Hormones in international meat production: biological, sociological and consumer issues.

Science.gov (United States)

Galbraith, Hugh

2002-12-01

Beef and its products are an important source of nutrition in many human societies. Methods of production vary and include the use of hormonal compounds ('hormones') to increase growth and lean tissue with reduced fat deposition in cattle. The hormonal compounds are naturally occurring in animals or are synthetically produced xenobiotics and have oestrogenic (oestradiol-17beta and its esters; zeranol), androgenic (testosterone and esters; trenbolone acetate) or progestogenic (progesterone; melengestrol acetate) activity. The use of hormones as production aids is permitted in North American countries but is no longer allowed in the European Union (EU), which also prohibits the importation of beef and its products derived from hormone-treated cattle. These actions have resulted in a trade dispute between the two trading blocs. The major concern for EU authorities is the possibility of adverse effects on human consumers of residues of hormones and metabolites. Methods used to assess possible adverse effects are typical of those used by international agencies to assess acceptability of chemicals in human food. These include analysis of quantities present in the context of known biological activity and digestive, absorptive, post-absorptive and excretory processes. Particular considerations include the low quantities of hormonal compounds consumed in meat products and their relationships to endogenous production particularly in prepubertal children, enterohepatic inactivation, cellular receptor- and non-receptor-mediated effects and potential for interference with growth, development and physiological function in consumers. There is particular concern about the role of oestradiol-17beta as a carcinogen in certain tissues. Now subject to a 'permanent' EU ban, current evidence suggests that certain catechol metabolites may induce free-radical damage of DNA in cell and laboratory animal test systems. Classical oestrogen-receptor mediation is considered to stimulate

Effects of estradiol and progestogens on human breast cells: Regulation of sex steroid receptors

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Fang-Ping Chen

2013-09-01

Conclusions: The combination of E2 and various progestogens resulted in diverging effects on ERs and PRs expressions, which induced different effects on MCF-7 cell growth. Compared with P4, aberrant hormone and biological activity of synthetic progestin, by way of altered receptor expression, may be an important factor in affecting breast cell growth.

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

Science.gov (United States)

Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

1992-10-01

To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Simultaneous Determination of Hormonal Residues in Treated Waters Using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry

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Rayco Guedes-Alonso

2013-01-01

Full Text Available In the last years, hormone consumption has increased exponentially. Because of that, hormone compounds are considered emerging pollutants since several studies have determinted their presence in water influents and effluents of wastewater treatment plants (WWTPs. In this study, a quantitative method for the simultaneous determination of oestrogens (estrone, 17β-estradiol, estriol, 17α-ethinylestradiol, and diethylstilbestrol, androgens (testosterone, and progestogens (norgestrel and megestrol acetate has been developed to determine these compounds in wastewater samples. Due to the very low concentrations of target compounds in the environment, a solid phase extraction procedure has been optimized and developed to extract and preconcentrate the analytes. Determination and quantification were performed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS. The method developed presents satisfactory limits of detection (between 0.15 and 9.35 ng·L−1, good recoveries (between 73 and 90% for the most of compounds, and low relative standard deviations (under 8.4%. Samples from influents and effluents of two wastewater treatment plants of Gran Canaria (Spain were analyzed using the proposed method, finding several hormones with concentrations ranged from 5 to 300 ng·L−1.

Progestogens and Cushing's syndrome.

LENUS (Irish Health Repository)

Harte, C

2012-02-03

We report 3 patients where Medroxyprogesterone Acetate (MPA = Provera) and Megestrol Acetate (Megace) in doses used for therapy of breast cancer, caused clinical hypercortisolism and Cushing\\'s syndrome. Studies of the toxicity of Medroxyprogesterone Acetate list the commonest adverse events at 500 mg\\/day as weight gain, water retention, increased blood pressure, tremor, moon face, sweating, muscle cramps, vaginal bleeding and increased appetite. Glucocorticoid-like effects are seen in up to 30% of patients treated for longer than 6 weeks with mostly large doses of the order of 1500 mg\\/day but Cushing\\'s syndrome has been reported in patients taking 400 mg\\/day. Neither the glucocorticoid-like effects or Cushing\\'s syndrome have been previously observed with Megestrol Acetate. In the elderly female population receiving progestogens for neoplastic disease the progestogen itself could be an appreciable cause of morbidity both by causing glucocorticoid-like effects and Cushing\\'s syndrome but also by lack of awareness of the danger of sudden withdrawal of these compounds when the hypothalmic-pituitary-adrenal (HPA) axis is suppressed. The signs and symptoms could be easily overlooked unless appropriate testing for Cushing\\'s syndrome is carried out. While the progestogen may have to be continued indefinitely a dose decrease may be feasible with reduction of morbidity.

Oestrogen receptors in tumors of breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Levin, J; Kay, G; Da Fonseca, M [University of the Witwatersrand, Johannesburg (South Africa). Department of Nuclear Medicine; Lange, M [University of the Witwatersrand, Johannesburg (South Africa). Dept. of Surgery; De Moor, N G [University of the Witwatersrand, Johannesburg (South Africa). Department of Radiation Therapy; Savage, N [University of the Witwatersrand, Johannesburg (South Africa). Department of Physiological Chemistry

1978-04-15

Oestrogen receptors were measured in the cytoplasmic fraction of tumors from patients with breast cancer. Receptors were detected in 48% of patients, and 52% showed no receptors. A follow-up study of a small group of patients on hormone therapy is reported.

Prevalence and practice of oestrogen use among the male gym participants

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Turki Fahad Alharthi

2018-05-01

Full Text Available Background Oestrogen is the primary female sex hormone and has important functions in both female and male physiology. Recently oestrogen abuse among male gym participants had raised as it is considered to enhance gym performance and breast size. Aims This study assesses the prevalence of oestrogen use among male gym patrons in Saudi Arabia, their practice related to oestrogen abuse, and the profiles of users. Methods A cross-sectional study was conducted from February 2017 to May 2017 and included 4,860 male gym patrons. The participants were given a questionnaire with a total of 19 questions regarding socioeconomic information, knowledge and practices related to oestrogen, and lifestyle habits. Results The participants had a mean age of 28.6+6.2 years, 6.1 per cent of them abused oestrogen, and the most common forms used were ethinylestradiol (0.03mg and drospirenone (3mg. Furthermore, 80.7 per cent of the users used it before exercise only. Breast enlargement was the main reason for oestrogen use, and local drug stores were the main source. Compared to non-users, oestrogen users were older (P=0.322, reported lower incomes (P=0.395, were more likely to be active smokers (P=0.597, and had a longer duration of gym participation (P < 0.001. Conclusion The results indicate that 6.1 per cent of the surveyed male participants abused a combination of oestrogen and progesterone for breast enlargement, which was significantly more likely among males who had longer durations of gym participation.

Local oestrogen for vaginal atrophy in postmenopausal women.

Science.gov (United States)

Suckling, J; Lethaby, A; Kennedy, R

2006-10-18

Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the oestradiol-releasing ring). The objective of this review was to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy. We searched the Cochrane Menstrual Disorders and Subfertility Group Register of trials (searched January 2006), The Cochrane Library (2006,Issue 2), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), Current Contents (1993 to January 2006, Biological Abstracts (1969 to 2006), Social Sciences Index (1980 to January 2006), PsycINFO (1972 to February 2006), CINAHL (1982 to January 2006) and reference list of articles. We also contacted manufacturers and researchers in the field. The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis. Thirty-seven trials were identified: of these 18 were excluded. Included trials were assessed for quality and two reviewer authors extracted data independently. The ratios for dichotomous outcomes and means for continuous outcomes were calculated. The outcomes analysed were categorised under the headings of: efficacy, safety and acceptability. Nineteen trials with 4162 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy, with various outcome measures. When comparing the efficacy of different oestrogenic preparations (in the form of creams, pessaries, tablets and the oestradiol-releasing vaginal ring) in relieving the

Pattern of faecal 20-oxopregnane and oestrogen concentrations during pregnancy in wild plains zebra mares.

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Ncube, Hlengisizwe; Duncan, Patrick; Grange, Sophie; Cameron, Elissa Z; Barnier, Florian; Ganswindt, Andre

2011-07-01

Regulative endocrine mechanisms influence the reproductive behaviour and success of mammals, but they have been studied predominantly in domestic and captive animals. The study aims at describing the pattern of faecal 20-oxopregnane and oestrogen concentrations during pregnancy in wild plains zebra Equus quagga chapmani. Data were collected during wet and dry seasons 2007-2009. Enzyme Immunoassays were used to determine 20-oxopregnane and oestrogen concentrations in faecal samples (n=74) collected from individual mares (n=32) whose dates of foaling were known through long-term monitoring. Hormonal profiles were described with a General Additive Model (GAM: Hormone ∼ Days to Foaling). Faecal 20-oxopregnanes have a complex cycle during pregnancy (GAM, n=70, R(2)=0.616, p200 ng/g DW) of faecal 20-oxopregnanes associated with high (>160 ng/g DW) faecal oestrogen levels indicate mid-pregnancy in c.90% of cases (16/17). High faecal 20-oxopregnanes (>200 ng/g DW) and low faecal oestrogen levels (<160 ng/g DW) indicate late pregnancy, again in c.90% of cases. Two faecal samples would allow the stage of pregnancy to be determined with confidence. Copyright © 2011 Elsevier Inc. All rights reserved.

Hormonal contraception in women with polycystic ovary syndrome: choices, challenges, and noncontraceptive benefits.

Science.gov (United States)

de Melo, Anderson Sanches; Dos Reis, Rosana Maria; Ferriani, Rui Alberto; Vieira, Carolina Sales

2017-01-01

Polycystic ovary syndrome (PCOS) is an endocrine disorder among women of reproductive age characterized by chronic anovulation and polycystic ovary morphology and/or hyperandrogenism. Management of clinical manifestations of PCOS, such as menstrual irregularities and hyperandrogenism symptoms, includes lifestyle changes and combined hormonal contraceptives (CHCs). CHCs contain estrogen that exerts antiandrogenic properties by triggering the hepatic synthesis of sex hormone-binding globulin that reduces the free testosterone levels. Moreover, the progestogen present in CHCs and in progestogen-only contraceptives suppresses luteinizing hormone secretion. In addition, some types of progestogens directly antagonize the effects of androgens on their receptor and also reduce the activity of the 5α reductase enzyme. However, PCOS is related to clinical and metabolic comorbidities that may limit the prescription of CHCs. Clinicians should be aware of risk factors, such as age, smoking, obesity, diabetes, systemic arterial hypertension, dyslipidemia, and a personal or family history, of a venous thromboembolic event or thrombophilia. This article reports a narrative review of the available evidence of the safety of hormonal contraceptives in women with PCOS. Considerations are made for the possible impact of hormonal contraceptives on endocrine, metabolic, and cardiovascular health.

Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

DEFF Research Database (Denmark)

Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

2007-01-01

of alpha2A-adrenergic-receptor correlated positively with expression of oestrogen-receptor-alpha. CONCLUSIONS: The results fit the hypothesis that sex hormones play a role in altered fat distribution and insulin sensitivity of male patients with HIV-lipodystrophy. The effect of oestradiol...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression...

Oestrogen, an evolutionary conserved regulator of T cell differentiation and immune tolerance in jawed vertebrates?

Science.gov (United States)

Paiola, Matthieu; Knigge, Thomas; Duflot, Aurélie; Pinto, Patricia I S; Farcy, Emilie; Monsinjon, Tiphaine

2018-07-01

In teleosts, as in mammals, the immune system is tightly regulated by sexual steroid hormones, such as oestrogens. We investigated the effects of 17β-oestradiol on the expression of several genes related to T cell development and resulting T cell subpopulations in sea bass, Dicentrarchus labrax, for a primary lymphoid organ, the thymus, and two secondary lymphoid organs, the head-kidney and the spleen. In parallel, the oxidative burst capacity was assessed in leucocytes of the secondary lymphoid organs. Apoptosis- and proliferation-related genes, indicative of B and T cell clonal selection and lymphoid progenitor activity, were not affected by elevated oestrogen-levels. Sex-related oestrogen-responsiveness in T cell and antigen-presenting cell markers was observed, the expression of which was differentially induced by oestrogen-exposure in the three lymphoid organs. Remarkably, in the spleen, oestrogen increased regulatory T cell-related gene expression was associated with a decrease in oxidative burst capacity. To the best of our knowledge, this study indicates for the first time that physiological levels of oestrogen are likely to promote immune tolerance by modulating thymic function (i.e., T cell development and output) and peripheral T cells in teleosts, similar to previously reported oestrogenic effects in mammals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hormonal treatment for endometriosis associated pelvic pain

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Wu Shun Felix Wong

2011-01-01

Full Text Available AbstractBackground: Endometriosis is a common gynecological problem associated with chronic pelvic pain. Objective: To evaluate the effectiveness of current hormonal treatments of endometriosis associated pain.Materials and Methods: Randomized Controlled studies identified from databases of Medline and Cochrane Systemic Review groups were pooled. 7 RCTs were recruited for evaluation in this review. Data from these studies were pooled and meta-analysis was performed in three comparison groups: 1 Progestogen versus GnRHa; 2 Implanon versus Progestogen (injection; 3 Combined oral contraceptive pills versus placebo and progestogen. Response to treatment was measured as a reduction in pain score. Pain improvement was defined as improvement ≥1 at the end of treatment. Results: There was no significant difference between treatment groups of progestogen and GnRHa (RR: 0.036; CI:-0.030-0.102 for relieving endometriosis associated pelvic pain. Long acting progestogen (Implanon and Mirena are not inferior to GnRHa and depot medroxy progesterone acetate (DMPA (RR: 0.006; CI:-0.142-0.162. Combined oral contraceptive pills demonstrated effective treatment of relieving endometriosis associated pelvic pain when compared with placebo groups (RR:0.321CI-0.066-0.707. Progestogen was more effective than combined oral contraceptive pills in controlling dysmenorrhea (RR:-0.160; CI:-0.386-0.066, however, progestogen is associated with more side effects like spotting and bloating than the combined contraceptive pills. Conclusion: Combined oral contraceptive pills (COCP, GnRHa and progestogens are equally effective in relieving endometriosis associated pelvic pain. COCP and progestogens are relatively cheap and more suitable for long-term use as compared to GnRHa. Long-term RCT of medicated contraceptive devices like Mirena and Implanon are required to evaluate their long-term effects on relieving the endometriosis associated pelvic pain

Progestogens to Prevent Preterm Birth: A Review of the Research about Progestogens for Women at Risk

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... several ways: „ „ As a gel, cream, capsule, or suppository that you place in your vagina „ „ As a ... of progestogens (pills, shots, and vaginal gels or suppositories) can lower the risk of having a spontaneous ...

[Effects of progestogens on the metabolism of lipids and carbohydrates. Practical consequences (author's transl)].

Science.gov (United States)

Ghéron, G

Estrogens which are one of the components of contraceptive less than pills greater than are incriminated in many cardiovascular accidents. These occur as a result of metabolic disorders (involving lipids and carbohydrates), of modifications in coagulation factors, etc. The possible influence of progestogens was ignored for a long time. The widespread use of these compounds, prescribed for contraception as well as during hormonal replacement therapy for absolute or relative luteinic insufficiency, makes careful monitoring of lipid and carbohydrate metabolism imperative. This position is strengthened by a preliminary review of the literature which leads to several conclusions concerning lipid and carbohydrate metabolism.

Monitoring ovarian cycle and pregnancy in the giant anteater (Myrmecophaga tridactyla) by faecal progestagen and oestrogen analysis.

Science.gov (United States)

Patzl, M; Schwarzenberger, F; Osmann, C; Bamberg, E; Bartmann, W

1998-10-01

Oestrogen and progestagen metabolites were measured in the faeces of five female giant anteaters (Myrmecophaga tridactyla), to characterise the oestrous cycle and pregnancy. Faecal samples were collected twice weekly for a minimum of 6 months, and immunoreactive progestagens and oestrogens were analysed using enzyme immunoassays (EIA). For progestagens, two antibodies that cross-reacted with 20alpha-hydroxy- or 20-oxo-progestagens were used. Both assays effectively monitored ovarian cyclicity; however, the concentrations obtained using the antibody for 20alpha-hydroxy-progestagens were higher, and the hormonal changes were more pronounced. Regular ovarian cycles were identified in three of the five females. Average (+/-SEM) length of the oestrous cycle (n=10) was 51.4+/-5.6 days. Peak concentrations of 20alpha-hydroxy-progestagens ranged from 80-660 ng/g of faeces and those of oestrogens from 20-100 ng/g. Hormone concentrations were measured during parts of two pregnancies and during four post-partum periods. The length of one gestation (from oestrous oestrogen peak until parturition) was 184 days. In the second half of gestation, progestagen concentration started to increase above luteal phase values; in the week before parturition it was approximately 20 times higher than those during the luteal phase. Concentrations of excreted oestrogens began to increase after two thirds of gestation and exceeded that of the follicular phase by approximately 2.5-fold in the week before parturition. Onset of ovarian cyclicity after parturition varied from 4-11 weeks. In conclusion, the measurement of faecal immunoreactive progestagens and oestrogens in the giant anteater indicated an ovarian cycle of approximately 7 weeks in length and provided potentially useful data for successful breeding management.

Breast cancer and steroid metabolizing enzymes: the role of progestogens.

Science.gov (United States)

Pasqualini, Jorge R

2009-12-01

It is well documented that breast tissue, both normal and cancerous, contains all the enzymatic systems necessary for the bioformation and metabolic transformation of estrogens, androgens and progesterone. These include sulfatases, aromatase, hydroxysteroid-dehydrogenases, sulfotransferases, hydroxylases and glucuronidases. The control of these enzymes plays an important role in the development and pathogenesis of hormone-dependent breast cancer. As discussed in this review, various progestogens including dydrogesterone and its 20alpha-dihydro-derivative, medrogestone, promegestone, nomegestrol acetate and norelgestromin can reduce intratissular levels of estradiol in breast cancer by blocking sulfatase and 17beta-hydroxysteroid-dehydrogenase type 1 activities. A possible correlation has been postulated between breast cell proliferation and estrogen sulfotransferase activity. Progesterone is largely transformed in the breast; normal breast produces mainly 4-ene derivatives, whereas 5alpha-derivatives are most common in breast cancer tissue. It has been suggested that this specific conversion of progesterone may be involved in breast carcinogenesis. In conclusion, treatment with anti-aromatases combined with anti-sulfatase or 17beta-hydroxysteroid-dehydrogenase type 1 could provide new therapeutic possibilities in the treatment of patients with hormone-dependent breast cancer. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Reproductive effects from oestrogen activity in polluted water

Energy Technology Data Exchange (ETDEWEB)

Sumpter, J.P. [Brunel Univ., Uxbridge (United Kingdom). Dept. of Biology and Biochemistry

1998-12-31

A new area of ecotoxicology, now usually called endocrine disruption, has arisen in the last few years. However, despite the present topicality of this issue, some of the best documented examples of endocrine disruption were reported a decade or more ago (see, for example, Fry, 1995). The issue is concerned with the effects of chemicals that mimic endogenous hormones on the physiology of exposed wildlife and humans. As many of these xenohormones minic steroid hormones, especially oestrogens and androgens, most of the reported effects have involved effects on the reproductive system of exposed organisms. Many of these reported effects on wildlife have concerned aquatic, rather than terrestrial, organisms (even the well-documented effects on birds are primarily concerned with water birds, which feed predominantly on fish); the reproductive abnormalities seen in alligators living in some lakes in Florida and the oestrogenic effects on fish reported in British rivers (this example is discussed in detail below) provide good examples of the type of effects observed in aquatic organisms. This predominance of effects on aquatic organisms could reflect an unconscious bias of the interests of research scientists (are there more wildlife biologists interested in aquatic, rather than terrestrial, animals?), but is perhaps more likely a consequence of the fact that the aquatic environmemnt is the ultimate `sink` for the international or unintentional disposal of much waste. (orig.)

Oestrogen influences on mitochondrial gene expression and respiratory chain activity in cortical and mesencephalic astrocytes.

Science.gov (United States)

Araújo, G W; Beyer, C; Arnold, S

2008-07-01

The regulation of mitochondrial energy metabolism plays an essential role in the central nervous system (CNS). Abnormalities of the mitochondrial respiratory chain often accompany neurodegenerative diseases. This makes mitochondria a perfect target for strategies of cellular protection against toxic compounds and pathological conditions. Steroid hormones, such as oestrogen, are well-known to fulfil a protective role in the brain during ischaemic and degenerative processes. Because astrocytes function as the major energy supplier in the CNS, we have analysed oestrogen effects on the mitochondrial respiratory chain of this cell type. In our studies, we applied semi- and quantitative polymerase chain reaction analysis of gene expression and polarographic measurements of the respiratory chain activity of mitochondria. We observed that structural and functional properties were regulated dependent on the oestrogen exposure time and the brain region, but independent of the nuclear oestrogen receptors. We could demonstrate that long-term oestrogen exposure increases the subunit gene expression of respiratory chain complexes and the mitochondrial DNA content, thereby indicating an up-regulation of the amount of mitochondria per cell together with an increase of mitochondrial energy production. This could represent an important indirect mechanism by which long-term oestrogen exposure protects neurones from cell death under neurotoxic conditions. On the other hand, we observed short-term effects of oestrogen on the activity of mitochondrial, proton-pumping respiratory chain complexes. In astrocytes from the cortex, respiratory chain activity was decreased, whereas it was increased in astrocytes from the mesencephalon. An increased production of reactive oxygen species would be the consequence of an increased respiratory chain activity in mesencephalic astrocytes. This could explain the different efficiencies of oestrogen-mediated short-term protection in distinct brain

Steroid hormonal bioactivities, culprit natural and synthetic hormones and other emerging contaminants in waste water measured using bioassays and UPLC-tQ-MS.

