color intensity of cell RGBbv, is the higher the expression of NF-κB in cells. ANOVA test was performed to compare the expression of NF-κB.Results: NF-κB expression as indicated by color intensity in control group was 114.84 ± 9.02. NF-κB expression in E2 treatment groups were respectively: E2 10 pg/mL: 106.30 ± 13.95; E2 100 pg/mL: 82.47 ± 4.72; E2 300 pg/mL: 82.24 ± 2.67; E2 600 pg/mL: 69.05 ± 6.47; E2 1000 pg/mL: 68.49 ± 2.37. There was progressive decline in color intensity of cells with E2 treatment indicating the increase expression of NF-κB. Significant differences with the control group occurred in doses of E2 100, 300, 600, dan 1000 pg/mL.Conclusion: Treatment of CHM trophoblast culture with escalating doses of E2 was associated with the increase of NF-κB expression in a dose dependent manner. (Med J Indones. 2013;22:197-201. doi: 10.13181/mji.v22i4.599Keywords: 17-β Estradiol, Hydatidiform mole, NF-κB

  10. Effect of oocyte selection, estradiol and antioxidant treatment on in vitro maturation of oocytes collected from prepubertal Boer goats

    Directory of Open Access Journals (Sweden)

    George W. Smith

    2010-02-01

    Full Text Available Development of improved procedures for in vitro maturation of oocytes collected from prepubertal goats has applications for in vitro embryo production and accompanying strategies for genetic improvement. The objective of described studies was to determine the effects of oocyte grade, in vitro maturation time, antioxidant supplementation and concentrations of estradiol in the maturation medium on in vitro maturation of oocytes harvested from 1-6 mm follicles present on the ovaries (obtained from an abattoir of 1-6 month-old prepubertal Boer goats. Rates of progression to metaphase II were greater for grade 1 oocytes (>3 compact layers of cumulus cells and evenly granulated cytoplasm than grade 2 oocytes (in vitro maturation in the presence of high concentrations of estradiol (10 and 100 mg/mL on progression to metaphase II was observed, and no effect was observed in response to 1 mg/mL estradiol treatment as compared with control. Results suggest that oocyte selection and beta-mercaptoethanol supplementation can positively influence progression to metaphase II of oocytes harvested from ovaries of prepubertal goats, whereas high concentrations of estradiol are inhibitory to in vitro maturation.

  11. Evaluation of the Discriminative Potential of a Novel Biomarker for Estradiol Treatments in Bovine Animals

    NARCIS (Netherlands)

    Regal, P.; Blokland, M.H.; Fente, C.A.; Sterk, S.S.; Cepeda, A.; Ginkel, van L.A.

    2015-01-01

    The endogenous occurrence of natural hormones obstructs the application of classical targeted methods as confirmatory options. In the case of estradiol, the ultimate confirmation of its exogenous administration relies on gas chromatography coupled to combustion/isotope ratio mass spectrometry

  12. The effect of 17β-estradiol on gene expression of calcitonin gene-related peptide and some pro-inflammatory mediators in peripheral blood mononuclear cells from patients with pure menstrual migraine

    Directory of Open Access Journals (Sweden)

    Azam Karkhaneh

    2015-09-01

    Results:Treatment with 17β-estradiol had a biphasic effect on expression of CGRP. We found that 17β-estradiol treatment at pharmacological dose significantly increases mRNA expression of CGRP in both groups (P

  13. Deficits in latent inhibition induced by estradiol replacement are ameliorated by haloperidol treatment

    Directory of Open Access Journals (Sweden)

    Anne eAlmey

    2013-10-01

    Full Text Available There are sex differences in the symptomatology of schizophrenia, and in the response to antipsychotic treatments. One hallmark symptom of schizophrenia is a deficit in selective attention. Selective attention can be measured using a latent inhibition (LI paradigm in humans; LI can be measured in rodents, and is used as an animal model of the selective attention deficits observed in schizophrenia. In the current experiments LI was used to clarify whether selective attention differs between male rats and ovariectomized (OVX female rats receiving different estradiol (E2 replacement regimens. An additional aim was to determine whether haloperidol's facilitation of LI is enhanced by E2. Males and OVX female rats were trained in a conditioned emotional response LI paradigm. Females received no E2 replacement, a chronic low dose of E2 via silastic capsule, or a high phasic dose of E2 via silastic capsule accompanied by E2 (10 ug/kg SC injections every fourth day. Actual plasma levels of E2 were determined using an enzyme linked immunosorbent assay. Rats were also administered a vehicle treatment, a 0.05mg/kg, or a 0.1mg/kg IP injection of haloperidol. Males and OVX females that did not receive E2 replacement both exhibited LI, but LI was not observed in the low and high E2 replacement groups. Haloperidol restored LI at a lower dose in the females receiving high E2 replacement compared to females receiving low E2 replacement, indicating that E2 replacement facilitates haloperidol in restoring LI.

  14. Estradiol-induced estrogen receptor-alpha trafficking.

    Science.gov (United States)

    Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

    2009-12-02

    Estradiol has rapid actions in the CNS that are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca(2+)](i)) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERalpha has an extracellular portion. In addition to the full-length ERalpha [apparent molecular weight (MW), 66 kDa], surface biotinylation labeled an ERalpha-immunoreactive protein (MW, approximately 52 kDa) identified by both COOH- and NH(2)-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 and 52 kDa ERalpha. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24-48 h reduced ERalpha levels, suggesting receptor downregulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERalpha-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERalpha trafficking to and from the membrane. Estradiol-induced [Ca(2+)](i) flux was also significantly increased at the time of peak ERalpha activation/internalization. These results demonstrate that ERalpha is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERalpha are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERalpha to augment and then terminate membrane-initiated signaling.

  15. Estradiol-induced estrogen receptor-α trafficking

    Science.gov (United States)

    Bondar, Galyna; Kuo, John; Hamid, Naheed; Micevych, Paul

    2010-01-01

    Estradiol has rapid actions in the central nervous system, which are mediated by membrane estrogen receptors (ERs) and activate cell signaling pathways through interaction with metabotropic glutamate receptors (mGluRs). Membrane-initiated estradiol signaling increases the free cytoplasmic calcium concentration ([Ca2+]i) that stimulates the synthesis of neuroprogesterone in astrocytes. We used surface biotinylation to demonstrate that ERα has an extracellular portion. In addition to the full length ERα (apparent M.W. 66 kDa), surface biotinylation labeled an ERα-immunoreactive protein (M.W. ~ 52 kDa) identified by both COOH- and NH2-directed antibodies. Estradiol treatment regulated membrane levels of both proteins in parallel: within 5 min, estradiol significantly increased membrane levels of the 66 kDa and 52 kDa ERα. Internalization, a measure of membrane receptor activation, was also increased by estradiol with a similar time course. Continuous treatment with estradiol for 24–48 hr reduced ERα levels, suggesting receptor down-regulation. Estradiol also increased mGluR1a trafficking and internalization, consistent with the proposed ERα-mGluR1a interaction. Blocking ER with ICI 182,780 or mGluR1a with LY 367385 prevented ERα trafficking to and from the membrane. Estradiol-induced [Ca2+]i flux was also significantly increased at the time of peak ERα activation/internalization. These results demonstrate that ERα is present in the membrane and has an extracellular portion. Furthermore, membrane levels and internalization of ERα are regulated by estradiol and mGluR1a ligands. The pattern of trafficking into and out of the membrane suggests that the changing concentration of estradiol during the estrous cycle regulates ERα to augment and then terminate membrane-initiated signaling. PMID:19955385

  16. Safety, efficacy and patient acceptability of drospirenone and estradiol in the treatment of menopausal vasomotor symptoms: a review

    Directory of Open Access Journals (Sweden)

    Sebastián Carranza-Lira

    2008-12-01

    Full Text Available Sebastián Carranza-LiraReproductive Medicine, UMAE Hospital de Ginecología y Obstetricia “Luis Castelazo Ayala” Instituto Mexicano del Seguro Social, MéxicoAbstract: During menopause vasomotor symptoms are one of the main complaints about which women seek medical advice. For symptom control, several therapies have been used, among which hormone therapy has produced good results. One of these is estrogen monotherapy, which unfortunately may induce endometrial hyperplasia in women with an intact uterus. A progestin must be added to avoid this risk. Progestins may induce several secondary effects such as breast tenderness, hirsutism, edema and unfavorable lipid profile modifications. Recently a new progestin called drospirenone has been synthesized and used in combination with estradiol for the treatment of postmenopausal women. This progestin is derived from spironolactone, and lacks estrogenic, androgenic and glucocorticoid activities. Several studies have evaluated safety, efficacy and patient tolerability, and have shown a good profile in all these parameters. All studies agree that the combination of estradiol 1 mg plus drospirenone 2 mg is a good choice for postmenopausal women with vasomotor symptoms.Keywords: estradiol, drospirenone, postmenopause, review

  17. Safety, efficacy, actions, and patient acceptability of drospirenone/ethinyl estradiol contraceptive pills in the treatment of premenstrual dysphoric disorder

    Directory of Open Access Journals (Sweden)

    Lesley L Breech

    2009-08-01

    Full Text Available Lesley L Breech, Paula K BravermanDivision of Adolescent Medicine, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USAAbstract: Premenstrual dysphoric disorder (PMDD is estimated to affect 3%–8% of reproductive age women. Multiple therapeutic modalities have been evaluated with varying efficacy for the associated somatic and mood symptoms. The majority of older studies had shown that oral contraceptive pills (OCs were most effective for the physical symptoms. However, newer OCs containing a novel progestin, drospirenone, have shown promise in alleviating both the somatic and affective/behavioral symptoms. This progestin, which is a derivative of spironolactone, has both antimineralocorticoid and antiandrogenic activity. A 24/4 formulation containing 20 µg of ethinyl estradiol has been found effective in randomized double-blind placebo-controlled trials utilizing established scales documenting symptoms associated with PMDD. Multiple studies have shown that drospirenone-containing OCs are safe without evidence of clinically adverse effects on carbohydrate metabolism, lipids, blood pressure, weight, serum potassium or increased thrombotic events compared to other low dose OCs. In addition, significant improvements have been demonstrated in acne, hirsutism, and fluid retention symptoms. Several open label studies demonstrated good patient compliance and reported satisfaction with the method. Because of the significant placebo effect demonstrated in the blinded placebo-controlled trials, additional large randomized placebo-controlled trials are needed to confirm the efficacy of the drospirenone OCs in the treatment of PMDD. However, this OC formulation appears to be a promising therapeutic modality.Keywords: drospirenone, premenstrual dysphoric disorder, premenstrual syndrome, oral contraceptive pill

  18. Involvement of CART in estradiol-induced anorexia.

    Science.gov (United States)

    Dandekar, Manoj P; Nakhate, Kartik T; Kokare, Dadasaheb M; Subhedar, Nishikant K

    2012-01-18

    Since estradiol exercises inhibitory effect on food intake, we wanted to find out if this influence of estradiol is mediated by cocaine- and amphetamine-regulated transcript peptide (CART), a well established anorectic agent in the brain. Ovariectomized (OVX) rats, replaced with estradiol to produce estrous-phase like conditions, showed a significant decrease in food intake as compared with that in OVX controls. Intracerebroventricular (icv) administration of CART (0.5-1 μg/rat) to OVX rats, resulted in a dose-dependent reduction in the food intake. The lower dose (0.25 μg) had no effect, and was considered subeffective. In estradiol replaced OVX rats, CART at subeffective dose, further reduced food intake. However, CART failed to reduce food intake in estradiol replaced OVX rats pretreated with anti-estrogenic agent tamoxifen (3 mg/kg, subcutaneous). Administration of CART antibody (1:500 dilution/rat, i.c.v.) significantly attenuated estradiol-induced anorexia in the OVX rats. While estradiol replacement significantly increased CART-immunoreactivity in the cells/fibers of paraventricular nucleus (PVN) of OVX rats, fibers in the anteroventral periventricular nucleus (AVPV), and cells/fibers in the arcuate nucleus (ARC) showed considerable reduction. These changes were attenuated following concurrent injection of tamoxifen to the estradiol replaced OVX rats. However, CART-immunoreactive cells/fibers in the periventricular area did not respond to any of the treatments. We suggest that estradiol treatment might influence the hypothalamic CART system in a site specific manner. While increased CART activity in the PVN might produce anorexia, reduction of CART in ARC and AVPV might represent a compensatory homeostatic response. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    Science.gov (United States)

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.

  20. Ovulation following gonadotrophin treatment and determination of serum estradiol and progesterone by radioimmunoassay

    International Nuclear Information System (INIS)

    Vesper, B.; Lisse, K.; Ittrich, G.

    1979-01-01

    The use of gonadotrophins to release ovulation is indicated in women with urgent desire for children and with negative response to clomiphene therapy. 69 patients treated with 100 therapeutic gonadotrophin series were examined. Estrogens and progesterone were determined by radioimmunoassay. The treatment resulted in ovulation in 54 women, 12 patients developed an ovarian reaction with an increase of estrogen, and in 34 cases no ovarian response was detectable. 6 women became pregnant during gonadotrophin therapy and further 2 after treatment

  1. Isoflavonoid-based bone-sparing treatments exert a low activity on reproductive organs and on hepatic metabolism of estradiol in ovariectomized rats

    International Nuclear Information System (INIS)

    Phrakonkham, Pascal; Chevalier, Joelle; Desmetz, Catherine; Pinnert, Marie-France; Berges, Raymond; Jover, Emmanuel; Davicco, Marie-Jeanne; Bennetau-Pelissero, Catherine; Coxam, Veronique; Artur, Yves; Canivenc-Lavier, Marie-Chantal

    2007-01-01

    The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological and molecular analyses on reproductive organs. The impact on the oxidative metabolism of estradiol and on associated cytochrome P450 (CYP) activities was evaluated in liver microsomes. The relative wet weights of both the uterus and the vagina were increased in the equol group, but no significant changes in proliferating cell nuclear antigen or hormone receptor mRNA expression were noticed. In contrast, genistein and daidzein did not induce uterotrophy but caused an overexpression of estrogen receptor α mRNA which could correspond to a long-lasting effect of physiological concentrations of estrogens. The hepatic metabolism of estradiol was influenced by daidzein which increased the synthesis of putative mutagenic derivatives. At the same time, genistein favored estrogen 2-hydroxylation, and equol decreased 4-hydroxyestrogen production. Surprisingly, no significant alteration in hepatic CYP activities was detected. Taken together, these results demonstrate that isoflavonoid-based bone-sparing treatments are able to cause side effects on other estrogen-sensitive target organs when given in the long-term

  2. Estradiol does not influence strategy choice but place strategy choice is associated with increased cell proliferation in the hippocampus of female rats.

    Science.gov (United States)

    Rummel, Julia; Epp, Jonathan R; Galea, Liisa A M

    2010-09-01

    Adult neurogenesis occurs in the hippocampus of most mammals. While the function of adult hippocampal neurogenesis is not known, there is a relationship between neurogenesis and hippocampus-dependent learning and memory. Ovarian hormones can influence learning and memory and strategy choice. In competitive memory tasks, higher levels of estradiol shift female rats towards the use of the place strategy. Previous studies using a cue-competition paradigm find that 36% of male rats will use a hippocampus-dependent place strategy and place strategy users had lower levels of cell proliferation in the hippocampus. Here, we used the same paradigm to test whether endogenous or exogenous ovarian hormones influence strategy choice in the cue-competition paradigm and whether cell proliferation was related to strategy choice. We tested ovariectomized estradiol-treated (10 microg of estradiol benzoate) or sham-operated female rats on alternating blocks of hippocampus-dependent and hippocampus-independent versions of the Morris water task. Rats were then given a probe session with the platform visible and in a novel location. Preferred strategy was classified as place strategy (hippocampus-dependent) if they swam to the old platform location or cue strategy (hippocampus-independent) if they swam to the visible platform. All groups showed a preference for the cue strategy. However, proestrous rats were more likely to be place strategy users than rats not in proestrus. Female place strategy users had increased cell proliferation in the dentate gyrus compared to cue strategy users. Our study suggests that 78% of female rats chose the cue strategy instead of the place strategy. In summary the present results suggest that estradiol does not shift strategy use in this paradigm and that cell proliferation is related to strategy use with greater cell proliferation seen in place strategy users in female rats. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  3. Impact of in vitro treatments of physiological levels of estradiol and progesterone observed in pregnancy on bovine monocyte-derived dendritic cell differentiation and maturation

    NARCIS (Netherlands)

    Pomeroy, Brianna; Klaessig, Suzanne; Schukken, Ynte

    2016-01-01

    The specific factors which regulate differentiation and maturation of dendritic cells in bovine pregnancy remain unclear. We evaluated the influence of physiologically relevant in vitro treatments of progesterone (PG) and estradiol (E2) observed in late pregnancy on the differentiation and

  4. Impact of in vitro treatments of physiological levels of estradiol and progesterone observed in pregnancy on bovine monocyte-derived dendritic cell differentiation and maturation

    NARCIS (Netherlands)

    Pomeroy, Brianna; Klaessig, Suzanne; Schukken, Ynte

    2016-01-01

    The specific factors which regulate differentiation and maturation of dendritic cells in bovine pregnancy remain unclear. We evaluated the influence of physiologically relevant in vitro treatments of progesterone (PG) and estradiol (E2) observed in late pregnancy on the differentiation and

  5. Ethinyl Estradiol-Drospirenon Versus Vitex Agnus-Castus Extract in Efficacy of the Treatment of Premenstrual Syndrome

    Directory of Open Access Journals (Sweden)

    Mustafa Kaplanoglu

    2014-12-01

    Full Text Available Aim: The premenstrual syndrome (PMS, which causes emotional and physical symptoms, is a common problem in reproductive age women. Several treatment modalities has been used in PMS. But controversial results has been observed in treatment . The present study was performed to compare vitex agnus castus (VAC and ethinyl estradiol-drospirenone (EE-Drs in the treatment of PMS. Material ve Method: It was a prospective, randomised, placebo-controlled study carried out in our clinic. A total of 120 patients were enrolled and randomly assigned to EE-Drs, VAC group or placebo group. Eligible patients were treated with EE-Drs, VAC extract and placebo for consecutive three cycles. Symptoms were documented with PMS diary (PMSD. Main efficacy variable was the reduction percentage of 15 symptom score documented in PMSD during the luteal phase of the third treatment cycle. Visual Anolog Scale (VAS was used in assessment of PMS semptoms. Results: After the treatment, there was statistically significant difference between the groups for anxiety (p

  6. Ethinyl Estradiol-Drospirenon Versus Vitex Agnus-Castus Extract in Efficacy of the Treatment of Premenstrual Syndrome

    Directory of Open Access Journals (Sweden)

    Mustafa Kaplanoglu

    2016-07-01

    Full Text Available Aim: The premenstrual syndrome (PMS, which causes emotional and physical symptoms, is a common problem in reproductive age women. Several treatment modalities has been used in PMS. But controversial results has been observed in treatment . The present study was performed to compare vitex agnus castus (VAC and ethinyl estradiol-drospirenone (EE-Drs in the treatment of PMS. Material ve Method: It was a prospective, randomised, placebo-controlled study carried out in our clinic. A total of 120 patients were enrolled and randomly assigned to EE-Drs, VAC group or placebo group. Eligible patients were treated with EE-Drs, VAC extract and placebo for consecutive three cycles. Symptoms were documented with PMS diary (PMSD. Main efficacy variable was the reduction percentage of 15 symptom score documented in PMSD during the luteal phase of the third treatment cycle. Visual Anolog Scale (VAS was used in assessment of PMS semptoms. Results: After the treatment, there was statistically significant difference between the groups for anxiety (p

  7. New developments in oral contraception: clinical utility of estradiol valerate/dienogest (Natazia® for contraception and for treatment of heavy menstrual bleeding: patient considerations

    Directory of Open Access Journals (Sweden)

    Nelson AL

    2012-12-01

    Full Text Available Anita L NelsonObstetrics and Gynecology, David Geffen School of Medicine at UCLA, Harbor UCLA Medical Center, Torrance, California, USAAbstract: Natazia® is a new oral contraceptive with estradiol valerate and dienogest in a unique multiphasic formulation that includes a shortened hormone-free interval. This new formulation has been approved for both contraception and also as a treatment for heavy menstrual bleeding in women who desire to use oral contraceptives as their method of birth control. It is marketed in the US as Natazia® and elsewhere as Qlaira®. This article will review the properties of each of the major new features of this pill: estradiol used in place of ethinyl estradiol, dienogest as the progestin, and the unique dosing pattern of this product. It will also summarize the results of the pivotal clinical trials of contraceptive effectiveness, bleeding patterns, safety and tolerability. The lessons learned from the clinical trials about the effectiveness of this formulation in the treatment of excessive menstrual bleeding will be summarized. Also, results of trials comparing this new pill to other popular formulations for "menstrually-related" symptoms and for potential female sexual dysfunction related to use of oral contraceptives will be presented. This review will suggest how all this information might be used to counsel women about how to use this pill most successfully.Keywords: oral contraceptives, estradiol valerate, dienogest, heavy menstrual bleeding, menorrhagia, dynamic dosing

  8. Stimulation of estradiol biosynthesis by tributyltin in rat hippocampal slices.

    Science.gov (United States)

    Munetsuna, Eiji; Hattori, Minoru; Yamazaki, Takeshi

    2014-01-01

    Hippocampal functions are influenced by steroid hormones, such as testosterone and estradiol. It has been demonstrated that hippocampus-derived steroid hormones play important roles in neuronal protection and synapse formation. Our research groups have demonstrated that estradiol is de novo synthesized in the rat hippocampus. However, the mechanism(s) regulating this synthesis remains unclear. It has been reported that tributyltin, an environmental pollutant, binds to the retinoid X receptor (RXR) and modifies estrogen synthesis in human granulosa-like tumor cells. This compound can penetrate the blood brain barrier, and tends to accumulate in the brain. Based on these facts, we hypothesized that tributyltin could influence the hippocampal estradiol synthesis. A concentration of 0.1 μM tributyltin induced an increase in the mRNA content of P450(17α) and P450arom in hippocampal slices, as determined using real-time PCR. The transcript levels of other steroidogenic enzymes and a steroidogenic acute regulatory protein were not affected. The estradiol level in rat hippocampal slices was subsequently determined using a radioimmunoassay. We found that the estradiol synthesis was stimulated by ∼2-fold following a 48-h treatment with 0.1 μM tributyltin, and this was accompanied by transcriptional activation of P450(17α) and P450arom. Tributyltin stimulated de novo hippocampal estradiol synthesis by modifying the transcription of specific steroidogenic enzymes.

  9. Estrus, ovulation, and serum progesterone, estradiol, and LH concentrations in mares after an increased photoperiod during winter.

    Science.gov (United States)

    Oxender, W D; Noden, P A; Hafs, H D

    1977-02-01

    On December 11, 1974, 15 seasonally anestrous mares were assigned at random to 1 of 3 experimental groups: outdoor-control, indoor-control, or indoor light-treated (a 16-hour photo-period). This experiment was terminated on April 21, 1975. The five mares in the indoor light-treated group ovulated 59.0+/-6.9 days later, which was 74 days earlier (P less than 0.01) than 2 of the 5 outdoor-controls (the other 3 ovulated after April 21 during a subsequent experiment) and 50 days earlier (P less than 0.05) than the indoor-controls. Durations of the 1st estrus for the 3 groups of mares were 13.3+/-3.6, 8.4+/-2.0, and 6.0+/-1.0 days for the indoor light-treated, indoor-control, and outdoor-control groups, respectively. The indoor light-treated mares averaged 4.2 estrous cycles before April 21, the indoor-control mares averaged 1.4 estrous cycles, and 2 of 5 outdoor-control mares ovulated 1 time during the experiment. The peripheral blood luteinizing hormone (LH), estradiol, and progesterone concentrations were minimal during winter anestrous. The hormone changes normally associated with estrous cycle activity in mares--maximal estradiol and luteinizing hormone concentrations near ovulation and maximal progesterone concentration during diestrus--were observed in all mares beginning at the 1st estrus. Hair loss was observed earlier in the light-treated mares, than in either of the other groups. In conclusion, a 16-hour photo-period initiated in early December for anestrous brood mares caused endocrinologically normal estrous cycles to begin within 2 months. This may allow breeding and foaling considerably earlier than normally expected.

  10. DNA demethylation by 5-aza-2-deoxycytidine treatment abrogates 17 beta-estradiol-induced cell growth and restores expression of DNA repair genes in human breast cancer cells.

    Science.gov (United States)

    Singh, Kamaleshwar P; Treas, Justin; Tyagi, Tulika; Gao, Weimin

    2012-03-01

    Prolonged exposure to elevated levels of estrogen is a risk factor for breast cancer. Though increased cell growth and loss of DNA repair capacity is one of the proposed mechanisms for estrogen-induced cancers, the mechanism through which estrogen induces cell growth and decreases DNA repair capacity is not clear. DNA hypermethylation is known to inactivate DNA repair genes and apoptotic response in cancer cells. Therefore, the objective of this study was to determine the role of DNA hypermethylation in estrogen-induced cell growth and regulation of DNA repair genes expression in breast cancer cells. To achieve this objective, the estrogen-responsive MCF-7 cells either pretreated with 5-aza-2-deoxycytidine (5-aza-dC) or untreated (as control) were exposed to 17 beta-estradiol (E2), and its effect on cell growth and expression of DNA repair genes were measured. The result revealed that 5-aza-dC abrogates the E2-induced growth in MCF-7 cells. An increased expression of OGG1, MSH4, and MLH1 by 5-aza-dC treatment alone, suggest the DNA hypermethylation as a potential cause for decreased expression of these genes in MCF-7 cells. The decreased expression of ERCC1, XPC, OGG1, and MLH1 by E2 alone and its restoration by co-treatment with 5-aza-dC further suggest that E2 reduces the expression of these DNA repair genes potentially through promoter hypermethylation. Reactivation of mismatch repair (MMR) gene MLH1 and abrogation of E2-induced cell growth by 5-aza-dC treatment suggest that estrogen causes increased growth in breast cancer cells potentially through the inhibition of MMR-mediated apoptotic response. In summary, this study suggests that estrogen increases cell growth and decreases the DNA repair capacity in breast cancer cells, at least in part, through epigenetic mechanism. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Insulin priming effect on estradiol-induced breast cancer metabolism and growth.

    Science.gov (United States)

    Wairagu, Peninah M; Phan, Ai N H; Kim, Min-Kyu; Han, Jeongwoo; Kim, Hyun-Won; Choi, Jong-Whan; Kim, Ki Woo; Cha, Seung-Kuy; Park, Kwang Hwa; Jeong, Yangsik

    2015-01-01

    Diabetes is a risk factor for breast cancer development and is associated with poor prognosis for breast cancer patients. However, the molecular and biochemical mechanisms underlying the association between diabetes and breast cancer have not been fully elucidated. Here, we investigated estradiol response in MCF-7 breast cancer cells with or without chronic exposure to insulin. We found that insulin priming is necessary and specific for estradiol-induced cancer cell growth, and induces anaplerotic shunting of glucose into macromolecule biosynthesis in the estradiol treated cells. Treatment with ERK or Akt specific inhibitors, U0126 or LY294002, respectively, suppressed estradiol-induced growth. Interestingly, molecular analysis revealed that estradiol treatment markedly increases expression of cyclin A and B, and decreases p21 and p27 in the insulin-primed cells. In addition, estradiol treatment activated metabolic genes in pentose phosphate (PPP) and serine biosynthesis pathways in the insulin-primed cells while insulin priming decreased metabolic gene expression associated with glucose catabolism in the breast cancer cells. Finally, we found that anti-diabetic drug metformin and AMPK ligand AICAR, but not thiazolidinediones (TZDs), specifically suppress the estradiol-induced cellular growth in the insulin-primed cells. These findings suggest that estrogen receptor (ER) activation under chronic hyperinsulinemic condition increases breast cancer growth through the modulation of cell cycle and apoptotic factors and nutrient metabolism, and further provide a mechanistic evidence for the clinical benefit of metformin use for ER-positive breast cancer patients with diabetes.

  12. Direct radioimmunoassay of 17. beta. -estradiol in ether extracts of bovine

    Energy Technology Data Exchange (ETDEWEB)

    Medina, M.B.

    Anabolic estrogens such as 17..beta..-estradiol or 17..beta..-estradiol benzoate are used to promote growth and increase feed efficiency in food-producing cattle. This paper describes a technique to produce a more specific antibody to 17..beta..-estradiol by intradermal immunization using microquantities of 6-(carboxymethyl)-17..beta..-estradiol oxime bovine serum albumin and the development of a radioimmunoassay (RIA) procedure to measure directly the amounts of 17..beta..-estradiol in ether extracts of bovine serum without using cleanup procedures. Results demonstrated that a specific and sensitive antibody was produced, and a titer of 1:10,000 was used in the RIA procedure. Antibody cross-reactivity with ..beta..-estradiol metabolites and other anabolic estrogens was negligible. The untreated bovine sera showed 0-24 pg of apparent 17..beta..-estradiol/mL, while 0-31 pg/mL total estrogens had been reported in the literature. This assay can measure 5-100 pg in 20-250..mu..L/sample. This method can be used before or immediately after slaughter to monitor the residual amounts of estradiol used in the treatment of cattle.

  13. Direct radioimmunoassay of 17β-estradiol in ether extracts of bovine

    International Nuclear Information System (INIS)

    Medina, M.B.

    1986-01-01

    Anabolic estrogens such as 17β-estradiol or 17β-estradiol benzoate are used to promote growth and increase feed efficiency in food-producing cattle. This paper describes a technique to produce a more specific antibody to 17β-estradiol by intradermal immunization using microquantities of 6-(carboxymethyl)-17β-estradiol oxime bovine serum albumin and the development of a radioimmunoassay (RIA) procedure to measure directly the amounts of 17β-estradiol in ether extracts of bovine serum without using cleanup procedures. Results demonstrated that a specific and sensitive antibody was produced, and a titer of 1:10,000 was used in the RIA procedure. Antibody cross-reactivity with β-estradiol metabolites and other anabolic estrogens was negligible. The untreated bovine sera showed 0-24 pg of apparent 17β-estradiol/mL, while 0-31 pg/mL total estrogens had been reported in the literature. This assay can measure 5-100 pg in 20-250μL/sample. This method can be used before or immediately after slaughter to monitor the residual amounts of estradiol used in the treatment of cattle

  14. Treatment of premenstrual dysphoric disorder (PMDD) with a novel formulation of drospirenone and ethinyl estradiol.

    Science.gov (United States)

    De Berardis, Domenico; Serroni, Nicola; Salerno, Rosa Maria; Ferro, Filippo Maria

    2007-08-01

    Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). Pharmacologic options studied for treating severe PMS and PMDD may include selective serotonin reuptake inhibitors, anxiolytic agents, gonadotropin-releasing hormone agonists and the diuretic spironolactone. However, the use of combined oral contraceptives (COC) may be a therapeutic option in treating PMS and PMDD. The combination of drospirenone with ethinylestradiol (EE/drospirenone) was approved for marketing as an oral contraceptive in Europe and the United States. The preparation is characterized by a high contraceptive efficacy in combination with excellent cycle control, good tolerability, and a favourable impact on lipid and glucose metabolism. Recently, some placebo-controlled, randomized studies have tested clinical efficacy and tolerability of this COC in the treatment of PMDD. The aim of the present review was to elucidate the possible benefits or disadvantages of PMDD treatment with this novel formulation of EE/drospirenone. The results of trials evaluating the use of EE/drospirenone combination in the treatment of PMDD are encouraging but further studies are needed. However, the reported clinical efficacy and the relative good tolerability of EE/drospirenone may contribute to widen the therapeutic spectrum of PMDD.

  15. Effects of estradiol and FSH on leptin levels in women with suppressed pituitary

    Directory of Open Access Journals (Sweden)

    Geber Selmo

    2012-06-01

    Full Text Available Abstract Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

  16. Effects of estradiol and FSH on leptin levels in women with suppressed pituitary.

    Science.gov (United States)

    Geber, Selmo; Brandão, Augusto H F; Sampaio, Marcos

    2012-06-15

    Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student's t-test and Pearson's correlation test. We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

  17. Fate of sulfamethoxazole, 4-nonylphenol, and 17beta-estradiol in groundwater contaminated by wastewater treatment plant effluent.

    Science.gov (United States)

    Barber, Larry B; Keefe, Steffanie H; Leblanc, Denis R; Bradley, Paul M; Chapelle, Francis H; Meyer, Michael T; Loftin, Keith A; Kolpin, Dana W; Rubio, Fernando

    2009-07-01

    Organic wastewater contaminants (OWCs) were measured in samples collected from monitoring wells located along a 4.5-km transect of a plume of groundwater contaminated by 60 years of continuous rapid infiltration disposal of wastewater treatment plant effluent. Fifteen percent of the 212 OWCs analyzed were detected, including the antibiotic sulfamethoxazole (SX), the nonionic surfactant degradation product 4-nonylphenol (NP), the solvent tetrachloroethene (PCE), and the disinfectant 1,4-dichlorobenzene (DCB). Comparison of the 2005 sampling results to data collected from the same wells in 1985 indicates that PCE and DCB are transported more rapidly in the aquiferthan NP, consistent with predictions based on compound hydrophobicity. Natural gradient in situ tracer experiments were conducted to evaluate the subsurface behavior of SX, NP, and the female sex hormone 17beta-estradiol (E2) in two oxic zones in the aquifer: (1) a downgradient transition zone at the interface between the contamination plume and the overlying uncontaminated groundwater and (2) a contaminated zone located beneath the infiltration beds, which have not been loaded for 10 years. In both zones, breakthrough curves for the conservative tracer bromide (Br-) and SX were nearly coincident, whereas NP and E2 were retarded relative to Br- and showed mass loss. Retardation was greater in the contaminated zone than in the transition zone. Attenuation of NP and E2 in the aquifer was attributed to biotransformation, and oxic laboratory microcosm experiments using sediments from the transition and contaminated zones show that uniform-ring-labeled 14C 4-normal-NP was biodegraded more rapidly 130-60% recovered as 14CO2 in 13 days) than 4-14C E2 (20-90% recovered as 14CO2 in 54 days). There was little difference in mineralization potential between sites.

  18. Fate of sulfamethoxazole, 4-nonylphenol, and 17β-estradiol in groundwater contaminated by wastewater treatment plant effluent

    Science.gov (United States)

    Barber, Larry B.; Keefe, Steffanie H.; LeBlanc, Denis R.; Bradley, Paul M.; Chapelle, Francis H.; Meyer, Michael T.; Loftin, Keith A.; Koplin, Dana W.; Rubio, Fernando

    2009-01-01

    Organic wastewater contaminants (OWCs) were measured in samples collected from monitoring wells located along a 4.5-km transect of a plume of groundwater contaminated by 60 years of continuous rapid infiltration disposal of wastewater treatment plant effluent. Fifteen percent of the 212 OWCs analyzed were detected, including the antibiotic sulfamethoxazole (SX), the nonionic surfactant degradation product 4-nonylphenol (NP), the solvent tetrachloroethene (PCE), and the disinfectant 1,4-dichlorobenzene (DCB). Comparison of the 2005 sampling results to data collected from the same wells in 1985 indicates that PCE and DCB are transported more rapidly in the aquifer than NP, consistent with predictions based on compound hydrophobicity. Natural gradient in situ tracer experiments were conducted to evaluate the subsurface behavior of SX, NP, and the female sex hormone 17β-estradiol (E2) in two oxic zones in the aquifer: (1) a downgradient transition zone at the interface between the contamination plume and the overlying uncontaminated groundwater and (2) a contaminated zone located beneath the infiltration beds, which have not been loaded for 10 years. In both zones, breakthrough curves for the conservative tracer bromide (Br−) and SX were nearly coincident, whereas NP and E2 were retarded relative to Br− and showed mass loss. Retardation was greater in the contaminated zone than in the transition zone. Attenuation of NP and E2 in the aquifer was attributed to biotransformation, and oxic laboratory microcosm experiments using sediments from the transition and contaminated zones show that uniform-ring-labeled 14C 4-normal-NP was biodegraded more rapidly (30−60% recovered as 14CO2 in 13 days) than 4-14C E2 (20−90% recovered as 14CO2in 54 days). There was little difference in mineralization potential between sites.

  19. Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

    Science.gov (United States)

    Bowman, R E; Ferguson, D; Luine, V N

    2002-01-01

    Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current

  20. Blood Test: Estradiol

    Science.gov (United States)

    ... the bloodstream. Estradiol plays an important role in sexual development: It's the most important form of the hormone ... while low levels may indicate a delay in sexual development. Estradiol levels also give important information on the ...

  1. Effects of estradiol and FSH on maturation of the testis in the hypogonadal (hpg mouse

    Directory of Open Access Journals (Sweden)

    Mayhew Terry M

    2008-01-01

    Full Text Available Abstract Background The hypogonadal (hpg mouse is widely used as an animal model with which to investigate the endocrine regulation of spermatogenesis. Chronic treatment of these GnRH-deficient mice with estradiol is known to induce testicular maturation and restore qualitatively normal spermatogenesis. The aim of the current studies was to investigate whether these effects of estradiol are direct effects in the testis, or indirect actions via paradoxical stimulation of FSH secretion from the pituitary gland. Methods Initially, Western blot and immunohistochemistry were used to analyse tissues from hpg mice to identify potential sites of action of estradiol. In the main study, hpg mice were treated for 50 days with either an estradiol implant or daily injections of recombinant human FSH, or a combination of both, to determine whether estradiol would have an additive or synergistic effect with FSH on testis development, as assessed by histological analysis and stereological quantification of Leydig, Sertoli and germ cell proliferation. Results Western blot analysis revealed ERα immunoreactive bands of appropriate molecular weight in extracts of testis and pituitary glands from hpg mice, and immunohistochemical studies confirmed ERα in nuclei of anterior pituitary cells and Leydig and peritubular cells in hpg mice. Histological and morphometric analyses revealed that estradiol treatment alone was as effective as FSH in promoting Sertoli cell production and proliferation of the seminiferous epithelium, resulting in the production of elongating spermatids. Combined estradiol and FSH treatment did not produce a greater effect than either treatment alone, though an increased dose of FSH significantly increased seminiferous tubule volume and testis weight and increase Sertoli cell numbers further within the same time frame. In contrast, estradiol caused substantial increases in the wet weight of the seminal vesicles, whereas FSH was without effect on

  2. The daidzein- and estradiol- induced anorectic action in CCK or leptin receptor deficiency rats.

    Science.gov (United States)

    Fujitani, Mina; Mizushige, Takafumi; Bhattarai, Keshab; Iwahara, Asami; Aida, Ryojiro; Kishida, Taro

    2015-01-01

    We investigated the effect of daidzein feeding and estradiol treatment on food intake in cholecystokinin-1 receptor (CCK1R) deficiency, leptin receptor (ObRb) deficiency rats and their wild-type rats. These rats underwent an ovariectomy or a sham operation. For the 5 week experiment, each rat was divided in three groups: control, daidzein (150 mg/kg diet), and estradiol (4.2 μg/rat/day) groups. In both CCK1R+ and CCK1R- rats, daidzein feeding and estradiol treatment significantly decreased food intake. Daidzein feeding significantly reduced food intake in ovariectomized ObRb- rats, although not in ObRb+ rats. Estradiol treatment significantly lowered food intake in ovariectomized ObRb+ and ObRb- rats. In the ovariectomized rats, estradiol treatment significantly increases uterine weight, while daidzein feeding did not change it, suggesting that daidzein might have no or weak estrogenic effect in our experiment. These results suggest that CCK1R and ObRb signalings were not essential for the daidzein- and estradiol-induced anorectic action.

  3. Faslodex inhibits estradiol-induced extracellular matrix dynamics and lung metastasis in a model of lymphangioleiomyomatosis.

    Science.gov (United States)

    Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D; Parkhitko, Andrey; Morrison, Tasha A; Silverman, Edwin K; Henske, Elizabeth P; Yu, Jane J

    2013-07-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)-2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)-2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM.

  4. Faslodex Inhibits Estradiol-Induced Extracellular Matrix Dynamics and Lung Metastasis in a Model of Lymphangioleiomyomatosis

    Science.gov (United States)

    Li, Chenggang; Zhou, Xiaobo; Sun, Yang; Zhang, Erik; Mancini, John D.; Parkhitko, Andrey; Morrison, Tasha A.; Silverman, Edwin K.; Henske, Elizabeth P.

    2013-01-01

    Lymphangioleiomyomatosis (LAM) is a destructive lung disease primarily affecting women. Genetic studies indicate that LAM cells carry inactivating tuberous sclerosis complex (TSC)–2 mutations, and metastasize to the lung. We previously discovered that estradiol increases the metastasis of TSC2-deficient cells in mice carrying xenograft tumors. Here, we investigate the molecular basis underlying the estradiol-induced lung metastasis of TSC2-deficient cells, and test the efficacy of Faslodex (an estrogen receptor antagonist) in a preclinical model of LAM. We used a xenograft tumor model in which estradiol induces the lung metastasis of TSC2-deficient cells. We analyzed the impact of Faslodex on tumor size, the extracellular matrix organization, the expression of matrix metalloproteinase (MMP)–2, and lung metastasis. We also examined the effects of estradiol and Faslodex on MMP2 expression and activity in tuberin-deficient cells in vitro. Estradiol resulted in a marked reduction of Type IV collagen deposition in xenograft tumors, associated with 2-fold greater MMP2 concentrations compared with placebo-treated mice. Faslodex normalized the Type IV collagen changes in xenograft tumors, enhanced the survival of the mice, and completely blocked lung metastases. In vitro, estradiol enhanced MMP2 transcripts, protein accumulation, and activity. These estradiol-induced changes in MMP2 were blocked by Faslodex. In TSC2-deficient cells, estradiol increased MMP2 concentrations in vitro and in vivo, and induced extracellular matrix remodeling. Faslodex inhibits the estradiol-induced lung metastasis of TSC2-deficient cells. Targeting estrogen receptors with Faslodex may be of efficacy in the treatment of LAM. PMID:23526212

  5. Effects of estradiol on worm burden and peripheral leukocytes in Parastrongylus malaysiensis-infected rats.

    Science.gov (United States)

    Kamis, A B; Ahmad, R A; Badrul-Munir, M Z

    1994-01-01

    Gonadectomized male laboratory rats were given 0.06 mg/kg estradiol benzoate daily for 14 days before being inoculated with 50 third-stage larvae of Parastrongylus malaysiensis. Hormone treatment was continued until the rats were killed. The numbers of larvae in the brain and of adult worms in the pulmonary area of the rats were determined every 7 days after the inoculation. It was found that the rats treated daily with estradiol benzoate had significantly and consistently higher numbers of larvae and adult worms as compared with the controls. The number of total leukocytes increased significantly after the rats were infected. The results show that estradiol-treated rats become susceptible to P. malaysiensis infection, which may indicate that the immunosuppressive effects of testosterone observed in earlier studies may partly be caused by estradiol that was peripherally aromatized from testosterone.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    Highlights: ► Estradiol induced stiffness changes of osteoblasts were quantified using AFM. ► Estradiol causes significant decrease in the stiffness of osteoblasts. ► Decreased stiffness was caused by decreased density of f-actin network. ► Stiffness changes were not associated with mineralized matrix of osteoblasts. ► 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 ∗ ) and corresponding cytoskeletal changes of human fetal osteoblasts (hFOB 1.19). The cells were cultured in either medium alone or medium supplemented with β-estradiol and then subjected to Atomic Force Microscopy indentation (AFM) to determine E ∗ . 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 ∗ 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 changes of osteoblasts were not associated with changes in the synthesized mineralized matrix of the cells. Thus, a decrease in osteoblast stiffness with estrogen treatment was

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

    Energy Technology Data Exchange (ETDEWEB)

    Muthukumaran, Padmalosini [Department of Bioengineering, National University of Singapore (Singapore); Lim, Chwee Teck [Department of Bioengineering, National University of Singapore (Singapore); Department of Mechanical Engineering, National University of Singapore (Singapore); Mechanobiology Institute, National University of Singapore (Singapore); Singapore-MIT Alliance for Research and Technology (SMART), National University of Singapore (Singapore); Lee, Taeyong, E-mail: bielt@nus.edu.sg [Department of Bioengineering, National University of Singapore (Singapore)

    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

  8. Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    L Karimzadeh

    2012-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is a low grade inflammatory disease characterized by hyperandrogenemia and chronic anovulation. C-reactive protein (CRP, released by adipocytes, plays a key role in PCOS. Apis mellifera honeybee venom (HBV contains a variety of biologically active components with various pharmaceutical properties. This study was designed to assess the possibility of HBV application as an anti-inflammatory therapeutic agent. To induce PCOS, 1 mg/100 g body weight estradiol valerate (EV was subcutaneously (SC injected into eight-week-old rats. After 60 days, 0.5 mg/kg HBV was administered SC for 14 consecutive days, and the results of PCOS treatment were investigated. Rats were then anesthetized with chloroform, and their ovaries and livers were surgically removed to determine histomorphometrical changes. Testosterone and 17-β-estradiol were detected by chemiluminescence immunoassay. In order to detect serum CRP, ELISA kit was used in three groups of EV-induced PCOS, HBV-treated PCOS and control animals. Thickness of the theca layer, number of cysts and the level of serum CRP significantly decreased in HBV group in comparison with PCOS group. Moreover, corpus luteum, as a sign of ovulation, was observed in HBV-treated ovaries which were absent in PCOS group. Our results suggest that the beneficial effect of HBV may be mediated through its inhibitory effect on serum CRP levels.

  9. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal tablets in the treatment of atrophic vaginitis: a randomized controlled trial.

    Science.gov (United States)

    Ekin, Murat; Yaşar, Levent; Savan, Kadir; Temur, Muzaffer; Uhri, Mehmet; Gencer, Işıl; Kıvanç, Esra

    2011-03-01

    To compare the effectiveness of the vaginal tablets of hyaluronic acid and estrodiol for the treatment of atrophic vaginitis. Forty-two postmenopausal women with symptoms of atrophic vaginitis were randomized to take vaginal tablets of 25 μg estradiol (n = 21) (group I) or 5 mg hyaluronic acid sodium salt (n = 21) (group II) for 8 weeks. The symptoms of atrophic vaginitis were evaluated by a self-assessed 4-point scale of composite score and the degree of epithelial atrophy was determined as, none, mild, moderate and severe. Vaginal pH and maturation index were measured and compared in both the groups. The symptoms were relieved significantly in both the groups (P Hyaluronic acid vaginal tablets can be used in patients with atrophic vaginitis who do not want to or can not take local estrogen treatment.

  10. Neonatal androgenization of hypogonadal (hpg male mice does not abolish estradiol-induced FSH production and spermatogenesis

    Directory of Open Access Journals (Sweden)

    Kerr Jeffrey B

    2005-09-01

    Full Text Available Abstract Background Testicular development is arrested in the hypogonadal (hpg mouse due to a congenital deficiency in hypothalamic gonadotropin-releasing hormone (GnRH synthesis. Chronic treatment of male hpg mice with estradiol induces FSH synthesis and secretion, and causes testicular maturation and qualitatively normal spermatogenesis. As estradiol negative feedback normally inhibits FSH production in the male, this study tested whether this paradoxical response to estradiol in the male hpg mouse might be due to inadequate masculinisation or incomplete defeminization in the neonatal period. Previous studies have demonstrated that treatment of hpg mice with testosterone propionate in the immediate neonatal period is necessary to allow full reproductive behaviors to be expressed following suitable endocrine stimulation at adult ages. Methods Hpg mice were treated with 100 μg testosterone propionate or vehicle on postnatal day 2. At 35 days of age, subgroups of these mice were treated with silastic implants containing estradiol or cholesterol. Reproductive behavior was scored in tests with steroid-primed female mice, then testicular development was assessed histologically, and measures of pituitary FSH content made at 85 days of age. Results The neonatal testosterone propionate treatment successfully defeminized female litter mates, as revealed by impaired vaginal opening and deficiencies in lordosis behavior, and it allowed appropriate male reproductive behavior to be expressed in a proportion of the hpg males when tested at an adult age. However, neonatal androgen supplementation did not block or even reduce the subsequent actions of estradiol in increasing pituitary FSH content, nor did it affect the ability of estradiol to induce qualitatively normal spermatogenesis. Conclusion The ability of the hpg male to show a "female" neuroendocrine response to estradiol is not a result of inadequate androgenization during neonatal development, and

  11. Follicular synchronization using transdermal estradiol patch and GnRH antagonists in the luteal phase; does it increase oocyte yield in poor responders to gonadotropin stimulation for in vitro fertilization (IVF)? A comparative study with microdose flare-up protocol.

    Science.gov (United States)

    Ata, Baris; Zeng, Xing; Son, Weon Y; Holzer, Hananel; Tan, Seang L

    2011-11-01

    The aim of this retrospective study was to compare the oocyte yield with the luteal estradiol patch (LPA) - GnRH antagonist and microdose (MD) flare-up protocols in anticipated poor responders. Fifty-seven women who underwent IVF treatment following stimulation with LPA or MD protocols at McGill Reproductive Centre were matched for age and markers of ovarian reserve. Numbers of oocytes collected (6 vs 7), mature oocytes collected (5 vs 5), and oocyte maturation rates (72% vs 74%) were similar. The numbers of good quality embryos available (2 vs 1) and embryos transferred (3 vs 3) were likewise similar. Embryo implantation rate of 16.7% and clinical pregnancy rate of 38.9% achieved in the LPA group were almost 50% higher than the corresponding figures at 10.3% and 22.2% in the MD group; however, the differences were not statistically significant (p > 0.05 for all comparisons). Although the results do not suggest an increased oocyte yield or follicular synchronization with the LPA protocol, the observed trend toward higher embryo implantation and clinical pregnancy rates requires further research.

  12. Effects of estradiol on norepinephrine and prostaglandin efflux in medial basal hypothalamus of ovariectomized rats

    International Nuclear Information System (INIS)

    Cardinali, D.P.; Fernandez Pardal, J.; Gimeno, M.F.; Gimeno, A.L.

    1982-01-01

    The spontaneous and K + -stimulated efflux of norepinephrine (NE) and the release of PGE 2 and PGF 2 α were examined in medial basal hypothalamus (MBH) of ovariectomized rats killed before and during the LH release that follows estradiol treatment. As compared to vehicle-treated, ovariectomized rats, estradiol-primed rats exhibited a 60% more increase in K + -stimulated 3 H-overflow of MBH slices preloaded with 3 H-NE at morning hours (1000 hours). Estradiol treatment did not result in further increase of K + -induced 3 H release from MBH slices at the time of LH release (1700 hours), nor affected labelled NE release in occipital cortex slices. A significant difference between K + -stimulated NE release of vehicle-treated spayed rats killed at 1000 and 1700 hours was observed, the latter showing 54% more release upon stimulus. PGE 2 efflux was time-dependent being highest at the evening in both vehicle- and estradiol-treated animals. The MBH of estrogenized rats released significantly more PGE 2 at the evening as compared to the controls. The release of PGF 2 α remained essentially unchanged regardless of estradiol treatment or time of day. The present results offer additional support to the involvement of MBH catecholamines and prostaglandins in the mechanism of LH secretion in the rat. (author)

  13. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

    2014-05-09

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  14. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    International Nuclear Information System (INIS)

    Souza, M.F.; Couto-Pereira, N.S.; Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M.; Nin, M.S.; Gomez, R.; Barros, H.M.T.

    2014-01-01

    Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse

  15. Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

    Directory of Open Access Journals (Sweden)

    M.F. Souza

    2014-06-01

    Full Text Available Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL, estradiol (0.05 mg/mL, progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

  16. Estradiol Transdermal Patch

    Science.gov (United States)

    ... menopause (change of life; the end of monthly menstrual periods). Transdermal estradiol is also used to prevent ... patch. Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

  17. Antagonism of brain insulin-like growth factor-1 receptors blocks estradiol effects on memory and levels of hippocampal synaptic proteins in ovariectomized rats

    Science.gov (United States)

    Nelson, Britta S.; Springer, Rachel C.; Daniel, Jill M.

    2013-01-01

    Rationale Treatment with estradiol, the primary estrogen produced by the ovaries, enhances hippocampus-dependent spatial memory and increases levels of hippocampal synaptic proteins in ovariectomized rats. Increasing evidence indicates that the ability of estradiol to impact the brain and behavior is dependent upon its interaction with insulin-like growth factor-1 (IGF-1). Objectives The goal of the current experiment was to test the hypothesis that the ability of estradiol to impact hippocampus-dependent memory and levels of hippocampal synaptic proteins is dependent on its interaction with IGF-1. Methods Adult rats were ovariectomized and implanted with estradiol or control capsules and trained on a radial-maze spatial memory task. After training, rats were implanted with intracerebroventricular cannulae attached to osmotic minipumps (flow rate 0.15 μl/hr). Half of each hormone treatment group received continuous delivery of JB1 (300 μg/ml), an IGF-1 receptor antagonist, and half received delivery of aCSF vehicle. Rats were tested on trials in the radial-arm maze during which delays were imposed between the 4th and 5th arm choices. Hippocampal levels of synaptic proteins were measured by western blotting. Results Estradiol treatment resulted in significantly enhanced memory. JB1 blocked that enhancement. Estradiol treatment resulted in significantly increased hippocampal levels of postsynaptic density protein 95 (PSD-95), spinophilin, and synaptophysin. JB1 blocked the estradiol-induced increase of PSD-95 and spinophilin and attenuated the increase of synaptophysin. Conclusions Results support a role for IGF-1 receptor activity in estradiol-induced enhancement of spatial memory that may be dependent on changes in synapse structure in the hippocampus brought upon by estradiol/IGF-1 interactions. PMID:24146138

  18. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17ß-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  19. Endometrial safety of ultra-low-dose estradiol vaginal tablets

    DEFF Research Database (Denmark)

    Simon, James; Nachtigall, Lila; Ulrich, Lian G

    2010-01-01

    To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy.......To evaluate the endometrial hyperplasia and carcinoma rate after 52-week treatment with ultra-low-dose 10-microgram 17β-estradiol vaginal tablets in postmenopausal women with vaginal atrophy....

  20. Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

    Science.gov (United States)

    Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

    2016-01-01

    Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

  1. Drospirenone/ethinyl estradiol versus rosiglitazone treatment in overweight adolescents with polycystic ovary syndrome: comparison of metabolic, hormonal, and cardiovascular risk factors.