Science.gov (United States)

Houtman, Corine J; Ten Broek, Rob; Brouwer, Abraham

2018-07-15

Emission of compounds with biological activities from waste water treatment plant (WWTP) effluents into surface waters is a topic of concern for ecology and drinking water quality. We investigated the occurrence of hormone-like activities in waste water sample extracts from four Dutch WWTPs and pursued to identify compounds responsible for them. To this aim, in vitro reporter gene bioassays for androgenic, anti-androgenic, estrogenic, glucocorticoid and progestogenic activity and a UPLC-tQ-MS target analysis method for 25 steroid hormones used in high volumes in pharmacy were applied. Principal component analysis of the data was performed to further characterize the detected activities and compounds. All five types of activities tested were observed in the WWTP samples. Androgenic and estrogenic activities were almost completely removed during WW treatment, anti-androgenic activity was only found in treated WW. Glucocorticoid and progestogenic activities persisted throughout the treatment. The androgenic activity in both influent could predominantly be attributed to the presence of androstenedione and testosterone. Anti-androgenic activity was explained by the presence of cyproterone acetate. The glucocorticoid activity in influent was fully explained by prednicarbate, triamcinolone acetonide, dexamethasone and amcinonide. In effluent however, detected hormones could only explain 10-32% of the activity, indicating the presence of unknown glucocorticoids or their metabolites in effluent. Progesterone and levonorgestrel could explain the observed progestogenic activity. The principle component analysis confirmed the way in which hormones fit in the spectrum of other emerging contaminants concerning occurrence and fate in WWTPs. Copyright © 2018 Elsevier B.V. All rights reserved.

Of Oestrogens and Sperm: A Review of the Roles of Oestrogens and Oestrogen Receptors in Male Reproduction

Czech Academy of Sciences Publication Activity Database

Dostálová, Pavla; Žatecká, Eva; Dvořáková-Hortová, Kateřina

2017-01-01

Roč. 18, č. 5 (2017), č. článku 904. E-ISSN 1422-0067 R&D Projects: GA ČR GA14-05547S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : oestrogens * oestrogen receptors * testes * sperm Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Reproductive biology (medical aspects to be 3) Impact factor: 3.226, year: 2016

Hormonal contraception in women with polycystic ovary syndrome: choices, challenges, and noncontraceptive benefits

Directory of Open Access Journals (Sweden)

de Melo AS

2017-02-01

Full Text Available Anderson Sanches de Melo, Rosana Maria dos Reis, Rui Alberto Ferriani, Carolina Sales Vieira Department of Gynecology and Obstetrics, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil Abstract: Polycystic ovary syndrome (PCOS is an endocrine disorder among women of reproductive age characterized by chronic anovulation and polycystic ovary morphology and/or hyperandrogenism. Management of clinical manifestations of PCOS, such as menstrual irregularities and hyperandrogenism symptoms, includes lifestyle changes and combined hormonal contraceptives (CHCs. CHCs contain estrogen that exerts antiandrogenic ­properties by triggering the hepatic synthesis of sex hormone-binding globulin that reduces the free testosterone levels. Moreover, the progestogen present in CHCs and in progestogen-only ­contraceptives suppresses luteinizing hormone secretion. In addition, some types of progestogens directly antagonize the effects of androgens on their receptor and also reduce the activity of the 5α reductase enzyme. However, PCOS is related to clinical and metabolic comorbidities that may limit the prescription of CHCs. Clinicians should be aware of risk factors, such as age, smoking, obesity, diabetes, systemic arterial hypertension, dyslipidemia, and a personal or family history, of a venous thromboembolic event or thrombophilia. This article reports a narrative review of the available evidence of the safety of hormonal contraceptives in women with PCOS. Considerations are made for the possible impact of hormonal contraceptives on endocrine, metabolic, and cardiovascular health. Keywords: polycystic ovary syndrome, hormonal contraceptive, lipid metabolism, carbohydrate metabolism, hyperandrogenism, thrombosis

A Rare Case of Oestrogen Dermatitis.

Science.gov (United States)

Bourgeault, Emilie; Bujold, Janie; Doucet, Marie-Eve

Oestrogen dermatitis is a rare disorder characterised by cyclical eruptions in association with a woman's menstrual cycle. A 43-year-old woman with an 8-year history of cyclical inguinal dermatitis, with a negative patch test, was tested with intradermal progesterone and oestrogen. Intradermal testing was positive for oestrogen only. In a female patient with cyclical dermatitis, it is important to consider oestrogen or progesterone dermatitis in the differential diagnosis.

Benefits and risks of hormonal contraception for women

Directory of Open Access Journals (Sweden)

Hagen, Anja

2007-08-01

Full Text Available Scientific background: A large proportion of women of reproductive age in Germany use various methods of pregnancy prevention (contraception, among them various hormone-based methods. Hormonal contraceptives may be divided into combined estrogen-progestogen contraceptives (pills, skin patches, vaginal rings, progestogen-only contraceptives (pills, injections, implants, hormone spirals and emergency contraceptives. Research questions: The evaluation addressed the question of benefits and risks of hormonal contraceptives, their economic effects as well as their ethical-social and legal implications.MethodsA systematic literature search was conducted in April 2006 starting from 2000. The evaluation is primarily based on systematic reviews. Results: In perfect use, all hormonal contraceptives excluding emergency contraceptives proved to be the most effective reversible contraceptive methods (rate of unintended pregnancies 0.05% to 0.3%. However, the typical use of oral contraceptives, injections, skin patches, and vaginal rings, which also considers possible application errors, showed a lower contraceptive efficacy (rate of unintended pregnancies 3% to 8%. It was lower than that of copper spirals. The risk of venous thromboembolism increased three to six times in users of hormonal contraceptives, the risks of stroke and myocardial infarction two to three times. The risk declined after discontinuation of use. The effects were estrogen-dose and progestogen-type dependent. The use of hormonal contraceptives showed a relative risk of ovarian and endometrial carcinomas of approximately 0.5 or 0.7, of breast and cervical cancer of approximately 1.2 or 1.6. The effect remained several years after discontinuation of use. The results concerning hepatocellular carcinoma suggested a carcinogenic effect. In women with acne, an improvement due to use of hormonal contraceptives was proven. Cervical chlamydial infections were more frequent in users of hormonal

Influence of hormonal contraceptives and the occurrence of stroke: integrative review

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Adman Câmara Soares Lima

Full Text Available ABSTRACT Objective: To identify scientific evidence regarding the influence of hormonal contraceptive use and the occurrence of stroke. Method: Integrative review of the literature, through database search using the descriptors "contraceptive agents", "contraceptive devices", "contraceptives, Oral" and "Stroke". Original studies in Portuguese, Spanish and English, published in full and available online were included. Studies that did not answer our guiding questions and duplicated studies were excluded. Results: Women using combined oral contraceptives have higher risk of stroke, even with a lower hormonal dosage and different types of progestogen, regardless of the duration of use. The use of contraceptives associated with smoking, hypertension, migraine, hypercholesterolemia, obesity and sedentary lifestyle increases the chance of stroke. Contraceptive patch and vaginal ring are associated to increased risk. Conclusion: Use of combined hormonal contraceptives, except for the injectable and the transdermal ones, increases the chance of occurrence of the event. Progestogen-only contraceptives were considered safe.

Evaluation of transcriptional activity of the oestrogen receptor with sodium iodide symporter as an imaging reporter gene.

Science.gov (United States)

Kang, Joo Hyun; Chung, June-Key; Lee, Yong Jin; Kim, Kwang Il; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

2006-10-01

Oestrogen receptors are ligand-dependent transcription factors whose activity is modulated either by oestrogens or by an alternative signalling pathway. Oestrogen receptors interact via a specific DNA-binding domain, the oestrogen responsive element (ERE), in the promoter region of sensitive genes. This binding leads to an initiation of gene expression and hormonal effects. To determine the transcriptional activity of the oestrogen receptor, we developed a molecular imaging system using sodium iodide symporter (NIS) as a reporter gene. The NIS reporter gene was placed under the control of an artificial ERE derived from pERE-TA-SEAP and named as pERE-NIS. pERE-NIS was transferred to MCF-7, human breast cancer cells, which highly expressed oestrogen receptor-alpha with lipofectamine. Stably expressing cells were generated by selection with G418 for 14 days. After treatment of 17beta-oestradiol and tamoxifen with serial doses, the (125)I uptake was measured for the determination of NIS expression. The inhibition of NIS activity was performed with 50 micromol x l(-1) potassium perchlorate. The MCF7/pERE-NIS treated with 17beta-oestradiol accumulated (125)I up to 70-80% higher than did non-treated cells. NIS expression was increased according to increasing doses of 17beta-oestradiol. MCF7/pERE-NIS treated with tamoxifen also accumulated (125)I up to 50% higher than did non-treated cells. Potassium perchlorate completely inhibited (125)I uptake. When MDA-MB231 cells, the oestrogen receptor-negative breast cancer cells, were transfected with pERE-NIS, (125)I uptake of MDA-MB-231/pERE-NIS did not increase. This pERE-NIS reporter system is sufficiently sensitive for monitoring transcriptional activity of the oestrogen receptor. Therefore, cis-enhancer reporter systems with ERE will be applicable to the development of a novel selective oestrogen receptor modulator with low toxicity and high efficacy.

Removal of natural hormones in dairy farm wastewater using reactive and sorptive materials.

Science.gov (United States)

Cai, Kai; Phillips, Debra H; Elliott, Christopher T; Muller, Marc; Scippo, Marie-Louise; Connolly, Lisa

2013-09-01

The objective of this study was to examine the oestrogen and androgen hormone removal efficiency of reactive (Connelly zero-valent iron (ZVI), Gotthart Maier ZVI) and sorptive (AquaSorb 101 granular activated carbon (GAC) and OrganoLoc PM-100 organoclay (OC)) materials from HPLC grade water and constructed wetland system (CWS) treated dairy farm wastewater. Batch test studies were performed and hormone concentration analysis carried out using highly sensitive reporter gene assays (RGAs). The results showed that hormonal interaction with these materials is selective for individual classes of hormones. Connelly ZVI and AquaSorb 101 GAC were more efficient in removing testosterone (Te) than 17β-estradiol (E2) and showed faster removal rates of oestrogen and androgen than the other materials. Gotthart Maier ZVI was more efficient in removing E2 than Te. OrganoLoc PM-100 OC achieved the lowest final concentration of E2 equivalent (EEQ) and provided maximum removal of both oestrogens and androgens. Copyright © 2013 Elsevier B.V. All rights reserved.

Oestrogen: an overlooked mediator in the neuropsychopharmacology of treatment response?

Science.gov (United States)

Keating, Charlotte; Tilbrook, Alan; Kulkarni, Jayashri

2011-05-01

Major depression (MD) and anorexia nervosa (AN) often present comorbidly and both share some affective symptoms, despite obvious phenotypic differences. In the illness phase, pathophysiological evidence indicates similar abnormalities in both clinical groups including dysfunction in the serotonin (5-HT) system (of which some abnormalities persist following recovery) and between 60% and 80% of patients in both groups present with significant hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis. First-line approach to treatment for MD involves modulation of the 5-HT system using selective serotonin reuptake inhibitors (SSRIs). For AN, treatment with SSRIs has been shown to be considerably less effective compared to MD. Both illnesses show marked dysregulation in the HPA axis. A consequence of SSRI treatment is a reduction and/or normalization of indices of the HPA axis [i.e. cortisol, adrenocorticotropic hormone (ACTH)], which is consistent with recovery levels in both clinical groups. Oestrogen (in high doses) has been shown to exert antidepressant effects and positively impact on MD symptoms as a treatment in its own right, or in combination with antidepressants, in women of menopausal age. It is proposed that a combination of SSRIs and oestrogen therapy may facilitate physiological normalization in MD in women of non-menopausal age and in AN. Preliminary evidence suggests oestrogen treatment alone is of some benefit to patients and it is proposed that a combination of SSRI and oestrogen will precipitate and potentially accelerate symptomatic remission. Should this approach be successful, it offers the capacity for improvement over traditional antidepressant use in women diagnosed with MD and a novel strategy for the treatment of AN, a serious clinical illness associated with the highest mortality of any psychiatric condition.

Transcriptome response to hormonal manipulation of follicle-enclosed oocytes in rainbow trout

Science.gov (United States)

Captive fish often display reproductive dysfunction associated with follicle maturation. Gonadotropins and the progestogen maturation-inducing hormones (MIH) are important regulators of follicle maturation; however, their actions including regulating follicle maturation are not fully understood. The...

Mouse bioassay to assess oestrogenic and anti-oestrogenic compounds: Hydroxytamoxifen, Diethylstilbestrol and Genistein

Czech Academy of Sciences Publication Activity Database

Köhlerová, Eva; Škarda, Josef

2004-01-01

Roč. 51, č. 5 (2004), s. 209-217 ISSN 0931-184X R&D Projects: GA ČR GA524/02/0406; GA AV ČR IBS5045302; GA AV ČR KSK5020115 Institutional research plan: CEZ:AV0Z5045916 Keywords : bioassay * anti-oestrogens * oestrogenicity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 0.471, year: 2004

A radioimmunoassay for equilin in post-menopausal plasma: plasma levels of equilin determined after oral administration of conjugated equine oestrogens (Premarin)

International Nuclear Information System (INIS)

Morgan, M.R.A.; Whittaker, P.G.; Fuller, B.P.; Dean, P.D.G.

1980-01-01

Preparations containing equilin are widely used in hormone therapy at the menopause. No suitable routine assay exists for this steroid. Antisera have been raised to equilin-3-hemisuccinyl-bovine serum albumin, and have been found to be highly specific for equilin. A direct sensitive assay for this steroid in post-menopausal plasma has been established. The implications of the cross-reaction data for the synthesis of oestrogen immunogens are discussed. Equilin has been assayed in samples obtained from oophorectomised women receiving conjugated equine oestrogens (Premarin). (author)

Headache And Hormones

Directory of Open Access Journals (Sweden)

Shukla Rakesh

2002-01-01

Full Text Available There are many reasons to suggest a link between headache and hormones. Migraine is three times common in women as compared to men after puberty, cyclic as well as non-cyclic fluctuations in sex hormone levels during the entire reproductive life span of a women are associated with changes in frequency or severity of migraine attack, abnormalities in the hypothalamus and pineal gland have been observed in cluster headache, oestrogens are useful in the treatment of menstrual migraine and the use of melatonin has been reported in various types of primary headaches. Headache associated with various endocrinological disorders may help us in a better understanding of the nociceptive mechanisms involved in headache disorders. Prospective studies using headache diaries to record the attacks of headache and menstrual cycle have clarified some of the myths associated with menstrual migraine. Although no change in the absolute levels of sex hormones have been reported, oestrogen withdrawal is the most likely trigger of the attacks. Prostaglandins, melatonin, opioid and serotonergic mechanisms may also have a role in the pathogenesis of menstrual migraine. Guidelines have been published by the IHS recently regarding the use of oral contraceptives by women with migraine and the risk of ischaemic strokes in migraineurs on hormone replacement therapy. The present review includes menstrual migraine, pregnancy and migraine, oral contraceptives and migraine, menopause and migraine as well as the hormonal changes in chronic migraine.

Progestogen-only injectable contraceptive: Experience of women in ...

African Journals Online (AJOL)

Background: Progestogen-only injectable contraceptive is a long-acting contraceptive given intramuscularly to give protection against unwanted pregnancy for a period of 2 or 3 months, depending on the type. Alterations in menstrual pattern are a well known side effect of this effective contraceptive method. Objectives: To ...

Oral contraceptives induced hepatotoxicity

OpenAIRE

B. Akshaya Srikanth; V. Manisree

2013-01-01

Oral Contraceptives are the pharmacological agents used to prevent pregnancy. These are divided as the combined and progestogen methods and are administered orally, transdermally, systemically and via vaginal route. All these methods contain both oestrogen and progestogen. Vigorous usage of oral contraceptives and anabolic steroids as associated with cholestasis, vascular lesions and hepatic neoplasm. Benign hepatic neoplasms are clearly associated with oral contraceptives. In this article we...

The effect of Ramadan fasting on LH, FSH, oestrogen, progesterone and leptin in pregnant women.

Science.gov (United States)

Khoshdel, A; Kheiri, S; Hashemi-Dehkordi, E; Nasiri, J; Shabanian-Borujeni, S; Saedi, E

2014-10-01

Many pregnant Muslim women fast during Ramadan. Leptin has an important role in the reproductive system and hormones. In this study, FSH, LH, oestrogen, progesterone and leptin were measured in the first, second and fourth week of Ramadan and the second week post-Ramadan, in 30 fasting pregnant women. Data were analysed using repeated measures ANOVA by SPSS. The weight and BMI did not change during the study. A significant change in FSH, oestrogen, progesterone and leptin was observed (p Ramadan. Progesterone increased at the end of Ramadan and the second week after. Oestrogen increased significantly during Ramadan and decreased after Ramadan. A decreasing trend was seen in LH during the Ramadan and 2 weeks after (p Ramadan. We found poor weight gain and hypoleptinaemia in pregnant fasted women during the study. Food restriction in pregnant fasted women during Ramadan may induce poor weight gain during pregnancy. These data confirm that Ramadan fasting by pregnant women may have potential risks during pregnancy. We recommend further study to evaluate long-term effects of Ramadan fasting during pregnancy in different countries with different food habits and traditions, to obtain reliable and documented data.

Enzyme immunoassay of oestrogen receptors in needle biopsies from human liver

DEFF Research Database (Denmark)

Becker, U; Andersen, J; Poulsen, H S

1991-01-01

For quantitative assessments of sex hormone receptors in liver tissue, ligand binding assays are inconvenient, as they require large biopsies (0.5-1.0 g). The present study shows that it is possible to measure oestrogen receptors (ER) quantitatively in needle biopsy specimens as small as 10 mg...... by modifications of a commercial enzyme immunoassay employing monoclonal antibodies. Sucrose gradient centrifugation and the dextran charcoal method served as reference methods. A consecutive series of needle biopsies from patients suspected of liver disease were investigated. The biopsies (n = 37) had a median...

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer

DEFF Research Database (Denmark)

Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei

2017-01-01

BACKGROUND: Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas...... was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p expression in polyps (p ..., no differences were observed when sporadic colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages...

Cyproterone acetate in the treatment of oestrogen hypersensitivity vulvovaginitis.

Science.gov (United States)

Nguyen, Yvonne; Bradford, Jennifer; Fischer, Gayle

2018-02-01

Oestrogen hypersensitivity vulvovaginitis is a rare chronic cyclical vulvovaginitis responsive to oestrogen suppression or antagonism. We present a case series of 16 patients with refractory cyclical vulvovaginitis, all of whom responded to oestrogen suppression with cyproterone acetate. © 2017 The Australasian College of Dermatologists.

Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

Science.gov (United States)

Haglund, Felix; Rosin, Gustaf; Nilsson, Inga-Lena; Juhlin, C Christofer; Pernow, Ylva; Norenstedt, Sophie; Dinets, Andrii; Larsson, Catharina; Hartman, Johan; Höög, Anders

2015-03-01

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness. © 2015 The authors.

Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity

International Nuclear Information System (INIS)

Axon, Andrew; May, Felicity E.B.; Gaughan, Luke E.; Williams, Faith M.; Blain, Peter G.; Wright, Matthew C.

2012-01-01

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings – sunset yellow and tartrazine – were identified as novel human ERα activators, activating the human ER with an EC 50% concentration of 220 and 160 nM, respectively.

Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity.

Science.gov (United States)

Axon, Andrew; May, Felicity E B; Gaughan, Luke E; Williams, Faith M; Blain, Peter G; Wright, Matthew C

2012-08-16

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERα activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A Five Year Review of the Complications of Progestogen only ...

African Journals Online (AJOL)

... and used progestogen only injectable contraceptives (depot medroxyprogesterone acetate and noerthistherone enantate) at the family planning units of the University of Port Harcourt Teaching Hospital between 1st January 2000 and 31st December 2004. The case files of these clients were retrieved their data extracted.

The effects of oestrogens and their receptors on cardiometabolic health.

Science.gov (United States)

Morselli, Eugenia; Santos, Roberta S; Criollo, Alfredo; Nelson, Michael D; Palmer, Biff F; Clegg, Deborah J

2017-06-01

Cardiovascular disease (CVD) is one of the leading causes of mortality in developed countries. The incidence of CVD is sexually dimorphic, and research has focused on the contribution of sex steroids to the development and progression of the cardiometabolic syndrome, which is defined as a clustering of interrelated risk factors that promote the development of atherosclerosis (which can lead to CVD) and type 2 diabetes mellitus. Data are inconclusive as to how sex steroids and their respective receptors increase or suppress the risk of developing the cardiometabolic syndrome and thus CVD. In this Review, we discuss the potential role, or roles, of sex hormones in cardiometabolic health by first focusing on the influence of oestrogens and their receptors on the risk of developing cardiometabolic syndrome and CVD. We also highlight what is known about testosterone and its potential role in protecting against the development of the cardiometabolic syndrome and CVD. Given the inconclusive nature of the data regarding the direct effects of each sex hormone, we advocate and highlight the importance of studying the relative levels and the ratio of sex hormones to each other, as well as the use of cross sex hormone therapy and its effect on cardiometabolic health.

Determination of oestrogen hormones in raw and treated water ...

African Journals Online (AJOL)

Hormones in water samples have been classified as 'emerging pollutants' and may pose a potential risk for humans. Hormones can be found in both surface and ground water at low concentrations. These compounds enter water streams through wastewater treatment plants (WWTP) and may elicit endocrine disruption to ...

Progestogens in singleton gestations with preterm prelabor rupture of membranes: a systematic review and metaanalysis of randomized controlled trials.

Science.gov (United States)

Quist-Nelson, Johanna; Parker, Pamela; Mokhtari, Neggin; Di Sarno, Rossana; Saccone, Gabriele; Berghella, Vincenzo

2018-03-31

Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes. Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone. The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately. Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate

Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women

DEFF Research Database (Denmark)

Warming, Lise; Ravn, Pernille; Spielman, Danièle

2004-01-01

bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy...

Circulating sex hormones and breast cancer risk factors in postmenopausal women : reanalysis of 13 studies

NARCIS (Netherlands)

Key, T. J.; Appleby, P. N.; Reeves, G. K.; Roddam, A. W.; Helzlsouer, K. J.; Alberg, A. J.; Rollison, D. E.; Dorgan, J. F.; Brinton, L. A.; Overvad, K.; Kaaks, R.; Trichopoulou, A.; Clavel-Chapelon, F.; Panico, S.; Duell, E. J.; Peeters, P. H. M.; Rinaldi, S.; Riboli, E.; Fentiman, I. S.; Dowsett, M.; Manjer, J.; Lenner, P.; Hallmans, G.; Baglietto, L.; English, D. R.; Giles, G. G.; Hopper, J. L.; Severi, G.; Morris, H. A.; Koenig, K.; Zeleniuch-Jacquotte, A.; Arslan, A. A.; Toniolo, P.; Shore, R. E.; Krogh, V.; Micheli, A.; Berrino, F.; Muti, P.; Barrett-Connor, E.; Laughlin, G. A.; Kabuto, M.; Akiba, S.; Stevens, R. G.; Neriishi, K.; Land, C. E.; Cauley, J. A.; Lui, Li Yung; Cummings, Steven R.; Gunter, M. J.; Rohan, T. E.

2011-01-01

BACKGROUND: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. METHODS: Cross-sectional analyses of breast cancer risk factors and circulating hormone

Oestrogen, headache and oral contraceptives | Utian | South African ...

African Journals Online (AJOL)

The possible relationship between headache and the oral contraceptive is considered. In the present study, no association has been demonstrat~d between oestrogen withdrawal (as produced by oophorectomy, or cessation of exogenous oestrogen replacement therapy in oophorectomised females) or by exogenous ...

Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study

Directory of Open Access Journals (Sweden)

Rylander Charlotta

2011-03-01

Full Text Available Abstract Background Postmenopausal hormone therapy (HT influences endogenous hormone concentrations and increases the risk of breast cancer. Gene expression profiling may reveal the mechanisms behind this relationship. Our objective was to explore potential associations between sex hormones and gene expression in whole blood from a population-based, random sample of postmenopausal women Methods Gene expression, as measured by the Applied Biosystems microarray platform, was compared between hormone therapy (HT users and non-users and between high and low hormone plasma concentrations using both gene-wise analysis and gene set analysis. Gene sets found to be associated with HT use were further analysed for enrichment in functional clusters and network predictions. The gene expression matrix included 285 samples and 16185 probes and was adjusted for significant technical variables. Results Gene-wise analysis revealed several genes significantly associated with different types of HT use. The functional cluster analyses provided limited information on these genes. Gene set analysis revealed 22 gene sets that were enriched between high and low estradiol concentration (HT-users excluded. Among these were seven oestrogen related gene sets, including our gene list associated with systemic estradiol use, which thereby represents a novel oestrogen signature. Seven gene sets were related to immune response. Among the 15 gene sets enriched for progesterone, 11 overlapped with estradiol. No significant gene expression patterns were found for testosterone, follicle stimulating hormone (FSH or sex hormone binding globulin (SHBG. Conclusions Distinct gene expression patterns associated with sex hormones are detectable in a random group of postmenopausal women, as demonstrated by the finding of a novel oestrogen signature.

Do hormonal contraceptives stimulate growth of neurofibromas? A survey on 59 NF1 patients

International Nuclear Information System (INIS)

Lammert, Marge; Mautner, Victor-Felix; Kluwe, Lan

2005-01-01

Neurofibromas are benign tumors of the peripheral nerves and hallmark of neurofibromatosis type 1 (NF1), a tumor suppressor gene syndrome. Neurofibromas mostly start developing at puberty and can increase in size and number during pregnancy. Expression of progesterone receptors has been found in 75% of the tumors. Many female NF1 patients are thus concerned about the possibility that hormonal contraceptives may stimulate the growth of their neurofibromas. A survey was carried out on 59 female NF1 patients who are practicing or have practiced hormonal contraception to examine the effect of the various contraceptives on the growth of neurofibromas. Majority (53 out of 58) of patients who received oral estrogen-progestogen or pure progestogen preparations reported no associated tumor growth. In contrast, significant tumor growth was reported by two patients who received depot contraceptive containing high dose of synthetic progesterone. Oral contraceptives do not seem to stimulate the growth of neurofibromas in NF1 patients. High doses of progesterone might stimulate the growth of neurofibromas and deserve more caution

Temporal changes in clinic and ambulatory blood pressure during cyclic post-menopausal hormone replacement therapy

DEFF Research Database (Denmark)

Sørensen, M B; Rasmussen, Verner; Jensen, Gorm Boje

2000-01-01

OBJECTIVE: Post-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes...... in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen. DESIGN AND METHODS: Sixteen healthy and normotensive post-menopausal women (age 55 +/- 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17beta-oestradiol plus...

Partial and weak oestrogenicity of the red wine constituent resveratrol: consideration of its superagonist activity in MCF-7 cells and its suggested cardiovascular protective effects.

Science.gov (United States)

Ashby, J; Tinwell, H; Pennie, W; Brooks, A N; Lefevre, P A; Beresford, N; Sumpter, J P

1999-01-01

It was recently reported that the red wine phytoestrogen resveratrol (RES) acts as a superagonist to oestrogen-responsive MCF-7 cells. This activity of RES was speculated to be relevant to the 'French paradox' in which moderate red wine consumption is reported to yield cardiovascular health benefits to humans. We report here that RES binds to oestrogen receptors (ER) isolated from rat uterus with an affinity approximately 5 orders of magnitude lower than does either the reference synthetic oestrogen diethylstilboestrol (DES) or oestradiol (E2). In comparison with E2 or DES, RES is only a weak and partial agonist in a yeast hER-alpha transcription assay and in cos-1 cell assays employing transient transfections of ER-alpha or ER-beta associated with two different ER-response elements. Resveratrol was also concluded to be inactive in immature rat uterotrophic assays conducted using three daily administrations of 0.03-120 mgkg(-1)/day(-1) RES (administered by either oral gavage or subcutaneous injection). These data weaken the suggestion that the oestrogenicity of RES may account for the reported cardiovascular protective effects of red wine consumption, and they raise questions regarding the extent to which oestrogenicity data derived for a chemical using MCF-7 cells (or any other single in vitro assay) can be used to predict the hormonal effects likely to occur in animals or humans.

Progestogens to prevent preterm birth in twin pregnancies: an individual participant data meta-analysis of randomized trials

Directory of Open Access Journals (Sweden)

Schuit Ewoud

2012-03-01

Full Text Available Abstract Background Preterm birth is the principal factor contributing to adverse outcomes in multiple pregnancies. Randomized controlled trials of progestogens to prevent preterm birth in twin pregnancies have shown no clear benefits. However, individual studies have not had sufficient power to evaluate potential benefits in women at particular high risk of early delivery (for example, women with a previous preterm birth or short cervix or to determine adverse effects for rare outcomes such as intrauterine death. Methods/design We propose an individual participant data meta-analysis of high quality randomized, double-blind, placebo-controlled trials of progestogen treatment in women with a twin pregnancy. The primary outcome will be adverse perinatal outcome (a composite measure of perinatal mortality and significant neonatal morbidity. Missing data will be imputed within each original study, before data of the individual studies are pooled. The effects of 17-hydroxyprogesterone caproate or vaginal progesterone treatment in women with twin pregnancies will be estimated by means of a random effects log-binomial model. Analyses will be adjusted for variables used in stratified randomization as appropriate. Pre-specified subgroup analysis will be performed to explore the effect of progestogen treatment in high-risk groups. Discussion Combining individual patient data from different randomized trials has potential to provide valuable, clinically useful information regarding the benefits and potential harms of progestogens in women with twin pregnancy overall and in relevant subgroups.

Laparoscopic findings in women with chronic pelvic pain

African Journals Online (AJOL)

Ovarian oestrogen production has been implicated; that many sufferers are relatively hyperoestrogenic with abnormal polycystic ovaries is evidence of this. and the venodilation is more marked on the side of the developing follicle. while ovarian suppression with high doses of progestogens has improved symptoms.

Immunolocalization of androgen and oestrogen receptors in the ventral lobe of rat (Rattus norvegicus) prostate after long-term treatment with ethanol and nicotine.

Science.gov (United States)

Fávaro, W J; Cagnon, V H A

2008-12-01

Nicotine and alcohol adversely affect prostate gland function. In this work, immunohistochemistry was used to investigate the immunoreactivity and distribution of androgen and alpha, beta-oestrogen receptors following chronic treatment with alcohol, nicotine or a combination of both substances, as well as to relate these results to the development of possible prostatic pathologies. Forty male rats were divided into four groups: the Control group received tap water; the Alcoholic group received diluted 10% Gay Lussac ethanol; the Nicotine group received a 0.125 mg/100 g body weight dose of nicotine injected subcutaneously on a daily basis (Sigma Chemical Company, St. Louis, MO, USA); the Nicotine-Alcohol group received simultaneous alcohol and nicotine treatment. After 90 days of treatment, samples of the ventral lobe of the prostate were collected and processed for immunohistochemistry, light microscopy and the quantification of serum hormonal concentrations. The results showed significantly decreased serum testosterone levels and increased serum oestrogen levels in the animals from the nicotine-alcohol, the alcoholic and the nicotine groups, as well as their hormonal receptor levels. Then, it was concluded that ethanol and nicotine compromised the prostatic hormonal balance, which is a crucial factor to maintain the morphological and physiological features of this organ.

Immunocharacteristics of oestrogen and androgen target cells in the anterior pituitary gland of the chick as embryo demonstrated by a combined method of autoradiography and immunohistochemistry

International Nuclear Information System (INIS)

Gasc, J.-M.; Sar, M.; Stumpf, W.E.

1980-01-01

The distribution of oestrogen and androgen target cells in the anterior pituitary gland of the chick embryo on days 10, 12 and 15 of incubation was studied 1 h after the injection of tritium-labelled steroid hormone using the thaw-mount autoradiographic technique. Oestradiol target cells were localized in the caudal zone that corresponds to the so-called 'caudal lobe', while androgen target cells were found throughout the rostral and caudal lobes of the anterior gland. With a combined autoradiography and immunohistochemistry technique, most of the oestrogen target cells showed immunoreactivity to turkey LH antiserum but not to adrenocorticotrophin (1-24) and β-thyrotrophin antisera. In contrast, androgen target cells did not show positive immunoreactivity to the three antisera used. The results suggested a direct and early involvement of oestrogens but not of androgens in the feedback regulation of pituitary gonadotrophin secretion in the chick embryo. (U.K.)

Histomorfometria da mama de ratas tratadas com estrogênio e/ou progestagênio Breast histomorphometry of rats treated with estrogen and/or progestogen

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Sueli Maria Preda dos Santos Torres

2011-04-01

Full Text Available OBJETIVO: Avaliar as alterações histomorfométricas nas mamas de ratas tratadas com estrogênio e/ou progestagênio por curto período de tempo. MÉTODOS: Foram divididas em quatro grupos 40 ratas ooforectomizadas: GC-recebeu veículo; GE-recebeu benzoato de estradiol (37,6 µg/animal; GP-recebeu acetato de medroxiprogesterona (11,28 mg/animal e, GEP-recebeu benzoato de estradiol (37,6 µg/animal e acetato de medroxiprogesterona (11,28 mg/animal. No grupo GE, o estradiol foi administrado durante sete dias, por via subcutânea. Já no grupo EP o estradiol foi administrado nos primeiros sete dias e o progestagênio por mais 23 dias, por via subcutânea. Vinte e quatro horas após a última administração dos hormônios, os animais foram anestesiados e o primeiro par de mamas inguinais removido, imerso em formaldeído a 10% e processado para inclusão em parafina, sendo os cortes corados pela Hematoxilina-Eosina. Foram avaliadas a morfologia e a área ocupada pelo parênquima mamário, sendo os dados submetidos à análise de variância complementado pelo teste de Kruskal-Wallis (p GEP > GC; p OBJECTIVE: To evaluate the breast histomorphometric changes in rats treated with estrogen and/or progestogen for a short period of time. METHODS: Forty oophorectomized rats were divided into four groups: GC, vehicle; GE, treated with estradiol benzoate (37.6 mg/animal; GP, treated with medroxyprogesterone acetate (11.2 mg/animal and GEP, treated with estradiol benzoate (37.6 mg/animal plus medroxyprogesterone acetate (11.28 mg/animal. In GE group, estradiol was administered subcutaneously for seven days; in GEP group, estradiol was administered once in a day for the first seven days and the progestogen over the next 23 days both subcutaneously. Twenty-four hours after the last hormone administration, the animals were killed upon deep anesthesia and the first inguinal breasts were removed, fixed in 10% formaldehyde and processed to be included in paraffin

Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2

International Nuclear Information System (INIS)

Ullrich, Nina D.; Koschak, Alexandra; MacLeod, Kenneth T.

2007-01-01

Oestrogen can modify the contractile function of vascular smooth muscle and cardiomyocytes. The negative inotropic actions of oestrogen on the heart and coronary vasculature appear to be mediated by L-type Ca 2+ channel (Ca v 1.2) inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that oestrogen directly inhibits the cardiovascular L-type Ca 2+ current, I CaL . The effect of oestrogen on I CaL was measured in Ca v 1.2-transfected HEK-293 cells using the whole-cell patch-clamp technique. The current revealed typical activation and inactivation profiles of nifedipine- and cadmium-sensitive I CaL . Oestrogen (50 μM) rapidly reduced I CaL by 50% and shifted voltage-dependent activation and availability to more negative potentials. Furthermore, oestrogen blocked the Ca 2+ channel in a rate-dependent way, exhibiting higher efficiency of block at higher stimulation frequencies. Our data suggest that oestrogen inhibits I CaL through direct interaction of the steroid with the channel protein

The Women's international study of long-duration oestrogen after menopause (WISDOM: a randomised controlled trial

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Meade Tom W

2007-02-01

Full Text Available Abstract Background At the time of feasibility work and final design of the trial there was no randomised control trial evidence for the long-term risks and benefits of hormone replacement therapy. Observational studies had suggested that long term use of estrogen was likely to be associated, amongst other things, with reduced risks of osteoporosis and ischaemic heart disease and increased risks of breast and endometrial cancer. Concomitant use of progestogens had been shown to protect against endometrial cancer, but there were few data showing how progestogen might affect estrogen actions on other conditions. Disease specific risks from observational studies suggested that, overall, long-term HRT was likely to be beneficial. Several studies showed that mortality from all causes was lower in HRT users than in non-users. Some secondary cardiovascular prevention trials were ongoing but evidence was also required for a range of outcomes in healthy women. The WISDOM trial was designed to compare combined estrogen and progestogen versus placebo, and estrogen alone versus combined estrogen and progestogen. During the development of WISDOM the Women's Health Initiative trial was designed, funded and started in the US. Design Randomised, placebo, controlled, trial. Methods The trial was set in general practices in the UK (384, Australia (94, and New Zealand (24. In these practices 284175 women aged 50–69 years were registered with 226282 potentially eligible. We sought to randomise 22300 postmenopausal women aged 50 – 69 and treat for ten years. The interventions were: conjugated equine estrogens, 0.625 mg orally daily; conjugated equine estrogens plus medroxyprogesterone acetate 2.5/5.0 mg orally daily; matched placebo. Primary outcome measures were: major cardiovascular disease, osteoporotic fractures, breast cancer and dementia. Secondary outcomes were: other cancers, all cause death, venous thromboembolism and cerebro-vascular disease. Results

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices.

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Radix, Asa; Sevelius, Jae; Deutsch, Madeline B

2016-01-01

Studies have shown that transgender women (TGW) are disproportionately affected by HIV, with an estimated HIV prevalence of 19.1% among TGW worldwide. After receiving a diagnosis, HIV-positive TGW have challenges accessing effective HIV treatment, as demonstrated by lower rates of virologic suppression and higher HIV-related mortality. These adverse HIV outcomes have been attributed to the multiple sociocultural and structural barriers that negatively affect their engagement within the HIV care continuum. Guidelines for feminizing hormonal therapy among TGW recommend combinations of oestrogens and androgen blockers. Pharmacokinetic studies have shown that certain antiretroviral therapy (ART) agents, such as protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and cobicistat, interact with ethinyl estradiol, the key oestrogen component of oral contraceptives (OCPs). The goal of this article is to provide an overview of hormonal regimens used by TGW, to summarize the known drug-drug interactions (DDIs) between feminizing hormonal regimens and ART, and to provide clinical care recommendations. The authors identified English language articles examining DDIs between oestrogen therapy, androgen blockers and ART published between 1995 and 2015 using PubMed, Cumulative Index to Nursing and Allied Health Literature and EBSCOhost. Published articles predominantly addressed interactions between ethinyl estradiol and NNRTIs and PIs. No studies examined interactions between ART and the types and doses of oestrogens found in feminizing regimens. DDIs that may have the potential to result in loss of virologic suppression included ethinyl estradiol and amprenavir, unboosted fosamprenavir and stavudine. No clinically significant DDIs were noted with other anti-retroviral agents or androgen blockers. There are insufficient data to address DDIs between ART and feminizing hormone regimens used by TGW. There is an urgent need for further research in this

Preparation of directly iodinated steroid hormones and related directly halogenated compounds

International Nuclear Information System (INIS)

Sahadevan, V.

1981-01-01

The preparation of directly iodinated radioactive steroid hormones is described for use in radioimmunoassays or radiolocalization and treatment of human breast tumours. The radioactive iodinated steroid hormone is prepared by reacting a parent steroid hormone with an alkali metal iodide containing radioactive 123 I, 125 I, 130 I or 131 I in the presence of hydrogen peroxide or chloramine-T. The parent steroid hormones include the adrenal corticosteroids, the estrogens, the progestogens, the progestins and the diuretic and antidiuretic agents. The radioactive iodinated steroid hormone is prepared by iodinating the parent steroid hormone directly on the cyclopentanophenanthrene nucleus. The radioactive iodinated steroid hormones have the same antigenicity and receptor site specificity as the parent steroid hormone. The invention is illustrated by 1) the method of iodination of estradiol-17β, 2) results for the percentage labelling of several steroids and steroid hormones, 3) results for the radioimmunoassay of 125 I-estradiol and 4) results for the binding of directly iodinated estradiol-17β in an estrogen receptor assay of human breast cancer. (U.K.)

Development of a transient expression assay for detecting environmental oestrogens in zebrafish and medaka embryos

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Lee Okhyun

2012-06-01

Full Text Available Abstract Background Oestrogenic contaminants are widespread in the aquatic environment and have been shown to induce adverse effects in both wildlife (most notably in fish and humans, raising international concern. Available detecting and testing systems are limited in their capacity to elucidate oestrogen signalling pathways and physiological impacts. Here we developed a transient expression assay to investigate the effects of oestrogenic chemicals in fish early life stages and to identify target organs for oestrogenic effects. To enhance the response sensitivity to oestrogen, we adopted the use of multiple tandem oestrogen responsive elements (EREc38 in a Tol2 transposon mediated Gal4ff-UAS system. The plasmid constructed (pTol2_ERE-TATA-Gal4ff, contains three copies of oestrogen response elements (3ERE that on exposure to oestrogen induces expression of Gal4ff which this in turn binds Gal4-responsive Upstream Activated Sequence (UAS elements, driving the expression of a second reporter gene, EGFP (Enhanced Green Fluorescent Protein. Results The response of our construct to oestrogen exposure in zebrafish embryos was examined using a transient expression assay. The two plasmids were injected into 1–2 cell staged zebrafish embryos, and the embryos were exposed to various oestrogens including the natural steroid oestrogen 17ß-oestradiol (E2, the synthetic oestrogen 17α- ethinyloestradiol (EE2, and the relatively weak environmental oestrogen nonylphenol (NP, and GFP expression was examined in the subsequent embryos using fluorescent microscopy. There was no GFP expression detected in unexposed embryos, but specific and mosaic expression of GFP was detected in the liver, heart, somite muscle and some other tissue cells for exposures to steroid oestrogen treatments (EE2; 10 ng/L, E2; 100 ng/L, after 72 h exposures. For the NP exposures, GFP expression was observed at 10 μg NP/L after 72 h (100 μg NP/L was toxic to the fish. We

Alcohol and dietary fibre intakes affect circulating sex hormones among premenopausal women.

Science.gov (United States)

Maskarinec, Gertraud; Morimoto, Yukiko; Takata, Yumie; Murphy, Suzanne P; Stanczyk, Frank Z

2006-10-01

The association of alcohol and fibre intake with breast cancer may be mediated by circulating sex hormone levels, which are predictors of breast cancer risk. To evaluate the relationship of alcohol and dietary fibre intake with circulating sex hormone levels among premenopausal women. A total of 205 premenopausal women completed a validated food-frequency questionnaire at baseline and after 2 years; blood samples taken at the same time were analysed for circulating sex hormone concentrations, including oestrone (E1), oestradiol (E2), free E2, progesterone, androstenedione and sex hormone-binding globulin, by radioimmunoassay. We used mixed models to estimate least-square means of sex hormone concentrations for alcohol intake categories and quartiles of dietary intake. After adjustment for covariates, alcohol consumption was moderately associated with higher circulating oestrogen levels; those who consumed more than one drink per day had 20% higher E2 (Ptrend=0.07) levels than non-drinkers. In contrast, higher dietary fibre intake was associated with lower serum levels of androstenedione (-8% between the lowest and highest quartiles of intake, Ptrend=0.06), but not oestrogens. Similarly, consumption of fruits (-12%, Ptrend=0.03), vegetables (-9%, Ptrend=0.15) and whole grains (-7%, Ptrend=0.07) showed inverse associations with androstenedione levels. The consistency of the observed differences in sex hormone levels associated with alcohol and fibre-rich foods indicates that these nutritional factors may affect sex hormone concentrations and play a role in breast cancer aetiology and prevention.

Growth of a progesterone receptor-positive meningioma in a female patient with congenital adrenal hyperplasia.