    Science.gov (United States)

    Tfayli, Hala; Ulnach, Julia Warren; Lee, SoJung; Sutton-Tyrrell, Kim; Arslanian, Silva

    2011-05-01

    Adolescents with polycystic ovary syndrome (PCOS) have insulin resistance and higher rates of the metabolic syndrome. Our objective was to compare the effects of 6 months treatment with drospirenone/ethinyl estradiol (EE) (3 mg/30 μg) vs. rosiglitazone (4 mg) daily on the hormonal and cardiometabolic profiles of overweight/obese adolescents with PCOS. We conducted a randomized, double-blinded, parallel clinical trial in an academic hospital, with n = 46 patients. The primary outcome measure was insulin sensitivity, hepatic with [6,6-(2)H(2)]glucose and peripheral with a 3-h hyperinsulinemic-euglycemic clamp. Other outcome measures included plasma androgen profile and response to ACTH stimulation, glucose and insulin response to oral glucose tolerance test, insulin secretion with a 2-h hyperglycemic clamp, fasting lipid profile, inflammatory markers, intima media thickness, aortic pulse wave velocity, body composition by dual-energy x-ray absorptiometry, and abdominal adiposity by computed tomography scan. Drospirenone/EE resulted in greater reductions in androgenemia. Neither treatment led to change in weight or body mass index, but rosiglitazone led to a significant decrease in visceral adiposity. Compared with drospirenone/EE, treatment with rosiglitazone improved hepatic and peripheral insulin sensitivity and lowered fasting and stimulated insulin levels during the oral glucose tolerance test. Treatment with drospirenone/EE was associated with elevations in total cholesterol, high-sensitivity C-reactive protein and leptin concentrations, whereas treatment with rosiglitazone led to lower triglycerides and higher adiponectin concentrations. Neither treatment affected intima media thickness or pulse wave velocity. In overweight/obese adolescents with PCOS, 6 months treatment with rosiglitazone was superior to drospirenone/EE in improving the cardiometabolic risk profile, and effective but inferior in attenuating hyperandrogenemia. Additional studies are needed to

  2. Male reproductive effects of octylphenol and estradiol in Fischer and Wistar rats

    DEFF Research Database (Denmark)

    Hossaini, Alireza; Dalgaard, Majken; Vinggaard, Anne

    2003-01-01

    to vehicle or 400 mg/kg bw of 4-tert-octylphenol administrated orally by gavage. Estradiol benzoate, at a dose of 40 mug/kg bw, was used as positive control agent. Treatment with estradiol benzoate decreased serum levels of testosterone, LH, FSH, inhibin and increased prolactin. Additionally, estradiol...... benzoate decreased the weight of all investigated reproductive organs, decreased sperm production and increased seminiferous tubular degeneration in both strains. More progressive effects on testis weight and histopathology were observed in the Fischer rats. Oral administration of octylphenol at 400 mg....../kg bw to both rat strains increased prolactin levels but had no effect on LH, FSH, testosterone or inhibin. In the octylphenol-treated Fischer rats the weights of the seminal vesicles and the levator ani/bulbocavernosus muscle were significantly decreased, whereas only the levator ani...

  3. Hepatic expression of heme oxygenase-1 and antioxidant response element-mediated genes following administration of ethinyl estradiol to rats

    International Nuclear Information System (INIS)

    Morio, Lisa A.; Leone, Angelique; Sawant, Sharmilee P.; Nie, Alex Y.; Brandon Parker, J.; Taggart, Peter; Barron, Alfred M.; McMillian, Michael K.; Lord, Peter

    2006-01-01

    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 μmol/kg, ip, a substrate and inducer of HO-1), with tin protoporphyrin IX (60 μmol/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 with

  4. Paradoxical action of fulvestrant in estradiol-induced regression of tamoxifen-stimulated breast cancer.

    Science.gov (United States)

    Osipo, Clodia; Gajdos, Csaba; Liu, Hong; Chen, Bin; Jordan, V Craig

    2003-11-05

    Long-term tamoxifen treatment of breast cancer can result in tamoxifen-stimulated breast cancer, in which estrogen inhibits tumor growth after tamoxifen withdrawal. We investigated the molecular mechanism(s) of estradiol-induced tumor regression by using an in vivo model of tamoxifen-stimulated human breast cancer. Growth of parental estradiol-stimulated MCF-7E2 and long-term tamoxifen-stimulated MCF-7TAMLT xenografts in athymic mice was measured during treatment with vehicle, estradiol, estradiol plus tamoxifen, tamoxifen alone, estradiol plus fulvestrant, or fulvestrant alone. Apoptosis was detected by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Protein expression was assessed by western blot analysis. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. All statistical tests were two-sided. MCF-7E2 tumor growth was stimulated by estradiol (cross-sectional area at week 13 = 1.06 cm2, 95% confidence interval [CI] = 0.82 to 1.30 cm2; Pestradiol-induced regression to 0.18 cm2 (95% CI = 0.15 to 0.21 cm2; P<.001), and tamoxifen or estradiol plus fulvestrant enhanced tumor growth to 1.00 cm2 (95% CI = 0.88 to 1.22 cm2). Estradiol increased the number of apoptotic cells in tumors by 23% (95% CI = 20% to 26%; P<.001) compared with all other treatments, decreased estrogen receptor alpha(ERalpha) protein expression, increased the expression of Fas mRNA and protein, decreased the expression of HER2/neu mRNA and protein and nuclear factor kappaB (NF-kappaB) protein but did not affect Fas ligand protein expression compared with control. Paradoxically, fulvestrant reversed this effect and stimulated MCF-7TAMLT tumor growth apparently through ERalpha-mediated regulation of Fas, HER2/neu, and NF-kappaB. Physiologic levels of estradiol induced regression of tamoxifen-stimulated breast cancer tumors, apparently by inducing the death receptor Fas and suppressing the antiapoptotic

  5. Increasing nursing treatment for pediatric procedural pain.

    Science.gov (United States)

    Bice, April A; Gunther, Mary; Wyatt, Tami

    2014-03-01

    Procedural pain management is an underused practice in children. Despite the availability of efficacious treatments, many nurses do not provide adequate analgesia for painful interventions. Complementary therapies and nonpharmacologic interventions are additionally essential to managing pain. Owing to the increasing awareness of inadequate nursing utilization of pharmacologic measures for procedural pain, this paper focuses only on analgesic treatments. The aim of this review was to examine how varying degrees of quality improvement affect nursing utilization of treatments for routine pediatric procedural pain. A comprehensive search of databases including Cinahl, Medline/Pubmed, Web of Science, Google Scholar, Psycinfo, and Cochrane Library was performed. Sixty-two peer-reviewed research articles were examined. Ten articles focusing on quality improvement in pediatric pain management published in English from 2001 to 2011 were included. Three themes emerged: 1) increasing nursing knowledge; 2) nursing empowerment; and 3) protocol implementation. Research critique was completed with the use of guidelines and recommendations from Creswell (2009) and Garrard (2011). The literature reveals that nurses still think that pediatric pain management is essential. Quality improvement increases nursing utilization of procedural pain treatments. Although increasing nursing knowledge improves pediatric pain management, it appears that nursing empowerment and protocol implementation increase nursing compliance more than just education alone. Nurses providing pain management can enhance their individual practice with quality improvement measures that may increase nursing adherence to institutional and nationally recommended pediatric procedural pain management guidelines. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  6. Retrieval of estradiol receptor in paraffin sections of resting porcine uteri by microwave treatment. Immunostaining patterns obtained with different primary antibodies.

    Science.gov (United States)

    Sierralta, W D; Thole, H H

    1996-05-01

    The unmasking of estradiol receptor in paraffin sections of Bouin's-fixed uterine tissue from ovariectomized gilts was attained with microwave treatment. Immunocytochemistry of the receptor was performed using a polyclonal or five monoclonal antibodies, two of which are commercially available, reacting with different domains of the protein and an amplified-peroxidase system for detection. With five of the antibodies, a predominance of nuclear staining was observed in cells of endometrial glands, while one monoclonal antibody (13H2), reacting with the receptor's domain E, showed a preference for the cytoplasmic receptor. In stroma, all antibodies detected more receptor in nuclei than in cytoplasm. In epithelium, the commercially available antibody H222, our monoclonals 13H2 and HT65, and the polyclonal antibody 402 demonstrated more receptor in cytoplasmic than in nuclear areas. In myometrium, the nuclei from longitudinal and ring muscles were definitely stained with the antibodies. We conclude that the accessibilities of the antibody epitopes of the receptor differ according to the functional uterine cell type.

  7. Estradiol blood test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003711.htm Estradiol blood test To use the sharing features on this page, ... of estrogens. How the Test is Performed A blood sample is needed . How to Prepare for the Test Your health care provider may tell you to ...

  8. Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

    Energy Technology Data Exchange (ETDEWEB)

    Di Paolo, T.; Falardeau, P.

    1987-08-31

    The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p < 0.001). Competition for (/sup 3/H)-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-(..beta..-..gamma..-imino)triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables.

  9. Guanine nucleotide regulation of dopamine receptor agonist affinity states in rat estradiol-induced pituitary tumors

    International Nuclear Information System (INIS)

    Di Paolo, T.; Falardeau, P.

    1987-01-01

    The authors have investigated dopamine (DA) receptor agonist high- and low-affinity states in female rate estradiol-induced prolactin (PRL)-secreting pituitary tumors and intact pituitary tissue. Estradiol treatment increased the anterior pituitary weight 9-fold and plasma prolactin levels 74-fold and these measures are correlated (R = 0.745, n = 73, p 3 H]-spiperone binding to the DA receptor by apomorphine was compared in normal and adenomatous pituitary tissue. The inhibition constants (Ki) and the proportions of the two apomorphine sites are unchanged in tumors compared to intact pituitary tissue. Guanosine 5'-[β-γ-imino]triphosphate (Gpp(NH)p) causes complete conversion of the high into low affinity dopaminergic agonist site in normal pituitary and in tumors. These results suggest that rats with primary estradiol-induced pituitary tumors have normal and functional DA receptors. 9 references, 2 tables

  10. Evidence that the [3H]estradiol-binding protein in pancreas is localized in exocrine cells

    International Nuclear Information System (INIS)

    Grossman, A.; Richardson, S.B.; Altszuler, N.; Lane, B.

    1985-01-01

    Extracts of rat pancreas contain significant amounts of an [ 3 H]estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer. Extraction with hypotonic buffer of pellets obtained by the isotonic procedure yielded most of the remaining [ 3 H]estradiol-binding activity. In an attempt to avoid errors resulting from incomplete homogenization and to detect possible changes in intracellular distribution of [ 3 H]estradiol-binding activity, pancreata were initially homogenized in isotonic buffer and centrifuged at high speed (100,000 X g; 1 hr). The pellet was then extracted with hypotonic buffer and centrifuged again at high speed, and both supernatants were analyzed for [ 3 H]estradiol-binding and amylase activities. Two or 14 days after treatment of male rats with streptozotocin, no apparent decline or redistribution of [ 3 H]estradiol-binding activity to the cytosol was noted despite extensive alteration of beta-islet cells, as determined by electron microscopic examination of sections of these pancreata and significant loss of insulin, as measured by RIA. Amylase activity was unaffected 2 days after streptozotocin treatment, but was depressed to about 1% of control levels at 14 days. Administration of insulin to the latter group of animals resulted in return of amylase to normal levels and a modest increase (approximately 50%) in [ 3 H]estradiol-binding activity

  11. A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

    Science.gov (United States)

    Zovkic, Iva B; McCormick, Cheryl M

    2017-11-14

    Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did

  12. Intrinsic mechanism of estradiol-induced apoptosis in breast cancer cells resistant to estrogen deprivation.

    Science.gov (United States)

    Lewis, Joan S; Meeke, Kathleen; Osipo, Clodia; Ross, Eric A; Kidawi, Noman; Li, Tianyu; Bell, Eric; Chandel, Navdeep S; Jordan, V Craig

    2005-12-07

    We previously developed an estrogen receptor (ER)-positive breast cancer cell line (MCF-7:5C) that is resistant to long-term estrogen deprivation and undergoes rapid and complete apoptosis in the presence of physiologic concentrations of 17beta-estradiol. Here, we investigated the role of the mitochondrial apoptotic pathway in this process. Apoptosis in MCF-7:5C cells treated with estradiol, fulvestrant, or vehicle (control) was investigated by annexin V-propidium iodide double staining and 4',6-diamidino-2-phenylindole (DAPI) staining. Apoptosis was also analyzed in MCF-7:5C cells transiently transfected with small interfering RNAs (siRNAs) to apoptotic pathway components. Expression of apoptotic pathway intermediates was measured by western blot analysis. Mitochondrial transmembrane potential (psim) was determined by rhodamine-123 retention assay. Mitochondrial pathway activity was determined by cytochrome c release and cleavage of poly(ADP-ribose) polymerase (PARP) protein. Tumorigenesis was studied in ovariectomized athymic mice that were injected with MCF-7:5C cells. Differences between the treatment groups and control group were determined by two-sample t test or one-factor analysis of variance. All statistical tests were two-sided. MCF-7:5C cells treated with estradiol underwent apoptosis and showed increased expression of proapoptotic proteins, decreased psim, enhanced cytochrome c release, and PARP cleavage compared with cells treated with fulvestrant or vehicle. Blockade of Bax, Bim, and p53 mRNA expression by siRNA reduced estradiol-induced apoptosis relative to control by 76% [95% confidence interval (CI) = 73% to 79%, P estradiol-induced apoptosis in long-term estrogen-deprived breast cancer cells. Physiologic concentrations of estradiol could potentially be used to induce apoptosis and tumor regression in tumors that have developed resistance to aromatase inhibitors.

  13. [Effect of estradiol on food intake, glucose and fat metabolism in mice C57BL/6J with mutation yellow at the agouti locus].

    Science.gov (United States)

    Iakovleva, T V; Makarova, E N; Kazantseva, A Iu; Bazhan, N M

    2012-05-01

    Mutation yellow at the agouti locus in mice (A(y)/a-mice) causes the increase of food intake and development of obesity and type 2 diabetes. In A(y)/a-females the disturbances of glucose and fat metabolisms occur after puberty. We have assumed that the mutation yellow violates the regulatory effect of estradiol on glucose and fat metabolism in mice. We investigated the effects of ovariectomy and estradiol treatment on body weight, food intake, glucose tolerance, plasma levels of glucose, insulin and etherified fatty acids in A(y)/a-females. C57Bl/6J females, not carrying yellow mutation at the agouti locus (a/a-mice), were used as a control. The data suggest that the yellow mutation did not affect estradiol regulation of food intake and glucose blood levels after a night of fasting, but, apparently, prevented estradiol participation in the regulation of glucose and fat metabolisms in the muscle and fat tissues.

  14. Effects of 17β-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Weichselbaum, R.R.

    1981-01-01

    The effects of 17β-estradiol, given either alone or with X-radiation, on the induction of malignant transformation were investigated in vitro. Treatment with 10 -6 M 17β-estradiol for 6 weeks, or 10 -5 M 17β-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicated an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation. (author)

  15. Biological activity and binding of estradiol to SK-Mel 23 human melanoma cells

    Directory of Open Access Journals (Sweden)

    Sarti M.S.M.V.

    2004-01-01

    Full Text Available Patients expressing estradiol receptors in melanoma cells have been reported to have a better prognosis. We therefore decided to investigate the in vitro effects of ß-estradiol and tamoxifen on the growth and tyrosinase activity of SK-Mel 23 human melanoma cells. Twenty-four-hour treatment with 0.4 nM ß-estradiol inhibited cell proliferation in 30% (0.70 ± 0.03 x 10(5 cells and increased tyrosinase activity in 50% (7130.5 ± 376.5 cpm/10(5 cells, as compared to untreated cells (1.0 ± 0.05 x 10(5 cells and 4769 ± 25.5 cpm/10(5 cells, respectively. Both responses were completely (100% blocked by 1 µM tamoxifen. Higher concentrations (up to 1.6 nM or longer treatments (up to 72 h did not result in a larger effect of the hormone on proliferation or tyrosinase activity. Competition binding assays demonstrated the presence of binding sites to [2,4,6,7-³H]-ß-estradiol, and that the tritiated analogue was displaced by the unlabeled hormone (1 nM to 100 µM, Kd = 0.14 µM, maximal displacement of 93% or by 10 µM tamoxifen (displacement of 60%. ß-estradiol also increased the phosphorylated state of two proteins of 16 and 46 kDa, after 4-h treatment, as determined by Western blot. The absorbance of each band was 1.9- and 4-fold the controls, respectively, as determined with Image-Pro Plus software. Shorter incubation periods with ß-estradiol did not enhance phosporylation; after 6-h treatment with the hormone, the two proteins returned to the control phosphorylation levels. The growth inhibition promoted by estradiol may explain the better prognosis of melanoma-bearing women as compared to men, and open new perspectives for drug therapy.

  16. Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

    International Nuclear Information System (INIS)

    Savergnini, S.Q.; Reis, A.M.; Santos, R.A.S.; Santos, P.E.B.; Ferreira, A.J.; Almeida, A.P.

    2012-01-01

    Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E 2 ; 5 µg·100 g −1 ·day −1 ) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E 2 treatment caused an increase in uterine weight. Although E 2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E 2 -treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval

  17. Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

    Energy Technology Data Exchange (ETDEWEB)

    Savergnini, S.Q.; Reis, A.M. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, R.A.S. [1Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Santos, P.E.B. [Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ferreira, A.J. [Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Almeida, A.P. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2012-11-01

    Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E{sub 2}; 5 µg·100 g{sup −1}·day{sup −1}) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E{sub 2} treatment caused an increase in uterine weight. Although E{sub 2} administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E{sub 2}-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

  18. Effects of Estradiol on Learned Helplessness and Associated Remodeling of Hippocampal Spine Synapses in Female Rats

    Science.gov (United States)

    Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S

    2009-01-01

    Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775

  19. CONCENTRATION OF ESTRADIOL IN DOGS (BITCHES IN SPRINGTIME

    Directory of Open Access Journals (Sweden)

    Edina Hajdarević

    2013-09-01

    Full Text Available Measuring of estradiol level in the peripheral blood in dog is important for the precise estrus detection. In proestrus, estradiol dominates. In estrus, however, estradiol progressively decreases while progesterone and LH increase, the latter shortly and abruptly. The research of Feldman and Nelson (7 indicates that the beginning of the sexual cycle of the female dog is the result of complex interaction of the environment, general health condition, condition of the ovaries, condition of the uterus, animal age, and some unidentified factors. Estradiol level in the peripheral circulation is starting to rise before the beginning of the proestrus, and during the proestrus the female dog is under the influence of estradiol (4. Our research included 30 female dogs on the territory of Tuzla Municipality, in the springtime. The female dogs were divided in three groups according to the breeding and living conditions: group A (female dogs living in the house environment; group B (female dogs living in the shelter; group C (female stray dogs. For the researched groups, estradiol level varied between 6,265 pg\\ml and 69,734 pg\\ml over the springtime. Of importance is the results can be applied in the evaluation of estrus in the female dogs, and when considering factors crucial for their sustainable reproduction potential.Key words: dogs, estradiol, spring

  20. 17 beta-estradiol and tamoxifen upregulate estrogen receptor beta expression and control podocyte signaling pathways in a model of type 2 diabetes.

    Science.gov (United States)

    Catanuto, Paola; Doublier, Sophie; Lupia, Enrico; Fornoni, Alessia; Berho, Mariana; Karl, Michael; Striker, Gary E; Xia, Xiaomei; Elliot, Sharon

    2009-06-01

    Diabetic nephropathy remains one of the most important causes of end-stage renal disease. This is particularly true for women from racial/ethnic minorities. Although administration of 17beta-estradiol to diabetic animals has been shown to reduce extracellular matrix deposition in glomeruli and mesangial cells, effects on podocytes are lacking. Given that podocyte injury has been implicated as a factor leading to the progression of proteinuria and diabetic nephropathy, we treated db/db mice, a model of type 2 diabetic glomerulosclerosis, with 17beta-estradiol or tamoxifen to determine whether these treatments reduce podocyte injury and decrease glomerulosclerosis. We found that albumin excretion, glomerular volume, and extracellular matrix accumulation were decreased in these mice compared to placebo treatment. Podocytes isolated from all treatment groups were immortalized and these cell lines were found to express the podocyte markers WT-1, nephrin, and the TRPC6 cation channel. Tamoxifen and 17beta-estradiol treatment decreased podocyte transforming growth factor-beta mRNA expression but increased that of the estrogen receptor subtype beta protein. 17beta-estradiol, but not tamoxifen, treatment decreased extracellular-regulated kinase phosphorylation. These data, combined with improved albumin excretion, reduced glomerular size, and decreased matrix accumulation, suggest that both 17beta-estradiol and tamoxifen may protect podocytes against injury and therefore ameliorate diabetic nephropathy.

  1. Effect of exogenous estradiol applied at different embryonic stages on sex determination, growth, and mortality in the leopard gecko (Eublepharis macularius).

    Science.gov (United States)

    Tousignant, A; Crews, D

    1994-01-01

    Temperature-dependent sex determination (TSD) occurs in three orders of reptiles. Several studies have examined the ability of estradiol to produce female hatchlings incubated at a male-producing temperature. The results of these experiments support the idea that estradiol could be used as a powerful tool in the conservation of endangered species with TSD by manipulating hatchling sex ratios. However, these experiments have concentrated on the mechanism of determination. This experiment was designed to test the efficacy of various dosages of estradiol applied at two different stages to alter the hatchling sex ratio as well as determining the potential use of such manipulation for conservation efforts by monitoring egg mortality and hatchling growth. The leopard gecko (Eublepharis macularius) exhibits TSD and reaches reproductive maturity in less than one year, making it an excellent model for evaluating the long-term effects of estradiol. The results demonstrate that estradiol has a dose-dependent effect on the hatchling sex ratio while only high dosages applied at the later stage of development showed increased mortality. Estrogen-determined females grew at the same rate as temperature-determined females and have produced viable hatchlings. Estradiol treatment of eggs from endangered species may provide a method of insuring female offspring when the TSD pattern is unknown or equipment for controlled incubation is unavailable.

  2. COMPARISON BETWEEN ESTRADIOL CYPIONATE AND GONADOTROPIN RELEASING HORMONE AS OVULATION SYNCHRONIZATION TREATMENTS FOR FIXED-TIME ARTIFICIAL INSEMINATION PROGRAMS IN BRAHMAN-CROSS HEIFERS IN A SUBTROPICAL REGION OF NORTHEASTERN MEXICO

    Directory of Open Access Journals (Sweden)

    Miguel Angel Dominguez

    2012-12-01

    Full Text Available Synchronization protocols with intravaginal progesterone releasing devices (CIDR and PGF2α were evaluated, with GnRH or estradiol cypionate (ECP added for fixed-time artificial insemination (FTAI in five counties in Tamaulipas, Mexico. Brahman-cross heifers (≥15 months old were selected based on body condition (≥3 on a 5-point scale and confirmed ovarian activity. The six treatments (n = 320 each were: T1 (9-d CIDR, ECP on insertion, PGF2α on day 9, ECP on day 10, FTAI 54 h after removal; T2 (7-d CIDR, ECP on insertion, PGF2α on day 7, ECP on day 8, FTAI 54 h after removal; T3 (7-d CIDR, GnRH on insertion, PGF2α on day 7, FTAI and GnRH 48 h after removal; T4 (7-d CIDR, GnRH on insertion, PGF2α on day 6, FTAI and GnRH 48 h after removal; T5 (7-d CIDR, GnRH on insertion, PGF2α on day 7, FTAI and GnRH 60 h after removal; and T6 (7-d CIDR, GnRH on insertion, PGF2α on day 7, FTAI alone 48 h after removal. Pregnancy was diagnosed ultrasonically 45 days after FTAI. Analyses included pregnancy rates and treatment costs (hormones and handling. Pregnancy rates ranged from 31.6 ± 3.9 to 48.0 ± 10.6%; neither treatment nor county affected these rates (p > 0.05. In conclusion, the inclusion of treatment costs showed two more economical treatments (T2 using estradiol or T3 using GnRH under the nutritional, weather and handling conditions present in the tropical region of southeastern Tamaulipas.

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

    Energy Technology Data Exchange (ETDEWEB)

    Baker, Michael E., E-mail: mbaker@ucsd.edu [Department of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693 (United States); Chang, David J. [Department of Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693 (United States)

    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.

  4. GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus.

    Science.gov (United States)

    McAllister, C E; Creech, R D; Kimball, P A; Muma, N A; Li, Q

    2012-08-01

    Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT(1A)) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT(1A) receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT(1A) receptor desensitization. We previously showed that estrogen receptor β is not necessary for 5-HT(1A) receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT(1A) receptor as measured by hormonal responses to the selective 5-HT(1A) receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT(1A) receptor signaling components including 5-HT(1A) receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT(1A) receptor protein but increased 5-HT(1A) mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT(1A) receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT(1A) receptor signaling pathway and desensitization of 5-HT(1A) receptor signaling. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Exposure to Ionizing Radiation Causes Long-Term Increase in Serum Estradiol and Activation of PI3K-Akt Signaling Pathway in Mouse Mammary Gland

    Energy Technology Data Exchange (ETDEWEB)

    Suman, Shubhankar [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States); Johnson, Michael D. [Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (United States); Fornace, Albert J. [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States); Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC (United States); Datta, Kamal, E-mail: kd257@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC (United States)

    2012-10-01

    Purpose: Exposure to ionizing radiation is an established risk factor for breast cancer. Radiation exposure during infancy, childhood, and adolescence confers the highest risk. Although radiation is a proven mammary carcinogen, it remains unclear where it acts in the complex multistage process of breast cancer development. In this study, we investigated the long-term pathophysiologic effects of ionizing radiation at a dose (2 Gy) relevant to fractionated radiotherapy. Methods and Materials: Adolescent (6-8 weeks old; n = 10) female C57BL/6J mice were exposed to 2 Gy total body {gamma}-radiation, the mammary glands were surgically removed, and serum and urine samples were collected 2 and 12 months after exposure. Molecular pathways involving estrogen receptor-{alpha} (ER{alpha}) and phosphatidylinositol-3-OH kinase (PI3K)-Akt signaling were investigated by immunohistochemistry and Western blot. Results: Serum estrogen and urinary levels of the oncogenic estrogen metabolite (16{alpha}OHE1) were significantly increased in irradiated animals. Immunostaining for the cellular proliferative marker Ki-67 and cyclin-D1 showed increased nuclear accumulation in sections of mammary glands from irradiated vs. control mice. Marked increase in p85{alpha}, a regulatory sub-unit of the PI3K was associated with increase in Akt, phospho-Akt, phospho-BAD, phospho-mTOR, and c-Myc in irradiated samples. Persistent increase in nuclear ER{alpha} in mammary tissues 2 and 12 months after radiation exposure was also observed. Conclusions: Taken together, our data not only support epidemiologic observations associating radiation and breast cancer but also, specify molecular events that could be involved in radiation-induced breast cancer.

  6. Dissipation of 17β-estradiol in composted poultry litter.

    Science.gov (United States)

    Hakk, Heldur; Sikora, Lawrence

    2011-01-01

    The excreted estrogen rate of all livestock in the United States is estimated at 134 kg d. The influence of manure treatment on the fate of estrogens is critical in deciding the recycling of over 300 million dry tons of livestock produced annually. The effects of two common manure management practices, heated composting and ambient temperature decomposition, on the fate of 17β-estradiol in poultry litter were determined. A mixture of poultry litter, wood chips, and straw was amended with [C]17β-estradiol and allowed to undergo decomposition with a laboratory-scale heated composter (HC) or room temperature incubation (RTI) for 24 d. Radiolabel in the finished products was fractionated into water-extractable, acetone-extractable, nonextractable, and mineralized fractions. Total 17β-estradiol radioactive residues in the HC and RTI ( = 2) treatments were not different ( > 0.05), except that statistically less 17β-estradiol was mineralized to CO during HC than RTI (1.1 vs. 10.0% for HC and RTI, respectively). Estrone was the major degradation product in extracts of HC and RTI treatments as determined by liquid chromatography/mass spectrometry analyses. The nonextractable residues indicated no quantitative differences among the humins between the treatments. An estimated 3% of the fortified estrogenicity remained after HC treatment, and 15% of the fortified estrogenicity remained after RTI treatment. If reduction of water-removable, biologically active 17β-estradiol is the treatment goal, then HC treatment would be slightly preferred over ambient temperature degradation. However, unmanaged, ambient temperature litter piles are less costly and time consuming for food animal producers and result in greater mineralization and similar immobilization of estradiol. by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  7. The Protective Effect of γ-aminobutyric Acid on Kidney Injury Induced by Renal Ischemia-reperfusion in Ovariectomized Estradiol-treated Rats.

    Science.gov (United States)

    Talebi, Nahid; Nematbakhsh, Mehdi; Monajemi, Ramesh; Mazaheri, Safoora; Talebi, Ardeshir; Vafapour, Marzieh

    2016-01-01

    Renal ischemia-reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender-related. This study was designed to investigate the role of γ-aminobutyric acid (GABA) against IRI in ovariectomized estradiol-treated rats. Thirty-five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham-operated, control, and GABA-treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery. The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements. The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P GABA significantly decreased the aforementioned parameters (P levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co-administration of estradiol and GABA could not protect the kidney against IRI.

  8. Basal and dynamic relationships between implicit power motivation and estradiol in women.

    Science.gov (United States)

    Stanton, Steven J; Schultheiss, Oliver C

    2007-12-01

    This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

  9. The effects of 17β-estradiol and a selective estrogen receptor modulator, bazedoxifene, on ovarian carcinogenesis.

    Science.gov (United States)

    Romero, Iris L; Lee, WooSeok; Mitra, Anirban K; Gordon, Ilyssa O; Zhao, Yan; Leonhardt, Payton; Penicka, Carla V; Mui, Keeley L; Krausz, Thomas N; Greene, Geoffrey L; Lengyel, Ernst

    2012-01-01

    To test if estrogen promotes carcinogenesis in vitro and in a genetic mouse model of ovarian cancer and whether its effects can be inhibited by a novel selective estrogen receptor modulator (SERM), bazedoxifene. Bazedoxifene was synthesized and it was confirmed that the drug abrogated the uterine stimulatory effect of 17β-estradiol in mice. To determine if hormones alter tumorigenesis in vivo LSL-K-ras(G12D/+)Pten(loxP/loxP) mice were treated with vehicle control, 17β-estradiol or bazedoxifene. Hormone receptor status of a cell line established from LSL-K-ras(G12D/+)Pten(loxP/loxP) mouse ovarian tumors was characterized using Western blotting and immunohistochemistry. The cell line was treated with hormones and invasion assays were performed using Boyden chambers and proliferation was assessed using MTT assays. In vitro 17β-estradiol increased both the invasion and proliferation of ovarian cancer cells and bazedoxifene reversed these effects. However, in the genetic mouse model neither treatment with 17β-estradiol nor bazedoxifene changed mean tumor burden when compared to treatment with placebo. The mice in all treatment groups had similar tumor incidence, metastatic nodules and ascites. While 17β-estradiol increases the invasion and proliferation of ovarian cancer cells, these effects do not translate into increased tumor burden in a genetic mouse model of endometrioid ovarian cancer. Likewise, while the SERM reversed the detrimental effects of estrogen in vitro, there was no change in tumor burden in mice treated with bazedoxifene. These findings demonstrate the complex interplay between hormones and ovarian carcinogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Transfer of estradiol to human milk. [Radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Nilsson, S.; Nygren, K.G.; Johansson, E.D.B.

    1978-11-15

    A radioimmunoassay for the measurement of estradiol in human milk is evaluated. The detection limit was found to be 25 pg of estradiol per milliliter of milk. In milk samples collected from four lactating women during three to four months and from one pregnant and lactating woman, the concentration of estradiol was found to be below the detection limit of the assay. When six lactating women were given vaginal suppositories containing 50 or 100 mg of estradiol, it was possible to estimate the estradiol concentration in milk. A ratio of transfer of estradiol from plasma to milk during physiologic conditions is calculated to be less than 100 : 10.

  11. Transfer of estradiol to human milk

    International Nuclear Information System (INIS)

    Nilsson, S.; Nygren, K.G.; Johansson, E.D.B.

    1978-01-01

    A radioimmunoassay for the measurement of estradiol in human milk is evaluated. The detection limit was found to be 25 pg of estradiol per milliliter of milk. In milk samples collected from four lactating women during three to four months and from one pregnant and lactating woman, the concentration of estradiol was found to be below the detection limit of the assay. When six lactating women were given vaginal suppositories containing 50 or 100 mg of estradiol, it was possible to estimate the estradiol concentration in milk. A ratio of transfer of estradiol from plasma to milk during physiologic conditions is calculated to be less than 100 : 10

  12. The effect of pregnancy and estradiol-17 beta treatment on the biliary transport maximum of dibromosulfophthalein, and the glucuronide conjugates of 5-phenyl-5-p-hydroxyphenyl[14C]hydantoin and [14C]morphine in the isolated perfused rat liver

    International Nuclear Information System (INIS)

    Auansakul, A.C.; Vore, M.

    1982-01-01

    The biliary transport maximum (Tm) of three organic axions was determined in the isolated perfused livers of untreated female (control), estradiol-17 beta (E2)-treated female (1 mg/kg/day, s.c. for 14 days), and pregnant (19-21 days of gestation) rats. Dibromosulfophthalein (DBSP), 5-phenyl-5-p-hydroxyphenyl[ 14 C]hydantoin (HPPH) and [ 14 C]morphine were infused continuously into the perfusate for a total dose of 41.2, 18, or 40.5 mumol, respectively. The concentration of [ 14 C]HPPH and [ 14 C]morphine declined in the perfusate, whereas the concentrations of [ 14 C]HPPH glucuronide and [ 14 C]morphine glucuronide increased during the 90-min experiment, indicating that the rate of formation of the glucuronide exceeded its rate of excretion in bile. E2 treatment decreased the Tm (nmol/min/g liver) for [ 14 C]HPPH glucuronide and [ 14 C]morphine glucuronide but not for DBSP, whereas pregnancy decreased the Tm for all three organic anions. Pregnancy, and to a lesser extent E2 treatment, increased liver weight. When expressed per whole liver, the Tm was not altered by pregnancy for any of three organic anions. E2 treatment increased the Tm for DBSP, had no effect on the Tm for HPPH glucuronide and decreased the Tm for [ 14 C]morphine glucuronide. These data suggest the presence of multiple carriers for organic anions which are differentially affected by estrogen treatment and pregnancy

  13. Radiosensitization dependent on p53 function in bronchial carcinoma cells by the isoflavone genistein and estradiol in vitro

    International Nuclear Information System (INIS)

    Hermann, R.M.; Fest, J.; Christiansen, H.; Hille, A.; Rave-Fraenk, M.; Nitsche, M.; Gruendker, C.; Viereck, V.; Jarry, H.; Schmidberger, H.

    2007-01-01

    Background and Purpose: Simultaneous radiotherapy with chemotherapy is a standard treatment for inoperable non-small cell lung cancer (NSCLC), but the clinical outcome still remains poor. To further intensify treatment, substances need to be identified, which increase the effect of radiation on tumor cells without further enhancing toxicity to normal tissue. Hormones have a different toxicity profile than radiation or cytostatic drugs. As NSCLC often express estrogen receptors (ERs), the combination of genistein or estradiol and radiation in vitro was investigated. Material and Methods: A549 NSCLC cells with an inducible expression of a mutated TP53 and fibroblasts of a male donor (DF-18) were examined. ER expression was immunocytologically confirmed in all studied cell lines. Clonogenic survival was measured after incubation of the cells with genistein or estradiol (0.01 μM and 10 μM as maximum clinically applicable dose) and irradiation with different doses (0-4 Gy). The differentiation state of fibroblasts after combined therapy was analyzed. Results: A549 cells expressing mutated TP53 were more radioresistant than TP53 wild-type cells. Incubation of nonfunctional TP53 cells with genistein or estradiol increased radiosensitivity in both tested concentrations. By contrast, radiosensitivity of A549 with wild-type TP53 and DF-18 was not altered by hormonal incubation. In DF-18 radiation induced growth arrest that was not increased by additional hormonal incubation. Conclusion: NSCLC cells with nonfunctional TP53 might be sensitized against radiation by genistein or estradiol. As genistein is better tolerable than estradiol in patients, additional studies are warranted to assess potential gains of this combination therapy

  14. Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

    Science.gov (United States)

    de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

    2007-10-01

    The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

  15. Collagen concentration on the facial skin of postmenopausal women after topical treatment with estradiol and genistein: a randomized double-blind controlled trial.

    Science.gov (United States)

    Silva, Lidia Aragão; Ferraz Carbonel, Adriana Aparecida; de Moraes, Andréa Regina Barbosa; Simões, Ricardo S; Sasso, Gisela Rodrigues da Silva; Goes, Lívia; Nunes, Winnie; Simões, Manuel Jesus; Patriarca, Marisa Teresinha

    2017-11-01

    The objective of this study is to compare the effects of topical estrogen and genistein (a soy isoflavone) on the facial skin collagen of postmenopausal women not undergoing systemic hormonal therapy. This is a prospective, double blind, randomized, controlled clinical trial. Volunteer women (N = 30) 45-55 year old from the Endocrine Gynecology sector of the Gynecology Department of the Federal University of São Paulo (UNIFESP). The Ethical Committee of the Federal University of São Paulo approved the study (report no. 386/2004; registration on ClinicalTrials.gov NCT01553773), were assigned to topical treatment with either estrogen or genistein for 24 weeks. We quantified and compared facial collagen concentration before and after each treatment by performing pre-auricular skin biopsies. Our data showed an increase in the amount of both type I and type III facial collagen by the end of both treatments. However, the outcomes of the estrogen GI (ER) group were superior to the genistein GII (GEN) group, with statistical significance p < 000.1 Conclusion: Treatment with topical estrogen is superior to genistein, but both have positive impacts on facial skin collagen. Nevertheless, it is still unclear whether prolonged use of genistein and other topical phytoestrogens could produce systemic effects and further research is needed to clarify this question.

  16. 17β-estradiol-induced ACSL4 protein expression promotes an invasive phenotype in estrogen receptor positive mammary carcinoma cells.

    Science.gov (United States)

    Belkaid, Anissa; Ouellette, Rodney J; Surette, Marc E

    2017-04-01

    Long chain acyl-CoA synthase-4 (ACSL4) expression has been associated with an aggressive phenotype in breast carcinoma cells, whereas its role in ERα-positive breast cancer has not been studied. ACSL4 prefers 20-carbon polyunsaturated fatty acid (PUFA) substrates, and along with other ACSLs has been associated with cellular uptake of exogenous fatty acids. 17β-estradiol induces proliferation and invasive capacities in ERα+ve breast carcinoma that is associated with modifications of cellular lipid metabolism. In this study, treatment of steroid-starved ERα-positive MCF-7 and T47D mammary carcinoma cells with 17β-estradiol resulted in increased cellular uptake of the PUFA arachidonic acid (AA) and eicosapentaenoic acid (EPA), important building blocks for cellular membranes, and increased ACSL4 protein levels. There was no change in the expression of the ACSL1, ACSL3 and ACSL6 protein isotypes. Increased ACSL4 protein expression was not accompanied by changes in ACSL4 mRNA expression, but was associated with a significant increase in the protein half-life compared to untreated cells. ERα silencing reversed the impact of 17β-estradiol on ACSL4 protein levels and half-life. Silencing of ACSL4 eliminated the 17β-estradiol-induced increase in AA and EPA uptake, as well as the 17β-estradiol-induced cell migration, proliferation and invasion capacities. ASCL4 silencing also prevented the 17β-estradiol induced increases in p-Akt and p-GSK3β, and decrease in E-cadherin expression, important events in epithelial to mesenchymal transition. Taken together, these results demonstrate that ACSL4 is a target of 17β-estradiol-stimulated ERα and is required for the cellular uptake of exogenous PUFA and the manifestation of a more malignant phenotype in ERα+ve breast carcinoma cells. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Exogenous estradiol enhances apoptosis in regressing post-partum rat corpora lutea possibly mediated by prolactin

    Directory of Open Access Journals (Sweden)

    Telleria Carlos M

    2005-08-01

    Full Text Available Abstract Background In pregnant rats, structural luteal regression takes place after parturition and is associated with cell death by apoptosis. We have recently shown that the hormonal environment is responsible for the fate of the corpora lutea (CL. Changing the levels of circulating hormones in post-partum rats, either by injecting androgen, progesterone, or by allowing dams to suckle, was coupled with a delay in the onset of apoptosis in the CL. The objectives of the present investigation were: i to examine the effect of exogenous estradiol on apoptosis of the rat CL during post-partum luteal regression; and ii to evaluate the post-partum luteal expression of the estrogen receptor (ER genes. Methods In a first experiment, rats after parturition were separated from their pups and injected daily with vehicle or estradiol benzoate for 4 days. On day 4 post-partum, animals were sacrificed, blood samples were taken to determine serum concentrations of hormones, and the ovaries were isolated to study apoptosis in situ. In a second experiment, non-lactating rats after parturition received vehicle, estradiol benzoate or estradiol benzoate plus bromoergocryptine for 4 days, and their CL were isolated and used to study apoptosis ex vivo. In a third experiment, we obtained CL from rats on day 15 of pregnancy and from non-lactating rats on day 4 post-partum, and studied the expression of the messenger RNAs (mRNAs encoding the ERalpha and ERbeta genes. Results Exogenous administration of estradiol benzoate induced an increase in the number of apoptotic cells within the CL on day 4 post-partum when compared with animals receiving vehicle alone. Animals treated with the estrogen had higher serum prolactin and progesterone concentrations, with no changes in serum androstenedione. Administration of bromoergocryptine blocked the increase in serum prolactin and progesterone concentrations, and DNA fragmentation induced by the estrogen treatment. ERalpha and

  18. Percutaneous 17ß-estradiol replacement therapy in hypertensive postmenopausal women

    Directory of Open Access Journals (Sweden)

    M.C. Osório-Wender

    1997-09-01

    Full Text Available The present study evaluated the short-term effects of percutaneous 17ß-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17ß-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued. Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 ± 27.21 to 35.09 ± 20.44 IU/l, P<0.05, and an increase in estradiol levels (15.06 ± 8.76 to 78.7 ± 44.6 pg/ml, P<0.05. There was no effect on LH (18.0 ± 9.5 to 14.05 ± 8.28 IU/l. Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17ß-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women

  19. Bovine teeth as a novel matrix for the control of the food chain: liquid chromatography-tandem mass spectrometry detection of treatments with prednisolone, dexamethasone, estradiol, nandrolone and seven β2-agonists.

    Science.gov (United States)

    Chiesa, Luca Maria; Nobile, Maria; Panseri, Sara; Biolatti, Bartolomeo; Cannizzo, Francesca Tiziana; Pavlovic, Radmila; Arioli, Francesco

    2017-01-01

    Veterinary drugs usually have rapid clearance rates in the liver and kidney, hampering their detection in conventional matrices such as the liver or urine. Pharmacological principles such as esterification may be applied to facilitate the administration of veterinary drugs and increase drug half-life. Prednisolone, whose therapeutic administration is regulated for food producing animals in the EU, is available in its acetate form as well as nandrolone, a banned anabolic steroid, which may be obtained as nandrolone phenylpropionate and estradiol as a benzoyl ester. While the distribution and accumulation of lipophilic and hydrophilic substances in human teeth have been well documented, studies on residues in bovine teeth are lacking. We hypothesised that analysis of bovine teeth could be used to detect both regulated and banned veterinary drugs. Steroids may be illegally used as growth promoters in food producing animals, alone or combined with β2-agonists; therefore, we developed, and validated, in accordance with the Commission Decision 2002/657/EC, two analytical confirmatory LC-MS/MS methods to detect these classes of compounds following a unique liquid extraction procedure. Finally, we analysed teeth from three male Friesian veal calves treated with intramuscular estradiol benzoate, oral prednisolone acetate or intramuscular nandrolone phenylpropionate in combination with oral ractopamine, respectively, and from seven bovines from the food chain. Teeth from treated animals were positive for their respective drugs, with the exception of nandrolone phenylpropionate. One sample from a food chain bovine was positive for isoxsuprine, one of the seven β2-agonists studied. Non-esterified forms of the steroids were not found. These results demonstrate that bovine teeth are a suitable matrix for the determination of pseudoendogenous substances or illicit administration of veterinary drugs.

  20. Synthesis of 123I-16 iodo estradiol

    International Nuclear Information System (INIS)

    Therain, F.; Gros, J.; Souchu, A.

    1982-01-01

    16α iodo estradiol has been demonstrated to have as good an affinity as estradiol for estrogen-receptors and, labeled with iodine 123, may provide a good scanning agent fot visualisation of tissues containing estrogen-repectors, especially mammary tumors. 123 I-16α iodo estradiol has been synthesized by an halogen exchange of 16ν bromo estradiol according to the procedure described by Hochberg for 125 I-16α iodo estradiol labeling. Radiochemical yields are much lower than with iodine 125 (1 to 30%) and extremely variable. Specific activity range from 1,000 to 2,000 Ci/mmole [fr

  1. Physiological and biochemical effects of 17β estradiol in aging female rat brain.

    Science.gov (United States)

    Kumar, Pardeep; Taha, Asia; Kale, R K; Cowsik, S M; Baquer, Najma Zaheer

    2011-07-01

    Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 μg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiol's beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Local effect of bisphenol A on the estradiol synthesis of ovarian granulosa cells from PCOS.

    Science.gov (United States)

    Wang, Yuan; Zhu, Qinling; Dang, Xuan; He, Yaqiong; Li, Xiaoxue; Sun, Yun

    2017-01-01

    Close relationship between polycystic ovary syndrome (PCOS) and bisphenol A (BPA) has drawn much attention in recent years, while the underlying mechanisms are poorly understood. In our study, we aim to detect BPA concentration in the follicular fluid and investigate its effect on estradiol synthesis in human granulosa cells from PCOS and non-PCOS patients. Follicular fluid and granulosa cells were collected from women who underwent controlled ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection. BPA concentration in the follicular fluid from PCOS patients (440.50 ± 63.70 pg/ml) was significantly higher than that from non-PCOS patients (338.00 ± 57.88 pg/ml). Expression of aromatase and estradiol synthesis in cultured granulosa cells was examined after treatment with BPA from 0.01 to 1 μM for 24 h. Expression of aromatase and estradiol synthesis was downregulated by BPA in a dose-dependent manner in PCOS, but no effect was observed in granulosa cells from non-PCOS patients. These findings provide evidence that increased BPA concentration in the follicular fluid of PCOS patients may play an important role in its pathogenesis by attenuating the expression of aromatase in granulosa cells.

  3. Estradiol stimulation of inositolphospholipid metabolism in human endometrial fibroblasts

    International Nuclear Information System (INIS)

    Iida, K.; Imai, A.; Tamaya, T.

    1989-01-01

    Stimulated inositolphospholipid turnover has been proposed to constitute a signal-transducing mechanism in many cell types. To determine the inositolphospholipid turnover during stimulation by 17 beta-estradiol, the turnover kinetics of phospholipids was investigated in human endometrial fibroblasts. In cells incubated with [ 32 P] phosphate for 1 h, estradiol rapidly and persisitently (for at least 30 min) enhanced the rate of 32 P-labeling of phosphatidic acid (PA). On the other hand, after a lag time of 5 min, 32 P-labeling of phosphatidylinositol (PI) was also increased also. These sequential 32 P-labeling of PA and PI demonstrated that inositolphospholipid turnover was stimulated in fibroblasts exposed to estradiol. The rapid estrogen-stimulated inositolphospholipid turnover may not be through the mechanism associated with classical action of estrogen

  4. Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

    OpenAIRE

    Kachadroka, Supatra; Hall, Alicia M.; Niedzielko, Tracy L.; Chongthammakun, Sukumal; Floyd, Candace L.

    2010-01-01

    Several groups have recently shown that 17β-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17β-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17β-estradiol-mediated protection by evaluating a delayed administration over a clinically relevan...

  5. Evidence that 17alpha-estradiol is biologically active in the uterine tissue: Antiuterotonic and antiuterotrophic action

    Directory of Open Access Journals (Sweden)

    Navarrete Erika

    2005-07-01

    -induced relaxation and calcium contractions in depolarized tissues were markedly prevented by 17alpha-estradiol, implying a reduction of extracellular calcium influx through voltage-operated calcium channels (VOCCs. Uterotrophic assay detected significant increase in uterine weight using 17alpha-estradiol, which was significantly minor as compared with 17beta-estradiol. 17alpha-Estradiol, at all doses ratios, significantly antagonized the hypertrophic response of 17beta-estradiol. Conclusion 17alpha-Estradiol induces a relaxing effect, which may be independent of the classical estrogen receptor, nongenomic action, apparently mediated by inactivation of VOCCs. 17alpha-Estradiol is also a weak estrogen agonist (uterotrophic response; likewise, 17alpha-estradiol may act as an antiestrogen (antiuterotrophic response. The overall data document a nongenomic relaxing action and a novel antiestrogenic action of 17alpha-estradiol, which are relevant in estrogen-mediated uterine physiology.

  6. The effects of 17β-estradiol plus drospirenone on anthropometric and biochemical measures of adiposity in menopausal women.

    Science.gov (United States)

    Karakus, Mesut; Gelisgen, Remise; Topcuoglu, Ata; Guralp, Onur; Topcuoglu, Deniz; Simsek, Gonul; Uludag, Seyfettin; Uzun, Hafize

    2012-11-01

    To assess whether there are changes on anthropometric and biochemical measures of adiposity in pre- and postmenopausal women and in the latter before and after 6 months treatment with 17β-estradiol plus drospirenone. Twenty postmenopausal and 20 premenopausal women were enrolled in a prospective comparative study. Postmenopausal women received 1 mg 17β-estradiol plus 2 mg drospirenone daily for 6 months. Measurements of body mass index (BMI), waist/hip ratio and plasmatic levels of insulin, glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, leptin, adiponectin, orexin-A, glucagon-like peptide-1 (GLP-1) and ghrelin were performed in premenopausal (group 1) and postmenopausal women and in the latter before (group 2a) and after (group 2b) 6 months treatment with 17β-estradiol plus drospirenone. No significant changes in BMIs, insulin and glucose were observed between group 1 and 2a; and group 2a and 2b. GLP-1 levels were significantly increased in group 1 compared to group 2a (p = 0.035). Leptin levels were significantly increased (p = 0.001) and GLP-1 levels were significantly decreased (p = 0.021) in group 2b compared to group 2a. HDL was significantly decreased while LDL and triglyceride levels were significantly increased in group 2a compared to group 1. (p = 0.030, p = 0.001, p = 0.020; respectively) LDL was significantly decreased (p = 0.010) in group 2b compared to group 2a. GLP-1 had a positive correlation with orexin-A (p correlation with leptin (p = 0.008, r = -0.345). Leptin was significantly higher and GLP-1 was significantly lower in women receiving 17β-estradiol plus drospirenone treatment. GLP-1 levels were significantly lower after the menopause compared to premenopausal levels. Orexin-A and GLP-1 were positively correlated.

  7. Optimal treatment increased the seed germination of Salvia verticillata L.

    Directory of Open Access Journals (Sweden)

    ALALEH KHAKPOOR

    2015-12-01

    Full Text Available Most seeds of the medicinal species are variable regarding their ecological compatibility with environmental conditions. Therefore, identifying the ecophysiological factors that affect dormancy and create optimal conditions for seed germination of medicinal plants is necessary for their culture and production. To evaluate the effect of different treatments on seed germination of medicinal species of Salvia verticillata, collected in the summer of 2010 in Eastern Azarbaijan, we have performed completely randomized experimental tests with 4 replications. The experimental design of treatment prior to growth included: scrape the skin with sandpaper, treatment with 500 ppm gibberellic acid for 24 and 48 h, treatment with citric acid for 10, 20 and 30 minutes, chilling for 2 and 4 weeks, treatment with warm water at 70°C and control treatment. Results showed that the effect of different treatments was significant on seed germination percent of the medicinal plant Salvia verticillata. Scrape the skin with sandpaper, citric acid treatment for 10, 20 and 30 minutes, and gibberellic acid treatment for 24 hours, increased the germination percentage compared to the control treatment. The most positive impact was observed on the dormancy breaking and germination of medicinal species Salvia verticillata.

  8. Estradiol levels in prepubertal boys and girls--analytical challenges

    DEFF Research Database (Denmark)

    Bay, Katrine; Andersson, Anna-Maria; Skakkebaek, Niels E

    2004-01-01

    Increasing evidence points at an important function of low concentrations of estradiol (E2) in prepubertal boys and girls. E2 serum levels in prepubertal children are, however, often immeasurable in conventional E2 assays. This strongly hampers further investigation of the physiological relevance...

  9. Effects of 17 beta-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

    International Nuclear Information System (INIS)

    Kennedy, A.R.; Weichselbaum, R.R.

    1981-01-01

    We have investigated the effects of 17 beta-estradiol, given both alone and with X-irradiation, on the induction of malignant transformation in vitro. Treatment with 10(-6)M 17 beta-estradiol for 6 weeks, or 10(-5)M 17 beta-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicate an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation

  10. Effects of 17 beta-estradiol on radiation transformation in vitro; inhibition of effects by protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, A.R.; Weichselbaum, R.R.

    1981-01-01

    We have investigated the effects of 17 beta-estradiol, given both alone and with X-irradiation, on the induction of malignant transformation in vitro. Treatment with 10(-6)M 17 beta-estradiol for 6 weeks, or 10(-5)M 17 beta-estradiol for only 5 days, induced malignant transformation in C3H 10T1/2 cells. Estradiol also acted as a cocarcinogen for X-ray induced transformation; the results indicate an additive effect when the cells were exposed to both agents together. The protease inhibitors antipain and leupeptin suppressed estradiol induced transformation as well as the additive effect observed for estradiol-radiation transformation.

  11. 17β-estradiol induces stearoyl-CoA desaturase-1 expression in estrogen receptor-positive breast cancer cells

    International Nuclear Information System (INIS)

    Belkaid, Anissa; Duguay, Sabrina R.; Ouellette, Rodney J.; Surette, Marc E.