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O'Shea, T; Crowley, R K; Farrell, M; MacNally, S; Govender, P; Feeney, J; Gibney, J; Sherlock, M

2016-01-01

Meningioma growth has been previously described in patients receiving oestrogen/progestogen therapy. We describe the clinical, radiological, biochemical and pathologic findings in a 45-year-old woman with congenital adrenal hyperplasia secondary to a defect in the 21-hydroxylase enzyme who had chronic poor adherence to glucocorticoid therapy with consequent virilisation. The patient presented with a frontal headache and marked right-sided proptosis. Laboratory findings demonstrated androgen excess with a testosterone of 18.1 nmol/L (0-1.5 nmol) and 17-Hydroxyprogesterone >180 nmol/L (transsexual patients undergoing therapy with high-dose oestrogen and progestogens. Progesterone receptor positivity has been described previously in meningiomas. 17-Hydroxyprogesterone is elevated in CAH and has affinity and biological activity at the progesterone receptor. Therefore, we hypothesise that patients who have long-standing increased adrenal androgen precursor concentrations may be at risk of meningioma growth. Patients with long-standing CAH (particularly if not optimally controlled) may present with other complications, which may be related to long-standing elevated androgen or decreased glucocorticoid levels.Chronic poor control of CAH is associated with adrenal myelolipoma and adrenal rest tissue tumours.Meningiomas are sensitive to endocrine stimuli including progesterone, oestrogen and androgens as they express the relevant receptors.

Oestrogen receptor beta isoform expression in sporadic colorectal cancer, familial adenomatous polyposis and progressive stages of colorectal cancer.

Science.gov (United States)

Stevanato Filho, Paulo Roberto; Aguiar Júnior, Samuel; Begnami, Maria Dirlei; Kuasne, Hellen; Spencer, Ranyell Matheus; Nakagawa, Wilson Toshihiko; Bezerra, Tiago Santoro; Kupper, Bruna Catin; Takahashi, Renata Maymi; Barros Filho, Mateus; Rogatto, Silvia Regina; Lopes, Ademar

2017-11-13

Among the sex hormones, oestrogen may play a role in colorectal cancer, particularly in conjunction with oestrogen receptor-β (ERβ). The expression of ERβ isoform variants and their correlations with familial adenomatous polyposis (FAP) syndrome and sporadic colorectal carcinomas are poorly described. This study aimed to investigate the expression levels of the ERβ1, ERβ2, ERβ4 and ERβ5 isoform variants using quantitative RT-PCR (921 analyses) in FAP, normal mucosa, adenomatous polyps and sporadic colorectal carcinomas. Decreased expression of ERβ isoforms was identified in sporadic polyps and in sporadic colorectal cancer as well as in polyps from FAP syndrome patients compared with normal tissues (p colorectal carcinomas were compared to normal mucosa tissues. These findings suggest an association of the ERβ isoform variants in individuals affected by germline mutations of the APC gene. Progressively decreased expression of ERβ was found in polyps at early stages of low-grade dysplasia, followed by T1-T2 and T3-T4 tumours (p colorectal cancer, the loss of expression was an independent predictor of recurrence, and ERβ1 and ERβ5 expression levels were associated with better disease-free survival (p = 0.002). These findings may provide a better understanding of oestrogens and their potential preventive and therapeutic effects on sporadic colorectal cancer and cancers associated with FAP syndrome.

Sexual function in prostatic cancer patients treated with radiotherapy, orchiectomy or oestrogens

International Nuclear Information System (INIS)

Bergman, B.; Damber, J.-E.; Littbrand, B.; Sjoegren, K.; Tomic, R.

1984-01-01

Sexual function in prostatic carcinoma patients was studied in 12 patients from each of three treatment groups: radiotherapy, orchiectomy and oestrogen treatment. Significant deterioration occurred in all groups. Although erectile potency was preserved in 9 of 12 patients treated with radiotherapy, 7 of these had a marked reduction in the frequency of sexual activity. Men subjected to orchiectomy or oestrogen treatment were seldom capable of having intercourse or of experiencing orgasm. However, oestrogen-treated men continued sexual activity with their partner more often than orchiectomised subjects. Patients receiving oestrogen treatment scored significantly higher for mental depression than those in the other two treatment groups. (author)

Sexual function in prostatic cancer patients treated with radiotherapy, orchiectomy or oestrogens

Energy Technology Data Exchange (ETDEWEB)

Bergman, B.; Damber, J.E.; Littbrand, B.; Sjoegren, K.; Tomic, R. (Umeaa Univ. (Sweden))

1984-02-01

Sexual function in prostatic carcinoma patients was studied in 12 patients from each of three treatment groups: radiotherapy, orchiectomy and oestrogen treatment. Significant deterioration occurred in all groups. Although erectile potency was preserved in 9 of 12 patients treated with radiotherapy, 7 of these had a marked reduction in the frequency of sexual activity. Men subjected to orchiectomy or oestrogen treatment were seldom capable of having intercourse or of experiencing orgasm. However, oestrogen-treated men continued sexual activity with their partner more often than orchiectomised subjects. Patients receiving oestrogen treatment scored significantly higher for mental depression than those in the other two treatment groups.

Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway

International Nuclear Information System (INIS)

Dorssers, Lambert CJ; Agthoven, Ton van; Brinkman, Arend; Veldscholte, Jos; Smid, Marcel; Dechering, Koen J

2005-01-01

Tamoxifen is effective for endocrine treatment of oestrogen receptor-positive breast cancers but ultimately fails due to the development of resistance. A functional screen in human breast cancer cells identified two BCAR genes causing oestrogen-independent proliferation. The BCAR1 and BCAR3 genes both encode components of intracellular signal transduction, but their direct effect on breast cancer cell proliferation is not known. The aim of this study was to investigate the growth control mediated by these BCAR genes by gene expression profiling. We have measured the expression changes induced by overexpression of the BCAR1 or BCAR3 gene in ZR-75-1 cells and have made direct comparisons with the expression changes after cell stimulation with oestrogen or epidermal growth factor (EGF). A comparison with published gene expression data of cell models and breast tumours is made. Relatively few changes in gene expression were detected in the BCAR-transfected cells, in comparison with the extensive and distinct differences in gene expression induced by oestrogen or EGF. Both BCAR1 and BCAR3 regulate discrete sets of genes in these ZR-75-1-derived cells, indicating that the proliferation signalling proceeds along distinct pathways. Oestrogen-regulated genes in our cell model showed general concordance with reported data of cell models and gene expression association with oestrogen receptor status of breast tumours. The direct comparison of the expression profiles of BCAR transfectants and oestrogen or EGF-stimulated cells strongly suggests that anti-oestrogen-resistant cell proliferation is not caused by alternative activation of the oestrogen receptor or by the epidermal growth factor receptor signalling pathway

Oestrogen receptor alpha in pulmonary hypertension.

Science.gov (United States)

Wright, Audrey F; Ewart, Marie-Ann; Mair, Kirsty; Nilsen, Margaret; Dempsie, Yvonne; Loughlin, Lynn; Maclean, Margaret R

2015-05-01

Pulmonary arterial hypertension (PAH) occurs more frequently in women with mutations in bone morphogenetic protein receptor type 2 (BMPR2) and dysfunctional BMPR2 signalling underpinning heritable PAH. We have previously shown that serotonin can uncover a pulmonary hypertensive phenotype in BMPR2(+/-) mice and that oestrogen can increase serotinergic signalling in human pulmonary arterial smooth muscle cells (hPASMCs). Hence, here we wished to characterize the expression of oestrogen receptors (ERs) in male and female human pulmonary arteries and have examined the influence of oestrogen and serotonin on BMPR2 and ERα expression. By immunohistochemistry, we showed that ERα, ERβ, and G-protein-coupled receptors are expressed in human pulmonary arteries localizing mainly to the smooth muscle layer which also expresses the serotonin transporter (SERT). Protein expression of ERα protein was higher in female PAH patient hPASMCs compared with male and serotonin also increased the expression of ERα. 17β-estradiol induced proliferation of hPASMCs via ERα activation and this engaged mitogen-activated protein kinase and Akt signalling. Female mice over-expressing SERT (SERT(+) mice) develop PH and the ERα antagonist MPP attenuated the development of PH in normoxic and hypoxic female SERT(+) mice. The therapeutic effects of MPP were accompanied by increased expression of BMPR2 in mouse lung. ERα is highly expressed in female hPASMCs from PAH patients and mediates oestrogen-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin can increase ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent PH in the mouse and increases BMPR2 expression. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Inadvertent P-hacking among trials and systematic reviews of the effect of progestogens in pregnancy? A systematic review and meta-analysis.

Science.gov (United States)

Prior, M; Hibberd, R; Asemota, N; Thornton, J G

2017-06-01

Progestogens have been evaluated in numerous trials and meta-analyses, many of which concluded they were effective. However, two large trials PROMISE and OPPTIMUM have recently concluded that progesterone was ineffective. This raises the possibility that earlier studies and reviews had been biased by either selective publication or selective choice of outcomes, so called "P-hacking". To compare the findings all progestogen trials and systematic reviews with those of trials with pre-registered primary outcomes which avoided selective outcome reporting. Search of PubMed, the Cochrane Library and trial registries. Registration PROSPERO CRD42016035303. Systematic reviews of randomised trials comparing progestogen with placebo in pregnancy and the individual trials included in those reviews. The subset of trials reporting a pre-registered primary outcome were compared with the totality of trials and reviews. For reviews all outcomes were included. For individual trials all outcomes reported in the systematic reviews were included. For the comparison group we recorded the registered primary outcome from trials that were either registered before they started, or registered during the recruitment phase and also double blind. Nineteen of twenty-nine meta-analyses concluded that progestogens were effective. Twenty-two trials reported their pre-registered primary outcomes. There was no effect of progesterone on primary registered dichotomous outcome RR 1.00 (95% CI 0.94-1.07). Only one of the 22 showed a nominally statistically significant benefit. When evaluated in registered double-blind trials with analysis restricted to predefined primary outcomes, progestational agents in pregnancy are ineffective. Progestogens to prevent pregnancy loss, an example of P-hacking. © 2017 Royal College of Obstetricians and Gynaecologists.

Immunolocalisation of oestrogen receptor beta in human tissues.

Science.gov (United States)

Taylor, A H; Al-Azzawi, F

2000-02-01

Oestrogens exert their actions via specific nuclear protein receptors that are members of the steroid/thyroid receptor superfamily of transcription factors. Recently, a second oestrogen receptor (ERbeta) has been cloned, and using reverse transcription-PCR and immunohistochemistry it has been shown to have a wide tissue distribution in the rat that is distinct from the classical oestrogen receptor, ERalpha. Using commercial polyclonal antisera against peptides specific to human ERbeta, we have determined the sites of ERbeta expression in archival and formalin-fixed human tissue and compared its expression with that of ERalpha. ERbeta was localised to the cell nuclei of a wide range of normal adult human tissues including ovary, Fallopian tube, uterus, lung, kidney, brain, heart, prostate and testis. In the ovary, ERbeta was present in multiple cell types including granulosa cells in small, medium and large follicles, theca and corpora lutea, whereas ERalpha was weakly expressed in the nuclei of granulosa cells, but not in the theca nor in the copora lutea. In the endometrium, both ERalpha and ERbeta were observed in luminal epithelial cells and in the nuclei of stromal cells but, significantly, ERbeta was weak or absent from endometrial glandular epithelia. Epithelial cells in most male tissues including the prostate, the urothelium and muscle layers of the bladder, and Sertoli cells in the testis, were also immunopositive for ERbeta. Significant ERbeta immunoreactivity was detected in most areas of the brain, with the exception of the hippocampus - a tissue that stained positively for ERalpha. In conclusion, the almost ubiquitous immunohistochemical localisation of ERbeta indicates that ERbeta may play a major role in the mediation of oestrogen action. The differential expression of ERalpha and ERbeta in some of these tissues suggests a more complex control mechanism in oestrogenic potential than originally envisioned.

Deep vein thrombosis and the oestrogen content in oral contraceptives. An epidemiological analysis.

Science.gov (United States)

Kierkegaard, A

1985-01-01

Epidemiological studies have pointed to a correlation between the oestrogen content of oral contraceptives and the risk of deep vein thrombosis (DVT). The correlation has been strongest in studies which partially consisted of adverse drug reaction reports to the Swedish Adverse Drug Reaction Advisory Committee (SADRAC). The present study analyzes the epidemiological basis of the adverse drug reaction reports on DVT in women on oral contraceptives to SADRAC. It verifies the reported correlation between the oestrogen content of the pills and the risk of DVT but it also demonstrates that this correlation probably was secondary to differences in the diagnostic standard of DVT, to differences in reporting policies to SADRAC and to an age difference between women on low-oestrogen-pills and those on high-oestrogen pills and is thus due to bias. It is concluded that adverse drug reaction reporting on oral contraceptives has been very unreliable, for which reason it cannot support any epidemiological conclusion concerning the relative thrombogenicity of high-oestrogen pills compared with that of low-oestrogen pills.

Orchidectomy and oestrogen therapy revisited

DEFF Research Database (Denmark)

Iversen, P

1998-01-01

with gynaecomastia, loss of sexual function and unacceptable cardiovascular toxicity. Low dose oestrogens in combination with antiandrogens or antithrombotic agents may be better tolerated treatments. The route of administration is a crucial factor in the genesis of cardiovascular toxicity and parenterally...

Absence of systemic hormonal effects in an oestradiol diether topically active on the vaginal mucosa.

Science.gov (United States)

Wolff, J P; Cachelou, R; Guéritée, N

1982-12-01

The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study. They had also been treated for cancer of the cervix (27 women), endometrium (5), ovaries (5) or breast (1). All women presented with sexual troubles, mainly genital discomfort (dyspareunia or vaginism). In a double-blind fashion, gynaecological capsules containing either an oestradiol diether (ICD: promestriene) or only the excipient were administered for 40 consecutive days. At the end of the treatment, the FSH, LH, oestrone (E1) and oestradiol (E2) plasma levels were not found to be significantly different from the pre-therapeutic values. These results suggest that promestriene acts on the vaginal mucosa, therefore not being converted back into the hormone from which it was derived. Also, in its dietheroxide form, promestriene is incapable of crossing the malpighian (vaginal or epidermal) epithelium and of reaching the general blood circulation. This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated, as in patients who have an oestrogen-sensitive cancer in their medical history.

Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure

DEFF Research Database (Denmark)

Andersen, Helle Raun; Nielsen, Flemming; Nielsen, Jesper Bo

2007-01-01

-oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week. Conclusions: The study illustrates the usefulness of this biomarker for qualitative assessment...... with oestrogen-like properties in an occupational setting. Methods: Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity......, medium or high based on information collected by detailed interviews of the women and the employers. Results: In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno...

Study of the effects of radiation on prevention of gynaecomastia due to oestrogen therapy

Energy Technology Data Exchange (ETDEWEB)

Waterfall, N B; Glaser, M G [Charing Cross Group of Hospitals, London (UK)

1979-09-01

A study of the effects of irradiation in prevention of gynaecomastia due to oestrogen therapy for carcinoma is reported. Twenty patients were treated with oestrogens without radiotherapy, of these 17 developed gynaecomastia. Twenty-seven patients were treated with radiotherapy prior to oestrogens, of these only 3 developed gynaecomastia. Previous studies have shown similar results but have used larger doses of irradiation and recommended a delay of 1 month between radiotherapy and treatment. In this study a low dose of radiation was used and oestrogens were started immediately after radiotherapy.

Hormone therapy and risk of myocardial infarction: a national register study

DEFF Research Database (Denmark)

Nielsen, Lars Hougaard; Løkkegaard, Ellen Christine Leth; Andreasen, Anne Helms

2008-01-01

AIM: To assess the risk of myocardial infarction (MI) as a result of hormone therapy (HT), with focus on the influence of age, duration of HT, various regimens and routes, progestagen type, and oestrogen dose. METHODS AND RESULTS: All healthy Danish women (n = 698,098, aged 51-69) were followed d...

Partial characterization of a novel oestrogen-induced protein in the rat adenohypophysis.

Science.gov (United States)

Casabiell, X; Zugaza, J L; Pombo, C M; Bokser, L; Mulet, N; Casanueva, F F

1993-06-01

In order to detect putative markers of prolactin-secreting pituitary tumours, adult rats were subjected to long-term oestrogenization with oestradiol benzoate (OE2) on a monthly basis. At 6 months, anterior pituitaries were dissected and incubated either as tissue fragments or as dispersed cells with a [35S]methionine mix for labelling. Proteins released into the incubation medium and from tissue extracts were further analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and fluorography. Oestrogen induced the appearance in the incubation medium of a protein (OE2 band) with an M(r) of 38,000 under reducing conditions, and high specific activity. Surprisingly, such a protein was not detected in tissue extracts. The OE2 band was detectable by 7 days after the first dose of oestrogen, and remained throughout 1 year of treatment. The tumour cell line GH3 showed a similar OE2 band which was further enhanced by oestrogens. The protein was observed similarly in both female and male pituitary donors, either intact or gonadectomized, and also in rats of different strains, suggesting that its appearance was independent of the strain of rat and gonadal status. Furthermore, the OE2 band was specific for pituitary cells and not produced by other oestrogenized tissues. No alteration in the rate of generation or the electrophoretic pattern of the OE2 band was observed when pituitary cells from oestrogenized rats were metabolically labelled while being incubated with tunicamycin. Furthermore, a system for glycan detection, adsorption to Concanavalin A or incubation with endoglycosidase F also failed to show a clear amount of glycosylation of the oestrogen-induced protein. Both immunoprecipitation experiments and time-limited proteolysis with V8 protease ruled out the possibility that the OE2 band could be structurally related to either GH or prolactin. In conclusion, oestrogens induce the generation of a new monocatenary protein with an apparent M(r) of 38

Oestrogen inhibits human colonic motility by a non-genomic cell membrane receptor-dependent mechanism.

LENUS (Irish Health Repository)

Hogan, A M

2012-02-01

BACKGROUND: Classical effects of oestrogen involve activation of target genes after binding nuclear receptors. Oestrogenic effects too rapid for DNA transcription (non-genomic) are known to occur. The effect of oestrogen on colonic motility is unknown despite the prevalence of gastrointestinal symptoms in pregnant and premenopausal women. METHODS: Histologically normal colon was obtained from proximal resection margins of colorectal carcinoma specimens. Circular smooth muscle strips were microdissected and suspended in organ baths under 1 g of tension. After equilibration, they were exposed to 17beta-oestradiol (n = 8) or bovine serum albumin (BSA)-conjugated 17beta-oestradiol (n = 8). Fulvestrant, an oestrogen receptor antagonist, was added to some baths (n = 8). Other strips were exposed to calphostin C or cycloheximide. Carbachol was added in increasing concentrations and contractile activity was recorded isometrically. RESULTS: Oestrogen inhibited colonic contractility (mean difference 19.7 per cent; n = 8, P < 0.001). In keeping with non-genomic, rapid-onset steroid action, the effect was apparent within minutes and reversible. It was observed with both 17beta-oestradiol and BSA-conjugated oestrogen, and was not altered by cycloheximide. Effects were inhibited by fulvestrant, suggesting receptor mediation. CONCLUSION: Oestrogen decreases contractility in human colonic smooth muscle by a non-genomic mechanism involving cell membrane coupling.

Transdermal hormone therapy in postmenopausal women: A review of metabolic effects and drug delivery technologies

Directory of Open Access Journals (Sweden)

Nathan W Kopper

2008-10-01

Full Text Available Nathan W Kopper, Jennifer Gudeman, Daniel J ThompsonKV Pharmaceutical, St. Louis, MO, USAAbstract: Vasomotor symptoms (VMS associated with menopause can cause significant discomfort and decrease the quality of life for women in the peri-menopausal and post-menopausal stages of life. Hormone therapy (HT is the mainstay of treatment for menopausal symptoms and is currently the only therapy proven effective for VMS. Numerous HT options are available to treat VMS, including estrogen-only and estrogen-progestogen combination products to meet the needs of both hysterectomized and nonhysterectomized women. In addition to selecting an appropriate estrogen or estrogen-progestogen combination, consideration should be given to the route of administration to best suit the needs of the patient. Delivery systems for hormone therapy include oral tablets, transdermal patches, transdermal topical (nonpatch products, and intravaginal preparations. Oral is currently the most commonly utilized route of administration in the United States. However, evidence suggests that oral delivery may lead to some undesirable physiologic effects caused by significant gut and hepatic metabolism. Transdermal drug delivery may mitigate some of these effects by avoiding gut and hepatic first-pass metabolism. Advantages of transdermal delivery include the ability to administer unmetabolized estradiol directly to the blood stream, administration of lower doses compared to oral products, and minimal stimulation of hepatic protein production. Several estradiol transdermal delivery technologies are available, including various types of patches, topical gels, and a transdermal spray.Keywords: estradiol, hormone therapy, menopause, transdermal drug delivery, vasomotor symptoms

Phyto-oestrogens and their metabolites in milk produced on two pastures with different botanical compositions

DEFF Research Database (Denmark)

Adler, S. A.; Purup, S.; Hansen-Møller, J.

2014-01-01

. The objective of this study was to assess the effects of grazing a recently established pasture containing red clover (Trifolium pratense L.) and an older pasture containing a variety of sown and unsown plant species on milk concentrations of phyto-oestrogens. Sixteen Norwegian Red dairy cows [mean (standard......Phyto-oestrogens are a group of secondary plant metabolites that may bind to oestrogen receptors and exert oestrogenic or anti-oestrogenic effects in humans and can protect against cancer diseases. When ingested by dairy cows, phyto-oestrogens can be metabolised and transferred to the milk...... deviation); body weight 599 (45.1). kg, stage of lactation 73 (15.0) d in milk, milk yield 29.9 (2.90) kg/d at the start of the experiment] were divided into two groups and grazed either a short-term pasture (SP) or a long-term pasture (LP). The SP was representative of organically managed leys in Norway...

The reduction in visceral fat mass in response to growth hormone is more marked in men than in oestrogen-deficient women

DEFF Research Database (Denmark)

Franco, Celina; Koranyi, Josef; Brandberg, John

2008-01-01

and postmenopausal women. METHODS: Fifteen men and 15 age- and BMI-matched women with abdominal obesity (mean age: 58; range 51-64 years) were treated for one year with similar doses (0.47 vs. 0.51 mg/day) of GH. All women were postmenopausal not receiving oestrogen treatment. Insulin sensitivity was assessed using...