    2015-01-01

    To sustain cell growth, cancer cells exhibit an altered metabolism characterized by increased lipogenesis. Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the production of monounsaturated fatty acids that are essential for membrane biogenesis, and is required for cell proliferation in many cancer cell types. Although estrogen is required for the proliferation of many estrogen-sensitive breast carcinoma cells, it is also a repressor of SCD-1 expression in liver and adipose. The current study addresses this apparent paradox by investigating the impact of estrogen on SCD-1 expression in estrogen receptor-α-positive breast carcinoma cell lines. MCF-7 and T47D mammary carcinomas cells and immortalized MCF-10A mammary epithelial cells were hormone-starved then treated or not with 17β-estradiol. SCD-1 activity was assessed by measuring cellular monounsaturated/saturated fatty acid (MUFA/SFA) ratios, and SCD-1 expression was measured by qPCR, immunoblot, and immunofluorescence analyses. The role of SCD-1 in cell proliferation was measured following treatment with the SCD-1 inhibitor A959372 and following SCD-1 silencing using siRNA. The involvement of IGF-1R on SCD-1 expression was measured using the IGF-1R antagonist AG1024. The expression of SREBP-1c, a transcription factor that regulates SCD-1, was measured by qPCR, and by immunoblot analyses. 17β-estradiol significantly induced cell proliferation and SCD-1 activity in MCF-7 and T47D cells but not MCF-10A cells. Accordingly, 17β-estradiol significantly increased SCD-1 mRNA and protein expression in MCF-7 and T47D cells compared to untreated cells. Treatment of MCF-7 cells with 4-OH tamoxifen or siRNA silencing of estrogen receptor-α largely prevented 17β-estradiol-induced SCD-1 expression. 17β-estradiol increased SREBP-1c expression and induced the mature active 60 kDa form of SREBP-1. The selective SCD-1 inhibitor or siRNA silencing of SCD-1 blocked the 17β-estradiol-induced cell proliferation and increase in

  12. Neurobehavioral response to increased treatment dosage in chronic, severe aphasia

    Directory of Open Access Journals (Sweden)

    Jennifer L Mozeiko

    2014-04-01

    •\tIncreased activation in S2’s bilateral inferior frontal gyrus following the second treatment session indicates that a second Treatment Period can influence continued neuroplastic change in severe, chronic aphasia. •\tS1 appears to show the most activation following Treatment Period I. It is possible that his greater lesion volume or site did not allow for benefit from a second dose to the same degree as S2. •\tActivation changes (or lack thereof in both cases corresponded with performance on the naming task in the scanner, reflecting the effect of treatment. •\tFor S2, neuroimaging supported the behavioral results which favor a second dose of ILAT. For S1, behavioral results, particularly in his consistent increases on the BNT, are not supported by either the behavioral results in the scanner or the BOLD response.

  13. Increase in extraction yields of coals by water treatment

    Energy Technology Data Exchange (ETDEWEB)

    Masashi Iino; Toshimasa Takanohashi; Chunqi Li; Haruo Kumagai [National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan). Institute for Energy Utilization

    2004-10-01

    The effect of water treatment at 500 and 600 K on solvent extractions of Pocahontas No. 3 (PO), Upper Freeport (UF), and Illinois No. 6 (IL) coals was investigated. All the coals used show that the water treatments at 600 K increased the extraction yields greatly in the extractions with a 1:1 carbon disulfide/N-methyl-2-pyrrolidinone (CS{sub 2}/NMP) mixed solvent, NMP, or 1-methylnaphthalene (1-MN). However, the water treatments at 500 K and the heat treatments at 600 K without water gave only a slight increase in the yields. Characterizations of the water-treated coals were performed using ultimate and proximate compositions, Fourier transform infrared analysis, solvent swelling, nuclear magnetic resonance relaxation time, and viscoelasticity behavior. The swelling degree in methanol and toluene was increased by the water treatment at 600 K, suggesting that crosslinks become loosened by the treatment. The results of infrared analysis and the extraction temperature dependency of the extraction yields with NMP and 1-MN suggest that the loosening of {pi} - interactions, and of both {pi} - interactions and hydrogen bonds, are responsible for the yield enhancements for PO and UF coals, respectively. However, for IL coal, which exhibited a decrease in oxygen content and the amount of hydrogen-bonded OH, suggesting the occurrence of some chemical reactions, the yield enhancements may be due to the relaxation of hydrogen bonds and the removal of oxygen functional groups, such as the breaking of ether bonds. 17 refs., 3 figs., 5 tabs.

  14. Estradiol upregulates progesterone receptor and orphanin FQ colocalization in arcuate nucleus neurons and opioid receptor-like receptor-1 expression in proopiomelanocortin neurons that project to the medial preoptic nucleus in the female rat

    Science.gov (United States)

    Sanathara, Nayna M.; Moreas, Justine; Mahavongtrakul, Matthew; Sinchak, Kevin

    2014-01-01

    Background Ovarian steroids regulate sexual receptivity in the female rat by acting on neurons that converge on proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). Estradiol rapidly activates these neurons to release β-endorphin that activates MPN μ-opioid receptors (MOP) to inhibit lordosis. Lordosis is facilitated by the subsequent action of progesterone that deactivates the estradiol-induced MPN MOP activation. Orphanin FQ (OFQ/N; aka nociceptin) infusions into the ARH, like progesterone, deactivate MPN MOP and facilitate lordosis in estradiol-primed rats. OFQ/N reduces the activity of ARH β-endorphin neurons through post- and presynaptic mechanisms via its cognate receptor, ORL-1. Methods We tested the hypotheses that progesterone receptors (PR) are expressed in ARH OFQ/N neurons by immunohistochemistry and ORL-1 is expressed in POMC neurons that project to the MPN by combining Fluoro-Gold injection into the MPN and double-label fluorescent in situ hybridization (FISH). We also hypothesized that estradiol increases coexpression of PR-OFQ/N and ORL-1-POMC in ARH neurons of ovariectomized rats. Results The number of PR and OFQ/N immunopositive ARH neurons was increased as was their colocalization by estradiol treatment. FISH for ORL-1 and POMC mRNA revealed a subpopulation of ARH neurons that was triple-labeled indicating these neurons project to the MPN and coexpress ORL-1 and POMC mRNA. Estradiol was shown to upregulate ORL-1 and POMC expression in MPN-projecting ARH neurons. Conclusion Estradiol upregulates the ARH OFQ/N-ORL-1 system projecting to the MPN that regulates lordosis. PMID:24821192

  15. Increasing trend of metronidazole resistance in the treatment of ...

    African Journals Online (AJOL)

    Helicobacter pylori are gram negative spiral bacteria that colonize the human stomach. Infection with H. pylori is associated with chronic gastritis, peptic ulcer, gastric adenocarcinoma and gastric mucosaassociated lymphoid tissue (MALT) lymphoma. Antibiotic resistance is an ever increasing problem with the treatment of ...

  16. The role of histamine in estradiol-induced conditioned consumption reductions.

    Science.gov (United States)

    Hintiryan, Houri; Hayes, Unja L; Chambers, Kathleen C

    2005-01-31

    Conditioned consumption reductions (CCRs) develop toward novel taste stimuli as a consequence of associating those tastes with certain physiological changes. Few studies have focused on the neurochemical basis of this learned behavior. The purpose of these experiments was to reexamine the role of histamine in CCRs elicited by estradiol. Previous studies have suggested that histamine mediates CCRs induced by radiation, centrifugal rotation, and estradiol. However, because the animals were trained in a drug state, but tested in a nondrug state, it is possible that state-dependent learning confounded the results of these studies. The following series of experiments was performed to test this possibility for estradiol-induced CCRs. Implementing our own methodologies in Experiment 1, we demonstrated that an estradiol-induced CCR was blocked by treatment with the histamine 1 receptor blocker, chlorpheniramine maleate, before sucrose consumption during acquisition. In Experiment 2, identical states were maintained during acquisition and extinction by administering chlorpheniramine prior to sucrose exposure during both phases. The results indicated that chlorpheniramine blocked the estradiol-induced CCR. However, circumventing state-dependency in Experiment 3 by administering chlorpheniramine following exposure to sucrose during acquisition augmented the estradiol CCR. Taken together, the results of these experiments suggest that the ability of chlorpheniramine to abolish estradiol-induced CCRs is not due to state-dependency or to the antihistaminergic properties of chlorpheniramine. It is proposed that the results of all of the experiments can be accounted for by the aversive properties of chlorpheniramine.

  17. The increase in extraction yields of coals by water treatment

    Energy Technology Data Exchange (ETDEWEB)

    M. Iino; T. Takanohashi; C. Li; N. Kashimura; K. Masaki; T. Shishido; I. Saito; H. Kumagai [Institute for Energy Utilization, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki (Japan)

    2005-07-01

    We have reported that the water treatments of bituminous coals at 600 K for 1 h increased their extraction yields greatly (Energy Fuels, 2005, 18, 1414). In this paper the effect of coal rank on the extraction yields enhancement by the water treatment has been investigated using four Argonne Premium coals, i.e., Pocahontas No. 3 (PO), Upper Freeport (UF), Illinois No.6 (IL), and Beulah Zap (BZ) coals with C % (daf) in the range 67 - 90%. All the coals used show that the water treatments at 600 K increased the extraction yields greatly with a 1:1 carbon disulfide / N-methyl-2-pyrrolidinone mixed solvent (CS2 / NMP) at room temperature. While, the water treatments at 500 K or the heat treatments at 600 K without water gave little increase in the yields. Characterizations of the water-treated coals were carried out from ultimate and proximate compositions, FT-IR spectrum, solvent swelling, NMR relaxation time, and viscoelasticity behavior. The effect of extraction temperature on the extraction yield enhancement was also investigated using polar NMP or non-polar 1-MN solvent. From these results it is concluded that for high coal rank coals the loosening of non-covalent bonds is responsible for the extraction yields enhancement by the water treatment. The loosening non-covalent bonds may be {pi}-{pi} interactions between aromatic rings for PO, and both {pi}-{pi} interactions and hydrogen bonds for UF. While, for lower rank IL and BZ, which showed decrease in O% and hydrogen-bonded OH, the yield enhancements may be due to the loosening of hydrogen bonds and the removal of oxygen functional groups. 9 refs., 5 figs., 1 tab.

  18. Estradiol-promoted accumulation of receptor in nuclei of porcine endometrium cells. Immunogold electron microscopy of resting and estradiol-stimulated cells.

    Science.gov (United States)

    Sierralta, W D; Jakob, F; Thole, H; Engel, P; Jungblut, P W

    1992-01-01

    Endometrium was collected by curettage from castrated pigs, either untreated or exposed to estradiol in vivo by intrauterine injection, and processed for electron microscopy. The resin LR Gold was used for embedding, and sections were floated on droplets of 10 nm diameter gold particles, coated with the immunoglobulin-G1 (IgG1) fraction or its Fab2 fragment of a monospecific polyclonal antiserum raised in goats against the C-terminal half of the estradiol receptor. On average, only one gold particle per microns 2 became attached in the cytoplasmic area of untreated cells, whereas four were found over the nuclear area. These figures rose to 2-3/microns 2 and 15-26/microns 2, respectively, within 10 min after exposure to estradiol. The labeling intensities of nuclei in cell clusters and of coprocessed nuclei released from cells ruptured during curettage were identical in all situations. Nuclear pores were frequently tagged after estradiol treatment. The proportions of tagging densities in nuclei of untreated and estradiol-exposed cells corresponded to those of receptor contents measured in extracts of isolated nuclei by ligand binding. This correlation was not seen for the cytoplasmic compartment of untreated cells, the scarce tagging of which is interpreted by hidden antigenic determinants. Our morphological analyses support the conclusions drawn from biochemical data (Sierralta et al., 1992) of an estradiol-promoted translocation of receptor from the cytoplasm into the nucleus.

  19. Viral Vector Mediated Over-Expression of Estrogen Receptor–α in Striatum Enhances the Estradiol-induced Motor Activity in Female Rats and Estradiol Modulated GABA Release

    Science.gov (United States)

    Schultz, Kristin N.; von Esenwein, Silke A.; Hu, Ming; Bennett, Amy L.; Kennedy, Robert T.; Musatov, Sergei; Toran-Allerand, C. Dominique; Kaplitt, Michael G.; Young, Larry J.; Becker, Jill B.

    2009-01-01

    Classical estrogen receptor signaling mechanisms involve estradiol binding to intracellular nuclear receptors (estrogen receptor-α (ERα) and estrogen receptor-β (ERβ)) to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K+- evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERα located on the membrane of medium spiny GABAergic neurons. This experiment examined whether over-expression of ERα in the striatum would enhance the effect of estradiol on rotational behavior and the K+- evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERα cDNA (AAV.ERα) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERα in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared to controls and exhibited behavioral sensitization of contralateral rotations induced by a low dose of amphetamine. ERα over-expression also enhanced the inhibitory effect of estradiol on K+- evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior. PMID:19211896

  20. Viral vector-mediated overexpression of estrogen receptor-alpha in striatum enhances the estradiol-induced motor activity in female rats and estradiol-modulated GABA release.

    Science.gov (United States)

    Schultz, Kristin N; von Esenwein, Silke A; Hu, Ming; Bennett, Amy L; Kennedy, Robert T; Musatov, Sergei; Toran-Allerand, C Dominique; Kaplitt, Michael G; Young, Larry J; Becker, Jill B

    2009-02-11

    Classical estrogen receptor-signaling mechanisms involve estradiol binding to intracellular nuclear receptors [estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta)] to promote changes in protein expression. Estradiol can also exert effects within seconds to minutes, however, a timescale incongruent with genomic signaling. In the brain, estradiol rapidly potentiates stimulated dopamine release in the striatum of female rats and enhances spontaneous rotational behavior. Furthermore, estradiol rapidly attenuates the K(+)-evoked increase of GABA in dialysate. We hypothesize that these rapid effects of estradiol in the striatum are mediated by ERalpha located on the membrane of medium spiny GABAergic neurons. This experiment examined whether overexpression of ERalpha in the striatum would enhance the effect of estradiol on rotational behavior and the K(+)-evoked increase in GABA in dialysate. Ovariectomized female rats were tested for rotational behavior or underwent microdialysis experiments after unilateral intrastriatal injections of a recombinant adeno-associated virus (AAV) containing the human ERalpha cDNA (AAV.ERalpha) into the striatum; controls received either the same vector into areas outside the striatum or an AAV containing the human alkaline phosphatase gene into the striatum (AAV.ALP). Animals that received AAV.ERalpha in the striatum exhibited significantly greater estradiol-induced contralateral rotations compared with controls and exhibited behavioral sensitization of contralateral rotations induced by a low-dose of amphetamine. ERalpha overexpression also enhanced the inhibitory effect of estradiol on K(+)-evoked GABA release suggesting that disinhibition of dopamine release from terminals in the striatum resulted in the enhanced rotational behavior.

  1. A peptide derived from alpha-fetoprotein inhibits the proliferation induced by estradiol in mammary tumor cells in culture.

    Science.gov (United States)

    Sierralta, Walter D; Epuñan, Maria J; Reyes, José M; Valladares, Luis E; Andersen, Thomas T; Bennett, James A; Jacobson, Herbert I; Pino, Ana M

    2008-01-01

    This study was aimed to obtain additional information on the activity of a cyclized 9-amino acid peptide (cP) containing the active site of alpha fetoprotein, which inhibits the estrogen-stimulated proliferation of tumor cells in culture and of xenografts in immunodeficient mice. Breast cancer cells cultured in the presence of 2 nM estradiol were exposed to cP for different periods and their proliferation, estradiol binding parameters, clustering tendency and expression of E-cadherin and p21Cip1 were analyzed by biochemical and cell biology methods. The proliferation of MCF7 cells was significantly decreased by the addition of 2 microg/ml cP to the medium. cP did not increase cell death rate nor alter the number of binding sites for estradiol nor the endogenous aromatase activity of MCF7 cells. cP also decreased the proliferation of estrogen-dependent ZR75-1 cells but had no effect on estrogen-independent MDA-MB-231 cells. An increased nuclear p21Cip1 expression detected after cP treatment suggests that cP slows MCF7 cell proliferation via this regulator. We propose that cP could represent a novel breast cancer therapeutic agent whose mechanism of action is different from that of tamoxifen or of inhibitors of aromatase.

  2. Preventive effects of oligomerized polyphenol on estradiol-induced prostatitis in rats.

    Science.gov (United States)

    Kim, Dong Suk; Lee, Eun Jin; Cho, Kang Su; Yoon, So Jung; Lee, Young Hoon; Hong, Sung Joon

    2009-06-30

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category III) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-alpha) were quantified, and phosphorylation of IkappaBa and histological changes were also evaluated in prostatic tissue. The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-alpha expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of IkappaBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of IkappaBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Estradiol to testosterone ratio in metabolic syndrome men aged started 40 years above

    Science.gov (United States)

    Kusuma, R.; Siregar, Y.; Mardianto

    2018-03-01

    Disruption of adipose tissue, an endocrine organ, could turn out into the so-called metabolic syndrome. Aging men with lowering testosterone were related to metabolic syndrome and excessive aromatase activity in adipose tissue would increase estradiol level. This study hypothesized that estradiol to testosterone ratio is increasedin aging, metabolic syndrome men. A total of 52 men were randomly recruited for this study. A blood samplewas drawn before 11.00 AM after 10 hoursof overnight fasting, then aliquot serum kept in -20°C pending the research. Subjects were divided evenly into the metabolic syndrome and nonmetabolicsyndrome group. The hormonal assaywas measured on the day of research. Then examined with student t-test. Estradiol level in metabolic syndrome group was increased, but insignificant differ to the other group. Testosterone level decreased and significantly different between groups. In conclusion, estradiol to testosterone ratio was increased in themetabolic syndrome group but insignificant.

  5. Effect of oral contraceptives containing estradiol and nomegestrol acetate or ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea.

    Science.gov (United States)

    Grandi, Giovanni; Napolitano, Antonella; Xholli, Anjeza; Tirelli, Alessandra; Di Carlo, Costantino; Cagnacci, Angelo

    2015-10-01

    To study the three cycles effect on primary dysmenorrhea of the monophasic 24/4 estradiol/nomegestrol acetate (E2/NOMAC) and of the 21/7 ethinyl-estradiol/chlormadinone acetate (EE/CMA) oral contraceptive. The tolerability and the effect of both preparations on metabolism and health-related quality of life were also evaluated. Prospective observational cohort study. Tertiary gynecologic center for pelvic pain. Subjects with primary dysmenorrhea requiring an oral contraceptive, who spontaneously selected either E2/NOMAC (n = 20) or EE/CMA (n = 20). Visual Analogue Scale (VAS) score for dysmenorrhea, Short Form-36 questionnaire for health-related quality of life, lipoproteins and days of menstrual bleeding (withdrawal bleeding during oral contraceptive). Mean age and body mass index (BMI) were similar between the two groups. The final analysis was performed on 34 women, 15 in E2/NOMAC and 19 in EE/CMA group. Compliance with treatment was significantly higher with EE/CMA (100%) than E2/NOMAC (75%) (p = 0.02). Both treatments significantly (p dysmenorrhea, similarly (E2/NOMAC by a mean of 74.7%, EE/CMA by a mean of 78.4%; p = 0.973). Only E2/NOMAC significantly increased SF-36 score (p = 0.001), both in physical (p = 0.001) and mental domains (p = 0.004). The mean number of days of menstrual bleeding was significantly reduced in E2/NOMAC group (from 4.86 ± 1.20 d to 2.64 ± 1.59 d, p = 0.0005 versus baseline, p = 0.007 versus EE/CMA group). BMI did not vary in either group. E2/NOMAC did not change lipoproteins and apoproteins while EE/CMA increased total cholesterol (p = 0.0114), HDL-cholesterol (p = 0.0008), triglycerides (p = 0.002), apoprotein-A1 (Apo-A1; p = 0.0006) and apopoprotein-B (Apo-B; p = 0.008), decreasing LDL/HDL ratio (p = 0.024). Both oral contraceptives reduced similarly primary dysmenorrhea, with E2/NOMAC also reducing withdrawal bleedings and being neutral on lipid metabolism.

  6. Estradiol RIA kit in clinical practice

    International Nuclear Information System (INIS)

    Friedrich, W.; Lisse, K.; Bienert, R.; Flentje, H.; Koerner, H.; Wilken, T.; Akademie der Wissenschaften der DDR, Berlin-Buch. Zentralinstitut fuer Isotopen- und Strahlenforschung)

    1985-01-01

    First clinical experience with a estradiol RIA kit developed in the Central Institute for Isotope- and Radiation Research is reported. The kit was used for the daily control of estradiol level in patients, which were treated within the program for in vitro fertilization and embryo transfer. The time of incubation could be shortened by means of a double antibody technique and by use of a precipitation mixture to 2 h. The intraassay variation is 9.2%, the interassay variation is 15.1%, the recovery rate is 94%. The sensitivity of the test (B 0 -3SD) is about 120 pmol/l. The estradiol RIA kit satisfies clinical requirements. (author)

  7. Niacin treatment increases plasma homocyst(e)ine levels.

    Science.gov (United States)

    Garg, R; Malinow, M; Pettinger, M; Upson, B; Hunninghake, D

    1999-12-01

    Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

  8. Risperidone treatment increases CB1 receptor binding in rat brain

    DEFF Research Database (Denmark)

    Secher, Anna; Husum, Henriette; Holst, Birgitte

    2010-01-01

    , the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

  9. Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons

    Science.gov (United States)

    Murphy, Diane D.; Cole, Nelson B.; Segal, Menahem

    1998-01-01

    Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons. We now demonstrate that estradiol down-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density. Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GABAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. PMID:9736750

  10. Metabolic clearance and blood production rates of estradiol in hyperthyroidism.

    Science.gov (United States)

    Ridgway, E C; Longcope, C; Maloof, F

    1975-09-01

    The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.

  11. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  12. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    International Nuclear Information System (INIS)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

  13. The pathway of estradiol-induced apoptosis in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Rastin, Maryam; Hatef, Mohammad Reza; Tabasi, Nafisseh; Mahmoudi, Mahmoud

    2012-03-01

    Systemic lupus erythematosus (SLE) is a disease with unknown etiology. The pathologic role of sex hormones and apoptosis in SLE has often been discussed. We studied the effects of estradiol in the pathway of induced apoptosis in Iranian SLE patients. T lymphocytes from 35 SLE patients and 20 age-matched controls were isolated and cultured in the presence of 10(-8) M 17-β estradiol. The expression levels of Fas, Fas ligand (FasL), Bcl-2, caspase-8, and caspase-9 mRNAs were determined semiquantitatively in comparison to the expression level of beta actin RNA. Estradiol exposure did not have any significant effects on the expression levels of Fas, Bcl-2, and caspase-9 in SLE patients and controls. However, the expression levels of FasL and caspase-8 were significantly increased in SLE patients, but not in controls. This suggests the probable involvement of extrinsic apoptosis pathway in estradiol-induced apoptosis in SLE.

  14. Estradiol or fluoxetine alters depressive behavior and tryptophan hydroxylase in rat raphe.

    Science.gov (United States)

    Yang, Fu-Zhong; Wu, Yan; Zhang, Wei-Guo; Cai, Yi-Yun; Shi, Shen-Xun

    2010-03-10

    The effects of 17beta-estradiol and fluoxetine on behavior of ovariectomized rats subjected to the forced swimming test and the expression of tryptophan hydroxylase (TPH) in dorsal and median raphe were investigated, respectively through time sampling technique of behavior scoring and immunohistochemistry. Both estradiol and fluoxetine increased swimming and decreased immobility in the forced swimming test. The forced swimming stress decreased integrated optical density of TPH-positive regions in dorsal and median raphe. Both estradiol and fluoxetine administration prevented integrated optical density of TPH-positive regions from being decreased by forced swimming stress. These observations suggest that both estradiol and fluoxetine have protective bearing on ovariectomized rats enduring forced swimming stress.

  15. Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

    International Nuclear Information System (INIS)

    Theron, C.N.

    1985-03-01

    A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

  16. Efeito do estradiol, dietas e duração do período seco sobre o consumo de matéria seca de vacas holandesas Effect of estradiol, diets and lenght of the dry period on feed intake of holstein cows

    Directory of Open Access Journals (Sweden)

    Lucia De Fátima Andrade Correia Teixeira

    2003-08-01

    to 260C, that calved in Autumn (season 1 and over 260C, (extreme temperatures and calved in summer (season 2. AD did not affect prepartum feed intake, however it increases intake when compared to CA in postpartum. The contrasts between treatments showed AD increased postpartum intake in 60 days period (P0,05.When diets associated with estradiol (AD30E and CD30E were contrasted with the others, they showed lower intakes, what means that exogenous estrogen reduces postpartum intake. No differences were observed when 30 days period without estradiol injection were compared to sixty days dry period. The days in relation to peripartum showed cubic effects on intake (P<0,01, increasing the intake in the first week postpartum. Both feed intake in prepartum and postpartum decreased in season 2, when contrasted to season 1 (P<0,01. In conclusion, however differences between treatments were not detected in prepartum, estradiol injection in prepartum can decrease feed intake.

  17. Immobilisation increases yeast cells' resistance to dehydration-rehydration treatment.

    Science.gov (United States)

    Borovikova, Diana; Rozenfelde, Linda; Pavlovska, Ilona; Rapoport, Alexander

    2014-08-20

    This study was performed with the goal of revealing if the dehydration procedure used in our new immobilisation method noticeably decreases the viability of yeast cells in immobilised preparations. Various yeasts were used in this research: Saccharomyces cerevisiae cells that were rather sensitive to dehydration and had been aerobically grown in an ethanol-containing medium, a recombinant strain of S. cerevisiae grown in aerobic conditions which were completely non-resistant to dehydration and an anaerobically grown bakers' yeast strain S. cerevisiae, as well as a fairly resistant Pichia pastoris strain. Experiments performed showed that immobilisation of all these strains essentially increased their resistance to a dehydration-rehydration treatment. The increase of cells' viability (compared with control cells dehydrated in similar conditions) was from 30 to 60%. It is concluded that a new immobilisation method, which includes a dehydration stage, does not lead to an essential loss of yeast cell viability. Correspondingly, there is no risk of losing the biotechnological activities of immobilised preparations. The possibility of producing dry, active yeast preparations is shown, for those strains that are very sensitive to dehydration and which can be used in biotechnology in an immobilised form. Finally, the immobilisation approach can be used for the development of efficient methods for the storage of recombinant yeast strains. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Chronic fluoxetine treatment increases daytime melatonin synthesis in the rodent

    Directory of Open Access Journals (Sweden)

    Gillian W Reierson

    2009-09-01

    Full Text Available Gillian W Reierson, Claudio A Mastronardi, Julio Licinio, Ma-Li WongCenter on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Circadian rhythm disturbances can occur as part of the clinical symptoms of major depressive disorder and have been found to resolve with antidepressant therapy. The pineal gland is relevant to circadian rhythms as it secretes the hormone melatonin following activation of the cyclic adenosine monophosphate (cAMP signaling cascade and of arylalkylamine N-acetyltransferase (AA-NAT, the rate-limiting enzyme for its synthesis. Cyclic AMP is synthesized by adenylate cyclases (AC and degraded by phosphodiesterases (PDEs. Little is known about the contribution of the PDE system to antidepressant-induced alterations in pineal cAMP signaling and melatonin synthesis. In the present study we used enzyme immunoassay to measure plasma melatonin levels and pineal cAMP levels and as well as quantitative real-time polymerase chain reaction to measure pineal expression of PDE, AC, and AA-NAT genes in rats chronically treated with the prototypic antidepressant fluoxetine. We found elevated melatonin synthesis with increased pineal AA-NAT gene expression and daytime plasma melatonin levels and downregulated cAMP signaling with increased PDE and unchanged AC pineal gene expression, and decreased content of pineal cAMP. We conclude that chronic fluoxetine treatment increases daytime plasma melatonin and pineal AA-NAT gene expression despite downregulated pineal cAMP signaling in the rodent.Keywords: antidepressant, melatonin, pineal, nucleotides, cyclic, phosphodiesterase, rat

  19. 17β-estradiol enhances memory duration in the main olfactory bulb in CD-1 mice.

    Science.gov (United States)

    Dillon, T Samuel; Fox, Laura C; Han, Crystal; Linster, Christiane

    2013-12-01

    Rodents rely heavily on odor detection, discrimination, and memory to locate food, find mates, care for pups, and avoid predators. Estrogens have been shown to increase memory retention in rodents performing spatial memory and object placement tasks. Here we evaluate the extent to which 17β-estradiol modulates memory formation and duration in the olfactory system. Adult CD-1 mice were gonadectomized and given either systemic 17β-estradiol replacement, local 17β-estradiol in the main olfactory bulb, or no replacement. Before performing the behavioral task the mice were given saline or PHTPP (an estrogen receptor β [ER-β] antagonist) via bilateral infusion into the main olfactory bulb. As the beta-type estrogen receptor (ER-β) is more abundant than the alpha-type estrogen receptor in the murine main olfactory bulb, the current study focuses on 17β-estradiol and its interactions with ERβ. Habituation, a simple, nonassociative learning task in which an animal is exposed to the same odor over successive presentations, was used to evaluate the animals' ability to detect odors and form an olfactory memory. To evaluate memory duration, we added a final trial of intertrial interval time (30 or 60 min) in which we presented the habituated odor. Neither surgical nor drug manipulation affected the ability of mice to detect or habituate to an odor. After habituation, gonadectomized 17β-estradiol-treated mice retained memory of an odor for 30 min, whereas non-estradiol-treated, 17β-estradiol+ERβ antagonist (PHTPP), and untreated male mice did not remember an odor 30 min after habituation. The results show that both systemic and local bulbar infusions of 17β-estradiol enhance odor memory duration in mice.

  20. Smoking increases the likelihood of Helicobacter pylori treatment failure.

    Science.gov (United States)

    Itskoviz, David; Boltin, Doron; Leibovitzh, Haim; Tsadok Perets, Tsachi; Comaneshter, Doron; Cohen, Arnon; Niv, Yaron; Levi, Zohar

    2017-07-01

    Data regarding the impact of smoking on the success of Helicobacter pylori (H. pylori) eradication are conflicting, partially due to the fact that sociodemographic status is associated with both smoking and H. pylori treatment success. We aimed to assess the effect of smoking on H. pylori eradication rates after controlling for sociodemographic confounders. Included were subjects aged 15 years or older, with a first time positive C 13 -urea breath test (C 13 -UBT) between 2007 to 2014, who underwent a second C 13 -UBT after receiving clarithromycin-based triple therapy. Data regarding age, gender, socioeconomic status (SES), smoking (current smokers or "never smoked"), and drug use were extracted from the Clalit health maintenance organization database. Out of 120,914 subjects with a positive first time C 13 -UBT, 50,836 (42.0%) underwent a second C 13 -UBT test. After excluding former smokers, 48,130 remained who were eligible for analysis. The mean age was 44.3±18.2years, 69.2% were females, 87.8% were Jewish and 12.2% Arabs, 25.5% were current smokers. The overall eradication failure rates were 33.3%: 34.8% in current smokers and 32.8% in subjects who never smoked. In a multivariate analysis, eradication failure was positively associated with current smoking (Odds Ratio {OR} 1.15, 95% CI 1.10-1.20, psmoking was found to significantly increase the likelihood of unsuccessful first-line treatment for H. pylori infection. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  1. Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells

    Directory of Open Access Journals (Sweden)

    Furlanetto T.W.

    2001-01-01

    Full Text Available Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 ± 0.370 to 2.085 ± 0.364 pmol I-/µg DNA at 1 ng/ml (P<0.02, to 1.970 ± 0.302 pmol I-/µg DNA at 10 ng/ml (P<0.003, and to 2.038 ± 0.389 pmol I-/µg DNA at 100 ng/ml (P<0.02. In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 ± 0.408 to 7.312 ± 0.506 pmol I-/µg DNA (P<0.02. A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis.

  2. Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.

    Science.gov (United States)

    Nishimura, Shotaro; Teshima, Akifumi; Kawabata, Fuminori; Tabata, Shoji

    2017-11-01

    Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions. © 2017 Japanese Society of Animal Science.

  3. L-Type Calcium Channels Modulation by Estradiol.

    Science.gov (United States)

    Vega-Vela, Nelson E; Osorio, Daniel; Avila-Rodriguez, Marco; Gonzalez, Janneth; García-Segura, Luis Miguel; Echeverria, Valentina; Barreto, George E

    2017-09-01

    Voltage-gated calcium channels are key regulators of brain function, and their dysfunction has been associated with multiple conditions and neurodegenerative diseases because they couple membrane depolarization to the influx of calcium-and other processes such as gene expression-in excitable cells. L-type calcium channels, one of the three major classes and probably the best characterized of the voltage-gated calcium channels, act as an essential calcium binding proteins with a significant biological relevance. It is well known that estradiol can activate rapidly brain signaling pathways and modulatory/regulatory proteins through non-genomic (or non-transcriptional) mechanisms, which lead to an increase of intracellular calcium that activate multiple kinases and signaling cascades, in the same way as L-type calcium channels responses. In this context, estrogens-L-type calcium channels signaling raises intracellular calcium levels and activates the same signaling cascades in the brain probably through estrogen receptor-independent modulatory mechanisms. In this review, we discuss the available literature on this area, which seems to suggest that estradiol exerts dual effects/modulation on these channels in a concentration-dependent manner (as a potentiator of these channels in pM concentrations and as an inhibitor in nM concentrations). Indeed, estradiol may orchestrate multiple neurotrophic responses, which open a new avenue for the development of novel estrogen-based therapies to alleviate different neuropathologies. We also highlight that it is essential to determine through computational and/or experimental approaches the interaction between estradiol and L-type calcium channels to assist these developments, which is an interesting area of research that deserves a closer look in future biomedical research.

  4. Maternal fructose intake disturbs ovarian estradiol synthesis in rats.

    Science.gov (United States)

    Munetsuna, Eiji; Yamada, Hiroya; Yamazaki, Mirai; Ando, Yoshitaka; Mizuno, Genki; Ota, Takeru; Hattori, Yuji; Sadamoto, Nao; Suzuki, Koji; Ishikawa, Hiroaki; Hashimoto, Shuji; Ohashi, Koji

    2018-06-01

    Recent increases in fructose consumption have raised concerns regarding the potential adverse intergenerational effects, as maternal fructose intake may induce physiological dysfunction in offspring. However, no reports are available regarding the effect of excess maternal fructose on reproductive tissues such as the ovary. Notably, the maternal intrauterine environment has been demonstrated to affect ovarian development in the subsequent generation. Given the fructose is transferred to the fetus, excess fructose consumption may affect offspring ovarian development. As ovarian development and its function is maintained by 17β-estradiol, we therefore investigated whether excess maternal fructose intake influences offspring ovarian estradiol synthesis. Rats received a 20% fructose solution during gestation and lactation. After weaning, offspring ovaries were isolated. Offspring from fructose-fed dams showed reduced StAR and P450(17α) mRNA levels, along with decreased protein expression levels. Conversely, attenuated P450arom protein level was found in the absence of mRNA expression alteration. Consistent with these phenomena, decreased circulating levels of estradiol were observed. Furthermore, estrogen receptor α (ERα) protein levels were also down-regulated. In accordance, the mRNA for progesterone receptor, a transcriptional target of ERα, was decreased. These results suggest that maternal fructose might alter ovarian physiology in the subsequent generation. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Avaliação dos efeitos do estradiol e do FSH nos níveis de leptina em mulheres com supressão da função hipofisária Effects of estradiol and FSH on leptin levels in women with pituitary suppression

    Directory of Open Access Journals (Sweden)

    Selmo Geber

    2005-04-01

    Full Text Available OBJETIVO: identificar a correlação entre os níveis séricos de leptina e os níveis de estradiol e do hormônio folículo-estimulante (FSH em mulheres com supressão da função hipofisária, e suas possíveis interferências no eixo reprodutivo. MÉTODOS: estudamos prospectivamente 64 pacientes submetidas à hiperestimulação ovariana controlada com FSH recombinante para tratamento pela técnica de reprodução assistida, devido a fator masculino ou tubário, e 20 pacientes em uso de valerato de estradiol, para preparo endometrial, em tratamento de doação de óvulos, por falha de resposta ovariana em ciclo prévio. Todas as pacientes utilizaram análogo de GnRH no início do tratamento, de forma a obter a supressão da função hipofisária. Para a análise estatística dos resultados, foram utilizados os testes chi2, t de Student e correlação de Pearson, quando adequado. Os resultados foram considerados significativos quando pPURPOSE: to identify the relationship between serum levels of leptin and the levels of estradiol and follicle-stimulating hormone (FSH in women with pituitary suppression and to evaluate its possible interference on the reproductive axis. METHODS: a total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction, due to a male or tubal factor, and 20 patients using estradiol valerate, for endometrial preparation in order to be submitted to oocyte donation treatment were studied. All patients used GnRH analogues before starting treatment in order to avoid premature LH surge. Data were analyzed statistically by the chi2 test, Student's t-test and the Pearson correlation test, when appropriate, with the level of significance set at p<0,05. RESULTS: it was observed that leptin levels correlated with body mass index (BMI even though they had not influenced growth rate of these hormones. A positive correlation was observed between estradiol and leptin levels in both

  6. Influence of flavone extract from cultivated saussurea on learning and memory in a mouse model of Alzheimer's disease A comparison with estradiol benzoate

    Institute of Scientific and Technical Information of China (English)

    Weiqiang Chen; Shuiming Gong; Yan Li; Ming Li; Zemin Yang; Lirong Zhang

    2011-01-01

    The present study established a mouse model of Alzheimer's disease, and investigated the effects of treatment with flavone extract from artificially cultivated saussurea. A positive control group was treated with estradiol benzoate, and learning and memory ability were examined in the 8-arm radial maze. The learning and recognition ability of mice with Alzheimer's disease treated with flavone extract was significantly improved and the number of hippocampal neurons was significantly increased in the flavone-treated and positive control groups compared with the model group. The results indicate that flavone extract from artificially cultivated saussurea can improve learning and memory deficits in mice with Alzheimer's disease, exerting effects similar to those of estradiol benzoate.

  7. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    International Nuclear Information System (INIS)

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E.

    2005-01-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial

  8. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity.

    Science.gov (United States)

    Mullins, Dana; Proulx, Denise; Saoudi, A; Ng, Cheng E

    2005-05-01

    Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 am or 3 HALO [hours after light onset]), late rest period (3 pm or 9 HALO), early active period (9 pm or 15 HALO), and late active period (3 am or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Treatment with either TPT or XR at 3 am demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 pm, in particular, showed increased toxicity without any enhanced efficacy. Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  9. Waiting Time Increases Risk of Attrition in Gambling Disorder Treatment

    DEFF Research Database (Denmark)

    Linnet, Jakob; Pedersen, Anders Sune

    2014-01-01

    Attrition is a well known problem in psychotherapeutic treatment. Patients with addiction have high attrition rates, and it is therefore important to identify factors that can improve completion rates in addiction. Here, we investigated the influence of waiting time as a predictor of treatment...

  10. Modulation of vitellogenin synthesis through estrogen receptor beta-1 in goldfish (Carassius auratus) juveniles exposed to 17-β estradiol and nonylphenol

    International Nuclear Information System (INIS)

    Soverchia, L.; Ruggeri, B.; Palermo, F.; Mosconi, G.; Cardinaletti, G.; Scortichini, G.; Gatti, G.; Polzonetti-Magni, A.M.

    2005-01-01

    Many synthetic chemicals, termed xenoestrogens, have been shown to interact as agonists with the estrogen receptor (ER) to elicit biological responses similar to those of natural hormones. To date, the regulation of vitellogenesis in oviparous vertebrates has been widely used for evaluation of estrogenic effects. Therefore, Carassius auratus juveniles were chosen as a fish model for studying the effects of estradiol-17β and different concentrations (10 -6 and 10 -7 M) of 4-nonylphenol (4-NP) on the expression of liver ERβ-1 subtype; plasma vitellogenin and sex steroids (androgens and estradiol-17β) were also evaluated together with the bioaccumulation process, through mass-spectrometry. C. auratus is a species widespread in the aquatic environment and, on the toxicological point of view, can be considered a good 'sentinel' species. Juveniles of goldfish were maintained in tanks with only tap water or water with different concentrations (10 -6 and 10 -7 M) of 4-nonylphenol (4-NP), or 10 -7 M of estradiol-17β. After 3 weeks of treatment, animals were anesthetized within 5 min after capture, and blood was immediately collected into heparinized syringes by cardiac puncture and stored at -70 deg. C; the gonads were fixed, then frozen and stored at -70 deg. C; the whole fish, liver, and muscle tissues were harvested and immediately stored at -70 deg. C for molecular biology experiments and bioaccumulation measurements. The estrogenic effects of 4-NP were evidenced by the presence of plasma vitellogenin in juveniles exposed both to estradiol-17β and the two doses of 4-NP; moreover, exposure to 4-NP also increased aromatization of androgens, as suggested by decreasing androgens and increasing estradiol-17β plasma levels. The changes of these parameters were in agreement with the increasing transcriptional rate of ERβ-1 mRNA in the liver, demonstrating that both estradiol-17β and 4-NP modulate the vitellogenin rate through interaction with the ERβ-1 subtype. The

  11. Estradiol Protects Proopiomelanocortin Neurons Against Insulin Resistance.

    Science.gov (United States)

    Qiu, Jian; Bosch, Martha A; Meza, Cecilia; Navarro, Uyen-Vy; Nestor, Casey C; Wagner, Edward J; Rønnekleiv, Oline K; Kelly, Martin J

    2018-02-01

    Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Because 17β-estradiol (E2) augments the excitability of the anorexigenic proopiomelanocortin (POMC) neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male mice but not in DIO female mice. However, the insulin response in POMC neurons was abrogated in ovariectomized DIO females but restored with E2 replacement. E2 increased T-type calcium channel Cav3.1 messenger RNA (mRNA) expression and whole-cell currents but downregulated stromal-interaction molecule 1 mRNA, which rendered POMC neurons more excitable and responsive to insulin-mediated TRPC5 channel activation. Moreover, E2 prevented the increase in suppressor of cytokine signaling-3 mRNA expression with DIO as seen in DIO males. As proof of principle, insulin [intracerebroventricular injection into the third ventricle (ICV)] decreased food intake and increased metabolism in female but not male guinea pigs fed a high-fat diet. The uncoupling of the insulin receptor from its downstream effector system was corroborated by the reduced expression of phosphorylated protein kinase B in the arcuate nucleus of male but not female guinea pigs following insulin. Therefore, E2 protects female POMC neurons from insulin resistance by enhancing POMC neuronal excitability and the coupling of insulin receptor to TRPC5 channel activation. Copyright © 2018 Endocrine Society.

  12. Modulation of the noradrenergic receptor at uterine level by the 17 β-estradiol influence

    International Nuclear Information System (INIS)

    Vanderlei, F.H.F.; Catanho, M.T.J.

    1991-01-01

    The present study was undertaken to asses the regulation of the noradrenergic receptor, by estrogens. We measured the uterotrophic response and the binding capacity of the noradrenergic receptor after the administration of 17 β-estradiol (E sub(2); 132 nmol/kg b.w., i.p.) to immature rats. The results showed that 2 and 4 hs after E sub(2) treatment, the total number of NA-receptors enhanced significantly (6 fold). Similarly, it was observed a significant increase in uterine weight, 24 h after E sub(2) administration. The results indicate that NA-receptors present in the uterus may be under a direct E sub(2) regulation, which suggests a possible participation on the uterotropic response induced by E sub(2). (author)

  13. Medroxyprogesterone acetate attenuates long-term effects of 17 beta-estradiol in coronary arteries from hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Pedersen, Susan H.; Nielsen, Lars Bo; Mortensen, Alicja

    2006-01-01

    Objective: The progestin component in hormone replacement treatment may oppose the effects of estrogen on vascular function. This study examined the effect of long-term treatment with 17 beta-estradiol (E-2) alone and in combination with two progestins on K+ and Ca2+-mediated mechanisms in coronary...... and increased the expression of L-type voltage-gated Ca2+ channel mRNA. NETA had no opposing effects. Hormone treatment did not affect large-conductance Ca2+, activated or ATP-sensitive K+ channels or cGMP-dependent protein kinase mRNA expression. Hyperlipidemia had no effect on vascular reactivity. Conclusion......: When E-2 is administered with MPA, effects of E-2 on nitric oxide and Ca2+ mediated vascular reactivity in rabbit coronary arteries are modulated. The results suggest that the progestin component in hormone replacement treatment may interfere with the supposed beneficial vascular effects of estrogen...

  14. Medroxyprogesterone acetate attenuates long-term effects of 17beta-estradiol in coronary arteries from hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Pedersen, S. H.; Nielsen, L. B.; Mortensen, A

    2006-01-01

    OBJECTIVE: The progestin component in hormone replacement treatment may oppose the effects of estrogen on vascular function. This study examined the effect of long-term treatment with 17beta-estradiol (E(2)) alone and in combination with two progestins on K(+) and Ca(2+)-mediated mechanisms...... and increased the expression of L-type voltage-gated Ca(2+) channel mRNA. NETA had no opposing effects. Hormone treatment did not affect large-conductance Ca(2+) activated or ATP-sensitive K(+) channels or cGMP-dependent protein kinase mRNA expression. Hyperlipidemia had no effect on vascular reactivity....... CONCLUSION: When E(2) is administered with MPA, effects of E(2) on nitric oxide and Ca(2+)-mediated vascular reactivity in rabbit coronary arteries are modulated. The results suggest that the progestin component in hormone replacement treatment may interfere with the supposed beneficial vascular effects...

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

    Science.gov (United States)

    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,…

  16. Estradiol modulates the anorexic response to central glucagon-like peptide 1.

    Science.gov (United States)

    Maske, Calyn B; Jackson, Christine M; Terrill, Sarah J; Eckel, Lisa A; Williams, Diana L

    2017-07-01

    Estrogens suppress feeding in part by enhancing the response to satiation signals. Glucagon-like peptide 1 (GLP-1) acts on receptor populations both peripherally and centrally to affect food intake. We hypothesized that modulation of the central GLP-1 system is one of the mechanisms underlying the effects of estrogens on feeding. We assessed the anorexic effect of 0, 1, and 10μg doses of GLP-1 administered into the lateral ventricle of bilaterally ovariectomized (OVX) female rats on a cyclic regimen of either 2μg β-estradiol-3-benzoate (EB) or oil vehicle 30min prior to dark onset on the day following hormone treatment. Central GLP-1 treatment significantly suppressed food intake in EB-treated rats at both doses compared to vehicle, whereas only the 10μg GLP-1 dose was effective in oil-treated rats. To follow up, we examined whether physiologic-dose cyclic estradiol treatment influences GLP-1-induced c-Fos in feeding-relevant brain areas of OVX females. GLP-1 significantly increased c-Fos expression in the area postrema (AP) and nucleus of the solitary tract (NTS), and the presence of estrogens may be required for this effect in the paraventricular nucleus of the hypothalamus (PVN). Together, these data suggest that modulation of the central GLP-1 system may be one of the mechanisms by which estrogens suppress food intake, and highlight the PVN as a region of interest for future investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Estradiol replacement enhances fear memory formation, impairs extinction and reduces COMT expression levels in the hippocampus of ovariectomized female mice.

    Science.gov (United States)

    McDermott, Carmel M; Liu, Dan; Ade, Catherine; Schrader, Laura A

    2015-02-01

    Females experience depression, posttraumatic stress disorder (PTSD), and anxiety disorders at approximately twice the rate of males, but the mechanisms underlying this difference remain undefined. The effect of sex hormones on neural substrates presents a possible mechanism. We investigated the effect of ovariectomy at two ages, before puberty and in adulthood, and 17β-estradiol (E2) replacement administered chronically in drinking water on anxiety level, fear memory formation, and extinction. Based on previous studies, we hypothesized that estradiol replacement would impair fear memory formation and enhance extinction rate. Females, age 4 weeks and 10 weeks, were divided randomly into 4 groups; sham surgery, OVX, OVX+low E2 (200nM), and OVX+high E2 (1000nM). Chronic treatment with high levels of E2 significantly increased anxiety levels measured in the elevated plus maze. In both age groups, high levels of E2 significantly increased contextual fear memory but had no effect on cued fear memory. In addition, high E2 decreased the rate of extinction in both ages. Finally, catechol-O-methyltransferase (COMT) is important for regulation of catecholamine levels, which play a role in fear memory formation and extinction. COMT expression in the hippocampus was significantly reduced by high E2 replacement, implying increased catecholamine levels in the hippocampus of high E2 mice. These results suggest that estradiol enhanced fear memory formation, and inhibited fear memory extinction, possibly stabilizing the fear memory in female mice. This study has implications for a neurobiological mechanism for PTSD and anxiety disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Foraging at wastewater treatment works increases the potential for ...

    African Journals Online (AJOL)

    Wastewater treatment works (WWTWs) are known to provide profitable foraging areas for insectivorous bats in Europe and the New World because of their association with high abundance of pollution-tolerant midges (Diptera). However, bats that feed on these insects may also accumulate metal pollutants such as cadmium ...

  19. Seroma indicates increased risk of lymphedema following breast cancer treatment

    DEFF Research Database (Denmark)

    Toyserkani, Navid Mohamadpour; Jørgensen, Mads Gustaf; Haugaard, Karen

    2017-01-01

    in one of the largest retrospective cohort studies. Material and methods We included all patients with unilateral breast cancer treated in the period of 2008-2014. Data regarding treatment and breast cancer characteristics were retrieved from the national breast cancer registry. Data regarding lymphedema...

  20. Electrokinetic Treatment for Model Caissons with Increasing Dimensions

    Directory of Open Access Journals (Sweden)

    Eltayeb Mohamedelhassan

    2012-01-01

    Full Text Available Electrokinetic treatment has been known in geotechnical engineering for over six decades, yet, the technique is rarely used. This stems from the absence of design guidelines and specifications for electrokinetic treatment systems. An important issue that need to be investigated and understood in order to devise guidelines from experimental results is the effect of the foundation element size on the outcome of the treatment. Also important is determining the optimum distance between the electrodes and estimating the energy consumption prior to treatment. This experimental study is a preliminary step in understanding some of the issues critical for the guidelines and specifications. Four model caissons with surface areas between 16000 and 128000 mm2 were embedded in soft clayey soil under water and treated for 168 hr with a dc voltage of 6 V. From the results, a distance between the anode (model caisson and the cathode equal 0.25 times the outside diameter of the model caisson was identified as optimum. Relationships between the surface area and axial capacity of the model caisson and the surface area and energy consumption were presented. The equations can be used to preliminary estimate the load capacity and the energy consumption for full-scale applications.

  1. Clinical effects of sirolimus treatment in patients with increased ...

    African Journals Online (AJOL)

    transplanted kidney function will be lost. However, the development of new immunosuppressors, such as sirolimus (SRL), make it possible to stop CNI treatment [6]. Treating renal transplant patients with immunosuppressive drugs other than CNIs has received more attention in recent years. SRL, a new generation of ...

  2. Ethinyl Estradiol and Etonogestrel Vaginal Ring

    Science.gov (United States)

    ... or infection of the vagina white or yellow vaginal discharge vaginal bleeding or spotting when it is not time ... Follow your doctor's directions for examining your breasts; report any lumps ... and ethinyl estradiol vaginal ring.Do not let anyone else use your ...

  3. Epoxiconazole-induced degeneration in rat placenta and the effects of estradiol supplementation.

    Science.gov (United States)

    Rey Moreno, Maria Cecilia; Fussell, Karma C; Gröters, Sibylle; Schneider, Steffen; Strauss, Volker; Stinchcombe, Stefan; Fegert, Ivana; Veras, Mariana; van Ravenzwaay, Bennard

    2013-06-01

    Epoxiconazole (CAS-No. 133855-98-8) was recently shown to cause both a marked depletion of maternal estradiol blood levels and a significantly increased incidence of late fetal mortality when administered to pregnant rats throughout gestation (GD 7-18 or 21); estradiol supplementation prevented this epoxiconazole effect in rats (Stinchcombe et al., 2013), indicating that epoxiconazole-mediated estradiol depletion is a critical key event for induction of late fetal resorptions in rats. For further elucidation of the mode of action, the placentas from these modified prenatal developmental toxicity experiments with 23 and 50 mg/kg bw/d epoxiconazole were subjected to a detailed histopathological examination. This revealed dose-dependent placental degeneration characterized by cystic dilation of maternal sinuses in the labyrinth, leading to rupture of the interhemal membrane. Concomitant degeneration occurred in the trophospongium. Both placentas supporting live fetuses and late fetal resorptions were affected; the highest degree of severity was observed in placentas with late resorptions. Placental degeneration correlated with a severe decline in maternal serum estradiol concentration. Supplementation with 0.5 and 1.0 μg of the synthetic estrogen estradiol cyclopentylpropionate per day reduced the severity of the degeneration in placentas with live fetuses. The present study demonstrates that both the placental degeneration and the increased incidence of late fetal resorptions are due to decreased levels of estrogen, since estrogen supplementation ameliorates the former and abolishes the latter. © 2013 Wiley Periodicals, Inc.

  4. The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 µg/levonorgestrel 100 µg + ethinyl estradiol 10 µg

    Directory of Open Access Journals (Sweden)

    Sheila Krishnan

    2010-08-01

    Full Text Available Sheila Krishnan, Jessica KileyDepartment of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois, USAAbstract: Extended-cycle oral contraceptives (OCs are increasing in popularity in the United States. A new extended-cycle OC that contains the lowest doses of ethinyl estradiol (EE and levonorgestrel (LNG + continuous EE throughout the cycle is now available. It provides 84 days of a low-dose, combined active pill containing levonorgestrel 100 µg and ethinyl estradiol 20 µg. Instead of 7 days of placebo following the active pills, the regimen delivers 7 days of ethinyl estradiol 10 µg. Existing studies reveal a similar efficacy and adverse effect profile compared with other extended-regimen OCs. Specifically, the unscheduled bleeding profile is similar to other extended-cycle OCs and improves with the increase in the duration of use. Although lower daily doses of hormonal exposure have potential benefit, to our knowledge, there are no published studies indicating that this specific regimen offers a lower incidence of hormone-related side effects or adverse events. In summary, this new extended-cycle OC provides patients a low-dose, extended-regimen OC option without sacrificing efficacy or tolerability.Keywords: continuous regimen, ethinyl estradiol, extended cycle, oral contraceptive

  5. α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.

    Science.gov (United States)

    Aquino, Nayara S S; Araujo-Lopes, Roberta; Henriques, Patricia C; Lopes, Felipe E F; Gusmao, Daniela O; Coimbra, Candido C; Franci, Celso R; Reis, Adelina M; Szawka, Raphael E

    2017-06-01

    Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge. Copyright © 2017 Endocrine Society.

  6. Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.

    Science.gov (United States)

    Phumsatitpong, Chayarndorn; Moenter, Suzanne M

    2018-01-01

    Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of reproduction, integrating various inputs that modulate fertility. Stress typically inhibits reproduction but can be stimulatory; stress effects can also be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released during the stress response may suppress reproduction independent of downstream glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH neuron firing activity. To test this, mice were ovariectomized (OVX) and either implanted with an estradiol capsule (OVX+E) or not treated further to examine the influence of estradiol on GnRH neuron response to CRH. Targeted extracellular recordings were used to record firing activity from green fluorescent protein-identified GnRH neurons in brain slices before and during CRH treatment; recordings were done in the afternoon when estradiol has a positive feedback effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30 nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice; both effects were reversible. The dose-dependent effects of CRH appear to result from activation of different receptor populations; a CRH receptor type-1 agonist increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist decreased firing activity. CRH and specific agonists also differentially regulated short-term burst frequency and burst properties, including burst duration, spikes/burst, and/or intraburst interval. These results indicate that CRH alters GnRH neuron activity and that estradiol is required for CRH to exert both stimulatory and inhibitory effects on GnRH neurons. Copyright © 2018 Endocrine Society.

  7. Effects of increasing age, dosage, and duration of PTH treatment on BMD increase--a meta-analysis

    DEFF Research Database (Denmark)

    Schwarz, Peter; Jorgensen, Niklas Rye; Mosekilde, Leif

    2012-01-01

    were included. By metaregression analysis, we found that the increase in spine BMD (Z-score) after PTH treatment was blunted by increasing age (R (2) = 0.27; 2p = 0.01, slope -0.023 Z-scores per year, 11 studies). By increasing PTH dosage (μg/d), spine BMD increased significantly (2p = 0.......002) with a slope of +0.011 Z-scores/μg/d of teriparatide. Furthermore, the duration of treatment was positively correlated to spine BMD (P ......We studied the effects of increasing age, dosage, and duration of parathyroid hormone (PTH) treatment on changes in bone mineral density (BMD). Randomized placebo controlled trials on PTH treatment in men or women were retrieved from PubMed (1951 to present), Web of Science (1945 to present...

  8. Negative effect of 17-beta-estradiol on growth parameters of goldfish (Carassius auratus

    Directory of Open Access Journals (Sweden)

    Reza Tarkhani

    2015-03-01

    Full Text Available Objective: To evaluate the effects of 17-beta-estradiol on growth factors of goldfish (Carassius auratus. Methods: To perform the test, 17-beta-estradiol was given 3 months period to fish at different doses as followed: control group, Group 1: 10 mg/kg food, Group 2: 25 mg/kg food and Group 3: 50 mg/kg food. For this purpose, a solution of hormone in pure ethanol used to spray on food. Feeding was done 3 times daily as an appetite. Comparing the mean values measured for length and weight using ANOVA. Results: Indicated with increase length and weight, the effects of the hormone get more distinct, so that with increase concentration of hormone, reduce weight and length. Conclusions: Estradiol along with testosterone and progesterone regulates final stages of oocyte maturation and ovulation. Various studies have proven the different concentrations of this hormone has different effects on the growth of different fishes.

  9. Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation.

    Science.gov (United States)

    Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole; Shivers, Kai-Yvonne; Kemen, Lynne; Kreiter, Christopher M; Jenab, Shirzad; Inturrisi, Charles E; Quinones-Jenab, Vanya

    2011-07-01

    Estrogen modulates pain perception but how it does so is not fully understood. The aim of this study was to determine if estradiol reduces nociceptive responses in part via hypothalamic-pituitary-adrenal (HPA) axis regulation of cyclooxygenase (COX)-1/COX-2 activity. The first study examined the effects of estradiol (20%) or vehicle with concurrent injection nonsteroidal antiinflammatory drugs (NSAIDs) on formalin-induced nociceptive responding (flinching) in ovariectomized (OVX) rats. The drugs were ibuprofen (COX-1 and COX-2 inhibitor), SC560 (COX-1 inhibitor), or NS398 (COX-2 inhibitor). In a second study, estradiol's effects on formalin-induced nociception were tested in adrenalectomized (ADX), OVX, and ADX+OVX rats. Serum levels of prostaglandins (PG) PGE(2) and corticosterone were measured. Estradiol significantly decreased nociceptive responses in OVX rats with effects during both the first and the second phase of the formalin test. The nonsteroidal antiinflammatory drugs (NSAIDs) did not alter nociception at the doses used here. Adrenalectomy neither altered flinching responses in female rats nor reversed estradiol-induced antinociceptive responses. Estradiol alone had no effect on corticosterone (CORT) or prostaglandin levels after the formalin test, dissociating the effects of estradiol on behavior and these serum markers. Ibuprofen and NS398 significantly reduced PGE2 levels. CORT was not decreased by OVX surgery or by estradiol below that of ADX. Only IBU significantly increased corticosterone levels. Taken together, our results suggest that estradiol-induced antinociception in female rats is independent of COX activity and HPA axis activation. Copyright © 2010 Wiley-Liss, Inc.

  10. Body composition in lean women with polycystic ovary syndrome: effect of ethinyl estradiol and drospirenone combination.

    Science.gov (United States)

    Aydin, Kadriye; Cinar, Nese; Aksoy, Duygu Yazgan; Bozdag, Gurkan; Yildiz, Bulent Okan

    2013-03-01

    Limited data are available regarding the potential effects of oral contraceptives (OCs) on body fat distribution particularly in lean women with polycystic ovary syndrome (PCOS). In the current study, we aimed to evaluate the influence of ethinyl estradiol and drospirenone on body composition. Participants included 28 lean patients with PCOS and 28 age- and body mass index (BMI)-matched healthy women. The PCOS patients received ethinyl estradiol 30 mcg/drospirenone 3 mg for 6 months. Body composition parameters were assessed by bioelectrical impedance analysis. Serum androgens, lipids, insulin resistance and glucose metabolism measures were also determined. At baseline, the PCOS patients and controls had similar body composition, lipids, insulin resistance and glucose metabolism parameters. Total and trunk fat percentages were negatively correlated with sex hormone binding globulin and were positively correlated with homeostatic model assessment of insulin resistance and free androgen index in the PCOS group.. After 6 months of treatment in the PCOS patients, total fat percentage increased from 24.5%±7.1% to 26.0%±6.1% (p=.035) and trunk fat percentage increased from 20.2%±8.9% to 22.2%±7.1% (p=.014), although weight, BMI and waist to hip ratio (WHR) remained unchanged. Lean women with PCOS have similar body composition compared to healthy women. OC therapy for 6 months in PCOS patients results in an increased total and trunk fat percentage despite no change in clinical anthropometric measures including weight, BMI and WHR. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Increased Survival after Gemfibrozil Treatment of Severe Mouse Influenza▿

    Science.gov (United States)

    Budd, Alison; Alleva, Lisa; Alsharifi, Mohammed; Koskinen, Aulikki; Smythe, Victoria; Müllbacher, Arno; Wood, Jeff; Clark, Ian

    2007-01-01

    Gemfibrozil, an agent that inhibits production of proinflammatory cytokines in addition to its clinically useful lipid-lowering activity, increased survival in BALB/c mice that were already ill from infection by influenza virus A/Japan/305/57 (H2N2). Gemfibrozil was administered intraperitoneally once daily from days 4 to 10 after intranasal exposure to the virus. Survival increased from 26% in vehicle-treated mice (n = 50) to 52% in mice given gemfibrozil at 60 mg/kg/day (n = 46) (P = 0.0026). If this principle translates to patients, a drug already approved for human use, albeit by a different route for another purpose, might be adapted relatively fast for use against influenza, conceivably including human infection with a derivative of the avian H5N1 strain. PMID:17562808

  12. Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham Heart Study.

    Science.gov (United States)

    Jasuja, Guneet Kaur; Travison, Thomas G; Davda, Maithili; Murabito, Joanne M; Basaria, Shehzad; Zhang, Anqi; Kushnir, Mark M; Rockwood, Alan L; Meikle, Wayne; Pencina, Michael J; Coviello, Andrea; Rose, Adam J; D'Agostino, Ralph; Vasan, Ramachandran S; Bhasin, Shalender

    2013-06-01

    Age trends in estradiol and estrone levels in men and how lifestyle factors, comorbid conditions, testosterone, and sex hormone-binding globulin affect these age trends remain poorly understood, and were examined in men of the Framingham Heart Study. Estrone and estradiol concentrations were measured in morning fasting samples using liquid chromatography tandem mass spectrometry in men of Framingham Offspring Generation. Free estradiol was calculated using a law of mass action equation. There were 1,461 eligible men (mean age [±SD] 61.1±9.5 years and body mass index [BMI] 28.8±4.5kg/m(2)). Total estradiol and estrone were positively associated with age, but free estradiol was negatively associated with age. Age-related increase in total estrone was greater than that in total estradiol. Estrone was positively associated with smoking, BMI, and testosterone, and total and free estradiol with diabetes, BMI, testosterone, and comorbid conditions; additionally, free estradiol was associated negatively with smoking. Collectively, age, BMI, testosterone, and other health and behavioral factors explained only 18% of variance in estradiol, and 9% of variance in estrone levels. Men in the highest quintile of estrone levels had significantly higher age and BMI, and a higher prevalence of smoking, diabetes, and cardiovascular disease than others, whereas those in the highest quintile of estradiol had higher BMI than others. Total estrone and estradiol levels in men, measured using liquid chromatography tandem mass spectrometry, revealed significant age-related increases that were only partially accounted for by cross-sectional differences in BMI, diabetes status, and other comorbidities and health behaviors. Longitudinal studies are needed to confirm these findings.

  13. mTOR is involved in 17β-estradiol-induced, cultured immature boar Sertoli cell proliferation via regulating the expression of SKP2, CCND1, and CCNE1.

    Science.gov (United States)

    Yang, Wei-Rong; Wang, Yong; Wang, Yi; Zhang, Jiao-Jiao; Zhang, Jia-Hua; Lu, Cheng; Wang, Xian-Zhong

    2015-04-01

    Mammalian target of rapamycin (mTOR) is known to be involved in mammalian cell proliferation, while S-phase kinase-associated protein 2 (SKP2) plays a vital role in the cell cycle. Within the testis, estrogen also plays an important role in Sertoli cell proliferation, although it is not clear how. The present study asked if mTOR is involved in 17β-estradiol-dependent Sertoli cell proliferation. We specifically assessed if extracellular signal-regulated kinase 1/2 (ERK1/2) and/or phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) exert convergent effects toward the activation of mTOR signaling, and if this signaling regulates the expression of SKP2 through retinoblastoma (RB) and early mitotic inhibitor 1 (EMI1) protein and on CCNE1 and CCND1 mRNA levels. Treatment with 17β-estradiol for 15-90 min activated mTOR, with mTOR phosphorylation peaking after 30 min. U0126 (5 μM), a specific inhibitor of (MEK1/2), and 10-DEBC (2 μM), a selective inhibitor of AKT, both significantly reduced 17β-estradiol-induced phosphorylation of mTOR. Rapamycin suppressed 17β-estradiol-induced Sertoli cell proliferation, appearing to act by reducing the abundance of SKP2, CCND1, and CCNE1 mRNA as well as RB and EMI1 protein. These data indicated that 17β-estradiol enhances Sertoli cell proliferation via mTOR activation, which involves both ERK1/2 and PI3K/AKT signaling. Activated mTOR subsequently increases SKP2 mRNA and protein expression by enhancing the expression of CCND1 and CCNE1, and inhibits SKP2 protein degradation by increasing EMI1 abundance. © 2015 Wiley Periodicals, Inc.

  14. In vitro bioactivity of 17alpha-estradiol.

    Science.gov (United States)

    Sievernich, André; Wildt, Ludwig; Lichtenberg-Fraté, Hella

    2004-12-01

    A miniaturised short-term in vitro assay based on the activation of the human estrogen receptor alpha and genetically modified yeast (Saccharomyces cerevisiae) cells was performed to explore the capacity of this system to monitor the bioactivity of estrogenic compounds, particularly 17alpha- and 17beta-estradiol. Together with the human estrogen receptor (hER)-alpha plasmid, the reporter plasmid containing a yeast-optimised version of the green fluorescent protein (yEGFP) linked to three repeats of the cis-acting estrogen hormone-responsive element (ERE) were expressed in a strain being deleted in the pleiotropic drug resistance transporters Pdr5, Snq2 and Yor1, known to facilitate efflux of organic compounds including steroids and chemotherapeutics. Agonists that bind to hER in vitro trigger estrogen receptor-mediated transcriptional activation of the GFP reporter gene monitored by fluorescence emission at 535 nm. The sensitivity of the assay was tested with various 17alpha- and 17beta-estradiol concentrations, yielding a detection limit of 5 pg/ml (0.018 nM) for the agonist 17beta-E2 in solvent and in human charcoal-stripped serum using a S. cerevisiae pdr5, snq2 and yor1 mutant strain. For 17alpha-estradiol only, at approximately 1500 pg/ml a similar fluorescence response compared to 100 pg/ml 17beta-E2 was observed implicating a much weaker potency of this stereoisomer. The specificity of the system was tested by expression of a truncated hER lacking the ligand-binding domain E and by administration of the androgen, 4-androsten 3,17 dione. Both controls did not yield an increase in fluorescence emission. This fluorescence emission assay enables detection of estrogenic biological activity induced by direct agonists, such as 17beta-E2 at concentrations similar to those found in human sera or by estrogen-like chemicals.

  15. β-arrestin regulates estradiol membrane-initiated signaling in hypothalamic neurons.

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    Angela M Wong

    Full Text Available Estradiol (E2 action in the nervous system is the result of both direct nuclear and membrane-initiated signaling (EMS. E2 regulates membrane estrogen receptor-α (ERα levels through opposing mechanisms of EMS-mediated trafficking and internalization. While ß-arrestin-mediated mERα internalization has been described in the cortex, a role of ß-arrestin in EMS, which underlies multiple physiological processes, remains undefined. In the arcuate nucleus of the hypothalamus (ARH, membrane-initiated E2 signaling modulates lordosis behavior, a measure of female sexually receptivity. To better understand EMS and regulation of ERα membrane levels, we examined the role of ß-arrestin, a molecule associated with internalization following agonist stimulation. In the present study, we used an immortalized neuronal cell line derived from embryonic hypothalamic neurons, the N-38 line, to examine whether ß-arrestins mediate internalization of mERα. β-arrestin-1 (Arrb1 was found in the ARH and in N-38 neurons. In vitro, E2 increased trafficking and internalization of full-length ERα and ERαΔ4, an alternatively spliced isoform of ERα, which predominates in the membrane. Treatment with E2 also increased phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2 in N-38 neurons. Arrb1 siRNA knockdown prevented E2-induced ERαΔ4 internalization and ERK1/2 phosphorylation. In vivo, microinfusions of Arrb1 antisense oligodeoxynucleotides (ODN into female rat ARH knocked down Arrb1 and prevented estradiol benzoate-induced lordosis behavior compared with nonsense scrambled ODN (lordosis quotient: 3 ± 2.1 vs. 85.0 ± 6.0; p < 0.0001. These results indicate a role for Arrb1 in both EMS and internalization of mERα, which are required for the E2-induction of female sexual receptivity.

  16. Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study

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    Mohammad Hossein Barzegar

    2017-12-01

    Full Text Available Background: Citrullus colocynthis (CCT is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. Objective: We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats’ model. Materials and Methods: 40 female adult Wistar rats divided into five groups (n=8each: Group I (control only injected by sesame oil as estradiol valerate solvent, group II (Sham was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly, and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III, 50mg/kg metformin (group IV, and CCT extract+ metformin (group V for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter. Histological study of ovary tissue carried out by hematoxylin-eosin staining. Results: There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Conclusion: Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS

  17. Effect of Citrullus colocynthis hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats model: An experimental study.

    Science.gov (United States)

    Barzegar, Mohammad Hossein; Khazali, Homayoun; Kalantar, Seyyed Mehdi; Khoradmehr, Arezoo

    2017-10-01

    Citrullus colocynthis (CCT) is used as the anti-diabetic and antioxidant agent. Polycystic ovarian syndrome (PCOS) is a reproductive disorder which level of gonadotropins and sexual hormones are imbalanced. We evaluated the effect of CCT hydro-alcoholic extract on hormonal and folliculogenesis process in estradiol valerate-induced PCOs rats' model. 40 female adult Wistar rats divided into five groups (n=8each: Group I (control) only injected by sesame oil as estradiol valerate solvent, group II (Sham) was orally received normal saline after estradiol valerate- induced polycystic ovarian syndrome (4 mg/rat estradiol valerate, intramuscularly), and three experimental groups, that after induction of PCOS within 60 days, received orally 50 mg/kg CCT extract (group III), 50mg/kg metformin (group IV), and CCT extract+ metformin (group V) for 20 days. The serum concentration level of luteinizing, testosterone and follicle stimulating hormones were measured using ELISA method and the serum concentration level of glucose were measured using the oxidative method (glucose meter). Histological study of ovary tissue carried out by hematoxylin-eosin staining. There was a significant reduction in luteinizing hormone and testosterone in III-V groups compared to Sham group, whereas follicle stimulating hormone in III-V groups was not significantly changed in comparison with Sham group. Histological investigations showed a significant increase in number of preantral and antral follicles and corpus luteum in the experimental groups compared to group II. Marked improvement in hormonal and histological symptoms of PCOS may be due to CCT effects hence, CCT can potentially be considered as an effective drug for treatment of PCOS.

  18. Effects of 17β-estradiol on emissions of greenhouse gases in simulative natural water body.

    Science.gov (United States)

    Ruan, Aidong; Zhao, Ying; Liu, Chenxiao; Zong, Fengjiao; Yu, Zhongbo

    2015-05-01

    Environmental estrogens are widely spread across the world and are increasingly thought of as serious contaminators. The present study looks at the influence of different concentrations of 17β-estradiol on greenhouse gas emissions (CO2 , CH4 , and N2 O) in simulated systems to explore the relationship between environmental estrogen-pollution and greenhouse gas emissions in natural water bodies. The present study finds that 17β-estradiol pollution in simulated systems has significant promoting effects on the emissions of CH4 and CO2 , although no significant effects on N2 O emissions. The present study indicates that 17β-estradiol has different effects on the different elements cycles; the mechanism of microbial ecology is under review. © 2015 SETAC.

  19. Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation

    International Nuclear Information System (INIS)

    Gazzerro, Patrizia; Abbondanza, Ciro; D'Arcangelo, Andrea; Rossi, Mariangela; Medici, Nicola; Moncharmont, Bruno; Puca, Giovanni Alfredo

    2006-01-01

    The retinoblastoma protein-interacting zinc-finger (RIZ) gene, a member of the nuclear protein methyltransferase superfamily, is characterized by the presence of the N-terminal PR domain. The RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the PR (PRDI-BF1 and RIZ homologous) domain, RIZ2 lacks it. RIZ gene expression is altered in a variety of human cancers and RIZ1 is now considered to be a candidate tumor suppressor. Estradiol treatment of MCF-7 cells produced a selective decrease of RIZ1 transcript and an increase of total RIZ mRNA. Experiments of chromatin immunoprecipitation indicated that RIZ2 protein expression was controlled by estrogen receptor and RIZ1 had a direct repressor function on c-myc gene expression. To investigate the role of RIZ gene products as regulators of the proliferation/differentiation transition, we analyzed the effects of forced suppression of RIZ1 induced in MCF-7 cells by siRNA of the PR domain-containing form. Silencing of RIZ1 expression stimulated cell proliferation, similar to the effect of estradiol on these cells, associated with a transient increase of c-myc expression

  20. New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness

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    Isabel Corraliza-Gorjón

    2017-12-01

    Full Text Available Antibodies have proven their high value in antitumor therapy over the last two decades. They are currently being used as the first-choice to treat some of the most frequent metastatic cancers, like HER2+ breast cancers or colorectal cancers, currently treated with trastuzumab (Herceptin and bevacizumab (Avastin, respectively. The impressive therapeutic success of antibodies inhibiting immune checkpoints has extended the use of therapeutic antibodies to previously unanticipated tumor types. These anti-immune checkpoint antibodies allowed the cure of patients devoid of other therapeutic options, through the recovery of the patient’s own immune response against the tumor. In this review, we describe how the antibody-based therapies will evolve, including the use of antibodies in combinations, their main characteristics, advantages, and how they could contribute to significantly increase the chances of success in cancer therapy. Indeed, novel combinations will consist of mixtures of antibodies against either different epitopes of the same molecule or different targets on the same tumor cell; bispecific or multispecific antibodies able of simultaneously binding tumor cells, immune cells or extracellular molecules; immunomodulatory antibodies; antibody-based molecules, including fusion proteins between a ligand or a receptor domain and the IgG Fab or Fc fragments; autologous or heterologous cells; and different formats of vaccines. Through complementary mechanisms of action, these combinations could contribute to elude the current limitations of a single antibody which recognizes only one particular epitope. These combinations may allow the simultaneous attack of the cancer cells by using the help of the own immune cells and exerting wider therapeutic effects, based on a more specific, fast, and robust response, trying to mimic the action of the immune system.

  1. Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

    Science.gov (United States)

    Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

    2011-01-01

    Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

  2. Topical estradiol does not interfere with the expression of the metalloproteinase-1 enzyme in photo exposed skin cells Estradiol tópico não interfere na expressão da enzima metaloproteinase-1 em células da pele fotoexposta

    Directory of Open Access Journals (Sweden)

    Luciana Neder

    2012-02-01

    Full Text Available BACKGROUND: In postmenopausal women there is a rapid destruction of dermal collagen, resulting in accelerated skin ageing, which is manifested by cutaneous atrophy, increased number and depth of wrinkles and sagging. This accelerated catabolism of the collagen is due to estrogen deficiency and increased synthesis of the metalloproteinase-1 enzyme, which degrades the dermal collagen. OBJECTIVES: To assess whether the use of topical estradiol 0.05% cream on photo exposed skin can inhibit the expression of the metalloproteinase-1 enzyme on the dermis and subsequently the rapid loss of collagen in women after menopause. METHODS: We included 40 postmenopausal women without hormone replacement therapy. Information about lifestyle, lipid profile, blood glucose level, thyroid hormones, mammography, Pap smear and transvaginal ultrasound were obtained to rule out associated diseases. Skin biopsy of the right preauricular region was performed before and after treatment with topical estradiol 0.05% for 30 days. The biopsy specimens were subjected to immunohistochemistry to identify the expression of the metalloproteinase-1 enzyme. RESULTS: There was no statistically significant difference on the expression of the metalloproteinase-1 enzyme in keratinocytes, fibroblasts and endothelial cells before and after treatment with topical estradiol for 30 days. CONCLUSION: Treatment with estradiol 0.05% cream, in photo exposed skin for 30 days, does not inhibit the production of metalloproteinase-1.FUNDAMENTOS: Na pós-menopausa, ocorre rápida destruição do colágeno dérmico, com consequente envelhecimento acelerado da pele, que se expressa com atrofia cutânea, aumento do número e da profundidade das rugas e flacidez. Esse catabolismo acelerado do colágeno ocorre por deficiência estrogênica e aumento na síntese da enzima metaloproteinase-1, que degrada o colágeno dérmico. OBJETIVOS: Avaliar se o uso de estradiol tópico a 0,05% em creme na pele

  3. Effects of bromocriptine on [3H]estradiol binding in cytosol of anterior pituitary

    International Nuclear Information System (INIS)

    De Nicola, A.F.; Weisenberg, L.S.; Arakelian, M.C.; Libertun, C.

    1981-01-01

    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 [ 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), [ 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

  4. Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

    Science.gov (United States)

    Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

    2000-04-03

    To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

  5. Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

    International Nuclear Information System (INIS)

    Montgomery, Bruce; Nelson, Peter S; Vessella, Robert; Kalhorn, Tom; Hess, David; Corey, Eva

    2010-01-01

    Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm 3 vs. 1195 ± 84 mm 3 , p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis

  6. Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules

    International Nuclear Information System (INIS)

    Koutsogiannaki, Sophia; Franzellitti, Silvia; Fabbri, Elena; Kaloyianni, Martha

    2014-01-01

    Highlights: •Oxidative parameters in Mytilus galloprovincialis hemocytes were measured. •Comparison between cadmium and 17β-estradiol cytotoxicity is discussed. •NHE, PKC, PI3-K, NADPH oxidase, NO synthase, JNK involvement was observed. •Protective role of cAMP is suggested. •Signaling molecules studied could constitute novel biomarkers. -- Abstract: The aim of the present study was to determine and compare the possible effects of exposure to an estrogen, 17β-estradiol and to a metal, cadmium on oxidative parameters of Mytilus galloprovincialis hemocytes and to elucidate the signaling pathways that probably mediate the studied effects exerted by these two chemicals. In addition, it was of interest to investigate if the studied parameters could constitute biomarkers for aquatic pollution monitoring. Our results suggest that micromolar concentrations of either cadmium or 17β-estradiol affected the redox status of mussels by modulating oxidative parameters and antioxidant enzymes gene expression in mussel M. galloprovincialis hemocytes. In particular, our results showed that treatment of hemocytes with either 5 μM of cadmium chloride or with 25 nM of 17β-estradiol for 30 min caused significant increased ROS production; this led to oxidative damage exemplified by significant increased DNA damage, protein carbonylation and lipid peroxidation, as well as increased mRNA levels of the antioxidant enzymes catalase (CAT), superoxide dismoutase (SOD) and glutathione S-transferase (GST). Furthermore, our results suggest that either cadmium or 17β-estradiol signal is mediated either through one of the already known pathways initiated by photatidyl-inositol 3-kinase (PI3 K) and reaching Na + /H + exchanger (NHE) probably through protein kinase C (PKC) or a kinase-mediated signaling pathway that involves in most of the cases NHE, PKC, Ca 2+ -dependent PKC isoforms, PI3-K, NADPH oxidase, nitric oxide (NO) synthase, c-Jun N-terminal kinase (JNK) and cyclic adenosine

  7. Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules

    Energy Technology Data Exchange (ETDEWEB)

    Koutsogiannaki, Sophia [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Franzellitti, Silvia [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Kaloyianni, Martha, E-mail: kaloyian@bio.auth.gr [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)

    2014-01-15

    Highlights: •Oxidative parameters in Mytilus galloprovincialis hemocytes were measured. •Comparison between cadmium and 17β-estradiol cytotoxicity is discussed. •NHE, PKC, PI3-K, NADPH oxidase, NO synthase, JNK involvement was observed. •Protective role of cAMP is suggested. •Signaling molecules studied could constitute novel biomarkers. -- Abstract: The aim of the present study was to determine and compare the possible effects of exposure to an estrogen, 17β-estradiol and to a metal, cadmium on oxidative parameters of Mytilus galloprovincialis hemocytes and to elucidate the signaling pathways that probably mediate the studied effects exerted by these two chemicals. In addition, it was of interest to investigate if the studied parameters could constitute biomarkers for aquatic pollution monitoring. Our results suggest that micromolar concentrations of either cadmium or 17β-estradiol affected the redox status of mussels by modulating oxidative parameters and antioxidant enzymes gene expression in mussel M. galloprovincialis hemocytes. In particular, our results showed that treatment of hemocytes with either 5 μM of cadmium chloride or with 25 nM of 17β-estradiol for 30 min caused significant increased ROS production; this led to oxidative damage exemplified by significant increased DNA damage, protein carbonylation and lipid peroxidation, as well as increased mRNA levels of the antioxidant enzymes catalase (CAT), superoxide dismoutase (SOD) and glutathione S-transferase (GST). Furthermore, our results suggest that either cadmium or 17β-estradiol signal is mediated either through one of the already known pathways initiated by photatidyl-inositol 3-kinase (PI3 K) and reaching Na{sup +}/H{sup +} exchanger (NHE) probably through protein kinase C (PKC) or a kinase-mediated signaling pathway that involves in most of the cases NHE, PKC, Ca{sup 2+}-dependent PKC isoforms, PI3-K, NADPH oxidase, nitric oxide (NO) synthase, c-Jun N-terminal kinase (JNK) and

  8. Analogues of estradiol as potential breast tumor imaging agents

    International Nuclear Information System (INIS)

    Gibson, R.E.; Rzeszotarski, W.J.; Ferriera, N.L.; Jagoda, E.M.; Reba, R.C.; Eckelman, W.C.

    1984-01-01

    The radioiodinated analogue of estradiol, 11β-methoxy-17α-[/sup 125/I]iodovinylestradiol (MIVE/sub 2/), has been shown to be a good candidate for the imaging of estrogen dependent breast tumors. Although there has been no extensive study on the sensitivity of radiotracers of this type, the authors have not observed localization of the radiotracer in metastatic lesions containing less than 20 fmole estrogen receptor/mg protein or in bone metasteses. In order to improve the sensitivity, they have examined several structural analogues of moxestrol (the parent structure for MIVE/sub 2/) for affinity to the ER isolated from immature rat uterus. The 11β-ethyl analogue (EEE/sub 2/) of ethynyl estradiol (EE/sub 2/) exhibits the highest affinity with the 11β-methyl analogue second best. Although the lipophilicity is also very high this compound should not be much more lipophilic than 16-iodoestradiol or MIVE/sub 2/ since the introduction of iodine increases the log P by greater than 1. The distribution of the tritiated derivative of EEE/sub 2/ is under study

  9. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium

    Directory of Open Access Journals (Sweden)

    Adela Banciu

    2018-05-01

    Full Text Available Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1, estrogen receptors (ESR1, ESR2, GPR30, and nuclear receptor coactivator 3 (NCOA3. Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM antagonized the effect of BAY K8644 (2.5 or 5 µM in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant

  10. Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium.

    Science.gov (United States)

    Banciu, Adela; Banciu, Daniel Dumitru; Mustaciosu, Cosmin Catalin; Radu, Mihai; Cretoiu, Dragos; Xiao, Junjie; Cretoiu, Sanda Maria; Suciu, Nicolae; Radu, Beatrice Mihaela

    2018-05-09

    Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1), estrogen receptors (ESR1, ESR2, GPR30), and nuclear receptor coactivator 3 (NCOA3). Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM) downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM) antagonized the effect of BAY K8644 (2.5 or 5 µM) in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant human uterine

  11. Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats

    International Nuclear Information System (INIS)

    Moreira, Paula I.; Custodio, Jose B.A.; Nunes, Elsa; Moreno, Antonio; Seica, Raquel; Oliveira, Catarina R.; Santos, Maria S.

    2007-01-01

    Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17β-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca 2+ delaying the opening of the permeability transition pore. The presence of 25 μM E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H 2 O 2 in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered

  12. A New MAP Kinase Protein Involved in Estradiol-Stimulated Reproduction of the Helminth Parasite Taenia crassiceps

    Science.gov (United States)

    Escobedo, Galileo; Soldevila, Gloria; Ortega-Pierres, Guadalupe; Chávez-Ríos, Jesús Ramsés; Nava, Karen; Fonseca-Liñán, Rocío; López-Griego, Lorena; Hallal-Calleros, Claudia; Ostoa-Saloma, Pedro; Morales-Montor, Jorge

    2010-01-01

    MAP kinases (MAPK) are involved in the regulation of cellular processes such as reproduction and growth. In parasites, the role of MAPK has been scarcely studied. Here, we describe the participation of an ERK-like protein in estrogen-dependent reproduction of the helminth parasite Taenia crassiceps. Our results show that 17β-estradiol induces a concentration-dependent increase in the bud number of in vitro cultured cysticerci. If parasites are also incubated in presence of an ERK-inhibitor, the stimulatory effect of estrogen is blocked. The expression of ERK-like mRNA and its corresponding protein was detected in the parasite. The ERK-like protein was over-expressed by all treatments. Nevertheless, a strong induction of phosphorylation of this protein was observed only in response to 17β-estradiol. Cross-contamination by host cells was discarded by flow cytometry analysis. Parasite cells expressing the ERK-like protein were exclusively located at the subtegument tissue by confocal microscopy. Finally, the ERK-like protein was separated by bidimensional electrophoresis and then sequenced, showing the conserved TEY activation motif, typical of all known ERK 1/2 proteins. Our results show that an ERK-like protein is involved in the molecular signalling during the interaction between the host and T. crassiceps, and may be considered as target for anti-helminth drugs design. PMID:20145710

  13. Expression of ErbB3-binding protein-1 (EBP1 during primordial follicle formation: role of estradiol-17ß.

    Directory of Open Access Journals (Sweden)

    Anindit Mukherjee

    Full Text Available The formation of primordial follicles involves the interaction between the oocytes and surrounding somatic cells, which differentiate into granulosa cells. Estradiol-17ß (E promotes primordial follicle formation in vivo and in vitro; however, the underlying mechanisms are poorly understood. The expression of an ERBB3-binding protein 1 (EBP1 is downregulated in 8-day old hamster ovaries concurrent with the increase in serum estradiol levels and the formation of primordial follicles. The objectives of the present study were to determine the spatio-temporal expression and putative E regulation of EBP1 in ovarian cells during perinatal development with respect to primordial follicle formation. Hamster EBP1 nucleic acid and amino acid sequences were more than 93% and 98% similar, respectively, to those of mouse and human, and contained nucleolar localization signal, RNA-binding domain and several phosphorylation sites. EBP1 protein was present in somatic cells and oocytes from E15, and declined in oocytes by P1 and in somatic cells by P5. Thereafter, EBP1 expression increased through P7 with a transient decline on P8 primarily in interstitial cells. EBP1 mRNA levels mirrored protein expression pattern. E treatment on P1 and P4 upregulated EBP1 expression by P8 whereas E treatment on P4 downregulated it by 72 h suggesting a compensatory upregulation due to E pretreatment. Treatment with an FSH-antiserum, which suppressed primordial follicle formation, prevented the decline in EBP1 levels, and the effect was reversed by E treatment. Therefore, the results provide the first evidence that EBP1 may play an important role in mediating the effect of E in the differentiation of somatic cells into granulosa cells during primordial follicle formation.

  14. Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor.

    Science.gov (United States)

    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.

  15. Does estradiol have an impact on the dipeptidyl peptidase IV enzyme activity of the Prevotella intermedia group bacteria?

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. The anti-inflammatory effect of montelukast, a cysteinyl leukotriene receptor-1 antagonist, against estradiol-induced nonbacterial inflammation in the rat prostate.

    Science.gov (United States)

    Said, Mahmoud M; Bosland, Maarten C

    2017-02-01

    There is no standard treatment of chronic nonbacterial prostatitis in humans. The current study was aimed to investigate the effect of montelukast, an antagonist of cysteinyl leukotriene receptor-1, against estrogen-induced, nonbacterial lateral lobe-specific prostate inflammation in rats. Male Wistar rats were randomized into five groups of six rats, including sham controls (group 1) and castrated rats (group 2), whereas nonbacterial prostatitis (NBP) was induced in groups 3-5 by castration followed by a daily subcutaneous injection of estradiol (0.25 mg/kg body weight) for 30 days. The rats were left otherwise untreated (group 3) or received a daily oral administration of montelukast (1 and 10 mg/kg body weight for groups 4 and 5, respectively) from the 17th day after castration for two consecutive weeks. Compared with sham controls, induction of NBP led to a significant increase in serum leukotriene B 4 (LTB4), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels, along with a significant upregulation in the transcript level of proinflammatory molecules (nuclear factor kappa beta [NF-κβ] and inducible nitric oxide synthase [iNOS]), chemokines (monocyte chemoattractant protein-1 [MCP-1] and eotaxin), and E-selectin in the lateral prostate. Histological examination revealed intense inflammation in the prostate with leukocyte infiltration and acinar degeneration following estradiol treatment of castrated rats. Montelukast significantly suppressed the increase in serum and prostate proinflammatory mediators/chemokines expression and abolished the histologically inflammatory changes in the lateral prostate. These findings indicate that montelukast inhibits estradiol-induced NBP in a rat model through anti-inflammatory mechanisms, suggesting its future beneficial effect for the treatment of clinical chronic NBP.

  17. Cortisol Interferes with the Estradiol-Induced Surge of Luteinizing Hormone in the Ewe1

    Science.gov (United States)

    Wagenmaker, Elizabeth R.; Breen, Kellie M.; Oakley, Amy E.; Pierce, Bree N.; Tilbrook, Alan J.; Turner, Anne I.; Karsch, Fred J.

    2008-01-01

    Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was ∼1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge. PMID:19056703

  18. Estradiol Therapy After Menopause Mitigates Effects of Stress on Cortisol and Working Memory.

    Science.gov (United States)

    Herrera, Alexandra Ycaza; Hodis, Howard N; Mack, Wendy J; Mather, Mara

    2017-12-01

    Postmenopausal estradiol therapy (ET) can reduce the stress response. However, it remains unclear whether such reductions can mitigate effects of stress on cognition. Investigate effects of ET on cortisol response to a physical stressor, cold pressor test (CPT), and whether ET attenuates stress effects on working memory. Women completed the CPT or control condition across two sessions and subsequently completed a sentence span task. General community: Participants were recruited from the Early vs Late Intervention Trial with Estradiol (ELITE). ELITE participants (mean age = 66, standard deviation age = 6.8) in this study did not suffer from any major chronic illness or use medications known to affect the stress response or cognition. Participants had received a median of randomized 4.7 years of estradiol (n = 21) or placebo (n = 21) treatment at time of participation in this study. Salivary cortisol and sentence span task performance. Women assigned to estradiol exhibited blunted cortisol responses to CPT compared with placebo (P = 0.017) and lesser negative effects of stress on working memory (P = 0.048). We present evidence suggesting ET may protect certain types of cognition in the presence of stress. Such estrogenic protection against stress hormone exposure may prove beneficial to both cognition and the neural circuitry that maintains and propagates cognitive faculties. Copyright © 2017 Endocrine Society

  19. Effects of estradiol and venlafaxine on insomnia symptoms and sleep quality in women with hot flashes.

    Science.gov (United States)

    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

    Determine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes. 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. Academic research centers. 339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day. 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). 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. NCT01418209 at www.clinicaltrials.gov. © 2014 Associated Professional Sleep Societies, LLC.

  20. Effects of ionizing irradiation on the estradiol and progesterone receptors in rat mammary tumors

    International Nuclear Information System (INIS)

    Janssens, J.P.; Wittevrongel, C.; Van Dam, J.; Goddeeris, P.; Lauwerijns, J.M.; De Loecker, W.

    1981-01-01

    The determination of estradiol and progesterone receptor concentrations in mammary tumors is useful in predicting the hormone responsiveness. As this assay is carried out on tumor tissue which may have been subjected to radiotherapy, the possibility of an ionizing irradiation affecting the steroid receptor levels in neoplastic tissue should be taken into account. The steroid receptor concentrations are examined in dimethylbenz(a)anthracene-induced tumors os Sprague-Dawley rats. The estradiol and the progesterone receptor titers become reduced significantly after treatment with 20 Gray while an application with 7 Gray does not affect the titer values. After treatment of the tumor with 20 Gray, the steroid receptor concentrations decrease progressively, reaching a maximal reduction 20 to 30 days after exposure. As radiation treatment affects the receptor concentrations, this should be kept in mind when interpreting the steroid receptor concentrations

  1. Sex differences in hippocampal estradiol-induced N-methyl-D-aspartic acid binding and ultrastructural localization of estrogen receptor-alpha.

    Science.gov (United States)

    Romeo, Russell D; McCarthy, J Brian; Wang, Athena; Milner, Teresa A; McEwen, Bruce S

    2005-01-01

    Estradiol increases dendritic spine density and synaptogenesis in the CA1 region of the female hippocampus. This effect is specific to females, as estradiol-treated males fail to show increases in hippocampal spine density. Estradiol-induced spinogenesis in the female is dependent upon upregulation of the N-methyl-D-aspartic acid (NMDA) receptor as well as on non-nuclear estrogen receptors (ER), including those found in dendrites. Thus, in the male, the inability of estradiol to induce spinogenesis may be related to a failure of estradiol to increase hippocampal NMDA receptors as well as a paucity of dendritic ER. In the first experiment, we sought to investigate this possibility by assessing NMDA receptor binding, using [(3)H]-glutamate autoradiography, in estradiol-treated males and females. We found that while estradiol increases NMDA binding in gonadectomized females, estradiol fails to modulate NMDA binding in gonadectomized males. To further investigate sex differences in the hippocampus, we conducted a second separate, but related, ultrastructural study in which we quantified ERalpha-immunoreactivity (ERalpha-ir) in neuronal profiles in the CA1 region of the hippocampus in intact males and females in diestrus and proestrus. Consistent with previous reports in the female, we found ERalpha-ir in several extranuclear sites including dendrites, spines, terminals and axons. Statistical analyses revealed that females in proestrus had a 114.3% increase in ERalpha-labeled dendritic spines compared to females in diestrus and intact males. Taken together, these studies suggest that both the ability of estrogen to increase NMDA binding in the hippocampus and the presence of ERalpha in dendritic spines may contribute to the observed sex difference in estradiol-induced hippocampal spinogenesis. Copyright (c) 2005 S. Karger AG, Basel.

  2. Effect of endogenous androgens on 17beta-estradiol-mediated protection after spinal cord injury in male rats.

    Science.gov (United States)

    Kachadroka, Supatra; Hall, Alicia M; Niedzielko, Tracy L; Chongthammakun, Sukumal; Floyd, Candace L

    2010-03-01

    Several groups have recently shown that 17beta-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17beta-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17beta-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17beta-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5- or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax/Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17beta-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonad-intact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17beta-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17beta-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.

  3. Antioxidant protection of LDL by physiological concentrations of 17 beta-estradiol. Requirement for estradiol modification.

    Science.gov (United States)

    Shwaery, G T; Vita, J A; Keaney, J F

    1997-03-18

    Exposure to estrogens reduces the risk for coronary artery disease and associated clinical events; however, the mechanisms responsible for these observations are not clear. Supraphysiological levels of estrogens act as antioxidants in vitro, limiting oxidation of low-density lipoprotein (LDL), an event implicated in atherogenesis. We investigated the conditions under which physiological concentrations of 17 beta-estradiol (E2) inhibit oxidative modification of LDL. Plasma incubated with E2 (0.1 to 100 nmol/L) for 4 hours yielded LDL that demonstrated a dose-related increase in resistance to oxidation by Cu2+ as measured by conjugated diene formation. This effect was dependent on plasma, because incubation of isolated LDL with E2 at these concentrations in buffered saline produced no effect on Cu(2+)-mediated oxidation. Incubation of plasma with E2 had no effect on LDL alpha-tocopherol content or cholesteryl ester hydroperoxide formation during the 4-hour incubation. Plasma incubation with [3H]E2 was associated with dose-dependent association of 3H with LDL. High-performance liquid chromatographic analysis of LDL derived from plasma incubated with [3H]E2 indicated that the majority of the associated species were not detectable as authentic E2 but as nonpolar forms of E2 that were susceptible to base hydrolysis consistent with fatty acid esterification of E2. Plasma-mediated association of E2 and subsequent antioxidant protection was inhibited by 5,5'-dithiobis(2-nitrobenzoic acid), an inhibitor of plasma acyltransferase activity. Exposure of LDL to physiological levels of E2 in a plasma milieu is associated with enhanced resistance to Cu(2+)-mediated oxidation and incorporation of E2 derivatives into LDL. This antioxidant capacity may be another means by which E2 limits coronary artery disease in women.

  4. High-dose estradiol improves cognition for women with AD: results of a randomized study.

    Science.gov (United States)

    Asthana, S; Baker, L D; Craft, S; Stanczyk, F Z; Veith, R C; Raskind, M A; Plymate, S R

    2001-08-28

    To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

  5. The value of creatine kinase, estradiol and progesterone levels in early diagnosis of ectopic pregnancies: a prospective controlled study

    Directory of Open Access Journals (Sweden)

    Feride Mimaroğlu

    2010-06-01

    Full Text Available INTRODUCTION: To evaluate the role of serum creatine kinase, progesterone and estradiol as a biochemical marker in the early diagnosis of tubal pregnancy. MATERIAL-METHODS: A prospective controlled study was carried out on 44 women with first trimester pregnancy. First group (n=22 with tubal pregnancy formed the study group and second group (n=22 with normal intrauterine pregnancy was taken as controls. Serum beta hCG, creatine kinase, progesterone and estradiol levels in the two groups were compared. Surgical treatment had choosen as a treatment modality of ectopic pregnancy. RESULTS: The optimal cutoff value of creatine kinase to be used for the prediction of ectopic pregnancy was 45 IU/l, which resulted in a sensitivity of 86%, specificity of 31%, positive predictive value 55 % and negative predictive value 70 %. The same values for estradiol and progesterone were detected >225 pg/ml, 100 %, 68 %, 75%, 100 % and >13 ng/mL, 95 %, 81 %, % 84, % 97 in discriminating ectopic pregnancies. According to AUC levels there was a significant difference between estradiol-creatine kinase levels, progesterone-estradiol levels and progesterone–creatin kinase levels (p values 0.024, 0.0082, and 0.0001, respectively. CONCLUSION: Serum creatine kinase values appear to be a useful marker in the diagnosis of ectopic pregnancy.

  6. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    International Nuclear Information System (INIS)

    Haakensen, Vilde D; Børresen-Dale, Anne-Lise; Helland, Åslaug; Bjøro, Trine; Lüders, Torben; Riis, Margit; Bukholm, Ida K; Kristensen, Vessela N; Troester, Melissa A; Homen, Marit M; Ursin, Giske

    2011-01-01

    High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the

  7. Estradiol-induced promotion of hepatocarcinogenesis in medaka: Relationship of foci of cellular alteration to neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Cooke, J.B.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    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.

  8. Impairment of the natriuretic peptide system in follitropin receptor knockout mice and reversal by estradiol: implications for obesity-associated hypertension in menopause.

    Science.gov (United States)

    Belo, Najara O; Sairam, M Ram; Dos Reis, Adelina M

    2008-03-01

    Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.

  9. The antidepressant-like effects of topiramate alone or combined with 17β-estradiol in ovariectomized Wistar rats submitted to the forced swimming test.

    Science.gov (United States)

    Molina-Hernández, Miguel; Téllez-Alcántara, N Patricia; Olivera-López, Jorge I; Jaramillo, M Teresa

    2014-09-01

    There is a significant delay in the clinical response of antidepressant drugs, and antidepressant treatments produce side effects. We examined the relationship between 17β-estradiol and topiramate in ovariectomized Wistar rats submitted to the forced swimming test (FST). Topiramate was administered alone or combined with 17β-estradiol to ovariectomized rats submitted to the FST. Topiramate (20 mg/kg, P swimming; these effects were antagonized by finasteride (50 mg/kg). In interaction experiments, topiramate (10 mg/kg) plus 17β-estradiol (5 micrograms per rat; P swimming behavior. Besides, 17β-estradiol (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects of topiramate (P < 0.05). In the open field test, topiramate alone or combined with 17β-estradiol (P < 0.05) reduced locomotion. Topiramate alone or combined with 17β-estradiol produced antidepressant-like actions; and 17β-estradiol shortened the onset of the antidepressant-like effects of topiramate.

  10. Estradiol Membrane-Initiated Signaling in the Brain Mediates Reproduction.

    Science.gov (United States)

    Micevych, Paul E; Mermelstein, Paul G; Sinchak, Kevin

    2017-11-01

    Over the past few years our understanding of estrogen signaling in the brain has expanded rapidly. Estrogens are synthesized in the periphery and in the brain, acting on multiple receptors to regulate gene transcription, neural function, and behavior. Various estrogen-sensitive signaling pathways often operate in concert within the same cell, increasing the complexity of the system. In females, estrogen concentrations fluctuate over the estrous/menstrual cycle, dynamically modulating estrogen receptor (ER) expression, activity, and trafficking. These dynamic changes influence multiple behaviors but are particularly important for reproduction. Using the female rodent model, we review our current understanding of estradiol signaling in the regulation of sexual receptivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Relationship between Estradiol and Antioxidant Enzymes Activity of Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Nasrin Sheikh

    2009-01-01

    Full Text Available Some evidence suggests the neuroprotection of estrogen provided by the antioxidant activity of this compound. The main objective of this study was to determine the level of estradiol and its correlation with the activity of antioxidant enzymes, total antioxidant status and ferritin from ischemic stroke subjects. The study population consisted of 30 patients with acute ischemic stroke and 30 controls. There was no significant difference between estradiol in stroke and control group. The activity of superoxide dismutase and level of ferritin was higher in stroke compared with control group (<.05, <.001, resp.. There was no significant correlation between estradiol and glutathione peroxidase, glutathione reductase, catalase, total antioxidant status, and ferritin in stroke and control groups. We observed inverse correlation between estradiol with superoxide dismutase in males of stroke patients (=−0.54, =.029. Our results supported that endogenous estradiol of elderly men and women of stroke or control group has no antioxidant activity.

  12. Bed rest and increased diuretic treatment in chronic congestive heart failure

    DEFF Research Database (Denmark)

    Abildgaard, U; Aldershvile, J; Ring-Larsen, H

    1985-01-01

    To elucidate the effect of bed rest used as an adjunct to increased diuretic treatment, twelve patients with chronic congestive heart failure (CHF) had a 50% increase in loop diuretic dosage and were allocated to either continuous bed rest or bed rest during nights only. The 24-hour bed rest group...... is a reasonable adjunct to diuretic treatment in patients with CHF....

  13. Increasing spelling achievement: an analysis of treatment procedures utilizing an alternating treatments design.

    OpenAIRE

    Ollendick, T H; Matson, J L; Esveldt-Dawson, K; Shapiro, E S

    1980-01-01

    Two studies which examine the effectiveness of spelling remediation procedures are reported. In both studies, an alternating treatment design was employed. In the first study, positive practice overcorrection plus positive reinforcement was compared to positive practice alone and a no-remediation control condition. In the second study, positive practice plus positive reinforcement was compared to a traditional corrective procedure plus positive reinforcement and a traditional procedure when u...

  14. Kombinasi Calcitriol dan Ethynil Ethyl Estradiol Meningkatkan Ekskresi Kalsium Urin dan Risiko Urolitiasis pada Tikus Ovariektomi

    Directory of Open Access Journals (Sweden)

    Hartiningsih Hartiningsih

    2017-06-01

    Full Text Available The high excretion of calcium (Ca in the urine can trigger the formation of urolith. Estrogen and calcitriol decrease urinary Ca excretion. This study aims to examine the combination of calcitriol and ethinyl ethyl estradiol against Ca urinary excretion and urolithiasis risk of ovariectomized rats. Twentyfive female Wistar rats eight weeks old were divided into five groups: i normal control (NK; ii ovariectomized control (OVK; iii ovariectomized + calcitriol (OVD; iv ovariectomized + ethinyl ethyl estradiol (OVE; and v ovariectomized + combination calcitriol and ethinyl ethyl estradiol (OVDE. Seven weeks post-ovariectomy, each rat was put in an individual metabolic cage for the study of Ca balance. At day 4 to 7 of the study, residual feed, urine, and feces were collected daily for Ca analysis. At day 8, the rats were euthanized, the left kidney were collected for histopathological examination. The results showed that combination of calcitriol and ethinyl ethyl estradiol in OVDE rats caused Ca intake and Ca intestinal absorption significantly higher, and urinary Ca excretion tended to be higher although not significantly different compared to OVK rats. Calcium excretion in OVK rat urine was higher compared to the NK rats. The kidney histopathological changes of OVK rats were not different from the NK rats. Histopathological examination of the OVDE group kidney showed protein deposition in the capsular of Bowman’s capsule and proximal tubules, atrophy of the proximal tubules, and necrosis, respectively. It is concluded that the combination of calcitriol with ethinyl ethyl estradiol in ovariectomized rats increased urinary Ca excretion and increased the risk of urolithiasis. ABSTRAK Tingginya ekskresi kalsium (Ca dalam urin dapat menjadi pemicu terbentuknya urolit. Estrogen dan calcitriol menurunkan ekskresi Ca urin. Penelitian ini dilakukan bertujuan untuk mengkaji kombinasi calcitriol dan ethynil ethyl estradiol terhadap ekskresi Ca dalam urin

  15. Effects of catecholamines on ovary morphology, blood concentrations of estradiol-17beta, progesterone, zinc, triglycerides and rate of ovulation in domestic hens.

    Science.gov (United States)

    Ebeid, T A; Eid, Y Z; El-Abd, E A; El-Habbak, M M

    2008-04-15

    The present study is an attempt to shed more light on the role of epinephrine (EP) and norepinephrine (NE) in regulating ovarian follicular development, folliculogenesis and ovulation in laying hens. Sixty Egyptian local cross females (Mandarah), 50 weeks old, were individually housed and equally divided into three treatments: control (saline, 0.9% NaCl), EP (0.15 mg epinephrine/hen/day) and NE (0.75 mg norepinephrine/hen/day) (n=20). Animals were injected intramuscularly once a day for 15 successive days. At the end of the experimental period, 10 females from each treatment were randomly chosen, weighed and killed by decapitation. Ovaries and oviducts and ovarian follicles were examined. Plasma concentrations of estradiol-17beta, progesterone, zinc and triglyceride were determined. Results indicated that the ovaries of NE- and EP-treated hens were more developed than those of control hens being heavier and containing more yellow yolk-filled follicles. EP or NE significantly increased the ovulation rate and plasma concentrations of estradiol-17beta, progesterone, zinc and triglyceride compared with control treatment. It could be concluded that catecholamines may have a part in promoting ovarian follicular development and in stimulating ovulation in laying hens at the end of their reproductive lives.

  16. Modulation of the Chlamydia trachomatis In vitro transcriptome response by the sex hormones estradiol and progesterone

    Directory of Open Access Journals (Sweden)

    Symonds Ian

    2011-06-01

    Full Text Available Abstract Background Chlamydia trachomatis is a major cause of sexually transmitted disease in humans. Previous studies in both humans and animal models of chlamydial genital tract infection have suggested that the hormonal status of the genital tract epithelium at the time of exposure can influence the outcome of the chlamydial infection. We performed a whole genome transcriptional profiling study of C. trachomatis infection in ECC-1 cells under progesterone or estradiol treatment. Results Both hormone treatments caused a significant shift in the sub-set of genes expressed (25% of the transcriptome altered by more than 2-fold. Overall, estradiol treatment resulted in the down-regulation of 151 genes, including those associated with lipid and nucleotide metabolism. Of particular interest was the up-regulation in estradiol-supplemented cultures of six genes (omcB, trpB, cydA, cydB, pyk and yggV, which suggest a stress response similar to that reported previously in other models of chlamydial persistence. We also observed morphological changes consistent with a persistence response. By comparison, progesterone supplementation resulted in a general up-regulation of an energy utilising response. Conclusion Our data shows for the first time, that the treatment of chlamydial host cells with key reproductive hormones such as progesterone and estradiol, results in significantly altered chlamydial gene expression profiles. It is likely that these chlamydial expression patterns are survival responses, evolved by the pathogen to enable it to overcome the host's innate immune response. The induction of chlamydial persistence is probably a key component of this survival response.