Simultaneous determination of estrogens and progestogens in honey using high performance liquid chromatography-tandem mass spectrometry

Science.gov (United States)

This work describes the development and validation of a method for the simultaneous determination of 13 estrogens and progestogens in honey by high performance liquid chromatography-tandem mass spectrometry. The target compounds were preconcentrated by solid phase extraction. Pretreatment variables ...

Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites.

Science.gov (United States)

Santillán, R; Pérez-Palacios, G; Reyes, M; Damián-Matsumura, P; García, G A; Grillasca, I; Lemus, A E

2001-09-14

Levonorgestrel (13beta-ethyl-17alpha-ethynyl-17beta-hydroxy-4-gonen-3-one), a potent contraceptive progestin stimulates growth and proliferation of cultured breast cancer cells through a receptor-mediated mechanism, even though levonorgestrel does not bind to the oestrogen receptor (ER). To assess whether the oestrogen-like effects induced by this synthetic progestin are exerted via its metabolic conversion products, we studied the binding affinity of three A-ring levonorgestrel derivatives to the ER and their capability to transactivate an oestrogen-dependent yeast system co-transfected with the human ER gene and oestrogen responsive elements fused to a beta-galactosidase reporter vector. The results demonstrated that the 3beta,5alpha reduced levonorgestrel derivative and to a lesser extent its 3alpha isomer interact with the oestrogen receptor, with a significantly lower relative binding affinity (2.4% and 0.4%, respectively) than that of oestradiol (100%), while levonorgestrel does not. Both levonorgestrel metabolites were able to activate, in a dose-dependent manner, the beta-galactosidase reporter gene in the yeast expression system, an effect that was precluded by a steroidal antioestrogen. The oestrogenic potency of levonorgestrel metabolites was significantly lower (750-fold) than that of oestradiol. Furthermore, high doses of 3beta,5alpha levonorgestrel (2.5 mg/day/6 days) induced an increase of oestrogen-dependent progestin receptor in the anterior pituitary of castrated rats. The overall data offer a plausible explanation for the weak oestrogenic effects induced by high, non-pharmacological doses of levonorgestrel.

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies : an individual participant data meta-analysis

NARCIS (Netherlands)

Schuit, E; Stock, S; Rode, L; Rouse, D J; Lim, A C; Norman, J E; Nassar, A H; Serra, V; Combs, C A; Vayssiere, C; Aboulghar, M M; Wood, S; Çetingöz, E; Briery, C M; Fonseca, E B; Worda, K; Tabor, A; Thom, E A; Caritis, S N; Awwad, J; Usta, I M; Perales, A; Meseguer, J; Maurel, K; Garite, T; Aboulghar, M A; Amin, Y M; Ross, S; Cam, C; Karateke, A; Morrison, J C; Magann, E F; Nicolaides, K H; Zuithoff, N P A; Groenwold, R H H; Moons, K G M; Kwee, A; Mol, B W J

BACKGROUND: In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). OBJECTIVES: To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies

Does endogenous serum oestrogen play a role in meibomian gland dysfunction in postmenopausal women with dry eye?

Science.gov (United States)

Golebiowski, Blanka; Badarudin, Noor; Eden, John; You, Jingjing; Hampel, Ulrike; Stapleton, Fiona

2017-02-01

To explore the relationship between serum concentration of sex hormones and dry eye symptoms and signs in postmenopausal women. A cross-sectional analysis was undertaken. Subjects were 46 postmenopausal women with dry eye (mean age 64.4±5.2 years, 13.7±6.4 years since menopause; not undergoing hormone replacement therapy). Ocular symptoms (Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI)), tear function (tear osmolarity, non-invasive tear break-up time, tear secretion), corneal and conjunctival staining, and meibomian gland (MG) appearance, were recorded. Venous blood was collected and serum concentrations of 17β-oestradiol (E2), 3-α-androstanediol-glucuronide (3α-diol-G), and dehydroepiandrosterone sulfate (DHEA-S) were determined using ELISA. Multiple linear regression analysis was used to examine predictors of dry eye symptoms and signs. Mean serum concentration of E2, 3α-diol-G and DHEA-S was 9.02±13.40 pg/mL, 1.59±1.02 ng/mL and 0.74±0.53 μg/mL, respectively. Ocular symptoms were elevated (mean scores 27.0±18.1 (OSDI) and 40.3±8.4 (OCI)) but signs were within normal ranges. Higher serum E2 concentration along with capped glands, lid telangiectasia and older age was a significant predictor of worse MG secretion quality (p0.05). Serum oestrogen appears to be a key factor in MG signs. Although serum hormone levels did not contribute significantly to dry eye symptoms in this study, it is possible that oestrogen plays a role through its effect on meibum secretion. These findings suggest that MG dysfunction underpins dry eye symptoms in non-Sjögren's dry eye in postmenopausal women. ACTRN12612000281897. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Oestrogen receptor evaluation in Pomeranian dogs with hair cycle arrest (alopecia X) on melatonin supplementation.

Science.gov (United States)

Frank, Linda A; Donnell, Robert L; Kania, Stephen A

2006-08-01

The role of oestrogen receptors in dogs with hair cycle arrest (alopecia X) was investigated by immunohistochemistry. The purpose of this study was to determine if hair regrowth in dogs with hair cycle arrest treated with melatonin was associated with a decrease in follicular oestrogen receptors. Fifteen Pomeranians (excluding intact females) with hair cycle arrest were enrolled. Two biopsies were obtained from alopecic areas of the trunk before and after 3 months on melatonin. Haematoxylin and eosin-stained tissues were examined and oestrogen receptor-alpha was demonstrated immunohistochemically. Common histopathological findings included hyperkeratosis, follicular keratosis, excessive tricholemmal keratinization (flame follicles), thin epidermis, few small anagen bulbs, epidermal pigmentation and melanin aggregates within follicular keratin. Melanin aggregates within basal cells and hair were an occasional finding. After 3 months, 40% (six) dogs had mild to moderate hair regrowth. Biopsies from six dogs showed histological evidence of an increase in anagen hairs and eight dogs had a decrease in epidermal pigmentation. Moderate to marked staining intensity of oestrogen receptor-alpha was noted in all sebaceous gland basal cells, all small hair bulbs and follicular epithelium of telogen hairs. There was no oestrogen receptor-alpha staining of nuclei within the epidermis, apocrine glands or dermal fibroblasts. Large anagen hair bulbs had minimal to no oestrogen receptor staining. Hair regrowth was not associated with a change in oestrogen receptor-alpha staining.

The body has a brake: micrin is a postulated new gonadal hormone curbing tissue overgrowth and restricting reproduction.

Science.gov (United States)

Hart, John E

2014-12-01

There is evidence for an unrecognised classical hormone secreted by the mammalian gonad. This postulated hormone--'micrin' (pronounced 'my-crin')--represents the body's brake against tissue overgrowth. When oestrogens are administered in high doses to female rats there is a considerable (non-artefactual) increase in the relative size and weight of organs such as the pituitary, adrenals, uterus and liver--suggesting an organotrophic (organ-building) role for endogenous oestrogens. This effect is exaggerated if the animals are first ovariectomized, indicating the removal of a negative ovarian factor, micrin. These organ enlargements can be reduced by pretreating the rats with large doses of antioestrogens such as clomiphene and tamoxifen. This antiestrogenic blockade of exogenous oestrogens is itself blunted by prior removal of the ovaries. It is proposed that antioestrogens (e.g. tamoxifen in breast cancer treatment) antagonize the organotrophic effects of oestrogens by competing for the oestrogen receptor peripherally and centrally and via an increase in the secretion of ovarian micrin. It is deduced that micrin is the testicular 'inhibin' proposed in the 1930s, not the molecule that now bears that name, which acts at the pituitary tier as a downregulator of follicle-stimulating hormone. The hallmark of micrin deficiency in the male rat is a pituitary hypertrophy that follows castration. This is reversible with a steroid-depleted aqueous bovine testicular extract, the micrin within which suppresses the hypothalamus, normalizing the pituitary. Micrin probably acts as a brake on peripheral tissues directly but also indirectly at the meta-level via the hypothalamic-pituitary axis, resetting a hypothalamic 'organostat' controlling organ and tissue masses, part of the 'organotrophic system' of internal size regulation. Besides endocrine (circulating) micrin from the gonads there is probably paracrine (locally acting) micrin produced in the brain. This is involved in a

Influence of hormonal contraceptives and the occurrence of stroke: integrative review.

Science.gov (United States)

Lima, Adman Câmara Soares; Martins, Larissa Castelo Guedes; Lopes, Marcos Venícios de Oliveira; Araújo, Thelma Leite de; Lima, Francisca Elisângela Teixeira; Aquino, Priscila de Souza; Moura, Escolástica Rejane Ferreira

2017-01-01

To identify scientific evidence regarding the influence of hormonal contraceptive use and the occurrence of stroke. Integrative review of the literature, through database search using the descriptors "contraceptive agents", "contraceptive devices", "contraceptives, Oral" and "Stroke". Original studies in Portuguese, Spanish and English, published in full and available online were included. Studies that did not answer our guiding questions and duplicated studies were excluded. Women using combined oral contraceptives have higher risk of stroke, even with a lower hormonal dosage and different types of progestogen, regardless of the duration of use. The use of contraceptives associated with smoking, hypertension, migraine, hypercholesterolemia, obesity and sedentary lifestyle increases the chance of stroke. Contraceptive patch and vaginal ring are associated to increased risk. Use of combined hormonal contraceptives, except for the injectable and the transdermal ones, increases the chance of occurrence of the event. Progestogen-only contraceptives were considered safe. Identificar evidências científicas acerca da influência do uso de anticoncepcionais hormonais na ocorrência do acidente vascular cerebral (AVC). Revisão integrativa da literatura, com pesquisa em bases de dados, utilizando os descritores "contraceptive agents", "contraceptive devices", "contraceptives, Oral" e "stroke". Foram incluídos artigos originais nos idiomas português, espanhol e inglês, publicados na íntegra e disponíveis eletronicamente. Foram excluídos artigos que não respondiam às questões norteadoras e repetidos. Usuárias de anticoncepcional oral combinado apresentam risco maior de AVC, mesmo com dosagem hormonal menor e diferentes tipos de progestágeno, independente do tempo de uso. A presença associada de tabagismo, hipertensão arterial, enxaqueca, hipercolesterolemia, obesidade e sedentarismo aumenta a chance desse desfecho. Adesivo anticoncepcional e anel vaginal s

Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor ...

African Journals Online (AJOL)

Oestrogen, testosterone, cytotoxin and cholinesterase inhibitor removal during reclamation of sewage to drinking water. ... Risks associated with sewage effluent and reclaimed sewage should be closely monitored; therefore water at the Gammams Sewage Treatment Plant (GSTP) inlet and outlet, as well as reclaimed water ...

Effect of forage on the content of phyto-oestrogens in bovine milk

DEFF Research Database (Denmark)

Andersen, Charlotte; Weisbjerg, Martin Riis; Hansen-Møller, Jens

2009-01-01

Phyto-oestrogens are believed to have a range of beneficial effects on predominant Western diseases. A few studies on phyto-oestrogens in milk exist and show that the composition can be affected by feeding. Therefore, the aim was to study how feeding of lucerne and grass/clover silages (GCSs) aff...

The contribution of SHBG to the variation in HOMA-IR is not dependent on endogenous oestrogen or androgen levels in postmenopausal women.

Science.gov (United States)

Davis, Susan R; Robinson, Penelope J; Moufarege, Alain; Bell, Robin J

2012-10-01

Sex hormone-binding globulin (SHBG) is a robust predictor of insulin resistance. Whether this is independent of circulating sex steroid levels remains uncertain. The aim of this study was to investigate the determinants of SHBG in postmenopausal women and whether the relationship between SHBG and insulin resistance is independent of oestrogen and androgen levels. A cross-sectional study of naturally and surgically menopausal women. Seven hundred and sixty three postmenopausal women not using any systemic hormone therapy, mean age 54·4 ± 5·8 years, recruited in the US, Canada, Australia, UK and Sweden between July 2004 and February 2005. Relationships between log-transformed (ln) SHBG and ln homoeostasis model assessment for insulin resistance (HOMA-IR) were explored, taking into account age, body mass index (BMI), blood pressure (BP) and circulating oestradiol, oestrone, testosterone and dihydrotestosterone. Taking into account age, race, years since menopause, menopause type, BMI, BP, prior postmenopausal hormone use and the sex steroids measured, 34·4% of the variation in SHBG could be explained by the model that included negative contributions by HOMA-IR, BMI and diastolic BP, and a positive contribution by total testosterone (P HOMA-IR, which was best explained by the model that included BMI, SHBG, systolic BP and surgical menopause, with each variable being positively related to HOMA-IR (r(2) = 0·3152, P = 0·03). The relationship between SHBG and HOMA-IR, as an estimate of insulin resistance, is not explained by endogenous oestrogen and androgen levels and is, at least in part, independent of BMI in postmenopausal women. © 2011 Blackwell Publishing Ltd.

Indomethacin inhibits the effects of oestrogen in the anterior pituitary gland of the rat.

Science.gov (United States)

Rosental, D G; Machiavelli, G A; Cherñavsky, A C; Speziale, N S; Burdman, J A

1989-06-01

Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, blocked the increase of oestrogen-binding sites in the nuclear subcellular fraction, an increase which occurs after the administration of oestradiol. Consequently the biological effects of oestrogens in the anterior pituitary gland of the rat (prolactin synthesis, concentration of progesterone-binding sites and cell proliferation) are diminished. The anterior pituitary gland synthesized prostaglandin F2 alpha (PGF2 alpha), PGE2 and PGD2 from arachidonic acid. This synthesis was blocked when indomethacin was added to the culture media. Oestrogen increased the concentration of PGE2: an increase that was partially prevented by indomethacin. Prostaglandins may have an important role on the effects of oestrogen in the anterior pituitary gland of the rat.

On the evocability of a positive oestrogen feedback action on LH secretion in transsexual men and women.

Science.gov (United States)

Dörner, G; Rohde, W; Seidel, K; Haas, W; Schott, G S

1976-03-01

In transsexual men with homosexual behaviour and intact testicular function, as well as in homosexual men with normal gender identity, following a negative oestrogen feedback effect a delayed positive oestrogen feedback action on LH secretion was evoked. By contrast, in transsexual men with hypo- or asexuality and intact testes or hypergonadotrophic hypo- or agonadism, as well as in heterosexual men with normal gender identity, a negative oestrogen feedback effect was not followed by a positive feedback action on LH release. In transsexual women with homosexual behaviour and oligo- and/or hypomenorrhoea, only a weak or at best moderate positive oestrogen feedback action on LH release was evocable, similarly as in castrated and oestrogen-primed heterosexual men. By contrast, in a transsexual woman with bisexual behaviour and eumenorrhoea, a strong positive oestrogen feedback action on LH secretion was evocable, as well as in heterosexual women with normal gender identity.

The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

Science.gov (United States)

Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

2011-10-01

The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience

Ketoprofen and antinociception in hypo-oestrogenic Wistar rats fed on a high sucrose diet.

Science.gov (United States)

Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; García-Martínez, Betzabeth Anali; López-Muñoz, Francisco Javier

2016-10-05

Non-steroidal anti-inflammatory drugs such as ketoprofen are the most commonly used analgesics for the treatment of pain. However, no studies have evaluated the analgesic response to ketoprofen in conditions of obesity. The aim of this study was to analyse the time course of nociceptive pain in Wistar rats with and without hypo-oestrogenism on a high sucrose diet and to compare the antinociceptive response using ketoprofen. Hypo-oestrogenic and naïve rats received a hyper caloric diet (30% sucrose) or water ad libitum for 17 weeks, the thermal nociception ("plantar test" method) and body weight were tested during this period. A biphasic response was observed: thermal latency decreased in the 4th week (hyperalgesia), while from 12th to 17th week, thermal latency increased (hypoalgesia) in hypo-oestrogenic rats fed with high sucrose diet compared with the hypo-oestrogenic control group. At 4th and 17th weeks, different doses of ketoprofen (1.8-100mg/kg p.o.), were evaluated in all groups. The administration of ketoprofen at 4th and 17th weeks showed dose-dependent effects in the all groups; however, a greater pharmacological efficacy was observed in the 4th week in the hypo-oestrogenic animals that received sucrose. Nevertheless, in all the groups significantly diminish the antinociceptive effects in the 17th week. Our data showed that nociception was altered in the hypo-oestrogenic animals that were fed sucrose (hyperalgesia and hypoalgesia). Ketoprofen showed a dose-dependent antinociceptive effect at both time points. However, hypo-oestrogenism plus high-sucrose diet modifies the antinociceptive effect of ketoprofen. Copyright © 2016 Elsevier B.V. All rights reserved.

Temporal changes in clinic and ambulatory blood pressure during cyclic post-menopausal hormone replacement therapy

DEFF Research Database (Denmark)

Sørensen, M B; Rasmussen, Verner; Jensen, Gorm Boje

2000-01-01

OBJECTIVE: Post-menopausal hormone replacement (HRT) might protect against cardiovascular disease, possibly by arterial vasodilation and reduced blood pressure. Progestogens are needed to avoid endometrial disease but vascular effects are controversial. The objective was to assess temporal changes...... in blood pressure (BP) by two measurement techniques during a cyclic hormone replacement regimen. DESIGN AND METHODS: Sixteen healthy and normotensive post-menopausal women (age 55 +/- 3 years) were studied in a placebo-controlled, randomized crossover study, and were randomized to 17beta-oestradiol plus...... and in the ninth weeks of treatment in both periods. RESULTS: Clinic systolic and diastolic BP were reduced after 10 days of oestradiol (-5.1 and -3.2 mmHg respectively, P

Phyto-oestrogen levels in foods : The design and construction of the VENUS database

NARCIS (Netherlands)

Kiely, M.; Faughnan, M.; Wähälä, K.; Brants, H.; Mulligan, A.

2003-01-01

The objective of the Vegetal Estrogens in Nutrition and the Skeleton (VENUS) project was to evaluate existing data on dietary exposure to compounds with oestrogenic and anti-oestrogenic effects present in plant foods as constituents or contaminants, and to identify and disseminate in vitro and in

Prenatal stress alters progestogens to mediate susceptibility to sex-typical, stress-sensitive disorders, such as drug abuse: a review

Directory of Open Access Journals (Sweden)

Cheryl A Frye

2011-10-01

Full Text Available Maternal-offspring interactions begin prior to birth. Experiences of the mother during gestation play a powerful role in determining the developmental programming of the central nervous system. In particular, stress during gestation alters developmental programming of the offspring resulting in susceptibility to sex-typical and stress-sensitive neurodevelopmental, neuropsychiatric and neurodegenerative disorders. However, neither these effects, nor the underlying mechanisms, are well understood. Our hypothesis is that allopregnanolone, during gestation, plays a particularly vital role in mitigating effects of stress on the developing fetus and may mediate, in part, alterations apparent throughout the lifespan. Specifically, altered balance between glucocorticoids and progestogens during critical periods of development (stemming from psychological, immunological, and/or endocrinological stressors during gestation may permanently influence behavior, brain morphology, and/or neuroendocrine-sensitive processes. 5α-reduced progestogens are integral in the developmental programming of sex-typical, stress-sensitive, and/or disorder-relevant phenotypes. Prenatal stress may alter these responses and dysregulate allopregnanolone and its normative effects on stress axis function. As an example of a neurodevelopmental, neuropsychiatric and/or neurodegenerative process, this review focuses on responsiveness to drugs of abuse, which is sensitive to prenatal stress and progestogen milieu. This review explores the notion that allopregnanolone may effect, or be influenced by, prenatal stress, with consequences for neurodevelopmental-, neuropsychiatric- and/or neurodegenerative- relevant processes, such as addiction.

The effects of transdermal testosterone and oestrogen therapy on dry eye in postmenopausal women: a randomised, placebo-controlled, pilot study.

Science.gov (United States)

Golebiowski, Blanka; Badarudin, Noor; Eden, John; Gerrand, Leanne; Robinson, Jennifer; Liu, Jinzhu; Hampel, Ulrike; You, Jingjing; Stapleton, Fiona

2017-07-01

Sex hormones could provide a future treatment avenue for dry eye post menopause. However, there are few well-controlled studies. This study investigates the impact of testosterone and oestrogen on dry eye symptoms and signs in postmenopausal women. A randomised double-blind placebo-controlled pilot study was conducted involving 40 women with dry eye (age 63.9±5.1 years, 13.2±6.3 years post menopause). Ten women were assigned to each of four treatment groups: transdermal testosterone, oestradiol, testosterone/oestradiol combination and placebo. Assessment at baseline and after 8 weeks: ocular symptoms, tear osmolarity, tear stability, tear secretion, meibomian gland assessment, corneal and conjunctival sensitivity, serum concentrations of 17β-oestradiol, 3-α-androstanediol-glucuronide and dehydroepiandrosterone sulfate. Differences from placebo were examined using one-way analysis of variance and Dunnett's t-test. Within-group analyses included paired t-tests and Spearman correlation. Dryness intensity after 8 weeks was significantly worse in the oestrogen group compared with placebo (p=0.04). No significant changes in other symptoms, tear function, meibomian gland function, lid morphology, corneal or conjunctival sensitivity were observed in any of the groups when compared with the change in placebo after 8 weeks. Within-group analyses showed increased tear secretion in the testosterone/oestradiol combination group (p=0.03) and a strong association between increased serum androgen and improved tear stability in the testosterone group (ρ=0.83,p=0.01). Oestrogen supplementation may worsen ocular symptoms in postmenopausal women with dry eye, whereas no impact of testosterone therapy on symptoms was apparent. The positive effects of oestrogen and testosterone on tear function require confirmation in a larger study, with sample size calculated from the data generated herein. Placebo control is essential in studies of dry eye therapies. ACTRN

Lack of oestrogenic effects of food preservatives (parabens) in uterotrophic assays

DEFF Research Database (Denmark)

Hossaini, A.; Larsen, Jens-Jørgen; Larsen, John Christian

2000-01-01

The oestrogenic activity of the parabens, methyl-, ethyl- and propyl p-hydroxybenzoate, widely used as antimicrobials in food, and butyl p-hydroxybenzoate, which is used in cosmetic products, and their shared main metabolite p-hydroxybenzoic acid was investigated in a mouse uterotrophic assay......, Immature B6D2F1 mice were treated with oral or subcutaneous doses of the test compounds for three consecutive days, p-Hydroxgybenzoic acid and butyl p-hydroxybenzoate were also tested by the subcutaneous route in a rat uterotrophic assay. A significant increase in the uterus weight at day 4 was considered...... an oestrogenic effect. In the mouse assay, none of the compounds tested produced any oestrogenic response at dose levels up to 100 mg/kg body weight per day, for ethyl p-hydroxybenzoate even at a dose level of 1000 mg/kg body weight per day. In immature Wistar rats, subcutaneous administration of butyl p...