  17. Randomized Controlled Trial of Low-Dose Estradiol and the SNRI Venlafaxine for Vasomotor Symptoms

    Science.gov (United States)

    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

  18. Effect of lead exposure on serum estradiol and certain haematological indices in female rats

    International Nuclear Information System (INIS)

    Abd El-Moneim, A.E.; El-Abiad, N.M.

    1996-01-01

    In this study, graded dosages of lead acetate (Pb Ac) 0,100,200 and 500 mg/liter were dissolved in tap water and offered freely to four groups of female rats to show the effect of lead (Pb) ingestion on serum estradiol (E 2 ) concentration. Changes in body weight (B.wt), relative liver, kidney, spleen weights were recorded. Blood lead content, red blood cells (RBC), white blood cells (WBC) counts, blood hemoglobin (Hb) content and hematocrit values were measured as indicators of elevated Pb exposure. After three months of treatment, as compared to control animals, all lead-treated rats showed a significant decrease in B.wt and significant increase in relative weights of liver and spleen. Kidney relative weight did not indicate significant differences between rats given tap water with or without Pb Ac. Blood Pb content and WBC count were higher and RBC count was lower in rats given leaded water. Both Hb and Hct values were insignificantly reduced in lead exposed rats. The treatment with 500 mg Pb Ac/liter of drinking water resulted in significant fall of serum E 2 to reach about half its value control group at end of the experiment, while, the decrease in serum E 2 was less significant in the group received 200 mg Pb Ac/liter tap water. 2 tabs

  19. Sexual Function in Women on Estradiol or Venlafaxine for Hot Flushes: A Randomized Controlled Trial

    Science.gov (United States)

    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

  20. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol

    International Nuclear Information System (INIS)

    Banu, Sakhila K.; Stanley, Jone A.; Sivakumar, Kirthiram K.; Arosh, Joe A.; Burghardt, Robert C.

    2016-01-01

    Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in > 50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50 ppm potassium dichromate) from postpartum days 1–21 through drinking water with or without RVT (10 mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E 2 ) biosynthesis and enhancing metabolic clearance of E 2 , increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E 2 levels by inhibiting hydroxylation, glucuronidation and sulphation of E 2 . This is the first study to report the protective effects of RVT against any toxicant in the ovary. - Highlights: • Resveratrol (RVT) protects the ovary against CrVI-toxicity. • RVT mitigated CrVI-induced apoptosis and follicle atresia. • RVT restored estradiol level against CrVI-toxicity. • RVT inhibited metabolic clearance of estradiol in the

  1. Resveratrol protects the ovary against chromium-toxicity by enhancing endogenous antioxidant enzymes and inhibiting metabolic clearance of estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Banu, Sakhila K., E-mail: skbanu@cvm.tamu.edu; Stanley, Jone A.; Sivakumar, Kirthiram K.; Arosh, Joe A.; Burghardt, Robert C.

    2016-07-15

    Resveratrol (RVT), a polyphenolic component in grapes and red wine, has been known for its cytoprotective actions against several diseases. However, beneficial effects of RVT against early exposure to endocrine disrupting chemicals (EDCs) have not been understood. EDCs are linked to several ovarian diseases such as premature ovarian failure, polycystic ovary syndrome, early menopause and infertility in women. Hexavalent chromium (CrVI) is a heavy metal EDC, and widely used in > 50 industries. Environmental contamination with CrVI in the US is rapidly increasing, predisposing the human to several illnesses including cancers and still birth. Our lab has been involved in determining the molecular mechanism of CrVI-induced female infertility and intervention strategies to mitigate CrVI effects. Lactating mother rats were exposed to CrVI (50 ppm potassium dichromate) from postpartum days 1–21 through drinking water with or without RVT (10 mg/kg body wt., through oral gavage daily). During this time, F1 females received respective treatments through mother's milk. On postnatal day (PND) 25, blood and the ovary, kidney and liver were collected from the F1 females for analyses. CrVI increased atresia of follicles by increasing cytochrome C and cleaved caspase-3; decreasing antiapoptotic proteins; decreasing estradiol (E{sub 2}) biosynthesis and enhancing metabolic clearance of E{sub 2}, increasing oxidative stress and decreasing endogenous antioxidants. RVT mitigated the effects of CrVI by upregulating cell survival proteins and AOXs; and restored E{sub 2} levels by inhibiting hydroxylation, glucuronidation and sulphation of E{sub 2}. This is the first study to report the protective effects of RVT against any toxicant in the ovary. - Highlights: • Resveratrol (RVT) protects the ovary against CrVI-toxicity. • RVT mitigated CrVI-induced apoptosis and follicle atresia. • RVT restored estradiol level against CrVI-toxicity. • RVT inhibited metabolic clearance of

  2. 17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

    2016-05-13

    17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

  3. Vocal Acoustic and Auditory-Perceptual Characteristics During Fluctuations in Estradiol Levels During the Menstrual Cycle: A Longitudinal Study.

    Science.gov (United States)

    Arruda, Polyanna; Diniz da Rosa, Marine Raquel; Almeida, Larissa Nadjara Alves; de Araujo Pernambuco, Leandro; Almeida, Anna Alice

    2018-03-07

    Estradiol production varies cyclically, changes in levels are hypothesized to affect the voice. The main objective of this study was to investigate vocal acoustic and auditory-perceptual characteristics during fluctuations in the levels of the hormone estradiol during the menstrual cycle. A total of 44 volunteers aged between 18 and 45 were selected. Of these, 27 women with regular menstrual cycles comprised the test group (TG) and 17 combined oral contraceptive users comprised the control group (CG). The study was performed in two phases. In phase 1, anamnesis was performed. Subsequently, the TG underwent blood sample collection for measurement of estradiol levels and voice recording for later acoustic and auditory-perceptual analysis. The CG underwent only voice recording. Phase 2 involved the same measurements as phase 1 for each group. Variables were evaluated using descriptive and inferential analysis to compare groups and phases and to determine relationships between variables. Voice changes were found during the menstrual cycle, and such changes were determined to be related to variations in estradiol levels. Impaired voice quality was observed to be associated with decreased levels of estradiol. The CG did not demonstrate significant vocal changes during phases 1 and 2. The TG showed significant increases in vocal parameters of roughness, tension, and instability during phase 2 (the period of low estradiol levels) when compared with the CG. Low estradiol levels were also found to be negatively correlated with the parameters of tension, instability, and jitter and positively correlated with fundamental voice frequency. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  4. 17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

    Science.gov (United States)

    Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M

    2016-12-01

    The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive

  5. 17-β estradiol and testosterone mineralization and incorporation into organic matter in broiler litter-amended soils.

    Science.gov (United States)

    Durant, Michelle B; Hartel, Peter G; Cabrera, Miguel L; Vencill, William K

    2012-01-01

    The presence of the hormones estradiol and testosterone in the environment is of concern because they adversely affect vertebrate sexual characteristics. Land spreading broiler litter introduces these hormones into the environment. We conducted two studies. The first study determined the mineralization of C-labeled estradiol and testosterone at three water potentials and three temperatures in four broiler litter-amended soils. With a few exceptions, the mineralization of each hormone either stayed the same or increased with increasing water content (both hormones) and increasing (estradiol) or decreasing (testosterone) temperature. Mineralization was dependent on soil type. The second study determined the incorporation of C-labeled estradiol and testosterone into (i) three soil organic matter (SOM) fractions (fulvic acid, humic acid, and humin) at two water potentials, two temperatures, and one sampling time, and (ii) at one water potential, one temperature, and seven sampling times. As time increased, higher temperature and water potential decreased percentages of C estradiol and testosterone in water- and acetone-soluble fractions and increased percentages in SOM fractions. However, the distribution of the two hormones in SOM fractions differed. For estradiol, higher temperature and water potential increased the percentage in all three SOM fractions. For testosterone, higher temperature and water potential increased the percentage of hormone in fulvic acid and humin. Although the mineralization studies suggest the potential for these hormones to still have environmental effects, the incorporation of the two hormones into SOM suggest that land spreading these hormones may actually be less of an environmental concern. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  6. Effect of Estradiol Prescribed during Luteal Phase of Art Cycles and Pregnancy Outcome

    Directory of Open Access Journals (Sweden)

    M Karimzadeh

    2007-01-01

    Full Text Available Introduction: Implantation is one of the most important steps in ART cycles and it depends upon embryo and endometrial reception. Different protocols have been suggested for getting better endometrium. It seems estrogen increases the endometrial reception and pregnancy rate by inducing changes in the hormonal status. The aim of this study was to evaluate the effect of estradiol(E2 on luteal phase support and pregnancy rate in ART cycles Methods: This prospective randomized study was done in Yazd at the IVF center from March until December, 2002. 68 patients who had undergone IVF or ICSI were enrolled in the study. Exclusion criteria was age>40, endometriosis and ovarian hyper stimulation syndrome. Induction ovulation protocol was long suppression with GnRH analogues.After embryo transfer, patients were divided in two groups randomly. Both groups received 100mg progesterone IM daily from the transfer day. Estradiol valerate 2 mg/day was added from the 7th transfer day to progesterone in Group I and continued if the BhCG became positive. Abortion and malformations were measured in all patients. Data analyzed with SPSS 11.0 and P value <0.05 considered statistically significant. Results: Pregnancy rate in the 34 patients of estradiol group (group I was 26.5%which was significantly higher than 11.8 %( 4 cases in the other group (Pvalue=0.034. Abortion rate was higher in estradiol group (3 cases, but there was no abortion in the progesterone group(P=0.119. 2 cases of major fetal malformations were observed in E2 supplementation group (P=0.246 . Conclusions: E2 suplementation to progesterone in the luteal phase of ART cycles, especially in the long GnRH analogues causes higher endometrial receptivity and pregnancy rate.

  7. 17β-Estradiol reduces nitric oxide production in the Guinea pig cochlea.

    Science.gov (United States)

    Heinrich, U-R; Brieger, J; Striedter, C; Fischer, I; Schmidtmann, I; Li, H; Mann, W J; Helling, K

    2013-11-01

    Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17β-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17β-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17β-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17β-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17β-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

    Science.gov (United States)

    Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

    2006-03-01

    Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

  9. Effect of Estradiol-17β Injection on Gonad Development of White Shrimp (Litopenaeus vannamei

    Directory of Open Access Journals (Sweden)

    . Tarsim

    2007-01-01

    Full Text Available The methods for hormonal control of shrimp reproduction are very limited, and only eyestalk ablation is used to induce ovarian development and spawning in shrimp farming. The occurrence of vertebrate-type steroid hormones in crustaceans have been reported, however, their physiological role are not sufficiently understood. The present study analyzed the effect of estradiol-17β injection on gonad development of white shrimp, Litopenaeus vannamei. The estradiol-17β dose 0.10 μg/g body weight were used. The treatments consisted of control, single injection (day 0 and double injection (day 0 and 6. The females broodstock were cultured for 12 days. The result showed that estradiol-17β had positive effect on gonad development. The gonado somatic index (GSI and oocytes diameter in treatment larger than the control. Double injection had highest effect with ∆GSI and oocytes diameter was 0.453  and 23.97 µm, respectively. The only oocytes previtelogenesis was found in gonad. It indicated that estradiol-17β important to induce endogenous vitellogenesis. Gonad development probably affected by gonad inhibiting hormone in the eyestalk. It was inhibited oocyte maturation. The polypeptide sub unit was observed in vitellin of ovari by SDS-PAGE. The molecular weights of approximately 95, 98, 109 and two units higher than 118 kDa of protein marker. Keywords: Gonad, estradiol-17β, oocyte, Litopenaeus vannamei   ABSTRAK Teknologi reproduksi dalam pembenihan udang belum mengalami perkembangan yang signifikan.  Pada umumnya untuk mempercepat kematangan gonad induk udang digunakan teknik ablasi. Mekanisme dan peranan hormon pada proses reproduksi udang belum banyak diketahui. Keberadaan hormon steroid pada krustase telah dikemukaan oleh beberapa peneliti, tetapi peranannya belum banyak diketahui.  Pada penelitian ini dikaji pengaruh penyuntikan hormon estradiol-17β pada perkembangan gonad induk udang putih (Litopenaeus vannamei.  Penelitian ini

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

    Directory of Open Access Journals (Sweden)

    Marcello Maggio

    2015-08-01

    Full Text Available 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

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

    Science.gov (United States)

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

    2015-08-05

    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. 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. 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 = 0.0009), and E2 persisted whereas the

  12. Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

    Science.gov (United States)

    Havermans, Remco C; Jansen, Anita T M

    2003-07-01

    Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

  13. The Role of Hippocampal Estradiol Receptor-α in a Perimenopausal Affective Disorders-Like Rat Model and Attenuating of Anxiety by Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Xun Wang

    2016-01-01

    Full Text Available Hormone replacement therapy is the principal treatment for perimenopausal affective disorders which can cause severe side effects. The present study compared the effects of electroacupuncture (EA and estradiol treatment on perimenopausal affective disorders at the behavioral and cellular levels. In this randomized experimental in vivo study, adult female rats were divided into intact, ovariectomy, chronic unpredictable stress (CUS, and ovariectomy and CUS combination groups. After week 6, all groups were subdivided to three subgroups of control, EA, and estradiol treatment. The behavioral parameters in the open field and the elevated plus maze tests were assessed before and after treatments. Alterations of serum steroid hormones and changes of estradiol receptor-α (ER-α immunofluorescence neurons in the hippocampus sections were evaluated. EA treatment caused more antianxiety effects than estradiol treatment in CUS group (P<0.05. Notably, estradiol and EA treatments had better significant behavioral effects when the models were not estrogen-deficient. Importantly, within each group, compared to the control group, the numbers of ER-α-positive neurons were significantly larger in EA subgroups. Therefore, EA had antianxiety effects on perimenopausal affective disorders caused by CUS but not by estrogen deficiency and upregulation of hippocampus ER-α neurons may contribute to its mechanism of action.

  14. Low dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene

    DEFF Research Database (Denmark)

    Nielsen, Mads; Raundahl, Jakob; Pettersen, Paola

    2009-01-01

    Objective: To investigate whether transdermal low dose estradiol treatment induces changes in mammographic density or heterogeneity compared to raloxifene. Secondarily, if these changes relate to changes in bone formation/resorption markers, and if these findings indicate elevation of breast canc...

  15. Estrogen and progesterone receptor assay using I-125 estradiol and H-3 promegestone as ligands: Results in female mammary carcinoma

    International Nuclear Information System (INIS)

    Glaubitt, D.; Hienz, H.A.; Bettges, G.; Carmanns, B.; Lichtenberg, T.; Akademisches Lehrkrankenhaus, Krefeld

    1984-01-01

    The determination of estrogen and progesterone receptors in the cytosol of carcinoma of the female breast has predictive value as to the success treatment of the patient. An improved estrogen and progesterone receptor assay using 1-125 labelled estradiol and a H-3 tagged synthetic gestagen (H-3 promegestone) as ligands proved to be highly praticable, especially time-saving. (orig.)

  16. Evaluation of Serum Testosterone and Estradiol Levels in Positive Hepatitis C Virus in Liver Insufficiency Patients

    International Nuclear Information System (INIS)

    Ibrahim, N.A.; Fekry, A.E.; Abdelgawad, M.R.; Ali, S.E.; Ali, W.I.

    2011-01-01

    Twenty-two positive HCV male patients with liver insufficiency were classified into 4 different groups: steatohepatitis (16), chronic hepatitis (17), cirrhosis (12) and HCC (7), beside 24 healthy subjects served as control to evaluate serum sex hormones testosterone and estradiol, and trace elements Zn and Cu in different liver insufficiency positive male HCV patients. The results of the present study showed significant decrease (P<0.05 and P<0.001) in serum testosterone level and testosterone/estradiol ratio in patients with different liver states when compared with control. The serum testosterone level was significantly decreased (P<0.05 and P<0.001)) in patients with cirrhosis than other patient groups. On the other hand, there was significant increase (P<0.01 and P<0.001) in serum estradiol level in all groups as compared with control. Serum testosterone/estradiol ratio was less affected and significantly increased (P<0.01 and P<0.001) in patients with steatohepatitis than other patient groups. Also, the results showed significant decrease (P<0.001) in serum Zn level in patients when compared with control and significant decrease (P<0.05) in cirrhosis as compared with HCC. Also, significant increase (P<0.01 and P<0.001) was determined in serum Cu level and Cu/Zn ratio in different groups as compared with control group. Serum Cu level was significantly decreased (P<0.05) in chronic hepatitis as compared with cirrhosis and HCC. On the other hand, serum Cu/Zn ratio was significantly increased in cirrhosis as compared with steatohepatitis and chronic hepatitis groups (P<0.05 and P<0.01). The patient groups can be detected by using either zinc, copper, testosterone or estradiol contents in serum. It could be concluded that the levels of serum sex hormones (testosterone and estradiol) and trace elements (Zn and Cu and their ratio) may used as markers for liver insufficiency and liver complications, especially in the early diagnosis and prediction of HCC in patients

  17. Regulation of 11 beta-hydroxysteroid dehydrogenase enzymes in the rat kidney by estradiol.

    Science.gov (United States)

    Gomez-Sanchez, Elise P; Ganjam, Venkataseshu; Chen, Yuan Jian; Liu, Ying; Zhou, Ming Yi; Toroslu, Cigdem; Romero, Damian G; Hughson, Michael D; de Rodriguez, Angela; Gomez-Sanchez, Celso E

    2003-08-01

    The 11beta-hydroxysteroid dehydrogenase (11betaHSD) type 1 (11betaHSD1) enzyme is an NADP+-dependent oxidoreductase, usually reductase, of major glucocorticoids. The NAD+-dependent type 2 (11betaHSD2) enzyme is an oxidase that inactivates cortisol and corticosterone, conferring extrinsic specificity of the mineralocorticoid receptor for aldosterone. We reported that addition of a reducing agent to renal homogenates results in the monomerization of 11betaHSD2 dimers and a significant increase in NAD+-dependent corticosterone conversion. Estrogenic effects on expression, dimerization, and activity of the kidney 11betaHSD1 and -2 enzymes are described herein. Renal 11betaHSD1 mRNA and protein expressions were decreased to very low levels by estradiol (E2) treatment of both intact and castrated male rats; testosterone had no effect. NADP+-dependent enzymatic activity of renal homogenates from E2-treated rats measured under nonreducing conditions was less than that of homogenates from intact animals. Addition of 10 mM DTT to aliquots from these same homogenates abrogated the difference in NADP+-dependent activity between E2-treated and control rats. In contrast, 11betaHSD2 mRNA and protein expressions were significantly increased by E2 treatment. There was a marked increase in the number of juxtamedullary proximal tubules stained by the antibody against 11betaHSD2 after the administration of E2. Notwithstanding, neither the total corticosterone and 11-dehydrocorticosterone excreted in the urine nor their ratio differed between E2- and vehicle-treated rats. NAD+-dependent enzymatic activity in the absence or presence of a reducing agent demonstrated that the increase in 11betaHSD2 protein was not associated with an increase in in vitro activity unless the dimers were reduced to monomers.

  18. Interaction of estradiol and high density lipoproteins on proliferation of the human breast cancer cell line MCF-7 adapted to grow in serum free conditions

    International Nuclear Information System (INIS)

    Jozan, S.; Faye, J.C.; Tournier, J.F.; Tauber, J.P.; David, J.F.; Bayard, F.

    1985-01-01

    The responsiveness of the human mammary carcinoma cell line MCF-7 to estradiol and tamoxifen treatment has been studied in different culture conditions. Cells from exponentially growing cultures were compared with cells in their initial cycles after replating from confluent cultures (''confluent-log'' cells). It has been observed that estradiol stimulation of tritiated thymidine incorporation decreases with cell density and that ''confluent-log'' cells are estrogen unresponsive for a period of four cell cycles in serum-free medium conditions. On the other hand, growth of cells replated from exponentially growing, as well as from confluent cultures, can be inhibited by tamoxifen or a combined treatment with tamoxifen and the progestin levonorgestrel. This growth inhibitory effect can be rescued by estradiol when cells are replated from exponentially growing cultures. The growth inhibitory effect cannot be rescued by estradiol alone (10(-10) to 10(-8) M) when cells are replated from confluent cultures. In this condition, the addition of steroid depleted serum is necessary to reverse the state of estradiol unresponsiveness. Serum can be replaced by high density lipoproteins but not by low density lipoproteins or lipoprotein deficient serum. The present data show that estradiol and HDL interact in the control of MCF-7 cell proliferation

  19. No Increased Risk of Cancer after Coal Tar Treatment in Patients with Psoriasis or Eczema

    NARCIS (Netherlands)

    Roelofzen, Judith H. J.; Aben, Katja K. H.; Oldenhof, Ursula T. H.; Coenraads, Pieter-Jan; Alkemade, Hans A.; van de Kerkhof, Peter C. M.; van der Valk, Pieter G. M.; Kiemeney, Lambertus A. L. M.

    Coal tar is an effective treatment for psoriasis and eczema, but it contains several carcinogenic compounds. Occupational and animal studies have shown an increased risk of cancer after exposure to coal tar. Many dermatologists have abandoned this treatment for safety reasons, although the risk of

  20. Effect of estradiol on planktonic growth, coaggregation, and biofilm formation of the Prevotella intermedia group bacteria.

    Science.gov (United States)

    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

  1. Effect of estradiol on the expression of angiogenic factors in epithelial ovarian cancer.

    Science.gov (United States)

    Valladares, Macarena; Plaza-Parrochia, Francisca; Lépez, Macarena; López, Daniela; Gabler, Fernando; Gayan, Patricio; Selman, Alberto; Vega, Margarita; Romero, Carmen

    2017-11-01

    Ovarian cancer presents a high angiogenesis (formation of new blood vessels) regulated by pro-angiogenic factors, mainly vascular endothelial growth factor (VEGF) and nerve growth factor (NGF). An association between endogenous levels of estrogen and increased risk of developing ovarian cancer has been reported. Estrogen action is mediated by the binding to its specific receptors (ERα and ERβ), altered ERα/ERβ ratio may constitute a marker of ovarian carcinogenesis progression. To determine the effect of estradiol through ERα on the expression of NGF and VEGF in epithelial ovarian cancer (EOC). Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III). Additionally, ovarian cancer explants were stimulated with NGF (0, 10 and 100 ng/ml) and ERα, ERβ and pERα levels were detected. Finally, human ovarian surface epithelial (HOSE) and epithelial ovarian cancer (A2780) cell lines were stimulated with estradiol, where NGF and VEGF protein levels were evaluated. In tissues, ERs were detected being pERα levels significantly increased in EOC-III samples compared with EOC-I (p<0.05). Additionally, ovarian explants treated with NGF increased pERα levels meanwhile total ERα and ERβ levels did not change. Cell lines stimulated with estradiol revealed an increase of NGF and VEGF protein levels (p<0.05). Estradiol has a positive effect on pro-angiogenic factors such as NGF and VEGF expression in EOC, probably through the activation of ERα; generating a positive loop induced by NGF increasing pERα levels in epithelial ovarian cells.

  2. Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial

    DEFF Research Database (Denmark)

    Cleemann, Line; Holm, Kirsten; Kobbernagel, Hanne

    2017-01-01

    OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS) with an increased risk of fractures, and body composition is characterized by increased body fat and decreased lean body mass. To evaluate the effect of two different doses of oral 17ß-estradiol in young TS women on bone...

  3. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    Directory of Open Access Journals (Sweden)

    Jensen JT

    2013-11-01

    Full Text Available Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®, estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™, and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®, have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort

  4. Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca^{2+} efflux in rat caudate nucleus and brain stem

    OpenAIRE

    PETROVIC, SNJEZANA; MILOSEVIC, MAJA; RISTIC-MEDIC, DANIJELA; VELICKOVIC, NATASA; DRAKULIC, DUNJA; GRKOVIC, IVANA; HORVAT, ANICA

    2015-01-01

    Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca^{2+} efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl_2 (0.6?0.75 µCi ^45CaCl_{2}) was used for Ca^{2+} transport monitoring. The results revealed that in the presence of ER antagonist 7\\alpha,17ß-[9[(4,4,5,5,5-...

  5. Quantifying the Role of Circulating Unconjugated Estradiol in Mediating the Body Mass Index-Breast Cancer Association.

    Science.gov (United States)

    Schairer, Catherine; Fuhrman, Barbara J; Boyd-Morin, Jennifer; Genkinger, Jeanine M; Gail, Mitchell H; Hoover, Robert N; Ziegler, Regina G

    2016-01-01

    Higher body mass index (BMI) and circulating estrogen levels each increase postmenopausal breast cancer risk, particularly estrogen receptor-positive (ER(+)) tumors. Higher BMI also increases estrogen production. We estimated the proportion of the BMI-ER(+) breast cancer association mediated through estrogen in a case-control study nested within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Participants included 143 women with invasive ER(+) breast cancer and 268 matched controls, all postmenopausal and never having used hormone therapy at baseline. We used liquid chromatography-tandem mass spectrometry to measure 15 estrogens and estrogen metabolites in baseline serum. We calculated BMI from self-reported height and weight at baseline. We estimated the mediating effect of unconjugated estradiol on the BMI-ER(+) breast cancer association using Aalen additive hazards and Cox regression models. All estrogens and estrogen metabolites were statistically significantly correlated with BMI, with unconjugated estradiol most strongly correlated [Pearson correlation (r) = 0.45]. Approximately 7% to 10% of the effect of overweight, 12% to 15% of the effect of obesity, and 19% to 20% of the effect of a 5 kg/m(2) BMI increase on ER(+) breast cancer risk was mediated through unconjugated estradiol. The BMI-breast cancer association, once adjusted for unconjugated estradiol, was not modified by further adjustment for two metabolic ratios statistically significantly associated with both breast cancer and BMI. Circulating unconjugated estradiol levels partially mediate the BMI-breast cancer association, but other potentially important estrogen mediators (e.g., bioavailable estradiol) were not evaluated. Further research is required to identify mechanisms underlying the BMI-breast cancer association. ©2015 American Association for Cancer Research.

  6. Development and evaluation of polymer nanoparticles for oral delivery of estradiol to rat brain in a model of Alzheimer's pathology.

    Science.gov (United States)

    Mittal, G; Carswell, H; Brett, R; Currie, S; Kumar, M N V Ravi

    2011-03-10

    The purpose of this study was to develop tween 80 (T-80) coated polylactide-co-glycolide (PLGA) nanoparticles that can deliver estradiol to the brain upon oral administration. Estradiol containing nanoparticles were made by a single emulsion technique and T-80 coating was achieved by incubating the re-constituted nanoparticles at different concentrations of T-80. The process of T-80 coating on the nanoparticles was optimized and the pharmacokinetics of estradiol nanoparticles was studied as a function of T-80 coating. The nanoparticles were then evaluated in an ovariectomized (OVX) rat model of Alzheimer's disease (AD) that mimics the postmenopausal conditions. The nanoparticles bound T-80 were found to proportionally increase from 9.72 ± 1.07 mg to 63.84 ± 3.59 mg with an increase in the initial concentration T-80 from 1% to 5% and were stable in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Orally administered T-80 coated nanoparticles resulted in significantly higher brain estradiol levels after 24h (1.969 ± 0.197 ng/g tissue) as compared to uncoated ones (1.105 ± 0.136 ng/g tissue) at a dose of 0.2mg/rat, suggesting a significant role of surface coating. Moreover, these brain estradiol levels were almost similar to those obtained after administration of the same dose of drug suspension via 100% bioavailable intramuscular route (2.123 ± 0.370 ng/g tissue), indicating the increased fraction of bioavailable drug reaching the brain when administered orally. Also, the nanoparticle treated group was successful in preventing the expression of amyloid beta-42 (Aβ42) immunoreactivity in the hippocampus region of brain. Together, the results indicate the potential of nanoparticles for oral delivery of estradiol to brain. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Unraveling estradiol metabolism and involvement in the reproductive cycle of non-vertebrate animals: The sea urchin model.

    Science.gov (United States)

    Silvia, Mercurio; Paolo, Tremolada; Nobile, Maria; Denise, Fernandes; Cinta, Porte; Michela, Sugni

    2015-12-01

    Estradiol (E2) is a well-known hormone in vertebrates whereas in invertebrates its unambiguous presence was verified only in some species. Weather this presence is also associated to similarly conserved roles in animal phylogeny is similarly uncertain. Due to their phylogenetic position, echinoderms represent ideal experimental models to provide evolutionary insights into estrogen appearance and function. Therefore, in this research, we investigated if E2 is truly present and has a role in the reproductive biology of the sea urchin Paracentrotus lividus. Presence of 17β estradiol in body fluids was confirmed by liquid chromatography-mass spectrometry. By immunological methods (RIA) we evaluated the physiological circulating E2 levels of adult specimens and, on the basis of these, we directly administered E2 to study its metabolism and its putative effects on gonad development at physiological doses. Although different E2 tested concentrations, a correspondent dose-dependent increase of hormone levels was not found in both body fluids and gonads, suggesting the presence of potent homeostatic/detoxification mechanisms. These latter do not involve enzymes such as aromatase-like, sulfotransferase-like and acyltransferase-like, whose activities were not affected by E2 administration. Despite the increase of endogenous E2, the treatment did not induce significant variations in none of the considered reproductive parameters. Overall, this research (1) provides definitive evidence of E2 presence in sea urchin tissues and (2) demonstrate that, differently from vertebrates and starfish, E2 does not play a key role in sea urchins reproductive processes. Intra-phylum differences suggest the existence of class-specific hormonal mechanisms and highlight the risk of Phylum generalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The flinders sensitive line rats, a genetic model of depression, show abnormal serotonin receptor mRNA expression in the brain that is reversed by 17beta-estradiol.

    Science.gov (United States)

    Osterlund, M K; Overstreet, D H; Hurd, Y L

    1999-12-10

    The possible link between estrogen and serotonin (5-HT) in depression was investigated using a genetic animal model of depression, the Flinders Sensitive Line (FSL) rats, in comparison to control Flinders Resistant Line rats. The mRNA levels of the estrogen receptor (ER) alpha and beta subtypes and the 5-HT(1A) and 5-HT(2A) receptors were analyzed in several limbic-related areas of ovariectomized FSL and FRL rats treated with 17beta-estradiol (0.15 microg/g) or vehicle. The FSL animals were shown to express significantly lower levels of the 5-HT(2A) receptor transcripts in the perirhinal cortex, piriform cortex, and medial anterodorsal amygdala and higher levels in the CA 2-3 region of the hippocampus. The only significant difference between the rat lines in ER mRNA expression was found in the medial posterodorsal amygdala, where the FSL rats showed lower ERalpha expression levels. Overall, estradiol treatment increased 5-HT(2A) and decreased 5-HT(1A) receptor mRNA levels in several of the examined regions of both lines. Thus, in many areas, estradiol was found to regulate the 5-HT receptor mRNA expression in the opposite direction to the alterations found in the FSL rats. These findings further support the implication of 5-HT receptors, in particular the 5-HT(2A) subtype, in the etiology of affective disorders. Moreover, the ability of estradiol to regulate the expression of the 5-HT(1A) and 5-HT(2A) receptor genes might account for the reported influence of gonadal hormones in mood and depression.

  9. Treatment of HeLa cells with Giloe (Tinospora cordifolia meirs) increases the radiosensitivity by increasing DNA damage

    International Nuclear Information System (INIS)

    Varma, Hari Krishna; Jagetia, Ganesh Chandra; Nayak, Vijayashree

    2014-01-01

    Radiotherapy is an important treatment modality and screening of phytoceuticals may enhance the clinical outcome of radiotherapy, therefore radiosensitizing activity of various guduchi (Tinospora cordifolia) extracts was studied in HeLa cells. Chromosomal aberrations were scored in HeLa cells treated with 10 μg/ml of aqueous, methanol, or methylene chloride guduchi extracts or doxorubicin before exposure to 0, 0.5, 1, 2 or 3 Gy of γ-radiation at 12, 24, 36 or 48 h post-irradiation. Irradiation of HeLa cells caused a dose dependent rise in the chromatid breaks, chromosome breaks, dicentric, centric rings, acentric fragments and total aberrations at all post-irradiation times and the dose response was linear quadratic for all types of aberrations scored. Chromatid breaks increased up to 12 h post-irradiation and declined steadily up to 48 h post-irradiation, whereas chromosome breaks, dicentric, acentric fragments and total aberrations elevated up to 24 h post-irradiation and declined thereafter. However, centric rings continued to rise steadily up to 48 h post-irradiation. Treatment of HeLa cells with aqueous, methanol or methylene chloride guduchi extract or doxorubicin before irradiation significantly enhanced various types of chromosomal aberrations and a maximum rise in the chromosome aberrations was observed in the HeLa cells treated with methylene chloride extract before irradiation when compared to other groups. Various guduchi extracts enhanced the effect of radiation in HeLa cells by increasing the molecular damage to cellular genome and their effect was similar to or even greater than doxorubicin (positive control) pretreatment, depending on the type of guduchi extract used. (author)

  10. Black cohosh inhibits 17β-estradiol-induced cell proliferation of endometrial adenocarcinoma cells.

    Science.gov (United States)

    Park, So Yun; Kim, Hee Ja; Lee, Sa Ra; Choi, Youn-Hee; Jeong, Kyungah; Chung, Hyewon

    2016-10-01

    This study was conducted to investigate the effect of black cohosh (BC) extract on the proliferation and apoptosis of Ishikawa cells. Ishikawa human endometrial adenocarcinoma cells were treated with or without BC (1, 5, 10 and 25 μM) and cell proliferation and cytotoxicity were measured by CCK-8 assays and flow cytometry analysis. Additionally, Ishikawa cells were treated with 17β-estradiol (E2), E2 + progesterone and E2 + BC (5 and 10 μM) and the effect of BC and progesterone on E2-induced cell proliferation was analyzed. BC decreased the proliferation of Ishikawa cells at a dose-dependent rate compared with the control group (p < 0.05). The proliferation of Ishikawa cells increased in the presence of E2, whereas the subsequent addition of progesterone or BC decreased proliferation to the level of the control group (p < 0.05). The inhibitory effect of BC on E2-induced cell proliferation was greater than the inhibitory effect of progesterone. In conclusion, BC induces apoptosis in Ishikawa cells and suppresses E2-induced cell proliferation in Ishikawa cells. BC could be considered a candidate co-treatment agent of estrogen-dependent tumors, especially those involving endometrial cells.

  11. Blocking estradiol synthesis affects memory for songs in auditory forebrain of male zebra finches.

    Science.gov (United States)

    Yoder, Kathleen M; Lu, Kai; Vicario, David S

    2012-11-14

    Estradiol (E2) has recently been shown to modulate sensory processing in an auditory area of the songbird forebrain, the caudomedial nidopallium (NCM). When a bird hears conspecific song, E2 increases locally in NCM, where neurons express both the aromatase enzyme that synthesizes E2 from precursors and estrogen receptors. Auditory responses in NCM show a form of neuronal memory: repeated playback of the unique learned vocalizations of conspecific individuals induces long-lasting stimulus-specific adaptation of neural responses to each vocalization. To test the role of E2 in this auditory memory, we treated adult male zebra finches (n=16) with either the aromatase inhibitor fadrozole (FAD) or saline for 8 days. We then exposed them to 'training' songs and, 6 h later, recorded multiunit auditory responses with an array of 16 microelectrodes in NCM. Adaptation rates (a measure of stimulus-specific adaptation) to playbacks of training and novel songs were computed, using established methods, to provide a measure of neuronal memory. Recordings from the FAD-treated birds showed a significantly reduced memory for the training songs compared with saline-treated controls, whereas auditory processing for novel songs did not differ between treatment groups. In addition, FAD did not change the response bias in favor of conspecific over heterospecific song stimuli. Our results show that E2 depletion affects the neuronal memory for vocalizations in songbird NCM, and suggest that E2 plays a necessary role in auditory processing and memory for communication signals.

  12. Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields)

    International Nuclear Information System (INIS)

    Kirson, Eilon D; Goldsher, Dorit; Wasserman, Yoram; Palti, Yoram; Schneiderman, Rosa S; Dbalý, Vladimír; Tovaryš, František; Vymazal, Josef; Itzhaki, Aviran; Mordechovich, Daniel; Gurvich, Zoya; Shmueli, Esther

    2009-01-01

    The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial. Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients. The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index ≤ 1). The sensitivity to chemotherapeutic treatment was increased by 1–3 orders of magnitude by adjuvant TTFields therapy (dose reduction indexes 23 – 1316). Similar findings were seen in an animal tumor model. Finally, 20 GBM patients were treated with TTFields for a median duration of 1 year. No TTFields related systemic toxicity was observed in any of these patients, nor was an increase in Temozolomide toxicity seen in patients receiving combined treatment. In newly diagnosed GBM patients, combining TTFields with Temozolomide treatment led to a progression free survival of 155 weeks and overall survival of 39+ months. These results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity

  13. Physical activity, heart rate, metabolic profile, and estradiol in premenopausal women

    DEFF Research Database (Denmark)

    Emaus, Aina; Veierød, Marit B; Furberg, Anne-Sofie

    2008-01-01

    PURPOSE: To study whether physical inactive women with a tendency to develop metabolic syndrome have high levels of 17beta-estradiol (E2) of importance for breast cancer risk. METHODS: Two hundred and four healthy women of reproductive age were assessed for self-reported leisure-time physical...... to important biologic mechanisms operating between a sedentary lifestyle and an increased breast cancer risk....

  14. A PTH/PTHrP receptor antagonist blocks the hypercalcemic response to estradiol-17b

    OpenAIRE

    Fuentes, J.; Guerreiro, P. M.; Modesto, Teresa; Rotllant, J.; Canario, Adelino V. M.; Power, Deborah

    2007-01-01

    Estradiol (E2) increases circulating calcium and phosphate levels in fish, thus acting as a hypercalcemic and hyperphosphatemic factor during periods of high calcium requirements, such as during vitellogenesis. Since parathyroid hormone (PTH)-related protein (PTHrP) has been shown to be calciotropic in fish, we hypothesized that the two hormones could be mediating the same process. Sea bream (Sparus auratus) juveniles receiving a single intraperitoneal injection of piscin...

  15. Estradiol pretreatment ameliorates impaired synaptic plasticity at synapses of insulted CA1 neurons after transient global ischemia

    Science.gov (United States)

    Takeuchi, Koichi; Yang, Yupeng; Takayasu, Yukihiro; Gertner, Michael; Hwang, Jee-Yeon; Aromolaran, Kelly; Bennett, Michael V.L.; Zukin, R. Suzanne

    2015-01-01

    Global ischemia in humans or induced experimentally in animals causes selective and delayed neuronal death in pyramidal neurons of the hippocampal CA1. The ovarian hormone estradiol administered before or immediately after insult affords histological protection in experimental models of focal and global ischemia and ameliorates the cognitive deficits associated with ischemic cell death. However, the impact of estradiol on the functional integrity of Schaffer collateral to CA1 (Sch-CA1) pyramidal cell synapses following global ischemia is not clear. Here we show that long term estradiol treatment initiated 14 days prior to global ischemia in ovariectomized female rats acts via the IGF-1 receptor to protect the functional integrity of CA1 neurons. Global ischemia impairs basal synaptic transmission, assessed by the input/output relation at Sch-CA1 synapses, and NMDA receptor (NMDAR)-dependent long term potentiation (LTP), assessed at 3 days after surgery. Presynaptic function, assessed by fiber volley and paired pulse facilitation, is unchanged. To our knowledge, our results are the first to demonstrate that estradiol at near physiological concentrations enhances basal excitatory synaptic transmission and ameliorates deficits in LTP at synapses onto CA1 neurons in a clinically-relevant model of global ischemia. Estradiol-induced rescue of LTP requires the IGF-1 receptor, but not the classical estrogen receptors (ER)-α or β. These findings support a model whereby estradiol acts via the IGF-1 receptor to maintain the functional integrity of hippocampal CA1 synapses in the face of global ischemia. PMID:25463028

  16. Effect of dietary estradiol-17β on growth performance, body composition and blood indices in Stellate sturgeon, Acipenser stellatus

    OpenAIRE

    Khara, H.; Meknatkhah, B.; Falahatkar, B.; Ahmadnezhad, M.; Poursaeid, S.

    2014-01-01

    This study was investigated the effects of dietary estradiol-17β (E2) on growth, body composition and blood indices in Acipenser stellatus. Fish (40.9 ± 1.1 g average initial weight; n = 60 per group) were fed with three different diets containing 0 (control), 25 and 50 mg kg-1 dietary estradiol contents to apparent satiation for seven months. The results suggested that growth rate were decreased as the E2 level was increased. No significant difference was observed in condition factor among d...

  17. Treatment with antidepressants and lithium is associated with increased risk of treatment with antiparkinson drugs: a pharmacoepidemiological study

    DEFF Research Database (Denmark)

    Brandt-Christensen, Anne Mette; Kvist, Tine Kajsa; Nielsen, F.M.

    2006-01-01

    OBJECTIVE: To estimate the risk for persons treated with antidepressants or lithium of subsequent treatment with antiparkinson drugs (APD). METHODS: The Danish national prescription database supplied data on all persons who received antidepressants, lithium, or antidiabetics (first control group......). A second control group was included comprising persons from the general population. Outcome was purchase of APD and the study period was 1995 to 1999. RESULTS: In total, 1 293 789 persons were included. The rate ratio of treatment with APD after treatment with antidepressants was 2.27 (95% CI 2.14 to 2.......42) for men and 1.50 (95% CI 1.43 to 1.58) for women. Figures for lithium were almost identical. CONCLUSION: Persons treated with antidepressants or lithium are at increased risk of subsequently treatment with APD, showing an association between anxiety/affective disorder and Parkinson's disease....

  18. Modulation of 17{beta}-estradiol-induced responses in fish by cytochrome P4501A1 inducing compounds

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, M.J.; Hinton, D.E. [Univ. of California, Davis, CA (United States)

    1995-12-31

    Some compounds which induce cytochrome P4501A1 (CYP1A1) are antiestrogenic in mammalian bioassay, and this effect is linked to aryl hydrocarbon (Ah) receptor. Liver of fish synthesizes estrogen-inducible egg yolk precursor protein vitellogenin (Vg) which is critical for oocyte maturation and ovarian development. To determine if Ah receptor-linked endocrine modulation could occur in fish liver, primary cultures of juvenile rainbow trout (Oncorhynchus mykiss) liver cells were co-administered 17{beta}-estradiol and CYP1A1 inducing compounds. Vitellogenin and albumin, estimated by ELISA measurement of concentration in the media 48 hrs after treatment, formed the basis for the test. Cellular CYP1A1 protein content and catalytic activity was estimated by ELISA and ethoxyresorufin-O-deethylase (EROD) activity assays respectively. Equivalent viability (mitochondrial dehydrogenase activity) and secretary functional capacity (albumin synthesis) were estimated and correlated with other results. In descending order, 2,3,4,7,8 pentachlorodibenzofuran (10{sup {minus}12} to 10{sup {minus}8} M) > 2,3,7,8 tetrachlorodibenzo-p-dioxin {approx_equal} 2,3,7,8 tetrachlorodibenzofuran (10{sup {minus}11} to 10{sup {minus}8} M) > {beta}-naphthoflavone (10{sup {minus}7} to 10{sup {minus}6} M) inhibited Vg synthesis in 17{beta}-estradiol treated liver cells. Potency of inhibition directly related to strength as an inducer of CYP1A1 protein. At 10-8 M, PCB congeners 77, 126, and 156 did not inhibit Vg synthesis and induced no or only moderate CYP1A1 protein. At 10-8 M, PCB congener 114, a weak CYP1A1 inducer, potentiated Vg synthesis relative to cells treated with 17{beta}-estradiol alone. This study increases their understanding of the consequences of hepatic CYP1A1 induction, forewarns of reproductive impairment of sexually maturing fishes exposed to CYP1A1 inducing compounds and argues for further, more detailed in vivo investigation.

  19. High estradiol and low progesterone are associated with high assertiveness in women.

    Science.gov (United States)

    Blake, Khandis R; Bastian, Brock; O'Dean, Siobhan M; Denson, Thomas F

    2017-01-01

    Sexual selection theory posits that women are more selective than men are when choosing a mate. This evolutionary theory suggests that "choosiness" increases during the fertile window because the costs and benefits of mate selection are highest when women are likely to conceive. Little research has directly investigated reproductive correlates of choice assertion. To address this gap, in the present research we investigated whether fertility, estradiol, and progesterone influenced general assertiveness in women. We recruited 98 naturally cycling, ethnically diverse women. Using a within-subjects design and ovarian hormone concentrations at fertile and non-fertile menstrual cycle phases, we measured implicit assertiveness and self-reported assertive behavior. To see if fertility-induced high assertiveness was related to increased sexual motivation, we also measured women's implicit sexual availability and interest in buying sexy clothes. Results showed that high estradiol and low progesterone predicted higher assertiveness. Sexual availability increased during periods of high fertility. Low progesterone combined with high estradiol predicted greater interest in buying sexy clothes. Results held when controlling for individual differences in mate value and sociosexual orientation. Our findings support the role of fluctuating ovarian hormones in the expression and magnitude of women's assertiveness. High assertiveness during the fertile window may be a psychological adaptation that promotes mate selectivity and safeguards against indiscriminate mate choice when conception risk is highest. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Efficacy of biorhythmic transdermal combined hormone treatment in relieving climacteric symptoms: a pilot study

    Directory of Open Access Journals (Sweden)

    B Formby

    2011-02-01

    Full Text Available B Formby, F SchmidtThe Rasmus Institute for Medical Research, Program in Reproductive Endocrinology, Santa Barbara, CA, USAObjective: To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system (lipophilic emulsion-type base to relieve climacteric symptoms. The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern.Design: An open, randomized, comparative, between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments. Saliva and serum values of 17β-estradiol and progesterone were quantitated before treatment and after 3 and 6 months. Pharmacokinetic data following transdermal administration of 17β-estradiol (0.3 mg, daily and progesterone (100 mg, daily were calculated from saliva levels using high-performance liquid chromatography analysis.Results: Improvement in climacteric symptoms was reported in 93% of women evaluated before and after 3 and 6 months of treatment. Values of saliva 17β-estradiol increased after 6 months from 0.6 ± 0.3 pg/mL to 14.1 ± 3.3 pg/mL, and the values of serum 17β-estradiol increased from 3.3 ± 2.8 pg/mL to 80.6 ± 21.9 pg/mL. Of responders, 88% characterized symptom relief as complete. No adverse health-related events were attributed to the bioidentical hormone therapy. Time to maximum saliva concentrations (Tmax, in all experimental cases, was observed after 6 hours. Baseline values were reached within 24 hours, indicating a diurnal rhythm of 17β-estradiol seen in normally cyclic women over the 24-hour period, ie, its daily biological rhythm.Conclusion: Percutaneous absorption of 17β-estradiol, as well as the absorption of progesterone, was associated with relief of climacteric symptoms. The cyclical transdermal delivery of combined bioidentical hormones may be

  1. GnRH Neuron Activity and Pituitary Response in Estradiol-Induced vs Proestrous Luteinizing Hormone Surges in Female Mice.

    Science.gov (United States)

    Silveira, Marina A; Burger, Laura L; DeFazio, R Anthony; Wagenmaker, Elizabeth R; Moenter, Suzanne M

    2017-02-01

    During the female reproductive cycle, estradiol exerts negative and positive feedback at both the central level to alter gonadotropin-releasing hormone (GnRH) release and at the pituitary to affect response to GnRH. Many studies of the neurobiologic mechanisms underlying estradiol feedback have been done on ovariectomized, estradiol-replaced (OVX+E) mice. In this model, GnRH neuron activity depends on estradiol and time of day, increasing in estradiol-treated mice in the late afternoon, coincident with a daily luteinizing hormone (LH) surge. Amplitude of this surge appears lower than in proestrous mice, perhaps because other ovarian factors are not replaced. We hypothesized GnRH neuron activity is greater during the proestrous-preovulatory surge than the estradiol-induced surge. GnRH neuron activity was monitored by extracellular recordings from fluorescently tagged GnRH neurons in brain slices in the late afternoon from diestrous, proestrous, and OVX+E mice. Mean GnRH neuron firing rate was low on diestrus; firing rate was similarly increased in proestrous and OVX+E mice. Bursts of action potentials have been associated with hormone release in neuroendocrine systems. Examination of the patterning of action potentials revealed a shift toward longer burst duration in proestrous mice, whereas intervals between spikes were shorter in OVX+E mice. LH response to an early afternoon injection of GnRH was greater in proestrous than diestrous or OVX+E mice. These observations suggest the lower LH surge amplitude observed in the OVX+E model is likely not attributable to altered mean GnRH neuron activity, but because of reduced pituitary sensitivity, subtle shifts in action potential pattern, and/or excitation-secretion coupling in GnRH neurons. Copyright © 2017 by the Endocrine Society.

  2. Estradiol is a critical mediator of macrophage-nerve cross talk in peritoneal endometriosis.

    Science.gov (United States)

    Greaves, Erin; Temp, Julia; Esnal-Zufiurre, Arantza; Mechsner, Sylvia; Horne, Andrew W; Saunders, Philippa T K

    2015-08-01

    Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1-differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

    Science.gov (United States)

    Greaves, Erin; Temp, Julia; Esnal-Zufiurre, Arantza; Mechsner, Sylvia; Horne, Andrew W.; Saunders, Philippa T.K.

    2016-01-01

    Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1–differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. PMID:26073038

  4. The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study.

    Directory of Open Access Journals (Sweden)

    Ching-Chung Liang

    Full Text Available Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO. Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment caused less infarction size than those infused after MCAO (post-treatment on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.

  5. Increasing consumer demand for tobacco treatments: Ten design recommendations for clinicians and healthcare systems.

    Science.gov (United States)

    Woods, Susan Swartz; Jaén, Carlos Roberto

    2010-03-01

    Health professionals play an important role in addressing patient tobacco use in clinical settings. While there is clear evidence that identifying tobacco use and assisting smokers in quitting affects outcomes, challenges to improve routine, clinician-delivered tobacco intervention persist. The Consumer Demand Initiative has identified simple design principles to increase consumers' use of proven tobacco treatments. Applying these design strategies to activities across the healthcare system, we articulate ten recommendations that can be implemented in the context of most clinical systems where most clinicians work. The recommendations are: (1) reframe the definition of success, (2) portray proven treatments as the best care, (3) redesign the 5A's of tobacco intervention, (4) be ready to deliver the right treatment at the right time, (5) move tobacco from the social history to the problem list, (6) use words as therapy and language that makes sense, (7) fit tobacco treatment into clinical team workflows, (8) embed tobacco treatment into health information technology, (9) make every encounter an opportunity to intervene, and (10) end social disparities for tobacco users. Clinical systems need to change to improve tobacco treatment implementation. The consumer- and clinician-centered recommendations provide a roadmap that focuses on increasing clinician performance through greater understanding of the clinician's role in helping tobacco users, highlighting the value of evidence-based tobacco treatments, employing shared decision-making skills, and integrating routine tobacco treatment into clinical system routines. Published by Elsevier Inc.

  6. Increased Mental Health Treatment Financing, Community-Based Organization's Treatment Programs, and Latino-White Children's Financing Disparities.

    Science.gov (United States)

    Snowden, Lonnie R; Wallace, Neal; Cordell, Kate; Graaf, Genevieve

    2017-09-01

    Latino child populations are large and growing, and they present considerable unmet need for mental health treatment. Poverty, lack of health insurance, limited English proficiency, stigma, undocumented status, and inhospitable programming are among many factors that contribute to Latino-White mental health treatment disparities. Lower treatment expenditures serve as an important marker of Latino children's low rates of mental health treatment and limited participation once enrolled in services. We investigated whether total Latino-White expenditure disparities declined when autonomous, county-level mental health plans receive funds free of customary cost-sharing charges, especially when they capitalized on cultural and language-sensitive mental health treatment programs as vehicles to receive and spend treatment funds. Using Whites as benchmark, we considered expenditure pattern disparities favoring Whites over Latinos and, in a smaller number of counties, Latinos over Whites. Using segmented regression for interrupted time series on county level treatment systems observed over 64 quarters, we analyzed Medi-Cal paid claims for per-user total expenditures for mental health services delivered to children and youth (under 18 years of age) during a study period covering July 1, 1991 through June 30, 2007. Settlement-mandated Medicaid's Early Periodic Screening, Diagnosis and Treatment (EPSDT) expenditure increases began in the third quarter of 1995. Terms were introduced to assess immediate and long term inequality reduction as well as the role of culture and language-sensitive community-based programs. Settlement-mandated increased EPSDT treatment funding was associated with more spending on Whites relative to Latinos unless plans arranged for cultural and language-sensitive mental health treatment programs. However, having programs served more to prevent expenditure disparities from growing than to reduce disparities. EPSDT expanded funding increased proportional

  7. Immediate early gene activity-regulated cytoskeletal-associated protein regulates estradiol-induced lordosis behavior in female rats.

    Science.gov (United States)

    Christensen, Amy; Dewing, Phoebe; Micevych, Pavel

    2015-01-01

    Sensory feedback is an important component of any behavior, with each instance influencing subsequent activity. Female sexual receptivity is mediated both by the steroid hormone milieu and interaction with the male. We tested the influence of repeated mating on the level of sexual receptivity in ovariectomized rats treated with estradiol benzoate (EB) once every fourth day to mimic the normal phasic changes of circulating estradiol. Females were divided into two groups: naïve, which were tested for lordosis behavior once, and experienced rats, which were tested for lordosis after each EB injection. To monitor the effect of mating, the number of neurons expressing the immediate early gene activity-regulated cytoskeleton-associated protein (Arc) were counted in the mediobasal hypothalamus. Females were unreceptive following the first EB treatment, but the mating induced Arc expression. In naïve rats, each subsequent EB injection increased the levels of sexual receptivity. This ramping was not observed in experienced rats, which achieved only a moderate level of sexual receptivity. However, experienced females treated with EB and progesterone were maximally receptive and did not have Arc expression. To test whether the expression of Arc attenuated lordosis, Arc antisense oligodeoxynucleotides (asODN) were microinjected into experienced females' arcuate nuclei. Arc expression was attenuated, and the experienced EB-treated females achieved maximal sexual receptivity. These results demonstrate that Arc expression in the hypothalamus might influence future sexual receptivity and provides evidence of learning in the arcuate nucleus. The loss of Arc results in unrestrained sexual receptivity. © 2014 Wiley Periodicals, Inc.