Oestrogen supplementation in gamete intrafallopian transfer (GIFT ...

African Journals Online (AJOL)

Enrique

2005-02-06

Feb 6, 2005 ... intrafallopian transfer (GIFT) — a prospective randomised study. ARTICLE. Objective. To investigate the impact of oestrogen supplementation from the early luteal to the late proliferative phase on biochemical and ongoing pregnancy rates in gamete intrafallopian transfer (GIFT). Methods. Ninety-five ...

In vivo relative quantitative proteomics reveals HMGB1 as a downstream mediator of oestrogen-stimulated keratinocyte migration.

Science.gov (United States)

Shin, Jung U; Noh, Ji Yeon; Lee, Ju Hee; Lee, Won Jai; Yoo, Jong Shin; Kim, Jin Young; Kim, Hyeran; Jung, Inhee; Jin, Shan; Lee, Kwang Hoon

2015-06-01

It is known that oestrogen influences skin wound healing by modulating the inflammatory response, cytokine expression and extracellular matrix deposition; accelerating re-epithelialization; and stimulating angiogenesis. To identify novel proteins associated with effects of oestrogen on keratinocyte, stable isotope labelling by amino acids in cell culture (SILAC)-based mass spectrometry was performed. Using SILAC, quantification of 1085 proteins was achieved. Among these proteins, 60 proteins were upregulated and 32 proteins were downregulated. Among significantly upregulated proteins, high-mobility group protein B1 (HMGB1) has been further evaluated for its role in the effect of oestrogen on keratinocytes. HMGB1 expression was strongly induced in oestrogen-treated keratinocytes in dose- and time-dependent manner. Further, HMGB1 was able to significantly accelerate the rate of HaCaT cell migration. To determine whether HMGB1 is involved in E2-induced HaCaT cell migration, cells were transfected with HMGB1 siRNA. Knockdown of HMGB1 blocked oestrogen-induced keratinocyte migration. Collectively, these experiments demonstrate that HMGB1 is a novel downstream mediator of oestrogen-stimulated keratinocyte migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Iodine-125-labelled tamoxifen is differentially cytoxic to cells containing oestrogen receptors

International Nuclear Information System (INIS)

Bloomer, W.D.; McLaughlin, W.H.; Weichselbaum, R.R.

1980-01-01

Tamoxifen, a non-steroidal anti-oestrogen competes with 17 - oestradiol for oestrogen receptor protein and is translocated to the nucleus. Carrier-free 125 I-TAM was tested for cytotoxicity in oestrogen receptor rich (human breast cancer MCF-7) and poor (V-79 Chinese hamster) cells. 125 I-TAM was differentially cytotoxic to MCF-7 cells. The D 37 values for MCF-7 and V-79 cells were 0.5 and 1.5 pCi/cell respectively. No radiotoxicity was observed with Na 125 I at doses equal to 125 I-TAM; iodide was effectively excluded from both cell lines and remained in the extracellular space. Also, nonradioactive 127 I-TAM and TAM were both non-toxic when tested at levels comparable to 125 I-TAM. It is suggested that the marked cytotoxicity in MCF-7 cells results from close approximation of 125 I with the genetic apparatus as a result of direct charging of specific nuclear receptors and/or translocation of 125 I-TAM receptor complexes from the cytoplasm to the nucleus, and that the minimal toxicity in V-79 cells reflects transmitted cytoplasmic radiation effects, limited direct nuclear charging and/or limited nuclear translocation resulting from the relative paucity of oestrogen in the cells. (U.K.)

Maintenance of ovulation inhibition with a new progestogen-only pill containing drospirenone after scheduled 24-h delays in pill intake

DEFF Research Database (Denmark)

Duijkers, Ingrid J M; Heger-Mahn, Doris; Drouin, Dominique

2016-01-01

by four placebo tablets. A previous study showed that this new drospirenone-only pill effectively inhibited ovulation. Clinical efficacy, however, can be affected by compliance, and delayed or forgotten pill intake often occurs in daily life. The aim of this study was to investigate if inhibition.......8%; only one subject in Group A fulfilled the ovulation criteria in Cycle 2. Follicular diameters in the regular-intake and the delayed-intake cycles were similar. CONCLUSION: Despite the 4-day hormone-free period and multiple intentional 24-h delays in tablet intake, ovulation inhibition was maintained...... inhibition by the new-generation oestrogen-free pill, containing 4-mg drospirenone for 24 days followed by a 4-day treatment-free period, was maintained despite four 24-h delays in tablet intake, so the impact of delayed intake on contraceptive reliability will be low....

Risk of low-energy hip, wrist, and upper arm fractures among current and previous users of hormone replacement therapy

DEFF Research Database (Denmark)

Hundrup, Yrsa Andersen; Høidrup, Susanne; Ekholm, Ola

2004-01-01

To examine the effect of oestrogen alone and in combination with progestin on the risk of low-energy, hip, wrist, and upper arm fractures. Additionally, to examine to what extent previous use, duration of use as well as recency of discontinuation of hormone replacement therapy (HRT) influences...

[Human growth hormone and Turner syndrome].

Science.gov (United States)

Sánchez Marco, Silvia Beatriz; de Arriba Muñoz, Antonio; Ferrer Lozano, Marta; Labarta Aizpún, José Ignacio; Garagorri Otero, Jesús María

2017-02-01

The evaluation of clinical and analytical parameters as predictors of the final growth response in Turner syndrome patients treated with growth hormone. A retrospective study was performed on 25 girls with Turner syndrome (17 treated with growth hormone), followed-up until adult height. Auxological, analytical, genetic and pharmacological parameters were collected. A descriptive and analytical study was conducted to evaluate short (12 months) and long term response to treatment with growth hormone. A favourable treatment response was shown during the first year of treatment in terms of height velocity gain in 66.6% of cases (height-gain velocity >3cm/year). A favourable long-term treatment response was also observed in terms of adult height, which increased by 42.82±21.23cm (1.25±0.76 SDS), with an adult height gain of 9.59±5.39cm (1.68±1.51 SDS). Predictors of good response to growth hormone treatment are: A) initial growth hormone dose, B) time on growth hormone treatment until starting oestrogen therapy, C) increased IGF1 and IGFBP-3 levels in the first year of treatment, and D) height gain velocity in the first year of treatment. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Use of radioimmunoassay procedures for the determination of sex hormones in animal tissues

International Nuclear Information System (INIS)

Hoffmann, B.

1983-01-01

Radioimmunoassay methods for the determination of sex steroids and other compounds with sex hormone-like activities in various edible animal tissues and endocrine glands have been developed. Reliability of these methods, allowing quantification in a range of 10 -11 M, has been adequately demonstrated. When applied to monitoring residues of anabolic sex hormones in edible tissues of veal calves, physiological baseline levels of some endogenous ''anabolic'' steroids (like testosterone, oestrogens) were established; in the case of xenobiotics residues at the scheduled time of slaughter could be quantified (trenbolone) and a regulatory method to implement the ban of diethylstilbestrol was introduced. (author)

Oestrogens and Osteoporosis | Utian | South African Medical Journal

African Journals Online (AJOL)

The interrelationship between oestrogens, endogenous and exogenous, their effects on plasma calcium, phosphorus and alkaline phosphatase metabolism, and the pathogenesis of osteoporosis are reviewed. Aspects of research conducted by me at Groote Schuur Hospital, Cape Town are incorporated in the discussion.

Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

NARCIS (Netherlands)

Brussaard, H.E.; Gevers Leuven, J.A.; Frölich, M.; Kluft, C.; Krans, H.M.J.

1997-01-01

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin- dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for

Oestrogens in saliva

International Nuclear Information System (INIS)

Rothschild, R.S.; Levine, L.S.; Hattingh, J.

1981-01-01

Matched plasma and saliva samples were obtained from a non-pregnant and pregnant group (last trimester) of female caucasians. Using a sensitive radioimmunoassay, 17β-oestradiol was measured, and the gingival index system of Loe (1967) was used to assess the gingival condition of each patient. The results showed that 17β-oestradiol could be measured in saliva but that the levels were extremely low and a very sensitive immunoassay was necessary. In the pregnant group, saliva represented 3 per cent of the plasma level. This was not the case in the non-pregnant group, probably because of the constantly changing free: bound plasma ratio. The results are discussed in relation to the fact that oestrogens are known to bind to the oral epithelium [af

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

Science.gov (United States)

Lagergren, Katarina; Ek, Weronica E; Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Casson, Alan G; Risch, Harvey A; Shaheen, Nicholas J; Bird, Nigel C; Reid, Brian J; Corley, Douglas A; Hardie, Laura J; Wu, Anna H; Fitzgerald, Rebecca C; Pharoah, Paul; Caldas, Carlos; Romero, Yvonne; Vaughan, Thomas L; MacGregor, Stuart; Whiteman, David; Westberg, Lars; Nyren, Olof; Lagergren, Jesper

2015-01-01

The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

Directory of Open Access Journals (Sweden)

Katarina Lagergren

Full Text Available The strong male predominance in oesophageal adenocarcinoma (OAC and Barrett's oesophagus (BO continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1, receptor beta (ESR2, and aromatase (CYP19A1, and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR, oxytocin protein (OXT, and cyclic ADP ribose hydrolase glycoprotein (CD38, were analysed using a gene-based approach, versatile gene-based test association study (VEGAS.Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058 and an increased risk of OAC and BO combined in males (p = 0.0023. Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035 and in males (p = 0.0012. We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

Female gonadal hormones and reproductive behaviors as key determinants of successful reproductive output of breeding whooping cranes (Grus americana)

Science.gov (United States)

Brown, Megan E; Converse, Sarah J.; Chandler, Jane N.; Shafer, Charles; Brown, Janine L; Keefer, Carol L; Songsasen, Nucharin

2016-01-01

Reproductive success of endangered whooping cranes (Grus americana) maintained ex situ is poor. As part of an effort to identify potential causes of poor reproductive success in a captive colony, we used non-invasive endocrine monitoring to assess gonadal and adrenal steroids of bird pairs with various reproductive outcomes and evaluated the relationships of hormones and behaviors to reproductive performance. Overall, reproductively successful (i.e., egg laying) females had significantly higher mean estrogen levels but lower mean progestogen concentrations than did unsuccessful females. Other hormones, including glucocorticoids and androgens, were not significantly different between successful and unsuccessful individuals. Observations of specific behaviors such as unison calling, marching, and the number of copulation attempts, along with overall time spent performing reproductive behaviors, were significantly higher in successful pairs. Our findings indicate that overall reproductive performance of whooping crane pairs is linked to female gonadal hormone excretion and reproductive behaviors, but not to altered adrenal hormone production.

Female gonadal hormones and reproductive behaviors as key determinants of successful reproductive output of breeding whooping cranes (Grus americana).

Science.gov (United States)

Brown, Megan E; Converse, Sarah J; Chandler, Jane N; Shafer, Charles; Brown, Janine L; Keefer, Carol L; Songsasen, Nucharin

2016-05-01

Reproductive success of endangered whooping cranes (Grus americana) maintained ex situ is poor. As part of an effort to identify potential causes of poor reproductive success in a captive colony, we used non-invasive endocrine monitoring to assess gonadal and adrenal steroids of bird pairs with various reproductive outcomes and evaluated the relationships of hormones and behaviors to reproductive performance. Overall, reproductively successful (i.e., egg laying) females had significantly higher mean estrogen levels but lower mean progestogen concentrations than did unsuccessful females. Other hormones, including glucocorticoids and androgens, were not significantly different between successful and unsuccessful individuals. Observations of specific behaviors such as unison calling, marching, and the number of copulation attempts, along with overall time spent performing reproductive behaviors, were significantly higher in successful pairs. Our findings indicate that overall reproductive performance of whooping crane pairs is linked to female gonadal hormone excretion and reproductive behaviors, but not to altered adrenal hormone production. Published by Elsevier Inc.

Cholesterol, coronary heart disease and oestrogens | Utian | South ...

African Journals Online (AJOL)

Present concepts of the interrelationship between oestrogens, endogenous and exogenous, and the development of atheromatosis and coronalY heart disease in the human female are reviewed. Aspects of research conducted by me at Groote Schuur Hospital, Cape Town, are incorporated in the discussion. The current ...

Exposure to 17β-Oestradiol Induces Oxidative Stress in the Non-Oestrogen Receptor Invertebrate Species Eisenia fetida.

Directory of Open Access Journals (Sweden)

Zbynek Heger

Full Text Available The environmental impacts of various substances on all levels of organisms are under investigation. Among these substances, endocrine-disrupting compounds (EDCs present a threat, although the environmental significance of these compounds remains largely unknown. To shed some light on this field, we assessed the effects of 17β-oestradiol on the growth, reproduction and formation of free radicals in Eisenia fetida.Although the observed effects on growth and survival were relatively weak, a strong impact on reproduction was observed (50.70% inhibition in 100 μg/kg of E2. We further demonstrated that the exposure of the earthworm Eisenia fetida to a contaminant of emerging concern, 17β-oestradiol (E2, significantly affected the molecules involved in antioxidant defence. Exposure to E2 results in the production of reactive oxygen species (ROS and the stimulation of antioxidant systems (metallothionein and reduced oxidized glutathione ratio but not phytochelatins at both the mRNA and translated protein levels. Matrix-assisted laser desorption/ionization (MALDI-imaging revealed the subcuticular bioaccumulation of oestradiol-3,4-quinone, altering the levels of local antioxidants in a time-dependent manner.The present study illustrates that although most invertebrates do not possess oestrogen receptors, these organisms can be affected by oestrogen hormones, likely reflecting free diffusion into the cellular microenvironment with subsequent degradation to molecules that undergo redox cycling, producing ROS, thereby increasing environmental contamination that also perilously affects keystone animals, forming lower trophic levels.

Use of radioimmunoassay procedures for the determination of sex hormones in animal tissues

Energy Technology Data Exchange (ETDEWEB)

Hoffmann, B. (Institut fuer Veterinaermedizin des Bundesgesundheitsamtes (Robert von Ostertag-Institut), Berlin (Germany, F.R.))

1983-07-01

Radioimmunoassay methods for the determination of sex steroids and other compounds with sex hormone-like activities in various edible animal tissues and endocrine glands have been developed. Reliability of these methods, allowing quantification in a range of 10/sup -11/ M, has been adequately demonstrated. When applied to monitoring residues of anabolic sex hormones in edible tissues of veal calves, physiological baseline levels of some endogenous ''anabolic'' steroids (like testosterone, oestrogens) were established; in the case of xenobiotics residues at the scheduled time of slaughter could be quantified (trenbolone) and a regulatory method to implement the ban of diethylstilbestrol was introduced.

Different critical perinatal periods and hypothalamic sites of oestradiol action in the defeminisation of luteinising hormone surge and lordosis capacity in the rat.

Science.gov (United States)

Sakakibara, M; Deura, C; Minabe, S; Iwata, Y; Uenoyama, Y; Maeda, K-I; Tsukamura, H

2013-03-01

Female rats show a gonadotrophin-releasing hormone (GnRH)/luteinising hormone (LH) surge in the presence of a preovulatory level of oestrogen, whereas males do not because of brain defeminisation during the developmental period by perinatal oestrogen converted from androgen. The present study aimed to identify the site(s) of oestrogen action and the critical period for defeminising the mechanism regulating the GnRH/LH surge. Animals given perinatal treatments, such as steroidal manipulations, brain local implantation of oestradiol (E(2) ) or administration of an NMDA antagonist, were examined for their ability to show an E(2) -induced LH surge at adulthood. Lordosis behaviour was examined to compare the mechanisms defeminising the GnRH/LH surge and sexual behaviour. A single s.c. oestradiol-benzoate administration on either the day before birth (E21), the day of birth (D0) or day 5 (D5) postpartum completely abolished the E(2) -induced LH surge at adulthood in female rats, although the same treatment did not inhibit lordosis. Perinatal castration on E21 or D0 partially rescued the E2-induced LH surge in genetically male rats, whereas castration from E21 to D5 totally rescued lordosis. Neonatal E(2) implantation in the anterior hypothalamus including the anteroventral periventricular nucleus (AVPV)/preoptic area (POA) abolished the E(2) -induced LH surge in female rats, whereas E(2) implantation in the mid and posterior hypothalamic regions had no inhibitory effect on the LH surge. Lordosis was not affected by neonatal E(2) implantation in any hypothalamic regions. In male rats, neonatal NMDA antagonist treatment rescued lordosis but not the LH surge. Taken together, these results suggest that an anterior hypothalamic region such as the AVPV/POA region is a perinatal site of oestrogen action where the GnRH/LH regulating system is defeminised to abolish the oestrogen-induced surge. The mechanism for defeminisation of the GnRH/LH surge system might be different from

Sex hormones and breast cancer risk in premenopausal women: collaborative reanalysis of seven prospective studies

Science.gov (United States)

2014-01-01

Background The relationships of circulating concentrations of oestrogens, progesterone and androgens with breast cancer and related risk factors in premenopausal women are not well understood. Methods Individual data on prediagnostic sex hormone and sex hormone binding globulin (SHBG) concentrations were contributed by 7 prospective studies. Analyses were restricted to women who were premenopausal and under age 50 at blood collection, and to breast cancer cases diagnosed before age 50. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for breast cancer associated with hormone concentrations were estimated by conditional logistic regression in up to 767 cases and 1699 controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. The associations of hormones with risk factors for breast cancer in control women were examined by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle and body mass index (BMI). All statistical tests were two-sided. Findings ORs for breast cancer associated with a doubling in hormone concentration were 1.19 (95% CI 1.06–1.35) for oestradiol, 1.17 (1.03–1.33) for calculated free oestradiol, 1.27 (1.05–1.54) for oestrone, 1.30 (1.10–1.55) for androstenedione, 1.17 (1.04–1.32) for dehydroepiandrosterone sulphate, 1.18 (1.03–1.35) for testosterone and 1.08 (0.97–1.21) for calculated free testosterone. Breast cancer risk was not associated with luteal phase progesterone (for a doubling in concentration OR=1.00 (0.92–1.09)), and adjustment for other factors had little effect on any of these ORs. The cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors. Interpretation Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women. PMID:23890780

A new progestogen-only medical therapy for outpatient management of acute, abnormal uterine bleeding: a pilot study.

Science.gov (United States)

Ammerman, Stacy R; Nelson, Anita L

2013-06-01

The objective of this investigation was to study short-term efficacy and feasibility of a new progestogen-only treatment for outpatient management of acute abnormal uterine bleeding. This was a prospective, single-arm, pilot clinical trial of a progestogen-only bridging treatment for acute abnormal uterine bleeding in nonpregnant, premenopausal women in the Gynecologic Urgent Care Clinic at Harbor-UCLA Medical Center. Subjects were administered a depo-medroxyprogesterone acetate 150 mg intramuscular injection and given medroxyprogesterone acetate 20 mg to be taken orally every 8 hours for 3 days. The primary outcome measures included a percentage of women who stopped bleeding in 5 days, time to bleeding cessation, reduction in numbers of pads used, side effects, and patient satisfaction. All 48 women stopped bleeding within 5 days; 4 women had spotting only at the time of their last contact during the 5 day follow-up. Mean time to bleeding cessation was 2.6 days. Side effects were infrequent and patient satisfaction was high. Injection of depo-medroxyprogesterone acetate 150 mg intramuscularly combined with 3 days of oral medroxyprogesterone acetate 20 mg every 8 hours for 9 doses is an effective outpatient therapy for acute abnormal uterine bleeding. Copyright © 2013 Mosby, Inc. All rights reserved.

Fate of selected pesticides, estrogens, progestogens and volatile organic compounds during artificial aquifer recharge using surface waters.

Science.gov (United States)

Kuster, Marina; Díaz-Cruz, Silvia; Rosell, Mònica; López de Alda, Miren; Barceló, Damià

2010-05-01

The artificial recharge of aquifers has become a valuable tool to increase water resources for drinking water production in many countries. In this work a total of 41 organic pollutants belonging to the classes of pesticides, estrogens, progestogens and volatile organic compounds (VOCs) have been monitored in the water from two artificial recharge plants located in Sweden and Denmark. The results from two sampling campaigns performed in each plant indicate good chemical status of the source water, as the contaminants detected were present at very low levels, far from those established in the legislation as maximum admissible concentrations (when existing) and far from those considered as a risk. Thus, of the 17 pesticides investigated, BAM (2,6-dichlorobenzamide), desethylatrazine, simazine, atrazine, terbuthylazine, diuron, metolachlor, and diazinon were the only compounds detected, and total pesticides levels were below 25ng L(-1), respectively. Estrone-3-sulfate was the only estrogen detected, at concentrations lower than 0.5ng L(-1). Progestogens were not found in any sample. Detected VOCs (benzene, toluene, ethylbenzene, and trichloroethylene) were below 0.04microg L(-1). The efficiency of elimination of these organic contaminants was poor as no significant decrease in their concentrations was observed through the recharge process.

[Utilization of hormone replacement therapy in Spain: Trends in the period 2000-2014].