  8. Rapid effects of 17beta-estradiol on epithelial TRPV6 Ca2+ channel in human T84 colonic cells.

    LENUS (Irish Health Repository)

    Irnaten, Mustapha

    2008-11-01

    The control of calcium homeostasis is essential for cell survival and is of crucial importance for several physiological functions. The discovery of the epithelial calcium channel Transient Receptor Potential Vaniloid (TRPV6) in intestine has uncovered important Ca(2+) absorptive pathways involved in the regulation of whole body Ca(2+) homeostasis. The role of steroid hormone 17beta-estradiol (E(2)), in [Ca(2+)](i) regulation involving TRPV6 has been only limited at the protein expression levels in over-expressing heterologous systems. In the present study, using a combination of calcium-imaging, whole-cell patch-clamp techniques and siRNA technology to specifically knockdown TRPV6 protein expression, we were able to (i) show that TRPV6 is natively, rather than exogenously, expressed at mRNA and protein levels in human T84 colonic cells, (ii) characterize functional TRPV6 channels and (iii) demonstrate, for the first time, the rapid effects of E(2) in [Ca(2+)](i) regulation involving directly TRPV6 channels in T84 cells. Treatment with E(2) rapidly (<5 min) enhanced [Ca(2+)](i) and this increase was partially but significantly prevented when cells were pre-treated with ruthenium red and completely abolished in cells treated with siRNA specifically targeting TRPV6 protein expression. These results indicate that when cells are stimulated by E(2), Ca(2+) enters the cell through TRPV6 channels. TRPV6 channels in T84 cells contribute to the Ca(2+) entry\\/signalling pathway that is sensitive to 17beta-estradiol.

  9. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    Energy Technology Data Exchange (ETDEWEB)

    Craig, Zelieann R., E-mail: zelieann@illinois.edu; Hannon, Patrick R., E-mail: phannon2@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2013-11-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P{sub 4}) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P{sub 4}, androstenedione (A), testosterone (T), estrone (E{sub 1}), and 17β-estradiol (E{sub 2}) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E{sub 2}. Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P{sub 4}, A, T, and E{sub 1} that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis

  10. Pregnenolone co-treatment partially restores steroidogenesis, but does not prevent growth inhibition and increased atresia in mouse ovarian antral follicles treated with mono-hydroxy methoxychlor

    International Nuclear Information System (INIS)

    Craig, Zelieann R.; Hannon, Patrick R.; Flaws, Jodi A.

    2013-01-01

    Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide, methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers, and increase follicle death in rodents, not much is known about the ovarian effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse antral follicle growth, increases follicle death, and inhibits steroidogenesis in vitro. Further, previous studies indicate that CYP11A1 expression and production of progesterone (P 4 ) may be the early targets of mono-OH MXC in the steroidogenic pathway. Thus, this study tested whether supplementing pregnenolone, the precursor of progesterone and the substrate for HSD3B, would prevent decreased steroidogenesis, inhibited follicle growth, and increased follicle atresia in mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle (dimethylsulfoxide), mono-OH MXC (10 μg/mL), pregnenolone (1 μg/mL), or mono-OH MXC and pregnenolone together for 96 h. Levels of P 4 , androstenedione (A), testosterone (T), estrone (E 1 ), and 17β-estradiol (E 2 ) in media were determined, and follicles were processed for histological evaluation of atresia. Pregnenolone treatment alone stimulated production of all steroid hormones except E 2 . Mono-OH MXC-treated follicles had decreased sex steroids, but when given pregnenolone, produced levels of P 4 , A, T, and E 1 that were comparable to those in vehicle-treated follicles. Pregnenolone treatment did not prevent growth inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively, these data support the idea that the most upstream effect of mono-OH MXC on steroidogenesis is by reducing the availability of pregnenolone, and that adding pregnenolone may not be sufficient to prevent inhibited follicle growth and survival. - Highlights: • Mono-OH MXC inhibited antral follicle steroidogenesis, growth, and survival. • Pregnenolone partially restored steroidogenesis in mono-OH MXC

  11. Fructose-rich diet and insulin action in female rat heart: Estradiol friend or foe?

    Science.gov (United States)

    Bundalo, Maja; Romic, Snjezana; Tepavcevic, Snezana; Stojiljkovic, Mojca; Stankovic, Aleksandra; Zivkovic, Maja; Koricanac, Goran

    2017-09-15

    Increased intake of fructose in humans and laboratory animals is demonstrated to be a risk factor for development of metabolic disorders (insulin resistance, metabolic syndrome, type 2 diabetes) and cardiovascular diseases. On the other hand, estradiol is emphasized as a cardioprotective agent. The main goal of this review is to summarize recent findings on damaging cardiac effects of fructose-rich diet in females, mostly experimental animals, and to evaluate protective capacity of estradiol. Published results of our and other research groups indicate mostly detrimental effects of fructose-rich diet on cardiac insulin signaling molecules, glucose and fatty acid metabolism, nitric oxide production and ion transport, as well as renin-angiotensin system and inflammation. Some of these processes are involved in cardiac insulin signal transmission, others are regulated by insulin or have an influence on insulin action. Administration of estradiol to ovariectomized female rats, exposed to increased intake of fructose, was mostly beneficial to the heart, but sometimes it was ineffective or even detrimental, depending on the particular processes. We believe that these data, carefully translated to human population, could be useful for clinicians dealing with postmenopausal women susceptible to metabolic diseases and hormone replacement therapy. Copyright © 2017. Published by Elsevier B.V.

  12. Estradiol and luteinizing hormone regulate recognition memory following subchronic phencyclidine: Evidence for hippocampal GABA action.

    Science.gov (United States)

    Riordan, Alexander J; Schaler, Ari W; Fried, Jenny; Paine, Tracie A; Thornton, Janice E

    2018-05-01

    The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP. To modulate E and LH, animals received estradiol capsules or Antide injections. Short-term episodic memory was assessed using the novel object recognition task (NORT). Brain expression of GAD67 was analyzed via western blot, and parvalbumin-containing cells were counted using immunohistochemistry. Some rats received hippocampal infusions of a GABA A agonist, GABA A antagonist, or GAD inhibitor before behavioral testing. We found that PCP reduced hippocampal GAD67 and abolished recognition memory. Antide restored hippocampal GAD67 and rescued recognition memory in PCP-treated animals. Estradiol prevented PCP's amnesic effect in NORT but failed to restore hippocampal GAD67. PCP did not cause significant differences in number of parvalbumin-expressing cells or cortical expression of GAD67. Hippocampal infusions of a GABA A agonist restored recognition memory in PCP-treated rats. Blocking hippocampal GAD or GABA A receptors in ovx animals reproduced recognition memory loss similar to PCP and inhibited estradiol's protection of recognition memory in PCP-treated animals. In summary, decreasing LH or increasing E can lessen short-term episodic memory loss, as measured by novel object recognition, in a PCP model of schizophrenia. Alterations in hippocampal GABA may contribute to both PCP's effects on recognition memory and the hormones' ability to prevent or reverse them. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. PROGESTERONE AND ESTRADIOL PROFILES DURING ESTROUS CYCLE AND GESTATION IN DWARF GOATS (CAPRA HIRCUS

    Directory of Open Access Journals (Sweden)

    S. A. KHANUM, M. HUSSAIN AND R. KAUSAR

    2008-01-01

    Full Text Available Serum progesterone and estradiol profiles during estrous cycle, gestation and parturition in four Dwarf goat females (Capra hircus were monitored. Blood sampling was carried out daily during estrous cycle and on alternate days during gestation till parturition. Observations regarding length of estrous cycle, gestation length, litter size and birth weight of kids were recorded. With the initiation of cyclicity, estradiol attained higher levels (7.7 ± 1.7 pg/ml at estrus phase and dropped down to the lower levels within 3 to 4 days post-estrus. Concomitantly, progesterone started to increase from the mean basal value of 0.1 ± 0.03 ng/ml on day-0 to 3.0 ± 0.9 ng/ml on day-6 of estrous cycle and reached the peak value of 7.7 ± 0.6 ng/ml on day-12. From day-15, a decline was observed in progesterone values till the end of the cycle. A second estradiol rise of 14.0 ± 1.2pg/ml was observed on day-18 of the cycle. The mean estrous cycle length was 18.2 ± 2.1 days. During gestation, higher progesterone levels were maintained in the range of 4.3–11.0 ng/ml. Estradiol remained at lower concentrations for 30-50 days of gestation, then gradually increased and reached 270 ± 13.0 pg/ml a few days before parturition. It dropped again to basal values within 1-2 days postpartum. The mean gestation length in Dwarf goats was 144.8 ± 3.9 days and the litter size was 1.8 ± 0.5. It was concluded that Dwarf goat is a prolific breed, having a short gestation length with multiple births being common.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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. - Highlights: • E2 was effectively transformed in soil through reactions mediated by laccase. • The reaction behaviors in soil differ significantly from those in water. • E2 was preferably bound to the humic acids in soil. • Laccase treatment resulted in changes in the structures of the humic acids. - E2 was effectively transformed in soil by preferably binding to the humic acids through reactions mediated by laccase

  15. Kisspeptin system in ovariectomized mice: Estradiol and progesterone regulation.

    Science.gov (United States)

    Marraudino, Marilena; Martini, Mariangela; Trova, Sara; Farinetti, Alice; Ponti, Giovanna; Gotti, Stefano; Panzica, GianCarlo

    2018-06-01

    The kisspeptin system is clustered in two main groups of cell bodies (the periventricular region, RP3V and the arcuate nucleus, ARC) that send fibers mainly to the GnRH neurons and in a few other locations, including the paraventricular nucleus, PVN. In physiological conditions, gonadal hormones modulate the kisspeptin system with expression changes according to different phases of the estrous cycle: the highest being in estrus phase in RP3V and PVN (positive feedback), and in ARC during the diestrus phase (negative feedback). In this work we wanted to study these hormonal fluctuations during the estrous cycle, investigating the role played by progesterone (P) or estradiol (E 2 ), alone or together, on the kisspeptin system. Gonadectomized CD1 female mice were treated with P, E 2 or both (E 2  + P), following a timing of administration that emulates the different phases of estrous cycle, for two cycles of 4 days. As expected, the two cell groups were differentially affected by E 2 ; the RP3V group was positively influenced by E 2 (alone or with the P), whereas in the ARC the administration of E 2 did not affect the system. However P (alone) induced a rise in the kisspeptin immunoreactivity. All the treatments significantly affected the kisspeptin innervation of the PVN, with regional differences, suggesting that these fibers arrive from both RP3V and ARC nuclei. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Increased Oil Recovery from Mature Oil Fields Using Gelled Polymer Treatments

    Energy Technology Data Exchange (ETDEWEB)

    Willhite, G.P.; Green, D.W.; McCool, S.

    2001-03-28

    Gelled polymer treatments were applied to oil reservoirs to increase oil production and to reduce water production by altering the fluid movement within the reservoir. This report is aimed at reducing barriers to the widespread use of these treatments by developing methods to predict gel behavior during placement in matrix rock and fractures, determining the persistence of permeability reduction after gel placement, and by developing methods to design production well treatments to control water production. Procedures were developed to determine the weight-average molecular weight and average size of polyacrylamide samples in aqueous solutions. Sample preparation techniques were key to achieving reproducible results.

  17. Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

    Science.gov (United States)

    Sibille, Kimberly T; Bartsch, Felix; Reddy, Divya; Fillingim, Roger B; Keil, Andreas

    2016-03-01

    Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Flutamide versus a cyproterone acetate-ethinyl estradiol combination in moderate acne: a pilot randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Adalatkhah H

    2011-07-01

    Full Text Available Hassan Adalatkhah1, Farhad Pourfarzi2, Homayoun Sadeghi-Bazargani31Department of Dermatology, 2Department of Social Medicine, Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil; 3Statistics and Epidemiology Department, Faculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, IranBackground: The use of oral flutamide is rarely investigated in acne therapy. The aim of this study was to compare the efficacy of oral flutamide with that of a cyproterone-estradiol combination in treating acne lesions.Methods: A randomized clinical trial enrolled patients with moderate acne into two equal groups to receive either oral flutamide or the cyproterone-estradiol combination for 6 months. Lesion count, Acne Severity Index, and Global Acne Grading system (GAGS scores were used to assess improvement in acne lesions. The dichotomous measurement scale for primary endpoint assessment was defined as improvement from moderate to mild acne based on GAGS score. Patient satisfaction and dermal fat were also assessed. Intention to treat and per protocol analyses were done, reporting related effect sizes.Results: Both treatments resulted in substantial improvement in acne lesions. Although flutamide seemed to have higher efficacy, an intention to treat analysis did not find the two treatment protocols to be different. The relative risk in intention to treat analysis was 1.8 (95% confidence interval [CI] 0.89–1.6, and was 1.33 (95% CI 1.03–1.72 for the per protocol analysis. The number needed to treat for flutamide compared with the cyproterone-estradiol combination was 7.7 and 4.2 in the intention to treat and per protocol analyses, respectively.Conclusion: Flutamide appears to be more effective than a cyproterone-estradiol combination in some aspects of acne treatment, but this requires confirmation in a larger trial.Keywords: acne vulgaris, flutamide, cyproterone acetate, ethinyl estradiol, androgen antagonists

  19. Glutamine synthetase and alanine transaminase expression are decreased in livers of aged vs. young beef cows and GS can be upregulated by 17β-estradiol implants.

    Science.gov (United States)

    Miles, E D; McBride, B W; Jia, Y; Liao, S F; Boling, J A; Bridges, P J; Matthews, J C

    2015-09-01

    Aged beef cows (≥ 8 yr of age) produce calves with lower birth and weaning weights. In mammals, aging is associated with reduced hepatic expression of glutamine synthetase (GS) and alanine transaminase (ALT), thus impaired hepatic Gln-Glu cycle function. To determine if the relative protein content of GS, ALT, aspartate transaminase (AST), glutamate transporters (EAAC1, GLT-1), and their regulating protein (GTRAP3-18) differed in biopsied liver tissue of (a) aged vs. young (3 to 4 yr old) nonlactating, nongestating Angus cows (Exp. 1 and 2) and (b) aged mixed-breed cows with and without COMPUDOSE (17β-estradiol) ear implants (Exp. 3), Western blot analyses were performed. In Exp. 1, 12 young (3.62 ± 0.01 yr) and 13 aged (10.08 ± 0.42 yr) cows grazed the same mixed forage for 42 d (August-October). In Exp. 2, 12 young (3.36 ± 0.01 yr) and 12 aged (10.38 ± 0.47 yr) cows were individually fed (1.03% of BW) a corn-silage-based diet to maintain BW for 20 d. For both Exp. 1 and 2, the effect of cow age was assessed by ANOVA using the MIXED procedure of SAS. Cow BW did not change ( ≥ 0.17). Hepatic ALT (78% and 61%) and GS (52% and 71%) protein content (Exp. 1 and 2, respectively) was decreased ( ≤ 0.01), whereas GTRAP3-18 (an inhibitor of EAAC1 activity) increased ( ≤ 0.01; 170% and 136%) and AST, GLT-1, and EAAC1 contents did not differ ( ≥ 0.17) in aged vs. young cows. In Exp. 2, free concentrations (nmol/g) of Glu, Ala, Gln, Arg, and Orn in liver homogenates were determined. Aged cows tended to have less ( = 0.10) free Gln (15.0%) than young cows, whereas other AA concentrations did not differ ( 0.26). In Exp. 3, 14 aged (> 10 yr) cows were randomly allotted ( = 7) to sham or COMPUDOSE (25.7 mg of 17β-estradiol) implant treatment (TRT), and had ad libitum access to alfalfa hay for 28 d. Blood and liver biopsies were collected 14 and 28 d after implant treatment. Treatment, time after implant (DAY), and TRT × DAY effects were assessed by ANOVA using

  20. Cyclodextrin-facilitated bioconversion of 17 beta-estradiol by a phenoloxidase from Mucuna pruriens cell cultures

    NARCIS (Netherlands)

    Woerdenbag, H.J.; Pras, N.; Frijlink, H.W.; Lerk, C.F.; Malingré, T.M.

    1990-01-01

    After complexation with beta-cyclodextrin, the phenolic steroid 17 beta-estradiol could be ortho-hydroxylated into a catechol, mainly 4-hydroxyestradiol, by a phenoloxidase from in vitro grown cells of Mucuna pruriens. By complexation with beta-cyclodextrin the solubility of the steroid increased

  1. Pituitary, ovarian and additional contraceptive effects of an estradiol-based combined oral contraceptive: results of a randomized, open-label study.

    Science.gov (United States)

    Endrikat, Jan; Parke, Susanne; Trummer, Dietmar; Serrani, Marco; Duijkers, Ingrid; Klipping, Christine

    2013-02-01

    The estrogen step-down/progestogen step-up 28-day estradiol valerate/dienogest (E(2)V/DNG) oral contraceptive effectively inhibits ovulation; however, limited data are available regarding its effects on estradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or its additional extraovarian contraceptive effects. In this secondary analysis, 100 women received E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26 and placebo on days 27-28 for one treatment cycle. Measures included the presence/absence of cervical mucus; endometrial thickness; and serum E2, progesterone, and gonadotropin levels. E2, progesterone, LH and FSH levels did not exhibit the typical ovulatory increase and remained relatively stable during the cycle. E(2)V/DNG reduced mean maximal endometrial thickness and proportion of women with visible cervical mucus. All parameters returned to pretreatment levels during the posttreatment cycle. E(2)V/DNG provides extraovarian contraceptive effects (reducing endometrial thickness and cervical mucus production) in addition to inhibiting ovulation, assuring contraceptive efficacy. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Effect of two oral doses of 17beta-estradiol associated with dydrogesterone on thrombin generation in healthy menopausal women: a randomized double-blind placebo-controlled study.

    Science.gov (United States)

    Rousseau, Alexandra; Robert, Annie; Gerotziafas, Grigoris; Torchin, Dahlia; Zannad, Faiez; Lacut, Karine; Libersa, Christian; Dasque, Eric; Démolis, Jean-Louis; Elalamy, Ismail; Simon, Tabassome

    2010-04-01

    Oral hormone therapy is associated with an increased risk of venous thrombosis. Drug agencies recommend the use of the lowest efficient dose to treat menopausal symptoms for a better risk/ratio profile, although this profile has not been totally investigated yet. The aim of the study was to compare the effect of the standard dose of 17beta-estradiol to a lower one on thrombin generation (TG). In a 2-month study, healthy menopausal women were randomized to receive daily 1mg or 2 mg of 17beta-estradiol (E1, n = 24 and E2, n = 26; respectively) with 10 mg dydrogesterone or placebo (PL, n = 22). Plasma levels factors VII, X, VIII and II were assessed before and after treatment as well as Tissue factor triggered TG, which allows the investigation of the different phases of coagulation process. The peak of thrombin was higher in hormone therapy groups (E1: 42.39 +/- 50.23 nm, E2: 31.08 +/- 85.86 nm vs. 10.52 +/- 40.63 nm in PL, P = 0.002 and P = 0.01). Time to reach the peak was also shortened (PL: 0.26 +/- 0.69 min vs. E1: -0.26 +/- 0.80 min, E2: -0.55 +/- 0.79 min, P <10(-3) for both comparisons) and mean rate index of the propagation phase of TG was significantly increased. Among the studied clotting factors, only the levels of FVII were significantly increased after treatment administration. The two doses of 17beta-estradiol induced in a similar degree an acceleration of the initiation and propagation phase of tissue factor triggered thrombin generation and a significant increase of FVII coagulant activity.

  3. Steroid sex hormone dynamics during estradiol-17β induced gonadal differentiation in Paralichthys olivaceus (Teleostei)

    Science.gov (United States)

    Sun, Peng; You, Feng; Liu, Mengxia; Wu, Zhihao; Wen, Aiyun; Li, Jun; Xu, Yongli; Zhang, Peijun

    2010-03-01

    Steroid sex hormones, such as estradiol-17β (E2) and testosterone (T), are important regulators of sex change in fish. In this study, we examined the effects of E2 treatment on the dynamics of E2 and T during gonadal differentiation in the olive flounder Paralichthys olivaceus using histology and radioimmunoassay (RIA). Flounder larvae were divided into five groups (G0-G4), and fed with 0 (control), 0.2, 2, 20 and 100 mg E2/kg feed from 35 to 110 day post hatching (dph). Fish growth in the G1 and G2 groups was not significantly different from that of the control group ( P>0.05), while fish in the G3 and G4 groups were less active and showed growth depression and high mortality. The gonads of fish in the G3 and G4 groups were smaller and surrounded by hyperplastic connective tissue. The frequency of females in the G0-G4 groups was 54.5%, 75.0%, 100%, 100% and 93.3%, respectively. The RIA analyses of E2 and T showed that T levels decreased during gonadal differentiation, and increased slightly at the onset of ovarian differentiation, while E2 levels increased gradually and peaked at the onset of ovarian differentiation in the control group. In the E2-treated groups, T levels decreased before the onset of ovarian differentiation. E2 levels were high on the 48 dph, but declined to a lower level on the 54 dph, and then increased gradually during gonadal differentiation. And a sharp increase of E2 levels were observed in all E2-treated groups at the onset of ovarian differentiation. The data suggest that T and E2 play important roles during gonadal differentiation, and an E2 dose of 2 mg/kg feed could induce sex reversal in P. olivaceus.

  4. Pre- and Peri-/Post-Compaction Follistatin Treatment Increases In Vitro Production of Cattle Embryos.

    Directory of Open Access Journals (Sweden)

    Guo Zhenhua

    Full Text Available Our previous studies demonstrated that maternal (oocyte derived follistatin (FST expression is positively associated with bovine oocyte competence and exogenous follistatin treatment during the pre-compaction period of development (d 1-3 post insemination is stimulatory to bovine early embryogenesis in vitro [blastocyst rates and cell numbers/allocation to trophectoderm (TE]. In the present study, bovine embryos were treated with exogenous follistatin during d 1-3, d 4-7 and d 1-7 post insemination to test the hypothesis that embryotropic effects of exogenous follistatin are specific to the pre-compaction period (d 1-3 of early embryogenesis. Follistatin treatment during d 4-7 (peri-/post-compaction period of embryo culture increased proportion of embryos reaching blastocyst and expanded blastocyst stage and total cell numbers compared to controls, but blastocyst rates and total cell numbers were lower than observed following d 1-3 (pre-compaction follistatin treatment. Follistatin supplementation during d 1-7 of embryo culture increased development to blastocyst and expanded blastocyst stages and blastocyst total cell numbers compared to d 1-3 and d 4-7 follistatin treatment and untreated controls. A similar increase in blastocyst CDX2 mRNA and protein (TE cell marker was observed in response to d 1-3, d 4-7 and d 1-7 follistatin treatment. However, an elevation in blastocyst BMP4 protein (TE cell regulator was observed in response to d 1-3 and d 1-7, but not d 4-7 (peri-/post-compaction follistatin treatment. In summary, our study revealed the potential utility of follistatin treatment for increasing the success rate of in vitro embryo production in cattle. Such results also expand our understanding of the embryotropic actions of follistatin and demonstrate that follistatin actions on blastocyst development and cell allocation to the TE layer are not specific to the pre-compaction period.

  5. Increased Mindfulness Skills as Predictors of Reduced Trauma-Related Guilt in Treatment-Seeking Veterans.

    Science.gov (United States)

    Held, Philip; Owens, Gina P; Monroe, J Richard; Chard, Kathleen M

    2017-08-01

    The present study examined the predictive role of increased self-reported mindfulness skills on reduced trauma-related guilt in a sample of veterans over the course of residential treatment for posttraumatic stress disorder (PTSD; N = 128). The residential treatment consisted of seven weeks of intensive cognitive processing therapy (CPT) for PTSD, as well as additional psychoeducational groups, including seven sessions on mindfulness skills. Increased mindfulness skills describing, acting with awareness, and accepting without judgment were significantly associated with reductions in trauma-related guilt over the course of treatment. Increases in the ability to act with awareness and accept without judgment were significantly associated with reductions in global guilt, R 2 = .26, guilt distress, R 2 = .23, guilt cognitions, R 2 = .23, and lack of justification, R 2 = .11. An increase in the ability to accept without judgment was the only self-reported mindfulness skill that was associated with reductions in hindsight bias, β = -.34 and wrongdoing, β = -.44. Increases in self-reported mindfulness skills explained 15.1 to 24.1% of the variance in reductions in trauma-related guilt, suggesting that mindfulness skills may play a key role in reducing the experience of trauma-related guilt during psychotherapy. Our results provide preliminary support for the use of mindfulness groups as an adjunct to traditional evidence-based treatments aimed at reducing trauma-related guilt, though this claim needs to be tested further using experimental designs. Copyright © 2017 International Society for Traumatic Stress Studies.

  6. Normal endometrial stromal cells regulate 17β-estradiol-induced epithelial-mesenchymal transition via slug and E-cadherin in endometrial adenocarcinoma cells in vitro.

    Science.gov (United States)

    Zhang, Hui; Li, Hongyan; Qi, Shasha; Liu, Zhao; Fu, Yibing; Li, Mingjiang; Zhao, Xingbo

    2017-01-01

    Stroma-tumor communication participates in the pathogenesis of endometrial carcinomas. In previous studies, we found that normal stromal cells inhibited the growth of endometrial carcinoma cells. Here, we investigated the role of normal stromal cells in the epithelial-mesenchymal transition (EMT) of endometrial carcinoma cells and explored the possible mechanism implied. We found that conditioned medium (CM) by normal endometrial stromal cells (NSC) reduced cell growth and induced cell apoptosis in Ishikawa cells. CM by NSC inhibited 17β-estradiol-induced cell growth and apoptosis decrease in Ishikawa cells. Moreover, CM by NSC inhibited the migration and invasion, and 17β-estradiol-induced migration and invasion in Ishikawa cells. Meanwhile, CM by NSC decreased Slug expression and 17β-estradiol-induced Slug expression, increased E-cadherin expression and abolished 17β-estradiol-induced E-cadherin reduction in Ishikawa cells. In conclusion, normal stromal factors can inhibit 17β-estradiol-induced cell proliferation and apoptosis inhibition, and abolished 17β-estradiol-induced EMT in endometrial cancer cell via regulating E-cadherin and Slug expression.

  7. Estradiol enhances retention but not organization of hippocampus-dependent memory in intact male mice.

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Preharvest methyl jasmonate and postharvest UVC treatments: increasing stilbenes in wine.

    Science.gov (United States)

    Fernández-Marín, María Isabel; Puertas, Belén; Guerrero, Raúl F; García-Parrilla, María Carmen; Cantos-Villar, Emma

    2014-03-01

    Stilbene-enriched wine is considered to be an interesting new food product with added value due to its potential health-promoting properties. Stilbene concentration in grape is highly variable and rather scarce. However, it can be increased by stress treatments. For this reason, numerous pre- and postharvest grape treatments, and some combinations of them, have been tested to maximize stilbene content in grapes. In the present manuscript, Syrah grapes were treated with (i) methyl jasmonate (MEJA), (ii) ultraviolet light (UVC), and (iii) methyl jasmonate and ultraviolet light (MEJA-UVC) and compared with untreated grapes. Afterward, winemaking was developed. Wine achieved by combination of both treatments (MEJA-UVC) contained significantly higher stilbene concentration (trans-resveratrol and piceatannol) than its respective control (2.5-fold). Wine quality was improved in color-related parameters (color intensity, L*, a*, b*, ΔE*, anthocyanins, and tannin). Moreover, MEJA-UVC wines obtained the highest score in sensorial analysis. To the best of our knowledge, this is the first time that pre- and postharvest treatments are combined to increase stilbenes in wine. The effect of treatment combination (methyl jasmonate and UVC light) on grape and wine was evaluated. Our results highlight the positive effect of the treatments in stilbene content, color parameters, and sensorial analysis. Moreover, added-value by-products were achieved. © 2014 Institute of Food Technologists®

  9. Finishing broiler toms using an estradiol 17 beta implant together with a high energy-low protein final feed.

    Science.gov (United States)

    Moran, E T; Etches, R J

    1983-06-01

    Wrolstad Small White toms were implanted with 10 mg of estradiol 17 beta monopalmitate (EMP) at 8 weeks of age. Common corn-soybean meal feeds were given through to 12 weeks, then one-half the birds from control and EMP groups received either an adequate (16% protein, 3166 kcal ME/kg) or high energy-low protein (HE-LP, 12%, 3373 kcal) feed to 14 weeks. No differences in weight gain and feed conversion occurred between EMP and control treatments at 12 weeks but at 14 weeks when the HE-LP diet had been fed the implanted birds performed better than controls. The HE-LP feed led to body weights and feed efficiencies below that of toms given adequate diet. In all cases, EMP elicited male secondary sex characteristics rather than feminization. Processing losses were increased with EMP and when the HE-LP feed had been given. Both treatments also improved finish assessment and were additive to the extent that a substantial increase in grade occurred. Effects on carcass composition, yield of commercial cuts, and cooking loss were small. Implantation, reduced meat yield percentage of breast and thigh. The increase in grade advantage from combining EMP with a feed that forced fat deposition more than compensated for the adverse effects.

  10. Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

    Science.gov (United States)

    Grisendi, Valentina; Spada, Elena; Argento, Cindy; Plebani, Maddalena; Milani, Silvano; Seracchioli, Renato; Volpe, Annibale; La Marca, Antonio

    2014-06-01

    High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

  11. Why use of dienogest for the first contraceptive pill with estradiol?

    Science.gov (United States)

    Mueck, Alfred O; Seeger, Harald; Bühling, Kai J

    2010-02-01

    Dienogest (DNG) has the essential properties of an effective progestogen for use in a new contraceptive pill using estradiol valerate as estrogenic component -- it inhibits ovulation and protects against endometrial proliferation. DNG is a derivative of norethisterone (NET), but has a cyanomethyl- instead of an ethinyl-group in C17 position which may offer a variety of benefits regarding hepatic effects. The similarity to NET is reflected in the high endometriotropy and in similar pharmacokinetics like short plasma half-live and high bioavailability. However, DNG also elicits properties of progesterone derivatives like neutrality in metabolic and cardiovascular system and considerable antiandrogenic activity, the latter increased by lack of binding to SHBG as specific property of DNG. It has no glucocorticoid and antimineralocorticoid activity and has no antiestrogenic activity with the consequence that possible beneficial estradiol effects should not be antagonized. This may be of special importance for the tolerability and safety of the first pill with estradiol valerate instead of ethinylestradiol, although well-designed postmarketing studies are still ongoing to demonstrate what can be expected on the basis of pharmacology.

  12. 17 beta-estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Breinholt, V.; Dalsgaard, T.

    2001-01-01

    The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.20% nari...... and its antiatherogenic effect. - Mortensen, A., V. Breinholt, T. Dalsgaard, H. Frandsen, S. T. Lauridsen, J. Laigaard, B. Ottesen, and J-J. Larsen. 17 beta -Estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits.......The effects of 17 beta -estradiol (17 beta -E-2) or the phytoestrogen naringenin on spontaneous atherosclerosis were studied in 36 ovariectomized homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits receiving a semisynthetic control diet; this diet added 0.0040% 17 beta -E-2, or 0.......20% naringenin, for 16 weeks. The uterine weight was increased (P 17 beta -E-2 group compared with the controls. Total plasma cholesterol and triglycerides were not different from those in the controls, In lipoproteins, HDL...

  13. Methodology for Determining Increases in Radionuclide Inventories for the Effluent Treatment Facility Process

    International Nuclear Information System (INIS)

    Blanchard, A.

    1998-01-01

    A study is currently underway to determine if the Effluent Treatment Facility can be downgraded from a Hazard Category 3 facility to a Radiological Facility per DOE STD-1027-92. This technical report provides a methodology to determine and monitor increases in the radionuclide inventories of the ETF process columns. It also provides guidelines to ensure that other potential increases to the ETF radionuclide inventory are evaluated as required to ensure that the ETF remains a Radiological Facility

  14. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Reinisch, June M

    2003-01-01

    OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal...... neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code...... treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment...

  15. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Reinisch, June M

    2003-01-01

    treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment...... neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code...... 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug...

  16. Increasing the treatment motivation of patients with somatic symptom disorder: applying the URICA-S scale.

    Science.gov (United States)

    Mander, Johannes; Schaller, Georg; Bents, Hinrich; Dinger, Ulrike; Zipfel, Stephan; Junne, Florian

    2017-07-03

    Therapeutic intervention programs for somatic symptom disorder (SSD) show only small-to-moderate effect sizes. These effects are partly explained by the motivational problems of SSD patients. Hence, fostering treatment motivation could increase treatment success. One central aspect in SSD patients might be damage to motivation because of symptomatic relapses. Consequently, the aim of the present study was to investigate associations between motivational relapse struggle and therapeutic outcome in SSD patients. We assessed 84 inpatients diagnosed with SSD in the early, middle and late stages of their inpatient treatment. The maintenance subscale of the University of Rhode Island Change Assessment-Short (URICA-S) was applied as a measure to assess motivational relapse struggle. Additionally, patients completed measures of treatment outcome that focus on clinical symptoms, stress levels and interpersonal functioning. The results from multiple regression analyses indicate that higher URICA-S maintenance scores assessed in early stages of inpatient treatment were related to more negative treatment outcomes in SSD patients. SSD patients with ambivalent treatment motivation may fail in their struggle against relapse over the course of therapy. The URICA-S maintenance score assessed at therapy admission facilitated early identification of SSD patients who are at greater risk of relapse. Future studies should incorporate randomized controlled trials to investigate whether this subgroup could benefit from motivational interventions that address relapse.

  17. Attempts to increase storage stability of strawberry yoghurt by combination treatments

    International Nuclear Information System (INIS)

    Kiss, I.

    1975-01-01

    The aim of the experiments was to establish whether the microbiological stability of strawberry yoghurt might be improved by decreasing the microbial load of the fruit. The effect of heat treatment, freezing, irradiation and various combinations of these treatments upon cell count and sensory quality was investigated. It was established that none of the individual treatments was entirely satisfactory. Surfacial heat treatment at 55 0 C, freezing and irradiation with 0.4-0.6 Mrad substantially increased the storage life of strawberries or that of the yoghurt prepared with this fruit; when compared to yoghurt made with frozen strawberries by the dairy factory, the increase was 2.5 fold at 15 0 C and 3.5 fold at 2 0 C. The relative increase of storage life was lower at lower yeast-cell counts. The strawberries irradiated with doses above 0.2 Mrad showed aroma and flavour changes immediately upon treatment. This effect, however, was eliminated after some days. The yoghurt made with strawberries given a radiation treatment of 0.57 Mrad did not differ organoleptically from the yoghurt made with untreated strawberries. In the knowledge of the survival rate of yeasts after irradiation the D 10 values were established. These were found in the dose range between 0.043 and 0.087 Mrad. It was established that the applied heat treatment, freezing and irradiation at these dose levels and at 10 3 -10 4 cells per gram were not sufficient from the point of view of microbiological stability. (F.J.)

  18. Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells.

    Science.gov (United States)

    Sharma, Geetanjali; Prossnitz, Eric R

    2011-08-01

    Sexual dimorphism and supplementation studies suggest an important role for estrogens in the amelioration of glucose intolerance and diabetes. Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. The results of this study suggest that the activation of downstream signaling pathways by the GPER-selective ligand G-1 could represent a novel therapeutic strategy in the treatment of diabetes.

  19. Mechanisms of Estradiol-Induced Insulin Secretion by the G Protein-Coupled Estrogen Receptor GPR30/GPER in Pancreatic β-Cells

    Science.gov (United States)

    Sharma, Geetanjali

    2011-01-01

    Sexual dimorphism and supplementation studies suggest an important role for estrogens in the amelioration of glucose intolerance and diabetes. Because little is known regarding the signaling mechanisms involved in estradiol-mediated insulin secretion, we investigated the role of the G protein-coupled receptor 30, now designated G protein-coupled estrogen receptor (GPER), in activating signal transduction cascades in β-cells, leading to secretion of insulin. GPER function in estradiol-induced signaling in the pancreatic β-cell line MIN6 was assessed using small interfering RNA and GPER-selective ligands (G-1 and G15) and in islets isolated from wild-type and GPER knockout mice. GPER is expressed in MIN6 cells, where estradiol and the GPER-selective agonist G-1 mediate calcium mobilization and activation of ERK and phosphatidylinositol 3-kinase. Both estradiol and G-1 induced insulin secretion under low- and high-glucose conditions, which was inhibited by pretreatment with GPER antagonist G15 as well as depletion of GPER by small interfering RNA. Insulin secretion in response to estradiol and G-1 was dependent on epidermal growth factor receptor and ERK activation and further modulated by phosphatidylinositol 3-kinase activity. In islets isolated from wild-type mice, the GPER antagonist G15 inhibited insulin secretion induced by estradiol and G-1, both of which failed to induce insulin secretion in islets obtained from GPER knockout mice. Our results indicate that GPER activation of the epidermal growth factor receptor and ERK in response to estradiol treatment plays a critical role in the secretion of insulin from β-cells. The results of this study suggest that the activation of downstream signaling pathways by the GPER-selective ligand G-1 could represent a novel therapeutic strategy in the treatment of diabetes. PMID:21673097

  20. Increase in extraction yields of coals by water treatment: Beulah-Zap lignite

    Energy Technology Data Exchange (ETDEWEB)

    Masashi Iino; Toshimasa Takanohashi; Takahiro Shishido; Ikuo Saito; Haruo Kumagai [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan)

    2007-01-15

    In a previous paper, we have reported that water pretreatments of Argonne premium coals, Pocahontas No. 3 (PO), Upper Freeport (UF), and Illinois No. 6 (IL) at 600 K increased greatly the room-temperature extraction yields with a 1:1 carbon disulfide/N-methyl-2-pyrrolidinone (CS{sub 2}/NMP) mixed solvent. In this paper, the water treatment of Beulah-Zap (BZ) lignite has been carried out and the results obtained were compared with those for the three bituminous coals above. The extraction yields of BZ with CS{sub 2}/NMP increased from 5.5% for the raw coal to 21.7% by the water treatment at 600 K. Similar to the other three coals, the water treatments at 500 K gave little increase in the yields. The larger decrease in oxygen content and hydrogen-bonded OH and the increase in the methanol swelling ratio by the water treatment suggest that the yield enhancements for BZ are attributed to the removal of oxygen functional groups and the breaking of hydrogen bonds to a greater extent than that for IL. From the characterizations of the treated coals and the extraction temperature dependency of their extraction yields, it is suggested that, for high-coal-rank coals, PO and UF, the breaking of noncovalent bonds such as {pi}-{pi} interactions between aromatic layers and hydrogen bonds is responsible for the extraction yield enhancements. 14 refs., 3 figs., 2 tabs.

  1. Increase in natural killer cell activity during diethylcarbamazine treatment of patients with filariasis

    DEFF Research Database (Denmark)

    Pedersen, B K; Bygbjerg, Ib Christian; Svenson, M

    1987-01-01

    Two patients, one with Bancroftian filariasis and the other with onchocerciasis, and two healthy controls were treated with diethylcarbamazine (DEC). The natural killer (NK) cell activity of the two patients increased during DEC treatment to 2.5 and 2.8 times, respectively, while that of the cont...

  2. Kisspeptin Expression in Guinea Pig Hypothalamus: Effects of 17β-Estradiol

    Science.gov (United States)

    Bosch, Martha A.; Xue, Changhui; Rønnekleiv, Oline K.

    2013-01-01

    Kisspeptin is essential for reproductive functions in humans. As a model for the human we have used the female guinea pig, which has a long ovulatory cycle similar to that of primates. Initially, we cloned a guinea pig kisspeptin cDNA sequence and subsequently explored the distribution and 17β-estradiol (E2) regulation of kisspeptin mRNA (Kiss1) and protein (kisspeptin) by using in situ hybridization, real-time PCR and immunocytochemistry. In ovariectomized females, Kiss1 neurons were scattered throughout the preoptic periventricular areas (PV), but the vast majority of Kiss1 neurons were localized in the arcuate nucleus (Arc). An E2 treatment that first inhibits (negative feedback) and then augments (positive feedback) serum luteinizing hormone (LH) increased Kiss1 mRNA density and number of cells expressing Kiss1 in the PV at both time points. Within the Arc, Kiss1 mRNA density was reduced at both time points. Quantitative real-time PCR confirmed the in situ hybridization results during positive feedback. E2 reduced the number of immunoreactive kisspeptin cells in the PV at both time points, perhaps an indication of increased release. Within the Arc, the kisspeptin immunoreactivity was decreased during negative feedback but increased during positive feedback. Therefore, it appears that in guinea pig both the PV and the Arc kisspeptin neurons act cooperatively to excite gonadotropin-releasing hormone (GnRH) neurons during positive feedback. We conclude that E2 regulation of negative and positive feedback may reflect a complex interaction of the kisspeptin circuitry, and both the PV and the Arc respond to hormone signals to encode excitation of GnRH neurons during the ovulatory cycle. PMID:22173890

  3. Estradiol protective role in atherogenesis through LDL structure modification

    International Nuclear Information System (INIS)

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

    2016-01-01

    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. (paper)

  4. Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol.

    Science.gov (United States)

    Kuba, V M; Teixeira, M A M; Meirelles, R M R; Assumpção, C R L; Costa, O S

    2013-02-01

    To evaluate the influence of dydrogesterone on estimated cardiovascular risk of users of hormone replacement therapy (HRT) (with percutaneous 17β-estradiol in monotherapy and in combination with dydrogesterone) and HRT non-users through the Framingham score tool for a period of 2 years. Framingham scores were calculated from the medical records of patients treated for at least 2 years with 17β-estradiol alone or in combination with dydrogesterone, along with HRT non-users, through the analysis of patient medical records, followed for at least 2 years at Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione. Improvements in lipid profile, glucose and blood pressure levels, which reduced the estimated cardiovascular risk, were observed in the 17β-estradiol group. Similar changes were observed in the users of 17β-estradiol + dydrogesterone, suggesting that this progestogen does not attenuate the effects caused by 17β-estradiol. Both HRT groups showed a reduction in their Framingham score. In contrast to data from other HRT investigations on cardiovascular risk, these formulations proved to be safe, even in the first year of use.

  5. The potential impact of increased treatment rates for alcohol dependence in the United Kingdom in 2004.

    Science.gov (United States)

    Shield, Kevin D; Rehm, Jürgen; Rehm, Maximilien X; Gmel, Gerrit; Drummond, Colin

    2014-02-05

    Alcohol consumption has been linked to a considerable burden of disease in the United Kingdom (UK), with most of this burden due to heavy drinking and Alcohol Dependence (AD). However, AD is undertreated in the UK, with only 8% of those individuals with AD being treated in England and only 6% of those individuals with AD being treated in Scotland. Thus, the objective of this paper is to quantify the deaths that would have been avoided in the UK in 2004 if the treatment rate for AD had been increased. Data on the prevalence of AD, alcohol consumption, and mortality were obtained from the Adult Psychiatric Morbidity Survey, the Global Information System on Alcohol and Health, and the 2004 Global Burden of Disease study respectively. Data on the effectiveness of pharmacological treatment and Motivational Interviewing/Cognitive Behavioural Therapy were obtained from Cochrane reviews and meta-analyses. Simulations were used to model the number of deaths under different treatment scenarios. Sensitivity analyses were performed to model the effects of Brief Interventions and to examine the effect of using AD prevalence data obtained from the National Institute for Health and Clinical Excellence. In the UK, 320 female and 1,385 male deaths would have been avoided if treatment coverage of pharmacological treatment had been increased to 20%. This decrease in the number of deaths represents 7.9% of all alcohol-attributable deaths (7.0% of all alcohol-attributable deaths for women and 8.1% of all alcohol-attributable deaths for men). If we used lower AD prevalence rates obtained from the National Institute for Health and Clinical Excellence, then treatment coverage of pharmacological treatment in hospitals for 20% of the population with AD would have resulted in the avoidance of 529 deaths in 2004 (99 deaths avoided for women and 430 deaths avoided for men). Increasing AD treatment in the UK would have led to a large number of deaths being avoided in 2004. Increased AD

  6. The role of transdermal estrogen sprays and estradiol topical emulsion in the management of menopause-associated vasomotor symptoms

    Directory of Open Access Journals (Sweden)

    Amy M Egras

    2010-05-01

    Full Text Available Amy M Egras, Elena M UmlandJefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Vasomotor symptoms (VMS are among the most bothersome complaints of postmenopausal women. To date, the most widely studied and effective treatment for VMS is hormone replacement therapy, consisting of estrogen (in women without a uterus or estrogen plus progestin (in women with a uterus. Traditionally, oral estrogens have been used for treatment. However, over the years, additional estrogen formulations have been developed including transdermal patches; vaginal rings, creams, and tablets; and injectable preparations. Two newer formulations are transdermal estrogen spray and estradiol topical emulsion. This review evaluates the current literature assessing the use of these two newer formulations for the treatment of VMS associated with menopause.Keywords: menopause, vasomotor symptoms, transdermal estrogen spray, estradiol topical emulsion

  7. Increasing daily water intake and fluid adherence in children receiving treatment for retentive encopresis.

    Science.gov (United States)

    Kuhl, Elizabeth S; Hoodin, Flora; Rice, Jennifer; Felt, Barbara T; Rausch, Joseph R; Patton, Susana R

    2010-11-01

    To examine the efficacy of an enhanced intervention (EI) compared to standard care (SC) in increasing daily water intake and fluid goal adherence in children seeking treatment for retentive encopresis. Changes in beverage intake patterns and fluid adherence were examined by comparing 7-week diet diary data collected during participation in the EI to achieved data for families who had previously completed the SC. Compared to children in SC (n = 19), children in the EI (n = 18) demonstrated a significantly greater increase in daily water intake from baseline to the conclusion of treatment ( p ≤ .001), and were four and six times more likely to meet fluid targets in Phases 1 (Weeks 3-4) and 2 (Weeks 5-6) of fluid intervention, respectively (both p ≤ .001). Enhanced education and behavioral strategies were efficacious in increasing children's intake of water and improving fluid adherence. Future research should replicate the findings in a prospective randomized clinical trial to discern their effectiveness.

  8. Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts.

    Science.gov (United States)

    Schachner, Thomas; Oberhuber, Alexander; Zou, Yping; Tzankov, Alexandar; Ott, Harald; Laufer, Günther; Bonatti, Johannes

    2005-02-01

    Rapamycin is an immunosuppressive agent with marked antiproliferative properties and is effective in reducing in stent restenosis and vein graft neointimal hyperplasia. Apoptosis is one mechanism counterbalancing cellular proliferation. We therefore investigated the role of apoptosis in rapamycin treated vein grafts in a mouse model. C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group 200 microg of rapamycin were applied locally in pluronic gel. The control group did not receive local treatment. Vein grafts were harvested at 4 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL). In grafted veins without treatment (controls) neointimal thickness was 50 (12-58) microm at 4 weeks postoperatively. In 200 microg rapamycin treated grafts the neointimal thickness was 17 (5-55) microm. Rapamycin treated vein grafts showed a significantly increased rate of apoptosis in the adventitia as compared with controls (P=0.032). In the neointima the apoptosis rate was lower in both groups with no significant difference between rapamycin treated grafts and controls. We conclude that treatment of experimental vein grafts with rapamycin is associated with an increased apoptosis rate in the vascular wall and a trend towards reduction of neointimal hyperplasia. These results suggest that apoptosis may be a beneficial antiproliferative component for the treatment of vein graft disease.

  9. SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects.

    Science.gov (United States)

    Pace-Schott, E F; Gersh, T; Silvestri, R; Stickgold, R; Salzman, C; Hobson, J A

    2001-06-01

    Clinical lore and a small number of published studies report that the selective serotonin reuptake inhibitors (SSRIs) intensify dreaming. This study examines the dream effects of paroxetine and fluvoxamine in order to both increase clinical knowledge of these agents and to test an important potential method for probing the relationship between REM sleep neurobiology and dreaming in humans. Fourteen normal, paid volunteers (4 males, 10 females; mean age 27.4 year, range 22--39) free of medical or neuropsychiatric symptoms as well as of psychotropic or sleep affecting drugs completed a 31-day home-based study consisting of: 7 days drug-free baseline; 19 days on either 100 mg fluvoxamine (7 Ss) or 20 mg paroxetine (7 Ss) in divided morning and evening doses; and 5 days acute discontinuation. Upon awakening, subjects wrote dream reports, self-scored specific emotions in their reports and rated seven general dream characteristics using 5-point Likert scales. Dream reports were independently scored for bizarreness, movement and number of visual nouns by three judges. REM sleep-related measures were obtained using the Nightcap ambulatory sleep monitor. Mean dream recall frequency decreased during treatment compared with baseline. Dream report length and judge-rated bizarreness were greater during acute discontinuation compared with both baseline and treatment and this effect was a result of the fluvoxamine-treated subjects. The subjective intensity of dreaming increased during both treatment and acute discontinuation compared with baseline. Propensity to enter REM sleep was decreased during treatment compared with baseline and acute discontinuation and the intensity of REM sleep increased during acute discontinuation compared with baseline and treatment. The decrease in dream frequency during SSRI treatment may reflect serotonergic REM suppression while the augmented report length and bizarreness during acute SSRI discontinuation may reflect cholinergic rebound from

  10. Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression.

    Science.gov (United States)

    Roseman, Leor; Demetriou, Lysia; Wall, Matthew B; Nutt, David J; Carhart-Harris, Robin L

    2017-12-27

    Recent evidence indicates that psilocybin with psychological support may be effective for treating depression. Some studies have found that patients with depression show heightened amygdala responses to fearful faces and there is reliable evidence that treatment with SSRIs attenuates amygdala responses (Ma, 2015). We hypothesised that amygdala responses to emotional faces would be altered post-treatment with psilocybin. In this open-label study, 20 individuals diagnosed with moderate to severe, treatment-resistant depression, underwent two separate dosing sessions with psilocybin. Psychological support was provided before, during and after these sessions and 19 completed fMRI scans one week prior to the first session and one day after the second and last. Neutral, fearful and happy faces were presented in the scanner and analyses focused on the amygdala. Group results revealed rapid and enduring improvements in depressive symptoms post psilocybin. Increased responses to fearful and happy faces were observed in the right amygdala post-treatment, and right amygdala increases to fearful versus neutral faces were predictive of clinical improvements at 1-week. Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments' therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them. Based on the present results, we propose that psilocybin with psychological support is a treatment approach that potentially revives emotional responsiveness in depression, enabling patients to reconnect with their emotions. ISRCTN, number ISRCTN14426797. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Evaluation of increased milking frequency as an additional treatment for cows with clinical mastitis.

    Science.gov (United States)

    Krömker, Volker; Zinke, Claudia; Paduch, Jan-Hendrik; Klocke, Doris; Reimann, Anette; Eller, Georg

    2010-02-01

    This field study focused on the possible effects of increased milking frequency (milking four times a day in comparison with milking twice a day) on clinical and bacteriological cure rates of clinical, antibiotically treated mastitis cases. Parameters tested were clinical, microbiological and full (cytomicrobiological) cure as well as the development of milk yield after the clinical mastitis episode. Cows from a large dairy herd meeting the study criteria (n=93) were assigned to two treatment groups by a systematic randomization scheme (blocked by body temperature 39.5 degrees C). Both groups were randomly divided by experimental treatments: a) antibiotic intramammary treatment and milking 2-times a day; b) antibiotic intramammary treatment and milking 4-times a day. Treatments were initiated before the culture results were known. Cows were surveyed and evaluated on days 1-6, 24 and 31. No significant differences between treatment and control groups regarding clinical cure, microbiological cure, full cure and milk production could be established. Applying a 4-times a day milking regime did not lead to any significant effect, either positive or negative. Therefore, the results suggest that milking 4-times a day as a supporting therapy for mild, moderate and severe antimicrobially treated mastitis cases cannot be recommended.

  12. The Brazilian policy of withholding treatment for ADHD is probably increasing health and social costs

    Directory of Open Access Journals (Sweden)

    Carlos R. Maia

    2015-03-01

    Full Text Available Objective: To estimate the economic consequences of the current Brazilian government policy for attention-deficit/hyperactivity disorder (ADHD treatment and how much the country would save if treatment with immediate-release methylphenidate (MPH-IR, as suggested by the World Health Organization (WHO, was offered to patients with ADHD. Method: Based on conservative previous analyses, we assumed that 257,662 patients aged 5 to 19 years are not receiving ADHD treatment in Brazil. We estimated the direct costs and savings of treating and not treating ADHD on the basis of the following data: a spending on ADHD patients directly attributable to grade retention and emergency department visits; and b savings due to impact of ADHD treatment on these outcomes. Results: Considering outcomes for which data on the impact of MPH-IR treatment are available, Brazil is probably wasting approximately R$ 1.841 billion/year on the direct consequences of not treating ADHD in this age range alone. On the other hand, treating ADHD in accordance with WHO recommendations would save approximately R$ 1.163 billion/year. Conclusions: By increasing investments on MPH-IR treatment for ADHD to around R$ 377 million/year, the country would save approximately 3.1 times more than is currently spent on the consequences of not treating ADHD in patients aged 5 to 19 years.

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

    Science.gov (United States)

    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).

  14. Plasma and faecal testosterone and estradiol in chicken

    International Nuclear Information System (INIS)

    Mekchay, S.; Apichartsrungkoon, T.; Pongpiachan, P.

    1996-01-01

    Identification of sex in some kind of fowls can not be done by using their external appearances. Sex steroid hormone levels may be used as an indicator of sexual dimorphism in birds. The objective of this investigation was to measure plasma and faecal testosterone and estradiol concentrations in 8 male and 15 female chickens by using radioimmunoassay (RIA) technique. The relationship between plasma and faecal testosterone, and plasma and faecal estradiol are positively correlated. The correlation coefficients (r 2 ) between plasma and faecal steroids concentration were 0.621 (p<0.05) for testosterone and 0.692 (p<0.05) for estradiol. The average plasma and faecal sex steroid concentrations in male and female chickens were 10.05 ± 1.97 ng/ml and 511.50 ± 95.89 ng/g (for male testosterone), 24.85 ± 1.60 pg/ml and 49.65 ± 6.01 ng/g (for male estradiol), 0.79 ± 0.05 ng/ml and 134.20 ± 14.70 ng/ml (for female testosterone), 129.91 ± 19.30 pg/ml and 334.80 ± 15.62 ng/g (for female estradiol), respectively. Plasma and faecal testosterone and estradiol levels in male and female chickens are significant difference (p<0.01, p<0.01, p<0.001 and p<0.001 respectively). The results of this investigation suggested that plasma or faecal sex steroid concentrations can be used to discriminate sex of chicken which is show the possibility to use the plasma or faecal sex steroids for identification of sex in other bird species

  15. Patient education in groups increases knowledge of osteoporosis and adherence to treatment

    DEFF Research Database (Denmark)

    Nielsen, Dorthe; Ryg, Jesper; Nielsen, Winnie

    2010-01-01

    OBJECTIVE: Non-adherence to pharmacological treatment in osteoporosis is a well-recognized problem. We hypothesized that a group-based educational programme would increase patients' knowledge and level of adherence with medical treatment. METHODS: A total of 300 patients (32 men aged 65 ± 9 years...... and 268 women aged 63 ± 8 years), recently diagnosed with osteoporosis, were randomised to either an osteoporosis school programme (four classes of 8-12 participants over four weeks) or a control group. Teaching was multidisciplinary, based on patients' experiences and background and designed to encourage...... empowerment. Patients' knowledge about osteoporosis and adherence to treatment was assessed with self-completed questionnaires at baseline and after 3, 12, and 24 months. RESULTS: There were no significant differences at baseline between the two groups with respect to knowledge score or level of adherence...

  16. Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik Lykke; Reinisch, June M

    2003-01-01

    OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal...... neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code...... 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug...

  17. Continuous positive airway pressure treatment increases bronchial reactivity in obstructive sleep apnea patients.

    Science.gov (United States)

    Korczynski, Piotr; Gorska, Katarzyna; Przybylowski, Tadeusz; Bielicki, Piotr; Zielinski, Jan; Chazan, Ryszarda

    2009-01-01

    The effects of continuous positive airway pressure (CPAP) treatment on the function of the lower airways are poorly understood. One of the methods used to determine the influence of positive pressure breathing on lower airways is the bronchial hyperreactivity test. Some authors report that CPAP increases bronchial hyperreactivity, while others report decreases. To assess the influence of CPAP treatment on bronchial reactivity and the effects of bronchial hyperreactivity on compliance to CPAP treatment. The study group consisted of 101 obstructive sleep apnea syndrome patients (88 men and 13 women) with a mean age of 51 ± 11 years, mean apnea-hypopnea index of 53 ± 20 and mean body mass index of 32.6 ± 5.4. Patients were randomly assigned to a treatment group that received 3 weeks of CPAP therapy (group 1) or to a nontreatment control group (group 2). Pulmonary function tests and the methacholine bronchial provocation test were performed at baseline and 3 weeks later. There were no statistically significant differences between treated and control groups in anthropometry and polysomnography variables. At baseline, bronchial hyperreactivity was found in 6 patients from group 1 and 5 patients from group 2. A significant increase in bronchial reactivity was observed after CPAP treatment. Log PC20M decreased from 1.38 ± 0.30 at baseline to 1.26 ± 0.50 (p bronchial hyperreactivity during CPAP treatment were characterized by significantly lower FEV1, FVC and MEF50 values. CPAP produces statistically significant bronchial hyperreactivity. However, there were no clinical symptoms and it is not necessary to withdraw previous therapies. Copyright © 2009 S. Karger AG, Basel.

  18. Free ammonia pre-treatment of secondary sludge significantly increases anaerobic methane production.

    Science.gov (United States)

    Wei, Wei; Zhou, Xu; Wang, Dongbo; Sun, Jing; Wang, Qilin

    2017-07-01

    Energy recovery in the form of methane from sludge/wastewater is restricted by the poor and slow biodegradability of secondary sludge. An innovative pre-treatment technology using free ammonia (FA, i.e. NH 3 ) was proposed in this study to increase anaerobic methane production. The solubilisation of secondary sludge was significantly increased after FA pre-treatment at up to 680 mg NH 3 -N/L for 1 day, under which the solubilisation (i.e. 0.4 mg SCOD/mg VS; SCOD: soluble chemical oxygen demand; VS: volatile solids) was >10 times higher than that without FA pre-treatment (i.e. 0.03 mg SCOD/mg VS). Biochemical methane potential assays showed that FA pre-treatment at above 250 mg NH 3 -N/L is effective in improving anaerobic methane production. The highest improvement in biochemical methane potential (B 0 ) and hydrolysis rate (k) was achieved at FA concentrations of 420-680 mg NH 3 -N/L, and was determined as approximately 22% (from 160 to 195 L CH 4 /kg VS added) and 140% (from 0.22 to 0.53 d -1 ) compared to the secondary sludge without pre-treatment. More analysis revealed that the FA induced improvement in B 0 and k could be attributed to the rapidly biodegradable substances rather than the slowly biodegradable substances. Economic and environmental analyses showed that the FA-based technology is economically favourable and environmentally friendly. Since this FA technology aims to use the wastewater treatment plants (WWTPs) waste (i.e. anaerobic digestion liquor) to enhance methane production from the WWTPs, it will set an example for the paradigm shift of the WWTPs from 'linear economy' to 'circular economy'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood cells.

    Science.gov (United States)

    Birgegård, G; Sandhagen, B

    2001-01-01

    Some patients experience an improved well-being during treatment with recombinant human erythropoietin even with an unchanged Hb level. We have hypothesized that this may not be only a placebo effect. 2,3-diphosphoglycerate (2,3-DPG) in red blood cells increases in response to anaemia/hypoxia and causes a shift of the oxygen dissociation curve, allowing a more effective oxygen delivery. We have investigated red cell 2,3-DPG concentrations during erythropoietin treatment in healthy volunteers as a mediator of a possible physiological explanation. Thirteen healthy subjects with no iron deficiency were recruited and randomly assigned to a treatment group comprising five males and three females and a control group including three males and two females. The treatment group was treated with erythropoietin (Recormon), 20 IE/kg subcutaneously three times/week for 4 weeks. Blood samples were collected at each injection day and 10 days after the last injection and at corresponding times in the control group. B-Hb, red cell 2,3-DPG and P50 were measured by standard techniques and oxygen-releasing capacity was calculated. due to the sampling (26 ml each time, three times/week) the mean Hb level was lowered from 140.5 +/- 5.9 to 128.6 +/- 10.4 g/L in the control group whereas the erythropoietin treatment group maintained a mean Hb level of about 142 g/L (plevel curve as well as that for oxygen releasing capacity also differed significantly between the two groups (p levels. treatment with erythropoietin causes an increase in red cell 2,3-DPG levels.

  20. Treatment Resistant Epilepsy in Autism Spectrum Disorder: Increased Risk for Females.

    Science.gov (United States)

    Blackmon, Karen; Bluvstein, Judith; MacAllister, William S; Avallone, Jennifer; Misajon, Jade; Hedlund, Julie; Goldberg, Rina; Bojko, Aviva; Mitra, Nirmala; Giridharan, Radha; Sultan, Richard; Keller, Seth; Devinsky, Orrin

    2016-02-01

    The male:female ratio in autism spectrum disorder (ASD) averages greater than 4:1 while the male:female ratio of ASD with epilepsy averages less than 3:1. This indicates an elevated risk of epilepsy in females with ASD; yet, it is unknown whether phenotypic features of epilepsy and ASD differ between males and females with this comorbidity. The goal of this study is to investigate sex differences in phenotypic features of epilepsy and ASD in a prospective sample of 130 children and young adults with an initial ASD diagnosis and subsequent epilepsy diagnosis. All participants were characterized by standardized diagnostic inventories, parent/caregiver completed questionnaires, and medical/academic record review. Diagnostic classifications of epilepsy, ASD, and intellectual disability were performed by board certified neurologists and a pediatric neuropsychologist. Results demonstrated a lower male:female ratio (1.8:1) in individuals with ASD and treatment-resistant epilepsy relative to those with ASD and treatment-responsive epilepsy (4.9:1), indicating a higher risk of treatment-resistant epilepsy in females. Mild neuroimaging abnormalities were more common in females than males and this was associated with increased risk of treatment-resistance. In contrast, ASD symptom severity was lower in females compared with males. Findings distinguish females with ASD and epilepsy as a distinct subgroup at higher risk for a more severe epilepsy phenotype in the context of a less severe ASD phenotype. Increased risk of anti-epileptic treatment resistance in females with ASD and epilepsy suggests that comprehensive genetic, imaging, and neurologic screening and enhanced treatment monitoring may be indicated for this subgroup. Autism Res 2016, 9: 311-320. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  1. Reduced estradiol-induced vasodilation and poly-(ADP-ribose polymerase (PARP activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS.

    Directory of Open Access Journals (Sweden)

    Gabriella Masszi

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT. After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE. Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose polymerase (PARP activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  2. Reduced estradiol-induced vasodilation and poly-(ADP-ribose) polymerase (PARP) activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Masszi, Gabriella; Horvath, Eszter Maria; Tarszabo, Robert; Benko, Rita; Novak, Agnes; Buday, Anna; Tokes, Anna-Maria; Nadasy, Gyorgy L; Hamar, Peter; Benyó, Zoltán; Varbiro, Szabolcs

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  3. Night shift work and other determinants of estradiol, testosterone, and dehydroepiandrosterone sulfate among middle-aged nurses and midwives.

    Science.gov (United States)

    Peplonska, Beata; Bukowska, Agnieszka; Lie, Jenny Anne; Gromadzinska, Jolanta; Zienolddiny, Shanbeh

    2016-09-01

    The aims of our study were to (i) investigate the association between rotating night shift work and blood concentrations of estradiol, testosterone and dehydroepiandrosterone sulfate (DHEAS) and (2) evaluate the role of their non-occupational determinants. A cross-sectional study was conducted on 345 premenopausal and 187 postmenopausal nurses and midwives (263 women working rotating night shifts and 269 women working during days). Data from in-person interviews were used, anthropometric measurements were performed, and body mass index (BMI) and waist- to-hip ratio were calculated. Morning blood and spot urine samples were collected. Multiple linear regression models were fitted with hormone concentrations as dependent variables, and night shift work characteristics and demographic, reproductive, lifestyle and anthropometric determinants as independent variables. Modification of the effect by chronotype was examined. Among postmenopausal women, we observed a statistically significant positive association between the total duration of night shift work >15 years and estradiol level (Pnight work duration Night shift work characteristics were significantly associated with estradiol among morning-type postmenopausal women. The well-established associations between hormones and their major determinants, such as age and BMI, were confirmed. The findings of our study imply that prolonged night shift work may be associated with increased estradiol levels among postmenopausal women, especially among the morning-type postmenopausal women.

  4. Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

    Science.gov (United States)

    Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, Pkale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone. PMID:25084454

  5. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Hong-xia Xue

    2015-01-01

    Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  6. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

    Science.gov (United States)

    Xue, Hong-Xia; Fu, Wen-Yi; Cui, Hua-Dong; Yang, Li-Li; Zhang, Ning; Zhao, Li-Juan

    2015-05-01

    Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  7. IGF-1 levels may increase paradoxically with dopamine agonist treatment for prolactinomas.

    Science.gov (United States)

    Akirov, Amit; Greenman, Yona; Glaser, Benjamin; S'chigol, Irena; Mansiterski, Yossi; Eizenberg, Yoav; Shraga-Slutzky, Ilana; Shimon, Ilan

    2018-05-04

    Hyperprolactinemia is common in acromegaly and in these patients, insulin-like growth factor (IGF)-1 level may decrease with dopamine agonist. We report a series of patients with prolactinoma and a paradoxical increase of IGF-1 levels during cabergoline treatment. Clinical characteristics and response to treatment of patients with prolactinomas, in whom normal or slightly elevated baseline IGF-1 levels increased with cabergoline. The cohort consisted of ten prolactinoma patients (nine males, mean age 48 ± 14 years). Mean adenoma size was 23.8 ± 16.2 mm, with cavernous sinus invasion in eight. In five patients baseline IGF-1 levels were normal and in four levels were 1.2-1.5-fold the upper limit of the normal (ULN). One patient had IGF-1 measured shortly after initiating cabergoline and it was 1.4 × ULN. During cabergoline treatment (dose range 0.5-2 mg/week) PRL normalization was achieved in all and tumor shrinkage occurred in seven patients. The mean IGF-1 increase on cabergoline was 1.7 ± 0.4 × ULN. Cabergoline dose reduction or interruption was attempted in five patients and resulted in decreased IGF-1 levels in all, including normalization in two patients. Three patients were eventually diagnosed with acromegaly, one was referred for pituitary surgery followed by complete remission, another patient was switched to somatostatin analogue, and the third was treated by combination of somatostatin analogues with pegvisomant, with reduction of IGF-1 in all these patients. IGF-1 levels may increase to clinically significant levels during cabergoline treatment for PRL-adenoma. We suggest IGF-1 monitoring in all patients treated with dopamine agonists and not only in those presenting symptoms of acromegaly.

  8. Increased risk of treatment with antidepressants in stroke compared with other chronic illness

    DEFF Research Database (Denmark)

    Dam, Henrik; Harhoff, Mette; Andersen, Per Kragh

    2007-01-01

    The prevalence of depression and anxiety is higher in patients with stroke than in the general population but it is unclear whether patients with stroke are at an increased risk of being treated for depression and anxiety compared with patients with other chronic illness. The objective...... of the present study was to investigate whether the rate of treatment with antidepressants is increased in patients with stroke compared with patients with other chronic illness and compared with the general population. By linkage of nationwide case registers, all patients who received a main diagnosis of stroke...

  9. Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression

    Science.gov (United States)

    Nugent, Allison C; Carlson, Paul J; Bain, Earle E; Eckelman, William; Herscovitch, Peter; Manji, Husseini; Zarate, Carlos A; Drevets, Wayne C

    2013-01-01

    Abnormal serotonin type 1A (5-HT1A) receptor function and binding have been implicated in the pathophysiology of mood disorders. Preclinical studies have consistently shown that stress decreases the gene expression of 5-HT1A receptors in experimental animals, and that the associated increase in hormone secretion plays a crucial role in mediating this effect. Chronic administration of the mood stabilizers lithium and divalproex (valproate semisodium) reduces glucocorticoid signaling and function in the hippocampus. Lithium has further been shown to enhance 5-HT1A receptor function. To assess whether these effects translate to human subject with bipolar disorder (BD), positron emission tomography (PET) and [18F]trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazino]-ethyl)-N-(2-pyridyl) cyclohexanecarboxamide ([18F]FCWAY) were used to acquire PET images of 5-HT1A receptor binding in 10 subjects with BD, before and after treatment with lithium or divalproex. Mean 5-HT1A binding potential (BPP) significantly increased following mood stabilizer treatment, most prominently in the mesiotemporal cortex (hippocampus plus amygdala). When mood state was also controlled for, treatment was associated with increases in BPP in widespread cortical areas. These preliminary findings are consistent with the hypothesis that these mood stabilizers enhance 5-HT1A receptor expression in BD, which may underscore an important component of these agents' mechanism of action. PMID:23926239

  10. The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-α production.

    Science.gov (United States)

    Dimitrijević, Mirjana; Stanojević, Stanislava; Kuštrimović, Nataša; Mitić, Katarina; Vujić, Vesna; Aleksić, Iva; Radojević, Katarina; Leposavić, Gordana

    2013-11-01

    The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-α and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17β-estradiol on LPS-induced macrophage TNF-α and NO production. Results showed that: (a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-α, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-α production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-α and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity.

  11. Treatment with cinacalcet increases plasma sclerostin concentration in hemodialysis patients with secondary hyperparathyroidism.

    Science.gov (United States)

    Kuczera, Piotr; Adamczak, Marcin; Więcek, Andrzej

    2016-11-15

    Sclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes. Sclerostin decreases the osteoblast-related bone formation through the inhibition of the Wnt/β-catenin pathway. Osteocytes also express the Calcium sensing receptor which is a target for cinacalcet. The aim of this study was to assess the influence of six-month cinacalcet treatment on plasma sclerostin concentration in hemodialysed patients with secondary hyperparathyroidism (sHPT). In 58 hemodialysed patients with sHPT (PTH > 300 pg/ml) plasma sclerostin and serum PTH, calcium and phosphate concentrations were assessed before the first dose of cinacalcet and after 3 and 6 months of treatment. Serum PTH concentration decreased after 3 and 6 month of treatment from 1138 (931-1345) pg/ml to 772 (551-992) pg/ml and to 635 (430-839) pg/ml, respectively. Mean serum calcium and phosphate concentrations remained stable. Plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.66 (1.35-1.96) ng/ml, to 1.77 (1.43-2.12) ng/ml and to 1.87 (1.50-2.25) ng/ml, respectively. In 42 patients with cinacalcet induced serum PTH decrease plasma sclerostin concentration increased after 3 and 6 months of treatment from 1.51 (1.19-1.84) ng/ml to 1.59 (1.29-1.89) ng/ml and to 1.75 (1.42-2.01) ng/ml, respectively. Contrary, in the 16 patients without cinacalcet induced serum PTH decrease plasma sclerostin concentration was stable. Plasma sclerostin concentrations correlated inversely with serum PTH concentrations at the baseline and also after 6 months of treatment. 1. In hemodialysed patients with secondary hyperparathyroidism treatment with cinacalcet increases plasma sclerostin concentration 2. This effect seems to be related to decrease of serum PTH concentration.

  12. Estradiol Valerate-induced Polycystic Ovary Syndrome: An Animal Model Study

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    F Mesbah

    2011-01-01

    Full Text Available Introduction & Objective: Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder and one of the most common causes of an ovulation among women in their reproductive age. Presence of cysts in the ovaries alteration in the blood levels of gonadotropine hormones and gaining weight are some of the main characteristics of PCOS among humans. Our goal was to investigate the possible occurrence of such conditions in animal models of PCOS. Materials & Methods: Forty five Sprague Dawely rats were divided into 3 equal groups: the treatment and sham groups were intramuscularly injected by a single dose of Estradiol Valerate (4 mg/rat, dissolved in 0.4 ml and equal volume of olive oil, respectively, and the control group without any injection. During the 12 weeks of study, the animal’s weights were measured once a week. After 8 weeks, serum levels of testosterone, estrogen, progesterone, Follicular Stimulating Hormone (FSH, Latinizing Hormone (LH and glucose were measured. Following 12 weeks, ovaries were removed and prepared for light microscopy. Histological characteristics of ovaries were observed after hematoxylin-eosin staining. Results: Animal weight and serum level of testosterone were significantly reduced among PCOS induced rats while progesterone, LH and glucose levels were elevated. There was no significant difference in estradiol and FSH levels among different group of animals. Many cysts and degenerating follicles were observed in the treatment group. Conclusion: PCOS can be experimentally produced by a single injection of Estradiol Valerate in the rat, but some of the complex aspects of PCOS are not clearly defined.

  13. Radioimmunological determination of plasma androstenione and dehydroepiandrosterone levels in hirsute women before and during therapy using cyproterone acetate and ethinyl estradiol

    International Nuclear Information System (INIS)

    Holzer, R.

    1982-01-01

    Plasma androstendione and dehydroepiandrosterone levels were determined in 54 hirsute women before and after treatment with cyproterone acetate and ethinyl estradiol. Anderostenione levels were, on an average, significantly higher than in normal control persons (1.97+-0.97 ng/ml as compared to 1.54+-0.46 ng/ml) while the dehydroepiandrosterone levels were nearly twice as high (9.99+-5.71 ng/ml as compared to 5.17+-1.98 ng/ml). Increased cortisol and 17-ketosteroid levels were recorded only in a few women with raised androgen levels. The improved clinical picture after therapy was not in all cases accompanied by lower hormone levels. On the other hand, lower hormone levels were measured also in women who did not improve. There appears to be no close correlation between the clinical picture and the plasma androstendione and dehydroepiandrosterone levels. (orig./MG) [de

  14. Does fertility treatment increase the risk of uterine cancer? A meta-analysis.

    Science.gov (United States)

    Saso, Srdjan; Louis, Louay S; Doctor, Farah; Hamed, Ali Hassan; Chatterjee, Jayanta; Yazbek, Joseph; Bora, Shabana; Abdalla, Hossam; Ghaem-Maghami, Sadaf; Thum, Meen-Yau

    2015-12-01

    An ongoing debate over the last two decades has focused on whether fertility treatment in women may lead to an increased risk of developing uterine cancer over a period of time. Uterine cancer (including mainly endometrial carcinoma and the less common uterine sarcoma) is the commonest reproductive tract cancer and the fourth commonest cancer in women in the UK. Our objective was to assess the association between fertility drugs used in the treatment of female infertility (both as an independent therapy and during in vitro fertilization cycles) and the development of uterine cancer. A literature search was performed using Medline, Embase, Cochrane Library and Google Scholar databases for comparative studies until December 2014 to investigate a clinical significance of fertility treatment on the incidence of developing uterine cancer. General and MESH search headings, as well as the 'related articles' function were applied. All comparative studies of 'fertility treatment' versus 'non-fertility treatment' reporting the incidence of uterine cancer as an outcome were included. Uterine cancer incorporated the following terms: uterine cancer, uterine body tumours, uterine sarcomas and endometrial cancers. The primary outcome of interest was the uterine cancer incidence in all 'fertility treatment' versus 'non-fertility treatment' patient groups. Secondary outcomes of interest were: (a) uterine cancer incidence in 'IVF' versus 'non-IVF' patient groups; and (b) uterine cancer incidence according to type of fertility drug used. Odds ratio was the summary statistic. Random-effects modelling, graphical exploration and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. We included six studies in our final analysis, which comprised 776,224 patients in total. Of these, 103,758 had undergone fertility treatment and 672,466 had not. There was 100% agreement between the two reviewers regarding the data extraction. All the studies

  15. Chronic lithium treatment increased intracellular S100ß levels in rat primary neuronal culture.

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    Masoumeh Emamghoreishi

    2015-02-01

    Full Text Available S100ß a neurotrophic factor mainly released by astrocytes, has been implicated in the pathogenesis of bipolar disorder. Thus, lithium may exert its neuroprotective effects to some extent through S100ß. Furthermore, the possible effects of lithium on astrocytes as well as on interactions between neurons and astrocytes as a part of its mechanisms of actions are unknown. This study was undertaken to determine the effect of lithium on S100β in neurons, astrocytes and a mixture of neurons and astrocytes. Rat primary astrocyte, neuronal and mixed neuro-astroglia cultures were prepared from cortices of 18-day's embryos. Cell cultures were exposed to lithium (1mM or vehicle for 1day (acute or 7 days (chronic. RT-PCR and ELISA determined S100β mRNA and intra- and extracellular protein levels. Chronic lithium treatment significantly increased intracellular S100β in neuronal and neuro-astroglia cultures in comparison to control cultures (P<0.05. Acute and chronic lithium treatments exerted no significant effects on intracellular S100β protein levels in astrocytes, and extracellular S100β protein levels in three studied cultures as compared to control cultures. Acute and chronic lithium treatments did not significantly alter S100β mRNA levels in three studied cultures, compared to control cultures. Chronic lithium treatment increased intracellular S100ß protein levels in a cell-type specific manner which may favor its neuroprotective action. The findings of this study suggest that lithium may exert its neuroprotective action, at least partly, by increasing neuronal S100ß level, with no effect on astrocytes or interaction between neurons and astrocytes.

  16. FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment

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    Arianna Smerieri

    2014-10-01

    Full Text Available Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF. The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-, whereas winged helix forkhead (FOXO1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

  17. Using the internet to understand smokers' treatment preferences: informing strategies to increase demand.

    Science.gov (United States)

    Westmaas, J Lee; Abroms, Lorien; Bontemps-Jones, Jeuneviette; Bauer, Joseph E; Bade, Jeanine

    2011-08-26

    Most smokers attempt to quit on their own even though cessation aids can substantially increase their chances of success. Millions of smokers seek cessation advice on the Internet, so using it to promote cessation products and services is one strategy for increasing demand for treatments. Little is known, however, about what cessation aids these smokers would find most appealing or what predicts their preferences (eg, age, level of dependence, or timing of quit date). The objective of our study was to gain insight into how Internet seekers of cessation information make judgments about their preferences for treatments, and to identify sociodemographic and other predictors of preferences. An online survey assessing interest in 9 evidence-based cessation products and services was voluntarily completed by 1196 smokers who visited the American Cancer Society's Great American Smokeout (GASO) webpage. Cluster analysis was conducted on ratings of interest. In total, 48% (572/1196) of respondents were "quite a bit" or "very much" interested in nicotine replacement therapy (NRT), 45% (534/1196) in a website that provides customized quitting advice, and 37% (447/1196) in prescription medications. Only 11.5% (138/1196) indicated similar interest in quitlines, and 17% (208/1196) in receiving customized text messages. Hierarchical agglomerative cluster analysis revealed that interest in treatments formed 3 clusters: interpersonal-supportive methods (eg, telephone counseling, Web-based peer support, and in-person group programs), nonsocial-informational methods (eg, Internet programs, tailored emails, and informational booklets), and pharmacotherapy (NRT, bupropion, and varenicline). Only 5% (60/1196) of smokers were "quite a bit" or "very much" interested in interpersonal-supportive methods compared with 25% (298/1196) for nonsocial-informational methods and 33% (399/1196) for pharmacotherapy. Multivariate analyses and follow-up comparisons indicated that level of interest in

  18. Comparison of follicular dynamics, superovulatory response, and embryo recovery between estradiol based and conventional superstimulation protocol in buffaloes (Bubalus bubalis

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    Narinder Singh

    2015-08-01

    Full Text Available Aim: To evaluate the follicular dynamics, superovulatory response, and embryo recovery following superstimulatory treatment initiated at estradiol-17β induced follicular wave emergence and its comparison with conventional superstimulatory protocol in buffaloes. Materials and Methods: Six normal cycling pluriparous buffaloes, lactating, 90-180 days post-partum, and weighing between 500 and 660 kg were superstimulated twice with a withdrawal period of 35 days in between two treatments. In superstimulation protocol-1 (estradiol group buffaloes were administered estradiol-17β (2 mg, i.m. and eazibreed controlled internal drug release (CIDR was inserted intravaginally (day=0 at the random stage of the estrous cycle. On the day 4, buffaloes were superstimulated using follicle stimulating hormone (FSH 400 mg, divided into 10 tapering doses given at 12 hourly intervals. Prostaglandin F2α analogs (PGF2α was administered at day 7.5 and day 8, and CIDR was removed with the second PGF2α injection. In superstimulation protocol - 2 (conventional group buffaloes were superstimulated on the 10th day of the estrous cycle with same FSH dose regimen and similar timings for PGF2α injections. In both groups, half of the buffaloes were treated with luteinizing hormone (LH 25 mg and other half with 100 ug buserelin; gonadotrophin releasing hormone (GnRH analog at 12 h after the end of FSH treatment. All buffaloes in both protocols were inseminated twice at 12 and 24 h of LH/GnRH treatment. Daily ultrasonography was performed to record the size and number of follicles and superovulatory response. Results: Significantly higher number of small follicles (8 mm, corpora lutea, and transferable embryos was higher in buffaloes superstimulated at estradiol-induced follicular wave compared to the conventional protocol: Further the percentage of transferable embryos was significantly higher in buffaloes administered with LH compared to GnRH.

  19. INCREASED OIL RECOVERY FROM MATURE OIL FIELDS USING GELLED POLYMER TREATMENTS

    Energy Technology Data Exchange (ETDEWEB)

    G.P. Willhite; D.W. Green; C.S. McCool

    2003-05-01

    Gelled polymer treatments are applied to oil reservoirs to increase oil production and to reduce water production by altering the fluid movement within the reservoir. This report describes the results of a three-year research program aimed at reducing barriers to the widespread use of gelled polymer treatments by (1) developing methods to predict gel behavior during placement in matrix rock and fractures, (2) determining the persistence of permeability reduction after gel placement, and (3) developing methods to design production well treatments to control water production. The work focused on the gel system composed of polyacrylamide and chromium acetate. The molar mass of the polymer was about six million. Chromium(III) acetate reacted and formed crosslinks between polymer molecules. The crosslinked polymer molecules, or pre-gel aggregates, combine and grow to eventually form a 3-dimensional gel. A fundamental study to characterize the formation and growth of pre-gel aggregates was conducted. Two methods, flow field-flow fractionation (FFFF) and multi-angle laser light scattering (MALLS) were used. Studies using FFFF were inconclusive. Data taken using MALLS showed that at the gel time the average molar mass of gel aggregates increased by a factor of about three while the average size increase was approximately 50%. Increased acetate concentration in the gelant increases the gel time. The in situ performance of an added-acetate system was investigated to determine the applicability for in-depth treatments. Increased acetate concentrations delayed the development of increased flow resistance during gelant injection in short sandpacks. The development of increased flow resistance (in situ gelation) was extended from 2 to 34 days by increasing the acetate-to-chromium ratio from 38 to 153. In situ gelation occurred at a time that was approximately 22% of the bulk gelation time. When carbonate rocks are treated with gel, chromium retention in the rock may limit in

  20. Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration?

    Science.gov (United States)

    Sibille, KT; Bartsch, F; Reddy, D; Fillingim, RB; Keil, A

    2016-01-01

    Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promoting adaptive, treatment responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain’s response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimizing learning and positive central nervous system (CNS) adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research however has identified a wide spectrum of methods that can be used to “re-open” and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, which are non-invasive, inexpensive to administer, implementable in numerous settings, and may be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, providing evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain. PMID:26848123

  1. Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects.

    Science.gov (United States)

    Martina, Valentino; Benso, Andrea; Gigliardi, Valentina Ramella; Masha, Andi; Origlia, Carla; Granata, Riccarda; Ghigo, Ezio

    2006-03-01

    Several clinical and population-based studies suggest that dehydroepiandrosterone (DHEA) and its sulphate (DHEA-S) play a protective role against atherosclerosis and coronary artery disease in human. However, the mechanisms underlying this action are still unknown. It has recently been suggested that DHEA-S could delay atheroma formation through an increase in nitric oxide (NO) production. Twenty-four aged male subjects [age (mean +/- SEM): 65.4 +/- 0.7 year; range: 58.2-67.6 years] underwent a blinded placebo controlled study receiving DHEA (50 mg p.o. daily at bedtime) or placebo for 2 months. Platelet cyclic guanosine-monophosphate (cGMP) concentration (as marker of NO production) and serum levels of DHEA-S, DHEA, IGF-I, insulin, glucose, oestradiol (E(2)), testosterone, plasminogen activator inhibitor (PAI)-1 antigen (PAI-1 Ag), homocysteine and lipid profile were evaluated before and after the 2-month treatment with DHEA or placebo. At the baseline, all variables in the two groups were overlapping. All parameters were unchanged after treatment with placebo. Conversely, treatment with DHEA (a) increased (P < 0.001 vs. baseline) platelet cGMP (111.9 +/- 7.1 vs. 50.1 +/- 4.1 fmol/10(6) plts), DHEA-S (13.6 +/- 0.8 vs. 3.0 +/- 0.3 micromol/l), DHEA (23.6 +/- 1.7 vs. 15.3 +/- 1.4 nmol/l), testosterone (23.6 +/- 1.0 vs. 17.7 +/- 1.0 nmol/l) and E(2) (72.0 +/- 5.0 vs. 60.0 +/- 4.0 pmol/l); and (b) decreased (P < 0.05 vs. baseline) PAI-1 Ag (27.4 +/- 3.8 vs. 21.5 +/- 2.5 ng/ml) and low-density lipoprotein (LDL) cholesterol (3.4 +/- 0.2 vs. 3.0 +/- 0.2 mmol/l). IGF-I, insulin, glucose, triglycerides, total cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and homocysteine levels were not modified by DHEA treatment. This study shows that short-term treatment with DHEA increased platelet cGMP production, a marker of NO production, in healthy elderly subjects. This effect is coupled with a decrease in PAI-1

  2. Increased trends in the use of treatment-limiting decisions in a regional neurosurgical unit.

    Science.gov (United States)

    Wilson, William T; McMillan, Tristan; Young, Adam M H; White, Mark A J

    2017-04-01

    Treatment-limiting decisions (TLDs) are employed to actively withhold treatment from patients whom clinicians feel would derive no benefit or suffer detrimental effects from further intervention. The use of such decisions has been heavily discussed in the media and clinicians in the past have been reluctant to institute them, even though it is in the best interests of the patients. Their use is influenced by several ethical, religious and social factors all of which have changed significantly over time. This study reports the trends in use of TLDs in a regional neurosurgical unit over 23 years. Patient archives were reviewed to identify the number of admissions and procedures performed at the Institute of Neurological Sciences, Glasgow, in the years 1988, 1997 and 2011. Death certificate records were used to identify mortality in the unit in the year 2011. Patient records were used to obtain details of diagnosis, time from admission to death, and the presence and timing of a TLD. The results show an increase in the use of TLDs, with decisions made for 89% of those who died in 2011, compared to 68% in 1997 and 51% in 1988. The number of admissions has increased substantially since 1988 as has the percentage of patients undergoing surgery (46, 67 and 72% in 1988, 1997 and 2011, respectively). There is a trending increase in the number of patients who have a TLD in our regional neurosurgical unit. This demonstrates an increased willingness of clinicians to recognise poor prognosis and to withdraw or withhold treatment in these cases. Continued appropriate use of the TLD is recommended but it is to only ever reflect the best interests of the patient.

  3. Increased incidence of bowel cancer after non-surgical treatment of appendicitis.

    Science.gov (United States)

    Enblad, Malin; Birgisson, Helgi; Ekbom, Anders; Sandin, Fredrik; Graf, Wilhelm

    2017-11-01

    There is an ongoing debate on the use of antibiotics instead of appendectomy for treating appendicitis but diagnostic difficulties and longstanding inflammation might lead to increased incidence of bowel cancer in these patients. The aim of this population-based study was to investigate the incidence of bowel cancer after non-surgical treatment of appendicitis. Patients diagnosed with appendicitis but lacking the surgical procedure code for appendix removal were retrieved from the Swedish National Inpatient Register 1987-2013. The cohort was matched with the Swedish Cancer Registry and the standardised incidence ratios (SIR) with 95% confidence interval (95% CI) for appendiceal, colorectal and small bowel cancers were calculated. Of 13 595 patients with non-surgical treatment of appendicitis, 352 (2.6%) were diagnosed with appendiceal, colorectal or small bowel cancer (SIR 4.1, 95% CI 3.7-4.6). The largest incidence increase was found for appendiceal (SIR 35, 95% CI 26-46) and right-sided colon cancer (SIR 7.5, 95% CI 6.6-8.6). SIR was still elevated when excluding patients with less than 12 months since appendicitis and the incidence of right-sided colon cancer was elevated five years after appendicitis (SIR 3.5, 95% CI 2.1-5.4). An increased incidence of bowel cancer was found after appendicitis with abscess (SIR 4.6, 95% CI 4.0-5.2), and without abscess (SIR 3.5, 95% CI 2.9-4.1). Patients with non-surgical treatment of appendicitis have an increased short and long-term incidence of bowel cancer. This should be considered in the discussion about optimal management of patients with appendicitis. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  4. Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

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    Zahra Moinfar

    Full Text Available Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43 and estrogen receptors (ERs. Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2 on Cx43 expression in two glioma cell lines with variable native expression of Cx43.F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique.E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells.These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.

  5. The Intensity of Free Radical Processes and the Testosterone and Estradiol Levels in Seminal Fluid of Men with Different Types of Pathospermia - Personalized Approach

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    Shkurat T

    2016-05-01

    Full Text Available Background: We studied the intensity of free-radical processes and the testosterone and estradiol levels in seminal fluid of men with normospermia, asthenozoospermia, oligozoospermia, oligoasthenozoospermia, teratozoospermia. Results: An increased ability to generate reactive oxygen species in seminal fluid in patients with oligozoospermia was determined. Increased levels of testosterone and estradiol in semen were noted in pathospermia associated with reduced sperm motility. A positive correlation was found between the free-radical processes intensity and testosterone levels increase, and high correlation (r = 0.8 between the testosterone and estradiol levels in seminal fluid in patients with oligozoospermia was marked. Conclusion: The prooxidant and antioxidant processes conjugacy violation occurs in one of the pathospermia types - asthenozoospermia, which is reflected in the absence of all studied parameters correlation in the seminal fluid.

  6. Fluoxetine increases suicide ideation less than placebo during treatment of adults with minor depressive disorder.

    Science.gov (United States)

    Garlow, Steven J; Kinkead, Becky; Thase, Michael E; Judd, Lewis L; Rush, A John; Yonkers, Kimberly A; Kupfer, David J; Frank, Ellen; Schettler, Pamela J; Rapaport, Mark Hyman

    2013-09-01

    Some reports suggest an increase in suicide ideations and behaviors in patients treated with antidepressants. This is an analysis of the impact of fluoxetine on suicide ideations in outpatients with minor depressive disorder. Research subjects were adult outpatients with minor depressive disorder (N = 162), who received fluoxetine or placebo in a prospective, 12-week, double-blind randomized trial. The research participants were evaluated weekly with standard rating scales that included four suicide-related items: item 3 of the Hamilton Rating Scale for Depression (HRSD), item 18 of Inventory of Depressive Symptomatology (IDS-C), and items 15 and 59 of the Hopkins Symptom Checklist (SCL-90). Clinically significant intensification of suicide ideation was defined as an increase of ≥2 points on any of these items. Overall 60/162 subjects (37%) had an increase of ≥1 point during treatment and 17/162 (10.5%) of ≥2 points on at least one suicide item, with 12/81 (14.8%) placebo and 5/81 (6.2%) fluoxetine-treated subjects having a ≥2 point gain. Of the study participants with baseline suicide ideation, 9/22 (40.9%) placebo and 3/24 (12.5%) fluoxetine treated had ≥2 point increase (p = 0.04). Survival analysis revealed that subjects on placebo were significantly more likely (p = 0.050) to experience a ≥2 point increase on one or more item, a difference that emerged early and continued throughout the 12-week trial. Compared to placebo, fluoxetine was not associated with a clinically significant increase in suicide ideation among adults with minor depressive disorder during 12 weeks of treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Synthesis of 125I Labeled Estradiol-17-Hemisuccinate and Its Binding Study to Estrogen Receptors Using Scintillation Proximity Assay Method

    Directory of Open Access Journals (Sweden)

    Y. Susilo

    2012-12-01

    Full Text Available Research was carried out to obtain a selective ligand which strongly bind to estrogen receptors through determination of binding affinity of estradiol-17β-hemisuccinate. Selectivity of these compounds for estrogen receptor was studied using Scintillation Proximity Assay (SPA method. Primary reagents required in the SPA method including radioligand and receptor, the former was obtained by labeling of estradiol-17β-hemisuccinate with 125I, while MCF7 was used as the receptor. The labeling process was performed by indirect method via two-stage reaction. In this procedure, first step was activation of estradiol-17β-hemisuccinate using isobutylchloroformate and tributylamine as a catalist, while labeling of histamine with 125I was carried out using chloramin-T method to produce 125I-histamine. The second stage was conjugation of activated estradiol-17β-hemisuccinate with 125I-histamine. The product of estradiol-17β-hemisuccinate labeled 125I was extracted using toluene. Furtherly, the organic layer was purified by TLC system. Characterization of estradiol-17β-hemisuccinate labeled 125I from this solvent extraction was carried out by determining its radiochemical purity and the result was obtained using paper electrophoresis and TLC were 79.8% and 84.4% respectively. Radiochemical purity could be increased when purification step was repeated using TLC system, the result showed up to 97.8%. Determination of binding affinity by the SPA method was carried out using MCF7 cell lines which express estrogen receptors showed the value of Kd at 7.192 x 10-3 nM and maximum binding at 336.1 nM. This low value of Kd indicated that binding affinity of estradiol-17β-hemisuccinate was high or strongly binds to estrogen recepto

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  9. Effect of estradiol and oxytocin on ovine cervical relaxation

    African Journals Online (AJOL)

    Yomi

    2012-02-07

    Feb 7, 2012 ... The aim of this study was to examine the effect of estradiol (E2) and oxytocin ... Artificial insemination (AI) is a good way for the use of superior rams in reproduction but the conception rates in ... successful in sheep industry because it is costly, time .... during luteolysis and its abrogation in early pregnancy.

  10. 17 beta-estradiol affects osmoregulation in Fundulus heteroclitus

    NARCIS (Netherlands)

    Mancera, J.M.; Smolenaars, M.; Laiz-Carrion, R.; Rio, M. del; Wendelaar Bonga, S.E.; Flik, G.

    2004-01-01

    The effect of 17beta-estradiol (ED on osmoregulatory performance was examined in the euryhaline killifish, Fundulus heteroclitus. Fish were injected once with 1, 2 and 5 mug g(-1) E-2 and, 6 h after injection, transferred from I ppt seawater (SW) to full strength SW (40 ppt) or from SW to I ppt SW.

  11. Estimated Budget Impact of Increased Use of Mirabegron, A Novel Treatment for Overactive Bladder.

    Science.gov (United States)

    Perk, Sinem; Wielage, Ronald C; Campbell, Noll L; Klein, Timothy M; Perkins, Anthony; Posta, Linda M; Yuran, Thomas; Klein, Robert W; Ng, Daniel B

    2016-09-01

    Oral pharmacological treatment for overactive bladder (OAB) consists of antimuscarinics and the beta-3 adrenergic agonist mirabegron. Antimuscarinic adverse events (AEs) such as dry mouth, constipation, and blurry vision can result in frequent treatment discontinuation rates, leaving part of the OAB population untreated. Antimuscarinics also contribute to a patient's anticholinergic cognitive burden (ACB), so the Beers Criteria recommends cautious use of antimuscarinics in elderly patients who take multiple anticholinergic medications or have cognitive impairment. Since mirabegron does not affect the cholinergic pathways, it is unlikely to contribute to a patient's ACB. To estimate the health care costs associated with the pharmacological treatment of OAB with mirabegron and antimuscarinics from U.S. commercial payer and Medicare Advantage perspectives, using a budget impact model. For this budget impact model, 2 analyses were performed. The primary analysis estimated the budgetary impact of increasing the use of mirabegron in a closed patient cohort treated with oral pharmacological treatments. The secondary analysis modeled the economic impact in an open cohort by allowing untreated patients to begin treatment with mirabegron after potential contraindication, intolerance, or lack of effectiveness of antimuscarinics. The analyses were performed over a 3-year time horizon. The economic impact of increased mirabegron use was quantified using direct medical costs, including prescription costs and health resource utilization (HRU) costs. Costs of comorbidities included pharmacy and medical costs of treating OAB-related urinary tract infections (UTI), skin rashes, and depression. An analysis of a large single-site integrated health network database was commissioned to quantify ACB-related HRU in terms of the increases in yearly outpatient and emergency department visits. Based on this analysis, the model associated each unit increase in ACB score with increased HRU and

  12. Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance.

    Science.gov (United States)

    Preston, K L; Umbricht, A; Epstein, D H

    2000-04-01

    Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.

  13. Acute Stimulant Treatment and Reinforcement Increase the Speed of Information Accumulation in Children with ADHD.

    Science.gov (United States)

    Fosco, Whitney D; White, Corey N; Hawk, Larry W

    2017-07-01

    The current studies utilized drift diffusion modeling (DDM) to examine how reinforcement and stimulant medication affect cognitive task performance in children with ADHD. In Study 1, children with (n = 25; 88 % male) and without ADHD (n = 33; 82 % male) completed a 2-choice discrimination task at baseline (100 trials) and again a week later under alternating reinforcement and no-reinforcement contingencies (400 trials total). In Study 2, participants with ADHD (n = 29; 72 % male) completed a double-blind, placebo-controlled trial of 0.3 and 0.6 mg/kg methylphenidate and completed the same task utilized in Study 1 at baseline (100 trials). Children with ADHD accumulated information at a much slower rate than controls, as evidenced by a lower drift rate. Groups were similar in nondecision time and boundary separation. Both reinforcement and stimulant medication markedly improved drift rate in children with ADHD (ds = 0.70 and 0.95 for reinforcement and methylphenidate, respectively); both treatments also reduced boundary separation (ds = 0.70 and 0.39). Reinforcement, which emphasized speeded accuracy, reduced nondecision time (d = 0.37), whereas stimulant medication increased nondecision time (d = 0.38). These studies provide initial evidence that frontline treatments for ADHD primarily impact cognitive performance in youth with ADHD by improving the speed/efficiency of information accumulation. Treatment effects on other DDM parameters may vary between treatments or interact with task parameters (number of trials, task difficulty). DDM, in conjunction with other approaches, may be helpful in clarifying the specific cognitive processes that are disrupted in ADHD, as well as the basic mechanisms that underlie the efficacy of ADHD treatments.

  14. Increase of Long-chain Branching by Thermo-oxidative Treatment of LDPE

    Science.gov (United States)

    Rolón-Garrido, Víctor H.; Luo, Jinji; Wagner, Manfred H.

    2011-07-01

    Low-density polyethylene (LDPE) was exposed to thermal and thermo-oxidative treatment at 170 °C, and subsequently characterized by linear-viscoelastic measurements and in uniaxial extension. The Molecular Stress Function (MSF) model was used to quantify the elongational viscosities measured. For the thermally treated samples, exposure times between 2 and 6 hours were applied. Formation of long-chain branching (LCB) was found to occur only during the first two hours of thermal treatment. At longer exposure times, no difference in the level of strain hardening was observed. This was quantified by use of the MSF model: the nonlinear parameter fmax2 increased from fmax2 = 14 for the virgin sample to fmax2 = 22 for the samples thermally treated between 2 and 6 hours. For the thermo-oxidatively treated samples, which were exposed to air during thermal treatment between 30 and 90 minutes, the level of strain hardening increases drastically up to fmax2 = 55 with increasing exposure times from 30 up to 75 min due to LCB formation, and then decreases for an exposure time of 90 minutes due to chain scission dominating LCB formation. The nonlinear parameter β of the MSF model was found to be β = 2 for all samples, indicating that the general type of the random branching structure remains the same under all thermal conditions. Consequently only the parameter fmax2 of the MSF model and the linear-viscoelastic spectra were required to describe quantitatively the experimental observations. The strain hardening index, which is sometimes used to quantify strain hardening, follows accurately the trend of the MSF model parameter fmax2.

  15. Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

    Science.gov (United States)

    Shahid, Adangam Purath; Salini, Sasidharan; Sasidharan, Nanu; Padikkala, Jose; Raghavamenon, Achuthan Chathrattil; Babu, Thekkekara Devassy

    2015-09-01

    Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. Endometrial thickening was induced by intraperitoneal injection of estradiol (20 μg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

  16. Effects of ethinyl estradiol plus desogestrel on premenstrual symptoms in Iranian women.

    Directory of Open Access Journals (Sweden)

    Abbas Norouzi Javidan

    2014-11-01

    Full Text Available Marvelon®, a combined oral contraceptive, contains 30 μg ethinyl estradiol (EE and 150 μg desogestrel (DE, and has been shown to be a well-tolerated and effective combination that provides high contraceptive reliability and good cycle control. However, its efficacy has not been yet evaluated among Iranian women. Thus, the study aimed to determine the effect of oral contraceptive pill on treating premenstrual symptoms and on various parameters associated with well-being and health in a sample of Iranian. This clinical trial (before- after study was performed at the family-planning clinic of the centers under the supervision of Tehran University of Medical Sciences on sixty-one women. The study protocol was approved by the Ethics Committee of Tehran University of Medical Sciences and all participants received a 21/7-day regimen of oral contraceptive containing 150 μg desogestrel (DE and 30 μg ethinyl estradiol (EE for six cycles. Efficacy parameters included changes in premenstrual symptoms were also assessed. Clinical data was collected by calendar of premenstrual experiences (COPE at baseline and treatment cycles 1,2, 3 and 6. Clinical variables were measured including low-density lipoprotein (LDL, high-density lipoprotein (HDL and triglyceride levels for two timing periods (baseline and last visit. Linear mixed model analyses were used to analyze differences in changes of the four factors of premenstrual syndrome (PMS, weight and blood pressure during these timing periods. The mean age of the women was 28.52 (SD=6.75 years. Participants on average had been pregnant 1.13 (SD=1.16 times. The linear mixed model analyses indicated that premenstrual syndrome symptoms reduced significantly over time (P0.05. A combined oral contraceptive containing ethinyl estradiol and desogestrel has a positive effect on women's health and reduces premenstrual symptoms.

  17. Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

    International Nuclear Information System (INIS)

    Werner Fürst, Rainer; Pistek, Veronika Leopoldine; Kliem, Heike; Skurk, Thomas; Hauner, Hans; Meyer, Heinrich Herman Dietrich; Ulbrich, Susanne Ernestine

    2012-01-01

    Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

  18. Maternal low-dose estradiol-17β exposure during pregnancy impairs postnatal progeny weight development and body composition

    Energy Technology Data Exchange (ETDEWEB)

    Werner Fürst, Rainer [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); ZIEL PhD Graduate school ‘Epigenetics, Imprinting and Nutrition’, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Pistek, Veronika Leopoldine; Kliem, Heike [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Skurk, Thomas; Hauner, Hans [ZIEL Dep. Nutritional Medicine, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Klinikum rechts der Isar, Technische Universität München, 81675 München (Germany); Meyer, Heinrich Herman Dietrich [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany); Ulbrich, Susanne Ernestine, E-mail: ulbrich@wzw.tum.de [Physiology Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan (Germany)

    2012-09-15

    Endocrine disrupting chemicals with estrogenic activity play an important role as obesogens. However, studies investigating the most potent natural estrogen, estradiol-17β (E2), at low dose are lacking. We examined endocrine and physiological parameters in gilts receiving distinct concentrations of E2 during pregnancy. We then investigated whether adverse effects prevail in progeny due to a potential endocrine disruption. E2 was orally applied to gilts during the entire period of pregnancy. The concentrations represented a daily consumption at the recommended ADI level (0.05 μg/kg body weight/day), at the NOEL (10 μg/kg body weight/day) and at a high dosage (1000 μg/kg body weight/day). Plasma hormone concentrations were determined using enzyme immuno assays. Offspring body fat was assessed by dual-energy X-ray absorptiometry scanning. In treated gilts receiving 1000 μg E2/kg body weight/day we found significantly elevated plasma E2 levels during pregnancy, paralleled by an increased weight gain. While offspring showed similar weight at birth, piglets exhibited a significant reduction in weight at weaning even though their mothers had only received 0.05 μg E2/kg body weight/day. At 8 weeks of age, specifically males showed a significant increase in overall body fat percentage. In conclusion, prenatal exposure to low doses of E2 affected pig offspring development in terms of body weight and composition. In line with findings from other obesogens, our data suggest a programming effect during pregnancy for E2 causative for the depicted phenotypes. Therefore, E2 exposure may imply a possible contribution to childhood obesity. -- Highlights: ► We investigate the potential role of estradiol-17β (E2) as an obesogen. ► We orally apply E2 at the ADI, NOEL and a high dose to gilts during pregnancy. ► Offspring weight is similar at birth but reduced at weaning even after ADI treatment. ► Male offspring only exhibit an increase in overall body fat percentage

  19. Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis.

    Science.gov (United States)

    Zhang, Ling; Xiong, Wenqian; Xiong, Yao; Liu, Hengwei; Li, Na; Du, Yu; Liu, Yi

    2016-03-01

    Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease. © 2016 by the Society for the Study of Reproduction, Inc.

  20. Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731.

    Directory of Open Access Journals (Sweden)

    Dorota Lemancewicz

    2010-01-01

    Full Text Available Endometrioid carcinoma represents approximately 10% of cases of the malignant ovarian epithelial tumors. According to literature, the vitamin A (carotenoids and retinoids plays an essential role in cell proliferation, differentiation and apoptosis in both normal and neoplastic ovarian tissues. Apart from that, the retinoids alter a cytotoxic effect of chemiotherapeutics, i.e. docetaxel, on ovarian cancer cell lines. Retinoids act on cancer cells throughout different mechanism than taxanes, so they may be the potential candidates for the new treatment strategies of ovarian cancer. The aim of the study was to determine the effects of vitamin A family compounds (retinol, beta-carotene, lycopene, all-trans -, 9-cis - and 13-cis retinoic acid on the growth and proliferation of CRL-11731 endometrioid ovary cancer cell line and on docetaxel and estradiol activity in this culture. The assay was based on [3H] thymidine incorporation and the proliferative activity of PCNA- and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in CRL-11731 cells were also studied. Among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner. Only the concentration of 100 muM of docetaxel inhibited incorporation [3H] thymidine into CRL-11731 cancer cells. Retinol (33.4%+/-8.5, carotenoids (beta-carotene 20 muM 4.7%+/-2.9, 50 muM 2.2%+/-0.9; lycopene 10 muM 7.6%+/-0.8, 20 muM 5.2%+/-2.5, 50 muM 2.9%+/-1.2, and 13-cis retinoic acid (19.7%+/-2.2 combined with docetaxel (100 muM significantly decreased the percentage of proliferating cells (p<0.0001. The antiproliferative action of lycopene alone and in combination with docetaxel was also confirmed in immunohistochemical examination (decreased the percentage of PCNA and Ki67 positive cells. Also retinol (10 muM and lycopene (20 and 50 muM combined with estradiol (0.01 muM statistically decreased the percentage of

  1. Increased rate of treatment with antidepressants in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Kessing, Lars Vedel; Harhoff, Mette; Andersen, Per Kragh

    2008-01-01

    The prevalence of depression and anxiety is increased in patients with multiple sclerosis, but it has not been investigated whether these conditions are treated in clinical practice. The objective of this study was to investigate whether the rate of treatment with antidepressants is increased...... in patients with multiple sclerosis compared with patients with other chronic illnesses and compared with the general population. By linkage of nationwide case registers, all patients were identified, who had received a main diagnosis of multiple sclerosis or osteoarthritis at first admission or during...... outpatient contact in the period 1995-2000 in Denmark. Rates of subsequent purchase of antidepressants for these patients were calculated. In total, 417 patients with a main diagnosis of multiple sclerosis and 12 127 patients with a main diagnosis of osteoarthritis, at first discharge from hospital...

  2. Long-term IGF-I treatment of children with Laron syndrome increases adiposity.

    Science.gov (United States)

    Laron, Zvi; Ginsberg, Shira; Lilos, Pnina; Arbiv, Mira; Vaisman, Nahum

    2006-02-01

    Laron syndrome (LS) is an autosomal recessive disease caused by deletions or mutations in the GH receptor gene leading to an inability of insulin-like growth factor I (IGF-I) generation. Among the major resulting body changes are dwarfism and obesity. The only effective treatment is daily administration of biosynthetic IGF-I. Body composition determination by DEXA (dual energy X-ray absorptiometry) of three girls with LS treated by IGF-I for 1, 3 and 11 1/2 years, respectively, revealed that concomitantly with the increase in growth there was a significant increase in body adipose tissue to double or triple the normal values. Due to the underdevelopment of the muscular and skeletal systems body mass index (BMI) did not accurately reflect the degree of obesity. In conclusion, IGF-I similar to insulin, exerts an adipogenic effect.

  3. The potential use of genetics to increase the effectiveness of treatment programs for criminal offenders.

    Science.gov (United States)

    Beaver, Kevin M; Jackson, Dylan B; Flesher, Dillon

    2014-01-01

    During the past couple of decades, the amount of research examining the genetic underpinnings to antisocial behaviors, including crime, has exploded. Findings from this body of work have generated a great deal of information linking genetics to criminal involvement. As a partial result, there is now a considerable amount of interest in how these findings should be integrated into the criminal justice system. In the current paper, we outline the potential ways that genetic information can be used to increase the effectiveness of treatment programs designed to reduce recidivism among offenders. We conclude by drawing attention to how genetic information can be used by rehabilitation programs to increase program effectiveness, reduce offender recidivism rates, and enhance public safety.

  4. Irisin levels increase after treatment in patients with newly diagnosed Hashimoto thyroiditis.

    Science.gov (United States)

    Uc, Z A; Gorar, S; Mizrak, S; Gullu, S

    2018-05-18

    Irisin is a newly identified myokine secreted by skeletal muscle and has significant effects on body metabolism. Thyroidal functional state has a profound influence on the metabolism of human body. Therefore, the aim of this study was to investigate the possible changes in serum irisin concentrations before and after treatment in hypothyroid subjects. The study included 26 patients with overt hypothyroidism due to Hashimoto thyroiditis and 19 healthy subjects. Baseline serum thyroid function tests and presence of thyroid autoantibodies and levels of creatine kinase (CK) and irisin were measured in both groups. All measurements in the hypothyroid group were repeated after euthyroidism was achieved. Serum irisin levels were significantly lower in the hypothyroid groups than the control group (p treatment (p hypothyroid patients were treated to achieve euthyroidism. To the best of our knowledge, this is the first study providing insight that low serum irisin levels significantly increased following treatment to euthyroid state in overt hypothyroid patients with Hashimoto thyroiditis. Larger scale studies are needed to confirm these results and to ensure irisin as a possible biomarker of Hashimoto's thyroiditis.

  5. The learning curve of laparoscopic treatment of rectal cancer does not increase morbidity.

    Science.gov (United States)

    Luján, Juan; Gonzalez, Antonio; Abrisqueta, Jesús; Hernandez, Quiteria; Valero, Graciela; Abellán, Israel; Frutos, María Dolores; Parrilla, Pascual

    2014-01-01

    The treatment of rectal cancer via laparoscopy is controversial due to its technical complexity. Several randomized prospective studies have demonstrated clear advantages for the patient with similar oncological results to those of open surgery, although during the learning of this surgical technique there may be an increase in complications and a worse prognosis. Our aim is to analyze how the learning curve for rectal cancer via laparoscopy influences intra- and postoperative results and oncological markers. A retrospective review was conducted of the first 120 patients undergoing laparoscopic surgery for rectal neoplasia. The operations were performed by the same surgical team with a wide experience in the treatment of open colorectal cancer and qualified to perform advanced laparoscopic surgery. We analyzed sex, ASA, tumour location, neoadjuvant treatment, surgical technique, operating time, conversion, postoperative complications, length of hospital stay, number of lymph nodes, stage and involvement of margins. Significant differences were observed with regard to surgical time (224 min in the first group, 204 min in the second group), with a higher rate of conversion in the first group (22.5%) than in the second (11.3%). No significant differences were noted for rate of conservative sphincter surgery, length of hospital stay, post-surgical complications, number of affected/isolated lymph nodes or affected circumferential and distal margins. It is possible to learn this complex surgical technique without compromising the patient's safety and oncological outcome. Copyright © 2013 AEC. Published by Elsevier Espana. All rights reserved.

  6. Increasing Water System Efficiency with Ultrafiltration Pre-treatment in Power Plants

    International Nuclear Information System (INIS)

    Majamaa, Katariina; Suarez, Javier; Gasia Eduard

    2012-09-01

    Water demineralization with reverse osmosis (RO) membranes has a long and successful history in water treatment for power plants. As the industry strives for more efficient, reliable and compact water systems, pressurized hollow-fiber ultrafiltration (UF) has become an increasingly appealing pre-treatment technology. Compared to conventional, non- membrane based pretreatments, ultrafiltration offers higher efficiency in the removal of suspended solids, microorganisms and colloidal matter, which are all common causes for operational challenges experienced in the RO systems. In addition, UF is more capable of handling varying feed water qualities and removes the risk of particle carry-over often seen with conventional filtration techniques. Ultrafiltration is a suitable treatment technology for various water types from surface waters to wastewater, and the more fluctuating or challenging the feed water source is, the better the benefits of UF are seen compared to conventional pretreatments. Regardless of the feed water type, ultrafiltration sustains a constant supply of high quality feed water to downstream RO, allowing a more compact and cost efficient RO system design with improved operational reliability. A detailed focus on the design and operational aspects and experiences of two plants is provided. These examples demonstrate both economical UF operation and tangible impact of RO process improvement. Experience from these plants can be leveraged to new projects. (authors)

  7. Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles.

    Science.gov (United States)

    Peccate, Cécile; Mollard, Amédée; Le Hir, Maëva; Julien, Laura; McClorey, Graham; Jarmin, Susan; Le Heron, Anita; Dickson, George; Benkhelifa-Ziyyat, Sofia; Piétri-Rouxel, France; Wood, Matthew J; Voit, Thomas; Lorain, Stéphanie

    2016-08-15

    In preclinical models for Duchenne muscular dystrophy, dystrophin restoration during adeno-associated virus (AAV)-U7-mediated exon-skipping therapy was shown to decrease drastically after six months in treated muscles. This decline in efficacy is strongly correlated with the loss of the therapeutic AAV genomes, probably due to alterations of the dystrophic myofiber membranes. To improve the membrane integrity of the dystrophic myofibers at the time of AAV-U7 injection, mdx muscles were pre-treated with a single dose of the peptide-phosphorodiamidate morpholino (PPMO) antisense oligonucleotides that induced temporary dystrophin expression at the sarcolemma. The PPMO pre-treatment allowed efficient maintenance of AAV genomes in mdx muscles and enhanced the AAV-U7 therapy effect with a ten-fold increase of the protein level after 6 months. PPMO pre-treatment was also beneficial to AAV-mediated gene therapy with transfer of micro-dystrophin cDNA into muscles. Therefore, avoiding vector genome loss after AAV injection by PPMO pre-treatment would allow efficient long-term restoration of dystrophin and the use of lower and thus safer vector doses for Duchenne patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the hypothalamus is independent of estrogen receptor-beta.

    Science.gov (United States)

    Rossi, Dania V; Dai, Ying; Thomas, Peter; Carrasco, Gonzalo A; DonCarlos, Lydia L; Muma, Nancy A; Li, Qian

    2010-08-01

    Estradiol regulates serotonin 1A (5-HT(1A)) receptor signaling. Since desensitization of 5-HT(1A) receptors may be an underlying mechanism by which selective serotonin reuptake inhibitors (SSRIs) mediate their therapeutic effects and combining estradiol with SSRIs enhances the efficacy of the SSRIs, it is important to determine which estrogen receptors are capable of desensitizating 5-HT(1A) receptor function. We previously demonstrated that selective activation of the estrogen receptor, GPR30, desensitizes 5-HT(1A) receptor signaling in rat hypothalamic paraventricular nucleus (PVN). However, since estrogen receptor-beta (ERbeta), is highly expressed in the PVN, we investigated the role of ERbeta in estradiol-induced desensitization of 5-HT(1A) receptor signaling. We first showed that a selective ERbeta agonist, diarylpropionitrile (DPN) has a 100-fold lower binding affinity than estradiol for GPR30. Administration of DPN did not desensitize 5-HT(1A) receptor signaling in rat PVN as demonstrated by agonist-stimulated hormone release. Second, we used a recombinant adenovirus containing ERbeta siRNAs to decrease ERbeta expression in the PVN. Reductions in ERbeta did not alter the estradiol-induced desensitization of 5-HT(1A) receptor signaling in oxytocin cells. In contrast, in animals with reduced ERbeta, estradiol administration, instead of producing desensitization, augmented the ACTH response to a 5-HT(1A) agonist. Combined with the results from the DPN treatment experiments, desensitization of 5-HT(1A) receptor signaling does not appear to be mediated by ERbeta in oxytocin cells, but that ERbeta, together with GPR30, may play a complex role in central regulation of 5-HT(1A)-mediated ACTH release. Determining the mechanisms by which estrogens induce desensitization may aid in the development of better treatments for mood disorders. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Estradiol attenuates EGF-induced rapid uPAR mobilization and cell migration via the G-protein-coupled receptor 30 in ovarian cancer cells

    DEFF Research Database (Denmark)

    Henic, Emir; Noskova, Vera; Høyer-Hansen, Gunilla

    2009-01-01

    : rapid mobilization of uPAR from detergent-resistant domains, increased mRNA, and decreased degradation. G-protein-coupled receptor 30 (GPR30) is a newly identified membrane estrogen receptor (ER).The objective of this study was to explore the effects of 17beta-estradiol (E(2)) on uPAR expression...... for ERalpha, and quantitative polymerase chain reaction. Estradiol attenuates the stimulatory effect of EGF on cell migration and uPAR expression. Specifically, E(2) reduces the very rapid increase of detergent extractable uPAR, which occurs within minutes of EGF stimulation and probably represents...... agonist G1, mimicked the effect of E(2) on uPAR expression and cell migration. OVCAR-3 cells express mRNA for GPR30.Estradiol attenuates EGF-induced mobilization of ligated uPAR from detergent-resistant domains and subsequent migration in ovarian cancer cells. The response to various ER ligands indicates...

  10. RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate,17B-estradiol and casein

    Science.gov (United States)

    This data file describes the bioinformatics analysis of uterine RNA-seq data comparing genome wide effects of feeding soy protein isolate compared to casein to ovariectomized female rats age 64 days relative to treatment of casein fed rats with 5 ug/kg/d estradiol and relative to rats treated with e...

  11. The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment.

    Science.gov (United States)

    Basse, Clémence; Arock, Michel

    2015-12-15

    Nowadays, the mechanisms governing the occurrence of cancer are thought to be the consequence not only of genetic defects but also of epigenetic modifications. Therefore, epigenetic has become a very attractive and increasingly investigated field of research in order to find new ways of prevention and treatment of neoplasia, and this is particularly the case for breast cancer (BC). Thus, this review will first develop the main known epigenetic modifications that can occur in cancer and then expose the future role that control of epigenetic modifications might play in prevention, prognostication, follow-up and treatment of BC. Indeed, epigenetic biomarkers found in peripheral blood might become new tools to detect BC, to define its prognostic and to predict its outcome, whereas epi-drugs might have an increasing potential of development in the next future. However, if DNA methyltransferase inhibitors and histone desacetylase inhibitors have shown encouraging results in BC, their action remains nonspecific. Thus, additional clinical studies are needed to evaluate more precisely the effects of these molecules, even if they have provided encouraging results in cotreatment and combined therapies. This review will also deal with the potential of RNA interference (RNAi) as epi-drugs. Finally, we will focus on the potential prevention of BC through epigenetic based on diet and we will particularly develop the possible place of isothiocyanates from cruciferous vegetables or of Genistein from soybean in a dietary program that might potentially reduce the risk of BC in large populations. © 2014 UICC.

  12. Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes.

    Directory of Open Access Journals (Sweden)

    Dionysios C Watson

    2018-02-01

    Full Text Available B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH cells. We studied the effects of native heterodimeric IL-15 (hetIL-15 treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN. Following hetIL-15 treatment, multiplexed quantitative image analysis (histo-cytometry of LN revealed increased numbers of granzyme B+ T cells in B cell follicles and SHIV RNA was decreased in plasma and in LN. Based on these properties, hetIL-15 shows promise as a potential component in combination immunotherapy regimens to target AIDS virus sanctuaries and reduce long-term viral reservoirs in HIV-1 infected individuals.ClinicalTrials.gov NCT02452268.

  13. Evaluation of medical treatments to increase survival of ebullism in guinea pigs

    Science.gov (United States)

    Stegmann, Barbara J.; Pilmanis, Andrew A.; Wolf, E. G.; Derion, Toniann; Fanton, J. W.; Davis, H.; Kemper, G. B.; Scoggins, Terrell E.

    1993-01-01

    Spaceflight carriers run a constant risk of exposure to vacuum. Above 63,000 ft (47 mmHg), the ambient pressure falls below the vapor pressure of water at 37 C, and tissue vaporization (ebullism) begins. Little is know about appropriate resuscitative protocols after such an ebullism exposure. This study identified injury patterns and mortality rates associated with ebullism while verifying effectiveness of traditional pulmonary resuscitative techniques. Male Hartley guinea pigs were exposed to 87,000 ft for periods of 40 to 115 sec. After descent, those animals that did not breathe spontaneously were given artificial ventilation by bag and mask for up to 15 minutes. Those animals surviving were randomly assigned to one of three treatment groups--hyperbaric oxygen (HBO), ground-level oxygen (GLO2), and ground-level air (GLAIR). The HBO group was treated on a standard treatment table 6A while the GLO2 animals received O2 for an equivalent length of time. Those animals in the GLAIR group were observed only. All surviving animals were humanely sacrified at 48 hours. Inflation of the animal's lungs after the exposure was found to be difficult and, at times, impossible. This may be due to surfactant disruption at the alveolar lining. Electron microscopy identified a disruption of the surfactant layer in animals that did not survive initial exposure. Mortality was found to increase with exposure time: 40 sec--0 percent; 60 sec--6 percent; 70 sec--40 percent; 80 sec--13 percent; 100 sec--38 percent; 110 sec--40 percent; and 115 sec--100 percent. There was no difference in the delayed mortality among the treatment groups (HBO--15 percent, GLO2--11 percent, GLAIR--11 percent). However, since resuscitation was ineffective, the effectiveness of any post-exposure treatment was severely limited. Preliminary results indicate that reuscitation of guinea pigs following ebullism exposure is difficult, and that current techniques (such as traditional CPR) may not be appropriate.

  14. Increasing complexity: which drug class to choose for treatment of hypertension in the elderly?

    Directory of Open Access Journals (Sweden)

    Kaiser EA

    2014-03-01

    Full Text Available Edelgard Anna Kaiser,1 Ulrich Lotze,2 Hans Hendrik Schäfer1,31Roche Diagnostics International AG, Rotkreuz, Switzerland; 2Department of Internal Medicine, DRK-Manniske-Krankenhaus Bad Frankenhausen, Bad Frankenhausen, Germany; 3Institute of Anatomy II, University Hospital Jena, Friedrich-Schiller University, Jena, GermanyAbstract: Treatment of hypertension in the elderly is expected to become more complex in the coming decades. Based on the current landscape of clinical trials, guideline recommendations remain inconclusive. The present review discusses the latest evidence derived from studies available in 2013 and investigates optimal blood pressure (BP and preferred treatment substances. Three common archetypes are discussed that hamper the treatment of hypertension in the very elderly. In addition, this paper presents the current recommendations of the NICE 2011, JNC7 2013-update, ESH/ESC 2013, CHEP 2013, JNC8 and ASH/ISH guidelines for elderly patients. Advantages of the six main substance classes, namely diuretics, beta-blockers (BBs, calcium channel blockers (CCBs, angiotensin-converting enzyme inhibitors (ACEIs, angiotensin receptor blockers (ARBs, and direct renin inhibitors (DRIs are discussed. Medical and economic implications of drug administration in the very elderly are presented. Avoidance of treatment-related adverse effects has become increasingly relevant. Current substance classes are equally effective, with similar effects on cardiovascular outcomes. Selection of substances should therefore also be based on collateral advantages of drugs that extend beyond BP reduction. The combination of ACEIs and diuretics appears to be favorable in managing systolic/diastolic hypertension. Diuretics are a preferred and cheap combination drug, and the combination with CCBs is recommended for patients with isolated systolic hypertension. ACEIs and CCBs are favorable for patients with dementia, while CCBs and ARBs imply substantial cost

  15. Can treatment of nocturia increase testosterone level in men with late onset hypogonadism?

    Science.gov (United States)

    Kim, Jong Wook; Chae, Ji Yun; Kim, Jin Wook; Yoon, Cheol Yong; Oh, Mi Mi; Park, Hong Seok; Kim, Je Jong; Moon, Du Geon

    2014-04-01

    To assess the effect of desmopressin on serum testosterone level in men with nocturia and late onset hypogonadism. We prospectively enrolled men with nocturia and symptoms of late onset hypogonadism. Desmopressin (0.1 mg) was administered once daily to patients for 12 weeks, and we then compared serum testosterone levels, electrolytes, frequency volume chart indices, and changes in the International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Aging Male's Symptom scales before and after treatment. Patients with a history of cardiovascular disease or hyponatremia, those using hypnotics, and those who had primary hypogonadism or hypogonadotrophic hypogonadism were excluded from the study. Sixty-two men (mean age, 68.4 years) completed pre- and post-treatment questionnaires and underwent laboratory testing. At the end of the study, the testosterone levels in men with low testosterone levels (treatment (2.85 ± 0.58 to 3.97 ± 1.44 ng/mL; P = .001). Mean scores had decreased from 17.7 to 13.9 (IPSS), 3.8 to 3.2 (IPSS-Quality of Life), and 33.7 to 31.1 (Aging Male's Symptom). On the frequency volume chart, nocturnal urine volume, nocturnal polyuria index, actual number of nocturia events, nocturia index, and nocturnal bladder capacity index were significantly decreased. Desmopressin improved nocturia and other urinary symptoms. Moreover, serum testosterone levels increased significantly in men with low testosterone levels after 12-week desmopressin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Development of titanium alloys and surface treatments to increase the implants lifetime

    Directory of Open Access Journals (Sweden)

    Joan Lario-Femenía

    2016-12-01

    Full Text Available The population aging together with increase of life expectancy forces the development of new prosthesis which may present a higher useful life. The clinical success of implants is based on the osseointegration achievement. Therefore, metal implants must have a mechanical compatibility with the substituted bone, which is achieved through a combination of low elastic modulus, high flexural and fatigue strength. The improvement, in the short and long term, of the osseointegration depends on several factors, where the macroscopic design and dimensional, material and implant surface topography are of great importance. This article is focused on summarizing the advantages that present the titanium and its alloys to be used as biomaterials, and the development that they have suffered in recent decades to improve their biocompatibility. Consequently, the implants evolution has been recapitulated and summarized through three generations. In the recent years the interest on the surface treatments for metallic prostheses has been increased, the main objective is achieve a lasting integration between implant and bone tissue, in the shortest time possible. On this article various surface treatments currently used to modify the surface roughness or to obtain coatings are described it; it is worthy to mention the electrochemical oxidation with post-heat treated to modify the titanium oxide crystalline structure. After the literature review conducted for prepare this article, the ? titanium alloys, with a nanotubes surface of obtained by electrochemical oxidation and a subsequent step of heat treatment to obtain a crystalline structure are the future option to improve long term biocompatibility of titanium prostheses.

  17. Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma

    International Nuclear Information System (INIS)

    Inaba, Koji; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana

    2013-01-01

    There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

  18. Application of different 125I tracers in radioimmunoassays of estradiol-17β

    International Nuclear Information System (INIS)

    Bienert, R.; Flentje, H.; Herzmann, H.; Akademie der Wissenschaften der DDR, Leipzig. Zentralinstitut fuer Isotopen- und Strahlenforschung)

    1984-01-01

    Some different 125 I-labelled estradiol tracers were produced by direct radioiodizing of estradiol and also of the histamine and tyramine conjugates of estradiol-3-carboxymethylether (E 2 -3-CM) by means of the chloramine-T method. The linkage properties of these tracers were investigated in relation to the 3 H-labelled estradiol opposite to the antisera, which were produced against the cow serum albumin (RSA) conjugates of E 2 -3-CM and estradiol-6-carboxymethyloxime (E 2 -6-CMO). As suitable system for the radioimmunological estradiol determination could be revealed 4- 125 I-iodine estradiol in connection with one antiserum in each case of the radioligand antiserum combinations against E 2 -3-CM-RSA- and E 2 -6-CMO-RSA-conjugate. The double antibody method is used for separation in optimized RIA systems. The first and the second antibody reaction take place simultaneously. (author)

  19. Alpha-Fetoprotein, Identified as a Novel Marker for the Antioxidant Effect of Placental Extract, Exhibits Synergistic Antioxidant Activity in the Presence of Estradiol

    Science.gov (United States)

    Choi, Hye Yeon; Kim, Seung Woo; Kim, BongWoo; Lee, Hae Na; Kim, Su-Jeong; Song, Minjung; Kim, Sol; Kim, Jungho; Kim, Young Bong; Kim, Jin-Hoi; Cho, Ssang-Goo

    2014-01-01

    Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. PMID:24922551

  20. Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol.

    Directory of Open Access Journals (Sweden)

    Hye Yeon Choi

    Full Text Available Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol.

  1. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    Science.gov (United States)

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it.

  2. Aeration to degas CO{sub 2}, increase pH, and increase iron oxidation rates for efficient treatment of net alkaline mine drainage

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, C.S.; Dennis, A.; Kahler, A. [Bucknell University, Lewisburg, PA (United States). Dept. of Geology

    2009-07-15

    Passive treatment systems for mine drainage use no energy other than gravity, but they require greater area than active treatment systems. Researchers are considering 'hybrid' systems that have passive and active components for increased efficiency, especially where space limitations render passive-only technology ineffective. Flow-through reactor field experiments were conducted at two large net-alkaline anthracite mine discharges in central Pennsylvania. Assuming an Fe removal rate of 20 g m{sup -2} day{sup -1} and Fe loading from field data, 3.6 x 10{sup 3} and 3.0 x 10{sup 4} m{sup 2} oxidation ponds would be required for the passive treatment of Site 21 and Packer 5 discharges, respectively. However, only a small area is available at each site. This paper demonstrates aeration to drive off CO{sub 2}, increase pH, and increase Fe(II) oxidation rates, enabling treatment within a small area compared to passive treatment methods, and introduces a geochemical model to accurately predict these rates as well as semi-passive treatment system sizing parameters. Iron(II) oxidation modeling of actively aerated systems predicted that a 1-m deep pond with 10 times less area than estimated for passive treatment would lower Fe(II) concentrations to less than 1 mg L-1 at summer and winter temperatures for both sites. The use of active aeration for treatment Of CO{sub 2}-rich, net-alkaline discharges (including partially treated effluent from anoxic limestone drains) can result in considerably reduced treatment area for oxidation and may lower treatment costs, but settling of Fe hydroxides was not considered in this study. The reduced capital cost for earthmoving will need to be compared to energy and maintenance costs for aeration.

  3. Correlation of Estradiol Serum Levels with Classification of Osteoporosis Risk OSTA (Osteoporosis Self-Assessment Tools for Asian in Menopause Women

    Directory of Open Access Journals (Sweden)

    Eva Maya Puspita

    2017-01-01

    Full Text Available Background: In postmenopausal women, decreasing estrogen levels is a marker of ovarian dysfunction. Hypoestrogenic state has known increasing the risk of osteoporosis. Objective: To determine the correlation between estradiol serum levels with classification of osteoporosis risk OSTA (Osteoporosis Self-Assessment Tools for Asian in menopausal women. Methods: This study was case series study which examined estradiol serum in menopausal women by ELISA and assess the osteoporosis risk using osteoporosis risk classification OSTA. Total 47 samples was collected at Dr. H.Adam malik, dr. Pirngadi, and RSU Networking in Medan. This research was conducted from May to December 2016. Data were statistically analyzed, and presented with Spearman test. Results: In this study, we found the mean levels of estradiol in menopausal women was 18.62 ± 16.85 ng / ml with OSTA osteoporosis risk score of 2.09 ± 2.45. There was a significant positive correlation between estradiol and risk of osteoporosis OSTA with correlation coefficient r = 0.825 and p <0.05. Conclusion: There is a strong positive correlation between serum levels of estradiol with OSTA osteoporosis risk assessment in menopausal women.

  4. The α-fetoprotein knock-out mouse model suggests that parental behavior is sexually differentiated under the influence of prenatal estradiol

    Science.gov (United States)

    Keller, Matthieu; Pawluski, Jodi L.; Brock, Olivier; Douhard, Quentin; Bakker, Julie

    2010-01-01

    In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the α-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of α-fetoprotein against maternal estradiol and as a result represents a good model to determine the contribution of prenatal estradiol to the sexual differentiation of the brain and behavior. Female AFP-KO mice were defeminized and masculinized with regard to their neuroendocrine responses as well as sexual behavior. Since parental behavior is also strongly sexually differentiated in mice, we used the AFP-KO mouse model here to ask whether parental responses are differentiated prenatally under the influence of estradiol. It was found that AFP-KO females showed longer latencies to retrieve pups to the nest and also exhibited lower levels of crouching over the pups in the nest in comparison to WT females. In fact, they resembled males (WT and AFP-KO). Other measures of maternal behavior, for example the incidence of infanticide, tended to be higher in AFP-KO females than in WT females but this increase failed to reach statistical significance. The deficits observed in parental behavior of AFP-KO females could not be explained by any changes in olfactory function, novelty recognition or anxiety. Thus our results suggest that prenatal estradiol defeminizes the parental brain in mice. PMID:20109458

  5. Access to hepatitis C virus treatment: Lessons from implementation of strategies for increasing access to antiretroviral treatment.

    Science.gov (United States)

    Assefa, Yibeltal; Hill, Peter S; Williams, Owain D

    2018-05-01

    At September's 2017 United Nations General Assembly, a state-of-the-art HIV medicine was announced to be made available at just $75 per person per year. There have been a number of strategies that the global AIDS community and countries have utilized to reduce prices and make antiretrovirals (ARVs) accessible for people living with HIV/AIDS. There appears to be an opportunity for the treatment of hepatitis C virus infection using direct-acting antivirals (DAAs) to benefit from the often painful and laboured history of driving down the prices of ARVs. In general, the success of lowering prices for ARVs has stemmed from the politics needed to initially support generic entry into the on-patent market. The use of flexibilities present in the World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) have been used to overcome patent barriers, with the use of compulsory licenses and/or the threat of their use as instruments for strengthening the bargaining power in price negotiations. These strategies have been combined with new financing mechanisms that have promoted more effective procurement and price negotiations. Partnership among the different stakeholders has also been critical in this regard. Countries have also invested in their health systems and implemented several strategies to reduce stigma and discrimination to increase access to and improve utilization of ARVs. This article suggests that any future international initiatives to increase access to DAAs can learn from these lessons surrounding price reduction, improved financing, advocacy, as well as health systems strengthening and stigma reduction. Adopting and reconfiguring these strategies will also incur substantial savings in time, money and lives. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  6. Access to hepatitis C virus treatment: Lessons from implementation of strategies for increasing access to antiretroviral treatment

    Directory of Open Access Journals (Sweden)

    Yibeltal Assefa

    2018-05-01

    Full Text Available At September’s 2017 United Nations General Assembly, a state-of-the-art HIV medicine was announced to be made available at just $75 per person per year. There have been a number of strategies that the global AIDS community and countries have utilized to reduce prices and make antiretrovirals (ARVs accessible for people living with HIV/AIDS. There appears to be an opportunity for the treatment of hepatitis C virus infection using direct-acting antivirals (DAAs to benefit from the often painful and laboured history of driving down the prices of ARVs. In general, the success of lowering prices for ARVs has stemmed from the politics needed to initially support generic entry into the on-patent market. The use of flexibilities present in the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS have been used to overcome patent barriers, with the use of compulsory licenses and/or the threat of their use as instruments for strengthening the bargaining power in price negotiations.These strategies have been combined with new financing mechanisms that have promoted more effective procurement and price negotiations. Partnership among the different stakeholders has also been critical in this regard. Countries have also invested in their health systems and implemented several strategies to reduce stigma and discrimination to increase access to and improve utilization of ARVs. This article suggests that any future international initiatives to increase access to DAAs can learn from these lessons surrounding price reduction, improved financing, advocacy, as well as health systems strengthening and stigma reduction. Adopting and reconfiguring these strategies will also incur substantial savings in time, money and lives. Keywords: Acces to medicines, Hepatitis C virus, HIV, Antiretrovirals, Direct-acting antivirals

  7. Influence of Estradiol-17beta on Progesterone and Estrogen Receptor mRNA Expression in Porcine Follicular Granulosa Cells during Short-Term, In Vitro Real-Time Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Sylwia Ciesiółka

    2016-01-01

    Full Text Available Progesterone (P4 and estradiol (E2 play a significant role in mammalian reproduction. Our study demonstrated that separated porcine cumulus cells (CCs and/or granulosa cells (GCs might proliferate in vitro during short-term, real-time primary culture. The GCs were analyzed according to gene expression of the progesterone receptor (nuclear form (pgr, progesterone receptor membrane component 1 (pgrmc1, and estrogen-related receptor beta 3 (esrrb3 in relation to two housekeeping genes: actb and pbgd. GCs were cultivated in medium with the E2. Both pgr/actb and pgr/pbgd revealed higher expression between 24 and 168 h of IVC of prolonged E2 treatment and at 48 h of IVC after acute E2 administration. The pgrmc1/actb and pgrmc1/pbgd displayed increased expression after prolonged E2 treatment between 24 and 120 h of IVC. The highest level of esrrb3/actb at 120 and 144 h, as well as esrrb3/pbgd at 120 h, in untreated controls as compared to the hormone-stimulated group, was observed. We suggest that E2 significantly influences the upregulation of pgr, pgrmc1, and esrrb3 expression in porcine GCs during real-time cell proliferation. Since esrrb3 expression is stimulated by E2 in both an acute and prolonged manner, estradiol may be recognized as a potential estrogen receptor agonist in GCs.

  8. Physical-chemical pretreatment as an option for increased sustainability of municipal wastewater treatment plants

    NARCIS (Netherlands)

    Mels, A.

    2001-01-01

    Keywords : municipal wastewater treatment, physical-chemical pretreatment, chemically enhanced primary treatment, organic polymers, environmental sustainability

    Most of the currently applied municipal wastewater treatment plants in The Netherlands are

  9. Associação entre depressão na perimenopausa e níveis séricos de estradiol e hormônio folículo-estimulante Association between depression in the perimenopause and serum levels of estradiol (E2 and follicle-stimulating hormone (FSH

    Directory of Open Access Journals (Sweden)

    Cláudio N Soares

    2000-03-01

    Full Text Available OBJETIVOS: A perimenopausa é freqüentemente associada ao surgimento de alterações físicas e emocionais. Estudos prévios indicam uma associação entre variações dos hormônios folículo-estimulante (FSH, luteinizante (LH bem como de estrógenos e o surgimento de transtornos do humor, particularmente depressão. Este estudo investigou a correlação entre mudanças nos níveis de estradiol (E2 e FSH e a sintomatologia depressiva em mulheres na perimenopausa. MÉTODOS: Cinqüenta mulheres foram recrutadas nos atendimentos de uma clínica de menopausa e de um serviço psiquiátrico para realização de ensaio clínico com uso de 17 b-estradiol ou placebo. Selecionaram-se mulheres em perimenopausa (idade entre 40 e 55 anos, presença de alterações vasomotoras, irregularidade menstrual nos últimos 6 meses e/ou amenorréia há no máximo 12 meses, níveis de FSH>20 UI/L e com diagnóstico de transtorno depressivo pelo DSM-IV (transtorno depressivo maior, transtorno distímico ou transtorno depressivo sem outra especificação. Dosagens séricas iniciais e finais (semana 12 de FSH e E2, bem como avaliações da sintomatologia depressiva (escores da MADRS foram analisadas e suas correlações investigadas. RESULTADOS: As pacientes apresentaram mudanças (pOBJECTIVES: Previous studies suggest that the perimenopause is a period of increased risk for physical and emotional disturbances. The intense fluctuation in hormone levels during the perimenopause has been associated with the presence of depressive symptoms. The present study investigated the association between levels of estradiol (E2 and follicle-stimulating hormone (FSH and the severity of depressive symptoms of women in the perimenopause. METHODS: Fifty perimenopausal women (age: 40-55 years, all meeting DSM-IV criteria for depressive disorders [major depressive disorder, dysthymia or depressive disorders NOS], with irregular periods and FSH levels > 20 IU/L were selected from a larger

  10. Women-focused treatment agencies and process improvement: Strategies to increase client engagement

    Science.gov (United States)

    Wisdom, Jennifer P.; Hoffman, Kim; Rechberger, Elke; Seim, Kay; Owens, Betta

    2009-01-01

    Behavioral health treatment agencies often struggle to keep clients engaged in treatment. Women clients often have additional factors such as family responsibilities, financial difficulties, or abuse histories that provide extra challenges to remaining in care. As part of a national initiative, four women-focused drug treatment agencies used process improvement to address treatment engagement. Interviews and focus groups with staff assessed the nature and extent of interventions. Women-focused drug treatment agencies selected relational-based interventions to engage clients in treatment and improved four-week treatment retention from 66% to 76%. Process improvement interventions in women-focused treatment may be useful to improve engagement. PMID:20046914

  11. Healthcare financing systems for increasing the use of tobacco dependence treatment.

    Science.gov (United States)

    van den Brand, Floor A; Nagelhout, Gera E; Reda, Ayalu A; Winkens, Bjorn; Evers, Silvia M A A; Kotz, Daniel; van Schayck, Onno Cp

    2017-09-12

    Tobacco smoking is the leading preventable cause of death worldwide, which makes it essential to stimulate smoking cessation. The financial cost of smoking cessation treatment can act as a barrier to those seeking support. We hypothesised that provision of financial assistance for people trying to quit smoking, or reimbursement of their care providers, could lead to an increased rate of successful quit attempts. This is an update of the original 2005 review. The primary objective of this review was to assess the impact of reducing the costs for tobacco smokers or healthcare providers for using or providing smoking cessation treatment through healthcare financing interventions on abstinence from smoking. The secondary objectives were to examine the effects of different levels of financial support on the use or prescription of smoking cessation treatment, or both, and on the number of smokers making a quit attempt (quitting smoking for at least 24 hours). We also assessed the cost effectiveness of different financial interventions, and analysed the costs per additional quitter, or per quality-adjusted life year (QALY) gained. We searched the Cochrane Tobacco Addiction Group Specialised Register in September 2016. We considered randomised controlled trials (RCTs), controlled trials and interrupted time series studies involving financial benefit interventions to smokers or their healthcare providers, or both. Two reviewers independently extracted data and assessed the quality of the included studies. We calculated risk ratios (RR) for individual studies on an intention-to-treat basis and performed meta-analysis using a random-effects model. In the current update, we have added six new relevant studies, resulting in a total of 17 studies included in this review involving financial interventions directed at smokers or healthcare providers, or both.Full financial interventions directed at smokers had a favourable effect on abstinence at six months or longer when compared

  12. Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients.

    Science.gov (United States)

    Chang, L; Yakupov, R; Nakama, H; Stokes, B; Ernst, T

    2008-06-01

    The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection. Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging. HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs. These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention.

  13. Temperature increases on the external root surface during endodontic treatment using single file systems.

    Science.gov (United States)

    Özkocak, I; Taşkan, M M; Gökt Rk, H; Aytac, F; Karaarslan, E Şirin

    2015-01-01

    The aim of this study is to evaluate increases in temperature on the external root surface during endodontic treatment with different rotary systems. Fifty human mandibular incisors with a single root canal were selected. All root canals were instrumented using a size 20 Hedstrom file, and the canals were irrigated with 5% sodium hypochlorite solution. The samples were randomly divided into the following three groups of 15 teeth: Group 1: The OneShape Endodontic File no.: 25; Group 2: The Reciproc Endodontic File no.: 25; Group 3: The WaveOne Endodontic File no.: 25. During the preparation, the temperature changes were measured in the middle third of the roots using a noncontact infrared thermometer. The temperature data were transferred from the thermometer to the computer and were observed graphically. Statistical analysis was performed using the Kruskal-Wallis analysis of variance at a significance level of 0.05. The increases in temperature caused by the OneShape file system were lower than those of the other files (P file showed the highest temperature increases. However, there were no significant differences between the Reciproc and WaveOne files. The single file rotary systems used in this study may be recommended for clinical use.

  14. Increased cortisol awakening response after completing the summer treatment program in children with ADHD.

    Science.gov (United States)

    Okabe, Rumiko; Okamura, Hisayoshi; Egami, Chiyomi; Tada, Yasuhiro; Anai, Chizuru; Mukasa, Akiko; Iemura, Akiko; Nagamitsu, Shinichiro; Furusho, Junichi; Matsuishi, Toyojiro; Yamashita, Yushiro

    2017-08-01

    Little is known about the cortisol awakening response (CAR) in children with attention deficit hyperactivity disorder (ADHD). Here, we examined the CAR in children with ADHD and their mothers before, immediately after, and 4months after an intensive summer treatment program (STP). Participants were 37 children aged 7-12years who completed the STP in 2009 and 2010, and their mothers. Daily saliva samples for cortisol measurement were collected twice daily at awakening and 30min afterwards at pre-STP, post-STP, and during a follow-up measurement period. ADHD symptom scores were evaluated by parents, and participants completed the Kid-KINDL R QOL questionnaire. CAR was low in children with ADHD before the STP, and increased to the control range 4months after STP. Maternal CAR also tended to increase after STP. Changes in the CAR in children tended to correlate with an improved ADHD inattention scores (p=0.091), physical health (p=0.070), and school life subscales scores in the Kid-KINDL R (p=0.079). We demonstrated that STP improved the behavior and QOL of children with ADHD. Our results indicate that STP could lead to improvements in HPA axis function, as reflected by increased CAR after STP. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  15. Does IMRT increase the peripheral radiation dose? A comparison of treatment plans 2000 and 2010

    International Nuclear Information System (INIS)

    Salz, Henning; Eichner, Regina; Wiezorek, Tilo

    2012-01-01

    It has been reported in several papers and textbooks that IMRT treatments increase the peripheral dose in comparison with non-IMRT fields. But in clinical practice not only open fields have been used in the pre-IMRT era, but also fields with physical wedges or composed fields. The aim of this work is to test the hypothesis of increased peripheral dose when IMRT is used compared to standard conformal radiotherapy. Furthermore, the importance of the measured dose differences in clinical practice is discussed and compared with other new technologies for the cases where an increase of the peripheral dose was observed. For cancers of the head and neck, the cervix, the rectum and for the brain irradiation due to acute leukaemia, one to four plans have been calculated with IMRT or conformal standard technique (non-IMRT). In an anthropomorphic phantom the dose at a distance of 30 cm in cranio-caudal direction from the target edge was measured with TLDs using a linear accelerator Oncor registered (Siemens) for both techniques. IMRT was performed using step-and-shoot technique (7 to 11 beams), non-IMRT plans with different techniques. The results depended on the site of irradiation. For head and neck cancers IMRT resulted in an increase of 0.05 - 0.09% of the prescribed total dose (Dptv) or 40 - 70 mGy (Dptv = 65 Gy), compared to non-IMRT technique without wedges or a decrease of 0.16% (approx. 100 mGy) of the prescribed total dose compared to non-IMRT techniques with wedges. For the cervical cancer IMRT resulted in an increased dose in the periphery (+ 0.07% - 0.15% of Dptv or 30 - 70 mGy at Dptv = 45 Gy), for the rectal cancer in a dose reduction (0.21 - 0.26% of Dptv or 100 - 130 mGy at Dptv = 50 Gy) and for the brain irradiation in an increase dose (+ 0.05% of Dptv = 18 Gy or 9 mSv). In summary IMRT does not uniformly cause increased radiation dose in the periphery in the model used. It can be stated that these dose values are smaller than reported in earlier papers

  16. RNA-sequencing data analysis of uterus in ovariectomized rats fed with soy protein isolate, 17β-estradiol and casein

    Directory of Open Access Journals (Sweden)

    Martin J. Ronis

    2016-06-01

    Full Text Available This data file describes the bioinformatics analysis of uterine RNA-seq data comparing genome wide effects of feeding soy protein isolate compared to casein to ovariectomized female rats age 64 days relative to treatment of casein fed rats with 5 μg/kg/d estradiol and relative to rats treated with estradiol and also fed soy protein isolate. Complete raw data files were deposited in the gene Expression Omnibus (GEO at NCBI (http:/www.ncbi.nlm.nih.gov.geo/ under the GEO accession number GEO: GSE69819. Data presented here incudes a summary of the differential expression analysis with top 30 genes up- and down-regulated by soy protein isolate (SPI, estradiol (E2 and SPI+E2. Additional functional annotation analysis of KEGG pathways is also presented for each treatment, together with networks of interaction between those pathways. Further interpretation and discussion of this data can be found in the article “Uterine responses to feeding soy protein isolate and treatment with 17β-estradiol differ in ovariectomized female rats” Ronis et al. (2016 [1].

  17. A hormone pulse induces transient changes in the subcellular distribution and leads to a lysosomal accumulation of the estradiol receptor alpha in target tissues.

    Science.gov (United States)

    Qualmann, B; Kessels, M M; Thole, H H; Sierralta, W D

    2000-06-01

    An intrauterine pulse-stimulation with estradiol induced changes in the subcellular localization of estrogen receptor alpha in porcine endometrium, as detected with F(ab') fragments of various anti-receptor antibodies covalently linked to nanogold. The low-sterically hindered immunoreagents--recognizing different epitopes within the hormone binding domain--allowed for an efficient immunolabeling of estradiol receptor alpha, detecting it both in the cytoplasm and the nucleus of nonstimulated epithelium cells. In the cytoplasm, the receptor often seemed to be associated with actin filaments and the endoplasmatic reticulum. After the stimulation with estradiol, a predominantly nuclear localization and a labeling of nucleoli was observed. Our immunoelectron microscopy study demonstrates a localization of the receptor in cytoplasmic organelles that increased after the hormone pulse. These organelles exhibited the morphological properties of lysosomes and relocated to the perinuclear area. In analogous cytoplasmic organelles, the presence of cathepsin D was detected via indirect immunogold labeling, justifying their classification as lysosomes. Quantitative examinations revealed that not only the number of lysosomes in the proximity of the nucleus but also their immunostaining for estradiol receptor alpha increased significantly after the hormone pulse. Thus, estradiol induces both the rapid shift of receptor into the nucleus, a slower perinuclear accumulation of lysosomes and an increase of lysosomal ERalpha-immunoreactivity. These results suggest a role for lysosomes in the degradation of receptor shuttling out of the nucleus. This could serve as termination of the estradiol receptor alpha-dependent activation of target cells. This hypothesis is strengthened by the fact that the receptor content in uterine tissue declined drastically few hours after the hormone pulse.

  18. Adenosine monophosphate activated protein kinase (AMPK), a mediator of estradiol-induced apoptosis in long-term estrogen deprived breast cancer cells.

    Science.gov (United States)

    Chen, Haiyan; Wang, Ji-Ping; Santen, Richard J; Yue, Wei

    2015-06-01

    Estrogens stimulate growth of hormone-dependent breast cancer but paradoxically induce tumor regress under certain circumstances. We have shown that long-term estrogen deprivation (LTED) enhances the sensitivity of hormone dependent breast cancer cells to estradiol (E2) so that physiological concentrations of estradiol induce apoptosis in these cells. E2-induced apoptosis involve both intrinsic and extrinsic pathways but precise mechanisms remain unclear. We found that exposure of LTED MCF-7 cells to E2 activated AMP activated protein kinase (AMPK). In contrast, E2 inhibited AMPK activation in wild type MCF-7 cells where E2 prevents apoptosis. As a result of AMPK activation, the transcriptional activity of FoxO3, a downstream factor of AMPK, was up-regulated in E2 treatment of LTED. Increased activity of FoxO3 was demonstrated by up-regulation of three FoxO3 target genes, Bim, Fas ligand (FasL), and Gadd45α. Among them, Bim and FasL mediate intrinsic and extrinsic apoptosis respectively and Gadd45α causes cell cycle arrest at the G2/M phase. To further confirm the role of AMPK in apoptosis, we used AMPK activator AICAR in wild type MCF-7 cells and examined apoptosis, proliferation and expression of Bim, FasL, and Gadd45α. The effects of AICAR on these parameters recapitulated those observed in E2-treated LTED cells. Activation of AMPK by AICAR also increased expression of Bax in MCF-7 cells and its localization to mitochondria, which is a required process for apoptosis. These results reveal that AMPK is an important factor mediating E2-induced apoptosis in LTED cells, which is implicative of therapeutic potential for relapsing breast cancer after hormone therapy.

  19. High-fat diet with stress impaired islets' insulin secretion by reducing plasma estradiol and pancreatic GLUT2 protein levels in rats' proestrus phase.

    Science.gov (United States)

    Salimi, M; Zardooz, H; Khodagholi, F; Rostamkhani, F; Shaerzadeh, F

    2016-10-01

    This study was conducted to determine whether two estrus phases (proestrus and diestrus) in female rats may influence the metabolic response to a high-fat diet and/or stress, focusing on pancreatic insulin secretion and content. Animals were divided into high-fat and normal diet groups, then each group was subdivided into stress and non-stress groups, and finally, each one of these was divided into proestrus and diestrus subgroups. At the end of high-fat diet treatment, foot-shock stress was applied to the animals. Then, blood samples were taken to measure plasma factors. Finally, the pancreas was removed for determination of glucose transporter 2 (GLUT2) protein levels and assessment of insulin content and secretion of the isolated islets. In the normal and high-fat diet groups, stress increased plasma corticosterone concentration in both phases. In both study phases, high-fat diet consumption decreased estradiol and increased leptin plasma levels. In the high-fat diet group in response to high glucose concentration, a reduction in insulin secretion was observed in the proestrus phase compared with the same phase in the normal diet group in the presence and absence of stress. Also, high-fat diet decreased the insulin content of islets in the proestrus phase compared with the normal diet. High-fat diet and/or stress caused a reduction in islet GLUT2 protein levels in both phases. In conclusion, it seems possible that high-fat diet alone or combined with foot-shock, predispose female rats to impaired insulin secretion, at least in part, by interfering with estradiol levels in the proestrus phase and decreasing pancreatic GLUT2 protein levels.

  20. Increasing use of artemisinin-based combination therapy for treatment of malaria infection in Nigerian hospitals

    Directory of Open Access Journals (Sweden)

    Igboeli NU

    2010-12-01

    Full Text Available Objectives: This study aimed at describing the pattern of outpatient antimalarial drug prescribing in a secondary and a tertiary hospital, and to assess adherence to the National Antimalarial Treatment Guideline (ATG. Methods: An audit of antimalarial prescription files from the two health facilities for a period of six months in 2008 was conducted. Semi structured questionnaires were used to collect information from the doctors and pharmacists on their awareness and knowledge of the National Antimalarial Treatment Guideline. Results: Artemisinin-based combination therapies (ACTs were the most prescribed antimalarials. Overall, 81.4% of the total prescriptions contained ACTs, out of which 56.8% were artemether-lumefantrine. However, adherence to the drugs indicated by national guideline within the DU90% was 38.5% for the tertiary and 66.7 % for the secondary hospital. The standard practice of prescribing with generic name was still not adhered to as evidenced in the understudied hospitals. The percentage of health care providers that were aware of the ATG was 88.2% for doctors and 85.1% for pharmacists. However, 13.3% and 52.2% of doctors and pharmacists respectively could not properly list the drugs specified in the guideline. Amodiaquine was the most commonly preferred option for managing children aged 0 – 3 months with malaria infection against the indicated oral quinine.Conclusion: This study showed an increased use of artemisinin-based combination therapy for the treatment of uncomplicated malaria compared previous reports in Nigeria. This study also highlights the need for periodic in-service quality assurance among health professionals with monitoring of adherence to and assessment of knowledge of clinical guidelines to ensure the practice of evidence based medicine.

  1. Treatment timing for an orthopedic approach to patients with increased vertical dimension.

    Science.gov (United States)

    Baccetti, Tiziano; Franchi, Lorenzo; Schulz, Scott O; McNamara, James A

    2008-01-01

    The aim of this study was to investigate the role of treatment timing on the effectiveness of vertical-pull chincup (V-PCC) therapy in conjunction with a bonded rapid maxillary expander (RME) in growing subjects with mild-to-severe hyperdivergent facial patterns. The records of 39 subjects treated with a bonded RME combined with a V-PCC were compared with 29 untreated subjects with similar vertical skeletal disharmonies. Lateral cephalograms were analyzed before (T1) and after treatment or observation (T2). Both the treated and the untreated samples were divided into prepubertal and pubertal groups on the basis of cervical vertebral maturation (prepubertal treated group, 21 subjects; pubertal treated group, 18 subjects; prepubertal control group, 15 subjects; pubertal control group, 14 subjects). Mean change differences from T2 to T1 were compared in the 2 prepubertal and the 2 pubertal groups with independent-sample t tests. No statistically significant differences between the 2 prepubertal groups were found for any cephalometric skeletal measures from T1 to T2. When compared with the untreated pubertal sample, the group treated with the RME and V-PCC at puberty showed a statistically significant reduction in the inclination of the mandibular plane to the Frankfort horizontal (-2.2 mm), a statistically significant reduction in the inclination of the condylar axis to the mandibular plane (-2.2 degrees), and statistically significant supplementary growth of the mandibular ramus (1.7 mm). Treatment of increased vertical dimension with the RME and V-PCC protocol appears to produce better results during the pubertal growth spurt than before puberty, although the absolute amount of correction in the vertical skeletal parameters is limited.

  2. Mung bean nuclease treatment increases capture specificity of microdroplet-PCR based targeted DNA enrichment.

    Directory of Open Access Journals (Sweden)

    Zhenming Yu

    Full Text Available Targeted DNA enrichment coupled with next generation sequencing has been increasingly used for interrogation of select sub-genomic regions at high depth of coverage in a cost effective manner. Specificity measured by on-target efficiency is a key performance metric for target enrichment. Non-specific capture leads to off-target reads, resulting in waste of sequencing throughput on irrelevant regions. Microdroplet-PCR allows simultaneous amplification of up to thousands of regions in the genome and is among the most commonly used strategies for target enrichment. Here we show that carryover of single-stranded template genomic DNA from microdroplet-PCR constitutes a major contributing factor for off-target reads in the resultant libraries. Moreover, treatment of microdroplet-PCR enrichment products with a nuclease specific to single-stranded DNA alleviates off-target load and improves enrichment specificity. We propose that nuclease treatment of enrichment products should be incorporated in the workflow of targeted sequencing using microdroplet-PCR for target capture. These findings may have a broad impact on other PCR based applications for which removal of template DNA is beneficial.

  3. Chemical treatments for increasing the efficiency of B7 ordered packings

    International Nuclear Information System (INIS)

    Titescu, Gh.; Predescu, S.

    1997-01-01

    Efforts to improve the contact elements, particularly, the isotopic and mass exchange elements, resulted in a new highly performing ordered packing made of metallic net. Research directed to improve the functional characteristics of these packings, destined to heavy water separation processes by vacuum isotopic distillations, continued. A special goal was deposing oxide layers on the metallic surface to increase the wettability and, implicitly, the separation efficiency of the packings. Surface treatments are based on the contact of the material in given conditions with oxidizers such as KMnO 4 , H 2 O 2 , K 2 Cr 2 O 7 . At present, the experiments aim at correlating the functional characteristics and the morphologic characteristics of the oxide layers formed on their surface

  4. Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol

    International Nuclear Information System (INIS)

    Okamoto, Mayumi; Naka, Kyosuke; Kitagawa, Yuya; Ishiwata, Kiichi; Yoshimoto, Mitsuyoshi; Shimizu, Isao; Toyohara, Jun

    2015-01-01

    Introduction: Several lines of evidence suggest that C-7α-substituted estradiol derivatives are well tolerated by estrogen receptor (ER). In line with this hypothesis, we are interested in the design and synthesis of C-7α-substituted estrogens as molecular probes to visualize ER function. Methods: We have synthesized 7α-(3-[ 18 F]fluoropropyl) estradiol (C3-7α-[ 18 F]FES) as a potential radiopharmaceutical for ER imaging by positron emission tomography (PET). In vitro receptor binding and in vivo biodistribution and blocking studies in mature female mice, and in vivo metabolite analysis were carried out. Furthermore, in vivo ER-selective uptake was confirmed using ER-positive T-47D and ER-negative MDA-MB-231 tumor-bearing mice. We also compared the in vivo biodistribution of C3-7α-[ 18 F]FES with 16α-[ 18 F]FES. Results: C3-7α-[ 18 F]FES was produced in moderate yields (30.7% ± 15.1%, decay corrected) with specific activity of 32.0 ± 18.1 GBq/μmol (EOS). The in vitro binding affinity of C3-7α-FES to the ERα isoform was sufficient and equivalent to that of estradiol. C3-7α-[ 18 F]FES showed selective uptake in ER-rich tissues, such as the uterus (4.7%ID/g ± 1.2%ID/g at 15 minutes) and ovary (4.0%ID/g ± 1.0%ID/g at 5 minutes). The tissue time activity curves of these organs showed reversible kinetics, indicating suitability for quantitative analysis. The highest contrast was obtained at 120 minutes after injection of C3-7α-[ 18 F]FES in the uterus (uterus/blood = 18, uterus/muscle = 17.3) and ovary (ovary/blood = 6.3, ovary/muscle = 6.0). However, the level of selective uptake of C3-7α-[ 18 F]FES was significantly lower than that of 16α-[ 18 F]FES. Most radioactivity in the uterus was detected in unchanged form, although peripherally C3-7α-[ 18 F]FES was rapidly degraded to hydrophilic metabolites. In accordance with this peripheral metabolism, gradual increases in bone radioactivity were observed, indicating defluorination. Coinjection with

  5. Combined effects of rat Schwann cells and 17β-estradiol in a spinal cord injury model.

    Science.gov (United States)

    Namjoo, Zeinab; Moradi, Fa