Science.gov (United States)

Baladé Martínez, Laura; Montero Corominas, Dolores; Macías Saint-Gerons, Diego

2016-10-07

The objective of the study was to describe the trends of utilization, supply and prevalence of hormone replacement therapy (HRT) in Spain during the period 2000-2014. Annual prevalence of HRT use including the 95% CI was calculated for women aged≥40 using individual data from the national population-based database BIFAP. Annual and total-period consumptions were expressed in defined daily doses (DDD) per 1,000 inhabitants per day and were obtained from the databases of medications dispensed in community pharmacies and charged through official prescriptions to the Spanish National Health System. In the year 2000, overall HRT consumption was 33.12 DDDs/1000 inhabitans/day: 19.81 for oestrogen only, 6.88 for tibolone and 6.44 for combined oestrogen and progestagen. In 2014 overall HRT consumption was 5.32 DDDs/1000 inhabitans/day: 1.08 for oestrogen only, 1.61 for tibolone and 2.62 for combinations of oestrogen and progestagen. The marketed presentations of HRT decreased by 46.9%. Prevalence of HRT use in women aged≥40 in BIFAP was 7.19% (95% CI 6.97-7.40) in 2001 and 0.21% (95% CI 0.20-0.22) in 2014. Women aged 40-45 registered the highest prevalence of use in 2014: 0.71% (95% CI 0.66-0.76). A sharp decline in the consumption and prevalence of HRT has been observed in Spain since the publication of the Women's Health Initiative and Million Women Study and the regulatory measures taken restricting conditions of use, showing a similar trend to that of other western countries. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Detection and Quantification of Oestrogenic Endocrine Disruptors in ...

African Journals Online (AJOL)

The aim of this study was to detect the presence and quantify the total oestrogens (estriol (E1), estradiol (E2), and estrone (E3)) in Lake Victoria water with a view of assessing their contribution to the health status of fish. A total of 27 water samples; three from each of the nine sampling sites were collected in Mwanza gulf in ...

Effects of phyto-oestrogens on veal calf prostate histology

NARCIS (Netherlands)

Groot, M.J.

2006-01-01

In veal calf production plant-based proteins are frequently included in milk replacer fed to the animals. Since soy products, which are mostly used, are known for their high levels of phyto-oestrogens, the effects of these feeds on the veal calf prostate were examined. Goal was to determine whether

Hormone treatment of gender identity disorder in a cohort of children and adolescents.

Science.gov (United States)

Hewitt, Jacqueline K; Paul, Campbell; Kasiannan, Porpavai; Grover, Sonia R; Newman, Louise K; Warne, Garry L

2012-05-21

To describe the experience of hormone treatment of gender identity disorder (GID) in children and adolescents within a specialist clinic. Cohort study by medical record review of children aged 0-17 years referred during 2003-2011 for management at the GID clinic in a tertiary paediatric referral centre - the Royal Children's Hospital, Melbourne, Victoria. Clinical characteristics of the patient population, hormone treatment provided, frequency of referrals with time. Thirty-nine children and adolescents were referred for gender dysphoria. Seventeen individuals were pubertal with persistent GID, and were considered eligible for hormone treatment. Seven patients, comprising three biological males and four biological females, had legally endorsed hormone treatment. In this group, gender dysphoria was first noted at 3-6 years of age. Hormone treatment with GnRH analogue to suppress pubertal progression (phase 1) was given at 10-16 years of age. Treatment with cross-sex hormones (phase 2) was given at 15.6-16 years. One patient purchased cross-sex hormone treatment overseas. One patient received oestrogen and progesterone for menstrual suppression before phase 1. The annual frequency of new referrals increased continuously over the study period. Hormone treatment for pubertal suppression and subsequent gender transition needs to be individualised within stringent protocols in multidisciplinary specialist units.

Remarkable change in age-specific breast cancer incidence in the Swiss canton of Geneva and its possible relation with the use of hormone replacement therapy

International Nuclear Information System (INIS)

Bouchardy, Christine; Morabia, Alfredo; Verkooijen, Helena M; Fioretta, Gérald; Wespi, Yves; Schäfer, Peter

2006-01-01

This article aims to explain the reasons for the remarkable change in age of breast cancer occurrence in the Swiss canton of Geneva. We used population-based data from the Geneva cancer registry, which collects information on method of detection, stage and tumour characteristics since 1975. For patients diagnosed between 1997–2003, we obtained additional information on use of hormone replacement therapy from a large prospective study on breast cancer. Using generalized log linear regression analysis, we compared age-specific incidence rates with respect to period, stage, oestrogen receptor status, method of detection and use of hormone replacement therapy. In the periods 1975–1979 and 1985–1989, breast cancer risk increased with age, showing the highest incidence rates among women aged ≥ 85 years. From 1997, the age-specific incidence curve changed completely (p < 0.0001), showing an incidence peak at 60–64 years and a reduced incidence among elderly women. This incidence peak concerned mainly early stage and oestrogen positive cancers and was exclusively observed among women who ever used hormone replacement therapy, regardless whether the tumour was screen-detected or not. The increasing prevalence of hormone replacement therapy use during the 1990s could explain the important change in age-specific breast cancer incidence, not only by increasing breast cancer risk, but also by revealing breast cancer at an earlier age

Steroid hormones as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

Science.gov (United States)

Tutton, P J; Barkla, D H

1988-01-01

Glucocorticoid and mineralocorticoid receptors are present in normal epithelial cells of both the small and large intestine and there have also been contentious reports of androgen, oestrogen and progesterone receptors in the epithelium of the normal large intestine. The majority of reports suggest that stimulation of the intestinal glucocorticoid receptors results in increased proliferation of epithelial cells in the small bowel, as does stimulation of androgen receptors and possibly mineralocorticoid receptors. The proliferative response of the normal intestine to oestrogens is difficult to evaluate and that to progestigens appears not to have been reported. Epidemiological studies reveal a higher incidence of bowel cancer in premenopausal women than in men of the same age and yet there is a lower incidence of these tumors in women of higher parity. These findings have been atributted to a variety of non-epithelial gender characteristic such as differences in bile metabolism, colonic bacterial and fecal transit times. In experimental animals, androgens have also been shown to influence carcinogenesis and this could well be attributed to changes in food intake etc. However, many studies have now revealed steroid hormone receptors on colorectal tumor cells and thus a direct effect of the steroid hormones on the epithelium during and after malignant transformation must now be considered.

Access to emergency hormonal contraception from community pharmacies and family planning clinics

Science.gov (United States)

Lewington, Gaye; Marshall, Kay

2006-01-01

Aims To evaluate differences in the time taken to access progestogen-only emergency hormonal contraception (EHC) by young women from family planning (FP) or community pharmacy settings. Methods An observational study of 203 women requesting EHC from FP clinics and community pharmacies in South-west Kent Primary Care Trust (PCT) from December 2002 to October 2003. Results Access to EHC from community pharmacy was significantly faster than from FP clinics (16 h vs. 41 h, P < 0.001). Older teenagers tended to seek EHC more quickly and were more likely to have had a contraceptive failure rather than have used no contraception at all. Conclusion The results provide further support for pharmacist involvement in the supply of EHC. PMID:16669854

Efeitos agudos dos estrogênios associados a progestogênios sobre a trigliceridemia e reatividade vascular pós-prandial Acute effects of the use of estrogens in association with progestogens on postprandial triglyceridemia and vascular reactivity

Directory of Open Access Journals (Sweden)

Silvio C.M. Santos

2004-11-01

Full Text Available OBJETIVO: Avaliar se a terapia de reposição hormonal com estrogênios e progestogênios, em mulheres hipertensas na pós-menopausa, modifica a trigliceridemia e a reatividade vascular pós-prandial. MÉTODOS: Estudo controlado, duplo cego, cruzado contra placebo em 15 mulheres na pós-menopausa (idade de 50 a 70, média = 61,6 ± 6 anos, sorteadas para 2 semanas de placebo ou ingestão oral de 0,625 mg de estrogênios conjugados eqüinos e 2,5 mg de medroxiprogesterona e alimentadas com refeição rica em gorduras (897 calorias; 50,1% de gorduras. Foi medida a reatividade vascular (RV - % de variação dos diâmetros do vaso entre o jejum e 2h após a alimentação, usando-se método ultra-sonográfico automatizado. Foram também determinados o perfil lipídico e a glicose, em jejum e 2h após a alimentação rica em gorduras. RESULTADOS: Com o placebo, a reatividade vascular (RV diminuiu de 3,20 ± 17% em jejum para -2,1 ± 30%, 2h após a alimentação (p = 0,041, e com terapia de reposição hormonal, a reatividade vascular diminuiu de 6,14 ± 27% em jejum para -0,05±18%, 2h após a alimentação (p=NS. A trigliceridemia pós-prandial aumentou, 35 ± 25% com o placebo, e 12 ± 10% com a terapia de reposição hormonal (P OBJECTIVE: To assess whether hormone replacement therapy with estrogens in association with progestogens in postmenopausal hypertensive women alters postprandial triglyceridemia and vascular reactivity. METHODS: A double-blind, placebo-controlled, crossover study was carried out with 15 postmenopausal women (age range: 50 to 70 years, mean = 61.6 ± 6 years randomly assigned to 2 weeks of placebo or oral ingestion of 0.625 mg of equine conjugated estrogens and 2.5 mg of medroxyprogesterone, fed a high-fat diet (897 calories; 50.1% fat. Vascular reactivity (VR - % of vessel diameter variation in the fasting period and 2 hours after meals was measured by using the automated ultrasound method. Lipid profile and glycemia

Serum levels of oestrogen and some biochemical parameters in relation to reproductive activities and level of production in fowl

International Nuclear Information System (INIS)

El - Abiad, N.M.F.

1982-01-01

This work was carried out at the poultry experiment station department of animal production, faculty of agriculture zagazig university, benha branch. radioimmunological and biochemical assays were performed in the laboratories of radioimmunology and biochemistry unit of atomic energy establishment . It was intended to study: 1. The effect of oestrogen level along the time of egg formation on some parameters in blood serum related to metabolic efficiency. 2. The variations in oestrogen level and blood serum parameters due to clutch size of hens. 3.Changes in oestrogen levels and some blood constituents along the time of egg formation

The history of hormone therapy use and recent controversy related to heart disease and breast cancer arising from prevention trial outcomes.

Science.gov (United States)

Alexander, Ivy M

2012-01-01

The reasons for hormone therapy use have changed dramatically over time from being very popular for the purpose of preserving youth in women to menopause-related symptom management, disease prevention, and now back to menopause-related symptom management. Over time, several important risks associated with the use of hormone therapy have become evident, causing dramatic reductions in the use of hormone therapy for periods of time following identification of these risks. Most recently, randomized controlled prevention trials that evaluated hormone therapy for the purpose of reducing or preventing coronary heart disease among women have found that hormone therapy is associated with increased rather than decreased risks for coronary heart disease. The most recent of these trials again identified increased risks for breast cancer associated with estrogen plus progestogen therapy. The evolving evidence base from these randomized controlled prevention trials is complicated and in some cases contradictory. Specifically, the data suggest that the timing of when hormone therapy is initiated once a woman is postmenopausal may influence her risk for developing heart disease and breast cancer. In this article, contradictory evidence is carefully sifted so risks and benefits can be weighed by clinicians when partnering with women to individualize decisions about using hormone therapy. © 2012 by the American College of Nurse-Midwives.

Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse.

Science.gov (United States)

Meyer, Stephanie K; Probert, Philip M E; Lakey, Anne F; Axon, Andrew R; Leitch, Alistair C; Williams, Faith M; Jowsey, Paul A; Blain, Peter G; Kass, George E N; Wright, Matthew C

2017-05-05

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A new day dawns: women without oestrogen or is a balance best?

International Nuclear Information System (INIS)

Jordan, V Craig

2002-01-01

Building on the 30-year success story with tamoxifen, the question now is whether one agent can be used for treatment and prevention or should new medicines be targeted to specific applications? The early results with anastrozole suggest it could replace tamoxifen for treatment and should be tested as a preventive. Unfortunately, long-term testing of aromatase inhibitors will be required to avoid concerns about osteoporosis, Alzheimer's disease and coronary heart disease. Most importantly, the knowledge gained with tamoxifen has resulted in a new generation of selective oestrogen receptor modulators that can be used to prevent osteoporosis, breast cancer and uterine cancer. It is now clear that strategies utilising aromatase inhibitors and selective oestrogen receptor modulators will provide much needed options for individualised treatments

Differences in the rate of oestrogen-induced apoptosis in breast cancer by oestradiol and the triphenylethylene bisphenol

Science.gov (United States)

Obiorah, I E; Jordan, V C

2014-01-01

Background and Purpose Triphenylethylene (TPE)-like compounds were the first agents to be used in the treatment of metastatic breast cancer in postmenopausal women. Although structurally related to the anti-oestrogen, 4-hydroxytamoxifen, TPEs possess oestrogenic properties in fully oestrogenized breast cancer cells but do not induce apoptosis with short-term treatment in long-term oestrogen-deprived breast cancer cells. This study determined the differential effects of bisphenol, a TPE, on growth and apoptosis based on the modulation of the shape of the ligand–oestrogen receptor complex. Experimental Approach Apoptotic flow cytometric studies were used to evaluate apoptosis over time. Proliferation of the breast cancer cells was assessed using DNA quantification and cell cycle analysis. Real-time PCR was performed to quantify mRNA levels of apoptotic genes. Regulation of cell cycle and apoptotic genes was determined using PCR-based arrays. Key Results Bisphenol induced an up-regulation of cell cycle genes similar to those induced by 17β oestradiol (E2). Unlike the changes induced by E2 that occur after 24 h, the apoptosis evoked by bisphenol occurred after 4 days, with quantifiable apoptotic changes noted at 6 days. A prolonged up-regulation of endoplasmic reticulum stress and inflammatory stress response genes was observed with subsequent activation of apoptosis-related genes in the second week of treatment with bisphenol. Conclusions and Implications The bisphenol: ERα complex induces delayed biological effects on the growth and apoptosis of breast cancer cells. Both the shape of the complex and the duration of treatment control the initiation of apoptosis. PMID:24819221

Compounds from Cynomorium songaricum with Estrogenic and Androgenic Activities Suppress the Oestrogen/Androgen-Induced BPH Process.

Science.gov (United States)

Wang, Xueni; Tao, Rui; Yang, Jing; Miao, Lin; Wang, Yu; Munyangaju, Jose Edouard; Wichai, Nuttapong; Wang, Hong; Zhu, Yan; Liu, Erwei; Chang, Yanxu; Gao, Xiumei

2017-01-01

To investigate the phytoestrogenic and phytoandrogenic activities of compounds isolated from CS and uncover the role of CS in prevention of oestrogen/androgen-induced BPH. Cells were treated with CS compounds, and immunofluorescence assay was performed to detect the nuclear translocation of ER α or AR in MCF-7 or LNCaP cells; luciferase reporter assay was performed to detect ERs or AR transcriptional activity in HeLa or AD293 cells; MTT assay was performed to detect the cell proliferation of MCF-7 or LNCaP cells. Oestrogen/androgen-induced BPH model was established in rat and the anti-BPH, anti-estrogenic, and anti-androgenic activities of CS in vivo were further investigated. The nuclear translocation of ER α was stimulated by nine CS compounds, three of which also stimulated AR translocation. The transcriptional activities of ER α and ER β were induced by five compounds, within which only ECG induced AR transcriptional activity as well. Besides, ECG stimulated the proliferation of both MCF-7 cells and LNCaP cells. CS extract suppressed oestrogen/androgen-induced BPH progress in vivo by downregulation of E2 and T level in serum and alteration of the expressions of ER α , ER β , and AR in the prostate. Our data demonstrates that compounds from CS exhibit phytoestrogenic and phytoandrogenic activities, which may contribute to inhibiting the oestrogen/androgen-induced BPH development.

Circumventing the natural, frequent oestrogen waves of the female cheetah (Acinonyx jubatus) using oral progestin (Altrenogest).

Science.gov (United States)

Crosier, Adrienne E; Comizzoli, Pierre; Koester, Diana C; Wildt, David E

2017-08-01

Cheetah are induced ovulators, experiencing short, variable oestrogen waves year-round. Exogenous gonadotrophin administration induces ovulation, but success is variable and often improves if ovaries are quiescent. After affirming the presence of short-term oestrogenic waves, we examined the effect of the timing of administration of exogenous equine and human chorionic gonadotrophins (eCG-hCG) within the oestrogen concentration pattern on subsequent follicle development and oocyte and corpus luteum quality. We also investigated ovarian suppression using an oral progestin (Altrenogest, 7 days) and assessed whether Altrenogest moderated adrenal activity by reducing glucocorticoid metabolites. All cheetahs exhibited short (every ~7-10 days), sporadic, year-round increases in faecal oestradiol punctuated by unpredictable periods (4-10 weeks) of baseline oestradiol (anoestrous). Gonadotrophin (eCG-hCG) efficacy was not affected by oestradiol 'wave' pattern if administered ≥3 days after an oestrogen peak. Such cheetahs produced normative faecal progestagen patterns and higher numbers (P<0.06) of mature oocytes than females given gonadotrophins ≤2 days after an oestradiol peak. Altrenogest supplementation expanded the interval between oestradiol peaks to 12.9 days compared with 7.3 days without progestin pretreatment. Altrenogest-fed females excreted less (P<0.05) glucocorticoid metabolites than non-supplemented counterparts. Results show that Altrenogest is effective for suppressing follicular activity, may contribute to reduced glucocorticoid production and may result in more effective ovulation induction via gonadotrophin therapy.

Effects of supervised aerobic training on the levels of anti-Mullerian hormone and adiposity measures in women with normo-ovulatory and polycystic ovary syndrome.

Science.gov (United States)

Al-Eisa, Einas; Gabr, Sami Ali; Alghadir, Ahmad Hieder

2017-04-01

To evaluate the change in the levels of anti-Mullerian hormone, adiponectin, weight loss and fertility parameters in obese women with or without polycystic ovary syndrome, following 12 weeks of supervised aerobic exercise. This study was conducted from August 2013 to October 2014 among obese women with or without polycystic ovary syndrome referred to Obstetrics and Gynecology clinic, Mansoura University Hospital, Faculty of Medicine, Mansoura, Egypt. Patients were classified into three age-matched groups; group A had controls, group B had patients with polycystic ovary syndrome and group C had obese women. Anti-Mullerian hormone, adiponectin, follicle-stimulating hormone, oestrogen, fasting insulin, fasting glucose, homeostasis model of assessment of insulin resistance, antral follicle count, hirsutism score, weight, menstrual cyclicity and ovulatory function were assessed at baseline and following 12 weeks of supervised aerobic exercise. Statistical analysis was performed using SPSS 17. Of the 90 patients, there were 30(33.3%) in each group. The mean age was 28.7±3.84 years in group A, 27.9±4.1 years in group B and 27.6±5.7 in group C. The 30(33.3%) participants who responded to aerobic exercise interventions showed significant improvements in reproductive function), with lower baseline anti-Mullerian hormone levels, greater weight loss and higher adiponectin level compared to the the 30(33.3%) participants who did not respond to the exercise programme. Weight loss, fertility hormones, follicle-stimulating hormone, prolactin, oestrogen, antral follicle count, baseline anti-Mullerian hormone, and adiponectin were significantly correlated to the improvement in reproductive function (psyndromes, there were significant improvements in ovarian process with an ovulation rate of 13(43.3%) and a restoration of menstrual cycle with a rate of 17(56.7 %) following 12 weeks of supervised aerobic exercise. Moderate aerobic training for 12 weeks had a positive significant

Phyto-oestrogen excretion and rate of bone loss in postmenopausal women

NARCIS (Netherlands)

Kardinaal, A.F.M.; Morton, M.S.; Brüggemann-Rotgans, I.E.M.; Beresteijn, E.C.H. van

1998-01-01

Objective: The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake. Design: Secondary analysis of a 10-year follow-up study (1979-1989) among postmenopausal women in the

Oestrogenic activity in drinking waters from a rural area in the ...

African Journals Online (AJOL)

2007-02-27

Feb 27, 2007 ... rivers. Thus human exposure to environmental contaminants in drinking water is potentially high. Two rural ... and anogenital distance have been identified as new biological ... more sensitive ER-Calux assay confirmed the oestrogenic activ- ... on the nutritional status and dietary intake of children to deter-.

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

Science.gov (United States)

Ribas, Ricardo; Pancholi, Sunil; Rani, Aradhana; Schuster, Eugene; Guest, Stephanie K; Nikitorowicz-Buniak, Joanna; Simigdala, Nikiana; Thornhill, Allan; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dowsett, Mitch; Johnston, Stephen R; Martin, Lesley-Ann

2018-06-08

Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER + ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. A panel of ER + BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 wt or ESR1 Y537S , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER

Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse

OpenAIRE

Meyer, Stephanie K.; Probert, Philip M.E.; Lakey, Anne F.; Axon, Andrew R.; Leitch, Alistair C.; Williams, Faith M.; Jowsey, Paul A.; Blain, Peter G.; Kass, George E.N.; Wright, Matthew C.

2017-01-01

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oes...

Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies

Science.gov (United States)

Key, T J; Appleby, P N; Reeves, G K; Roddam, A W; Helzlsouer, K J; Alberg, A J; Rollison, D E; Dorgan, J F; Brinton, L A; Overvad, K; Kaaks, R; Trichopoulou, A; Clavel-Chapelon, F; Panico, S; Duell, E J; Peeters, P H M; Rinaldi, S; Fentiman, I S; Dowsett, M; Manjer, J; Lenner, P; Hallmans, G; Baglietto, L; English, D R; Giles, G G; Hopper, J L; Severi, G; Morris, H A; Hankinson, S E; Tworoger, S S; Koenig, K; Zeleniuch-Jacquotte, A; Arslan, A A; Toniolo, P; Shore, R E; Krogh, V; Micheli, A; Berrino, F; Barrett-Connor, E; Laughlin, G A; Kabuto, M; Akiba, S; Stevens, R G; Neriishi, K; Land, C E; Cauley, J A; Lui, Li Yung; Cummings, Steven R; Gunter, M J; Rohan, T E; Strickler, H D

2011-01-01

Background: Breast cancer risk for postmenopausal women is positively associated with circulating concentrations of oestrogens and androgens, but the determinants of these hormones are not well understood. Methods: Cross-sectional analyses of breast cancer risk factors and circulating hormone concentrations in more than 6000 postmenopausal women controls in 13 prospective studies. Results: Concentrations of all hormones were lower in older than younger women, with the largest difference for dehydroepiandrosterone sulphate (DHEAS), whereas sex hormone-binding globulin (SHBG) was higher in the older women. Androgens were lower in women with bilateral ovariectomy than in naturally postmenopausal women, with the largest difference for free testosterone. All hormones were higher in obese than lean women, with the largest difference for free oestradiol, whereas SHBG was lower in obese women. Smokers of 15+ cigarettes per day had higher levels of all hormones than non-smokers, with the largest difference for testosterone. Drinkers of 20+ g alcohol per day had higher levels of all hormones, but lower SHBG, than non-drinkers, with the largest difference for DHEAS. Hormone concentrations were not strongly related to age at menarche, parity, age at first full-term pregnancy or family history of breast cancer. Conclusion: Sex hormone concentrations were strongly associated with several established or suspected risk factors for breast cancer, and may mediate the effects of these factors on breast cancer risk. PMID:21772329

Analysis and occurrence of pharmaceuticals, estrogens, progestogens and polar pesticides in sewage treatment plant effluents, river water and drinking water in the Llobregat river basin (Barcelona, Spain)

Science.gov (United States)

Kuster, Marina; López de Alda, Maria José; Hernando, Maria Dolores; Petrovic, Mira; Martín-Alonso, Jordi; Barceló, Damià

2008-08-01

SummaryThis work investigated the presence of 21 emerging contaminants of various chemical groups (7 estrogens, 3 progestogens, 6 pharmaceuticals and personal care products (PPCPs), and 5 acidic pesticides) in the Llobregat river basin (NE Spain). Waters from the outlet of various sewage treatment plants (STP) and waterworks located along the river basin, as well as water samples from the river or its tributaries upstream and downstream of these plants were analysed in two pilot monitoring studies. Chemical analyses were performed by means of on-line or off-line solid-phase extraction followed by liquid chromatography-electrospray-tandem mass spectrometry. Methods detection limits (in ng/L) were ⩽0.85 for estrogens, ⩽3.94 for progestogens, ⩽30 for PPCPs, and ⩽0.99 for pesticides. Of the estrogens and progestogens analysed, only estrone-3-sulfate, estrone, estriol and progesterone were found to be present in the low nanogram per liter range in some of the samples investigated. Except for atenolol, all PPCPs studied (ibuprofen, diclofenac, clofibric acid, salicylic acid, and triclosan) could be identified at levels usually lower than 250 ng/L and up to 1200 ng/l (diclofenac). Of the various pesticides investigated (2,4-D, bentazone; MCPA, mecoprop and propanil) MCPA and 2,4-D were the most ubiquitous and abundant and bentazone the only one not detected. Individual concentrations were most often below 100 ng/L and never surpassed the EU limits.

Isolated oestrogen deficiency in male 30-year-old: persistent growth plates with severe osteopenia

International Nuclear Information System (INIS)

Smith, T.; Roberts, J.; Howman-Giles, R.; Cowell, C.; Jeremy, R.

2000-01-01

Full text: A 31-year-old male presented with right rib pain and generalised skeletal symptoms. He has a past history of multiple fractures following trauma. No history of childhood fractures. Asthma (No steroids). A product of a consanguineous marriage, he has one child aged 7. Examination showed 178.6cm male with normal sexual characteristics. No abnormality detected apart from tenderness over right ribs. Bone scan showed active growth plates and right and left rib fractures. X-rays demonstrated a bone age of 15 1/2 - 16 yrs and a compression fracture of L2. His bone mineral density is severely reduced. Metabolic investigations revealed Testosterone 27.4 nmol (N 11-35), oestradiol < 70 pmol/L, ultrasensitive assay 14 and 17 pmol/L (consistent with 8-year-old male), LH N, FSH N, 46 XY Karyotype. Alkaline phosphatase. 148 (N<120), Normal glucose tolerance test. This patient illustrates a very rare condition of oestrogen deficiency in a male, probably due to aromatase deficiency. This enzyme converts testosterone to oestradiol. It illustrates the role of oestrogen in fusing growth plates and maintaining bone mass in males with otherwise normal androgen levels. A similar clinical picture can result from an oestrogen receptor abnormality. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

The response to oestrogen deprivation of the cartilage collagen degradation marker, CTX-II, is unique compared with other markers of collagen turnover

DEFF Research Database (Denmark)

Bay-Jensen, Anne-Christine; Tabassi, Nadine C B; Sondergaard, Lene V

2009-01-01

The urinary level of the type II collagen degradation marker CTX-II is increased in postmenopausal women and in ovariectomised rats, suggesting that oestrogen deprivation induces cartilage breakdown. Here we investigate whether this response to oestrogen is also true for other type II collagen tu...

Oestrogen-deficient female aromatase knockout (ArKO) mice exhibit depressive-like symptomatology.

Science.gov (United States)

Dalla, C; Antoniou, K; Papadopoulou-Daifoti, Z; Balthazart, J; Bakker, J

2004-07-01

We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety or 'depressive-like' symptomatology due to chronic oestrogen deficiency. We also compared the neurochemical profile of ArKO and wild-type (WT) females, as oestrogens have been shown to modulate dopaminergic, serotonergic and noradrenergic brain activities. ArKO females did not differ from WT in spontaneous motor activity, exploration or anxiety. These findings are in line with the absence of major neurochemical alterations in hypothalamus, prefrontal cortex or striatum, which are involved in the expression of these behaviours. By contrast, ArKO females displayed decreased active behaviours, such as struggling and swimming, and increased passive behaviours, such as floating, in repeated sessions of the forced swim test, indicating that these females exhibit 'depressive-like' symptoms. Adult treatment with oestradiol did not reverse the behavioural deficits observed in the forced swim test, suggesting that they may be due to the absence of oestradiol during development. Accordingly, an increased serotonergic activity was observed in the hippocampus of ArKO females compared with WT, which was also not reversed by adult oestradiol treatment. The possible organizational role of oestradiol on the hippocampal serotonergic system and the 'depressive-like' profile of ArKO females provide new insights into the pathophysiology of depression and the increased vulnerability of women to depression.

Development of a Multi-class Steroid Hormone Screening Method using Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS)

Science.gov (United States)

Boggs, Ashley S. P.; Bowden, John A.; Galligan, Thomas M.; Guillette, Louis J.; Kucklick, John R.

2016-01-01

Monitoring complex endocrine pathways is often limited by indirect measurement or measurement of a single hormone class per analysis. There is a burgeoning need to develop specific direct-detection methods capable of providing simultaneous measurement of biologically relevant concentrations of multiple classes of hormones (estrogens, androgens, progestogens, and corticosteroids). The objectives of this study were to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for multi-class steroid hormone detection using biologically relevant concentrations, then test limits of detection (LOD) in a high-background matrix by spiking charcoal-stripped fetal bovine serum (FBS) extract. Accuracy was tested with National Institute of Standards and Technology Standard Reference Materials (SRMs) with certified concentrations of cortisol, testosterone, and progesterone. 11-Deoxycorticosterone, 11-deoxycortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, adrenosterone, androstenedione, cortisol, corticosterone, dehydroepiandrosterone, dihydrotestosterone, estradiol, estriol, estrone, equilin, pregnenolone, progesterone, and testosterone were also measured using isotopic dilution. Dansyl chloride (DC) derivatization was investigated maintaining the same method to improve and expedite estrogen analysis. Biologically relevant LODs were determined for 15 hormones. DC derivatization improved estrogen response two- to eight-fold, and improved chromatographic separation. All measurements had an accuracy ≤ 14 % difference from certified values (not accounting for uncertainty) and relative standard deviation ≤ 14 %. This method chromatographically separated and quantified biologically relevant concentrations of four hormone classes using highly specific fragmentation patterns and measured certified values of hormones that were previously split into three separate chromatographic methods. PMID:27039201

The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

LENUS (Irish Health Repository)

Kavanagh, Dara O

2012-02-01

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

NARCIS (Netherlands)

F.J. Couch (Fergus); K.B. Kuchenbaecker (Karoline); K. Michailidou (Kyriaki); G.A. Mendoza-Fandino (Gustavo A.); S. Nord (Silje); J. Lilyquist (Janna); C. Olswold (Curtis); B. Hallberg (Boubou); S. Agata (Simona); H. Ahsan (Habibul); K. Aittomäki (Kristiina); C.B. Ambrosone (Christine); I.L. Andrulis (Irene); H. Anton-Culver (Hoda); V. Arndt (Volker); B.K. Arun (Banu); B. Arver (Brita Wasteson); M. Barile (Monica); R.B. Barkardottir (Rosa); D. Barrowdale (Daniel); L. Beckmann (Lars); M.W. Beckmann (Matthias); J. Benítez (Javier); S.V. Blank (Stephanie); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); S.E. Bojesen (Stig); M.K. Bolla (Manjeet); B. Bonnani (Bernardo); H. Brauch (Hiltrud); H. Brenner (Hermann); B. Burwinkel (Barbara); S.S. Buys (Saundra S.); T. Caldes (Trinidad); M.A. Caligo (Maria); F. Canzian (Federico); T.A. Carpenter (Adrian); J. Chang-Claude (Jenny); S.J. Chanock (Stephen J.); W.K. Chung (Wendy K.); K.B.M. Claes (Kathleen B.M.); A. Cox (Angela); S.S. Cross (Simon); J.M. Cunningham (Julie); K. Czene (Kamila); M.B. Daly (Mary B.); F. Damiola (Francesca); H. Darabi (Hatef); M. de La Hoya (Miguel); P. Devilee (Peter); O. Díez (Orland); Y.C. Ding (Yuan); R. Dolcetti (Riccardo); S.M. Domchek (Susan); C.M. Dorfling (Cecilia); I. dos Santos Silva (Isabel); M. Dumont (Martine); A.M. Dunning (Alison); D. Eccles (Diana); H. Ehrencrona (Hans); A.B. Ekici (Arif); H. Eliassen (Heather); S.D. Ellis (Steve); P.A. Fasching (Peter); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); A. Försti (Asta); F. Fostira (Florentia); W.D. Foulkes (William); M.O.W. Friebel (Mark ); E. Friedman (Eitan); D. Frost (Debra); M. Gabrielson (Marike); M. Gammon (Marilie); P.A. Ganz (Patricia A.); S.M. Gapstur (Susan M.); J. Garber (Judy); M.M. Gaudet (Mia); S.A. Gayther (Simon); A-M. Gerdes (Anne-Marie); M. Ghoussaini (Maya); G.G. Giles (Graham); G. Glendon (Gord); A.K. Godwin (Andrew K.); M.S. Goldberg (Mark); D. Goldgar (David); A. González-Neira (Anna); M.H. Greene (Mark H.); J. Gronwald (Jacek); P. Guénel (Pascal); M.J. Gunter (Marc J.); L. Haeberle (Lothar); C.A. Haiman (Christopher A.); U. Hamann (Ute); T.V.O. Hansen (Thomas); S. Hart (Stewart); S. Healey (Sue); T. Heikkinen (Tuomas); B.E. Henderson (Brian); J. Herzog (Josef); F.B.L. Hogervorst (Frans); A. Hollestelle (Antoinette); M.J. Hooning (Maartje); R.N. Hoover (Robert); J.L. Hopper (John); K. Humphreys (Keith); D. Hunter (David); T. Huzarski (Tomasz); E.N. Imyanitov (Evgeny N.); C. Isaacs (Claudine); A. Jakubowska (Anna); M. James (Margaret); R. Janavicius (Ramunas); U.B. Jensen; E.M. John (Esther); M. Jones (Michael); M. Kabisch (Maria); S. Kar (Siddhartha); B.Y. Karlan (Beth Y.); S. Khan (Sofia); K.T. Khaw; M.G. Kibriya (Muhammad); J.A. Knight (Julia); Y.-D. Ko (Yon-Dschun); I. Konstantopoulou (I.); V-M. Kosma (Veli-Matti); V. Kristensen (Vessela); A. Kwong (Ava); Y. Laitman (Yael); D. Lambrechts (Diether); C. Lazaro (Conxi); E. Lee (Eunjung); L. Le Marchand (Loic); K.J. Lester (Kathryn); A. Lindblom (Annika); N.M. Lindor (Noralane); S. Lindstrom (Stephen); J. Liu (Jianjun); J. Long (Jirong); J. Lubinski (Jan); P.L. Mai (Phuong); E. Makalic (Enes); K.E. Malone (Kathleen E.); A. Mannermaa (Arto); S. Manoukian (Siranoush); S. Margolin (Sara); F. Marme (Federick); J.W.M. Martens (John); L. McGuffog (Lesley); A. Meindl (Alfons); A. Miller (Austin); R.L. Milne (Roger); P. Miron (Penelope); M. Montagna (Marco); S. Mazoyer (Sylvie); A.-M. Mulligan (Anna-Marie); T.A. Muranen (Taru); K.L. Nathanson (Katherine); S.L. Neuhausen (Susan); H. Nevanlinna (Heli); B.G. Nordestgaard (Børge); R. Nussbaum (Robert); K. Offit (Kenneth); E. Olah; O.I. Olopade (Olufunmilayo I.); J.E. Olson (Janet); A. Osorio (Ana); S.K. Park (Sue K.); P.H.M. Peeters; B. Peissel (Bernard); P. Peterlongo (Paolo); J. Peto (Julian); C. Phelan (Catherine); R. Pilarski (Robert); B. Poppe (Bruce); K. Pykäs (Katri); P. Radice (Paolo); N. Rahman (Nazneen); J. Rantala (Johanna); C. Rappaport (Christine); G. Rennert (Gad); A.L. Richardson (Andrea); M. Robson (Mark); I. Romieu (Isabelle); A. Rudolph (Anja); E.J.T. Rutgers (Emiel); M.-J. Sanchez (Maria-Jose); R. Santella (Regina); E.J. Sawyer (Elinor); D.F. Schmidt (Daniel); M.K. Schmidt (Marjanka); R.K. Schmutzler (Rita); F.R. Schumacher (Fredrick); R.J. Scott (Rodney); L. Senter (Leigha); P. Sharma (Priyanka); J. Simard (Jacques); C.F. Singer (Christian); O. Sinilnikova (Olga); P. Soucy (Penny); M.C. Southey (Melissa); D. Steinemann (Doris); M. Stenmark-Askmalm (Marie); D. Stoppa-Lyonnet (Dominique); A.J. Swerdlow (Anthony ); C. Szabo (Csilla); R. Tamimi (Rulla); W. Tapper (William); P.J. Teixeira; S.-H. Teo (Soo-Hwang); M.B. Terry (Mary Beth); M. Thomassen (Mads); D. Thompson (Deborah); L. Tihomirova (Laima); A.E. Toland (Amanda); R.A.E.M. Tollenaar (Rob); I.P. Tomlinson (Ian); T. Truong (Thérèse); H. Tsimiklis (Helen); A. Teulé (A.); R. Tumino (Rosario); N. Tung (Nadine); C. Turnbull (Clare); G. Ursin (Giski); C.H.M. van Deurzen (Carolien); E.J. van Rensburg (Elizabeth); R. Varon-Mateeva (Raymonda); Z. Wang (Zhaoming); S. Wang-Gohrke (Shan); E. Weiderpass (Elisabete); J.N. Weitzel (Jeffrey); A.S. Whittemore (Alice S.); H. Wildiers (Hans); R. Winqvist (Robert); X.R. Yang (Xiaohong R.); D. Yannoukakos (Drakoulis); S. Yao (Song); M.P. Zamora (Pilar); W. Zheng (Wei); P. Hall (Per); P. Kraft (Peter); C. Vachon (Celine); S. Slager (Susan); G. Chenevix-Trench (Georgia); P.D.P. Pharoah (Paul); A.A.N. Monteiro (Alvaro A. N.); M. García-Closas (Montserrat); D.F. Easton (Douglas F.); A.C. Antoniou (Antonis C.)

2016-01-01

textabstractCommon variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10-8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative

Cell life and death in the anterior pituitary gland: role of oestrogens.

Science.gov (United States)

Seilicovich, A

2010-07-01

Apoptotic processes play an important role in the maintenance of cell numbers in the anterior pituitary gland during physiological endocrine events. In this review, we summarise the regulation of apoptosis of anterior pituitary cells, particularly lactotrophs, somatotrophs and gonadotrophs, and analyse the possible mechanisms involved in oestrogen-induced apoptosis in anterior pituitary cells. Oestrogens exert apoptotic actions in several cell types and act as modulators of pituitary cell renewal, sensitising cells to both mitogenic and apoptotic signals. Local synthesis of growth factors and cytokines induced by oestradiol as well as changes in phenotypic features that enhance the responsiveness of anterior pituitary cells to pro-apoptotic factors may account for cyclical apoptotic activity in anterior pituitary cells during the oestrous cycle. Considering that tissue homeostasis results from a balance between cell proliferation and death and that mechanisms involved in apoptosis are tightly regulated, defects in cell death processes could have a considerable physiopathological impact.

Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival.

Science.gov (United States)

Zhang, Ying; Ji, Yajie; Li, Jianwei; Lei, Li; Wu, Siyu; Zuo, Wenjia; Jia, Xiaoqing; Wang, Yujie; Mo, Miao; Zhang, Na; Shen, Zhenzhou; Wu, Jiong; Shao, Zhimin; Liu, Guangyu

2018-04-01

To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially. This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints. The median follow-up time was 56.9 months (IQR 49.5-72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups. For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation

Novel G Protein-Coupled Oestrogen Receptor GPR30 Shows Changes in mRNA Expression in the Rat Brain over the Oestrous Cycle

Directory of Open Access Journals (Sweden)

Emma J. Spary

2012-02-01

Full Text Available Oestrogen influences autonomic function via actions at classical nuclear oestrogen receptors α and β in the brain, and recent evidence suggests the orphan G protein-coupled receptor GPR30 may also function as a cytoplasmic oestrogen receptor. We investigated the expression of GPR30 in female rat brains throughout the oestrous cycle and after ovariectomy to determine whether GPR30 expression in central autonomic nuclei is correlated with circulating oestrogen levels. In the nucleus of the solitary tract (NTS, ventrolateral medulla (VLM and periaqueductal gray (PAG GPR30 mRNA, quantified by real-time PCR, was increased in proestrus and oestrus. In ovariectomised (OVX rats, expression in NTS and VLM appeared increased compared to metoestrus, but in the hypothalamic paraventricular nucleus and PAG lower mRNA levels were seen in OVX. GPR30-like immunoreactivity (GPR30-LI colocalised with Golgi in neurones in many brain areas associated with autonomic pathways, and analysis of numbers of immunoreactive neurones showed differences consistent with the PCR data. GPR30-LI was found in a variety of transmitter phenotypes, including cholinergic, serotonergic, catecholaminergic and nitrergic neurones in different neuronal groups. These observations support the view that GPR30 could act as a rapid transducer responding to oestrogen levels and thus modulate the activity of central autonomic pathways.

Oestrogen receptors in breast tumours: associations with age, menopausal status and epidemiological and clinical features in 735 patients.

Science.gov (United States)

Elwood, J M; Godolphin, W

1980-11-01

Comparisons between oestrogen-receptor (RE)-positive or negative patients were made on a continuous series of 735 patients with primary breast tumours seen at the major treatment centre in British Columbia between 1975 and 1978. RE positivity was commoner in older patients, and was not associated with menopausal status independently of age. The concentration of receptor protein also increased with increasing age, but was not affected by menopausal status. Neither RE status nor quantity was associated with any of the epidemiological risk factors studied, which included parity, age at first birth, weight, family history and exposure to oestrogenic drugs and oral contraceptives. Patients with RE- tumours were more likely to present with symptoms other than a breast lump, pain or nipple inversion, and had less-differentiated tumours; they did not differ from RE+ patients in terms of stage, size of tumour, or interval from first symptom. These findings are discussed in terms of the biological origin and determinants of oestrogen receptors.

Prediction of in vitro and in vivo oestrogen receptor activity using hierarchical clustering

Science.gov (United States)

In this study, hierarchical clustering classification models were developed to predict in vitro and in vivo oestrogen receptor (ER) activity. Classification models were developed for binding, agonist, and antagonist in vitro ER activity and for mouse in vivo uterotrophic ER bindi...

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

DEFF Research Database (Denmark)

Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki

2016-01-01

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci...

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

NARCIS (Netherlands)

Couch, Fergus J; Kuchenbaecker, Karoline B; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomäki, Kristiina; Ambrosone, Christine; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K; Arver, Brita; Barile, Monica; Barkardottir, Rosa B; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W; Benitez, Javier; Blank, Stephanie V; Blomqvist, Carl; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J; Chung, Wendy K; Claes, Kathleen B M; Cox, Angela; Cross, Simon S; Cunningham, Julie M; Czene, Kamila; Daly, Mary B; Damiola, Francesca; Darabi, Hatef; de la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C; Dolcetti, Riccardo; Domchek, Susan M; Dorfling, Cecilia M; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M; Eccles, Diana M; Ehrencrona, Hans; Ekici, Arif B; Eliassen, Heather; Ellis, Steve; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Försti, Asta; Fostira, Florentia; Foulkes, William D; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D; Ganz, Patricia A; Gapstur, Susan M; Garber, Judy; Gaudet, Mia M; Gayther, Simon A; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G; Glendon, Gord; Godwin, Andrew K; Goldberg, Mark S; Goldgar, David E; González-Neira, Anna; Greene, Mark H; Gronwald, Jacek; Guénel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A; Hamann, Ute; Hansen, Thomas V O; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E; Herzog, Josef; Hogervorst, Frans B L; Hollestelle, Antoinette; Hooning, Maartje J; Hoover, Robert N; Hopper, John L; Humphreys, Keith; Hunter, David J; Huzarski, Tomasz; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G; Knight, Julia A; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L; Makalic, Enes; Malone, Kathleen E; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W M; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M; Muranen, Taru A; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Nordestgaard, Børge G; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Janet E; Osorio, Ana; Park, Sue K; Peeters, Petra H; Peissel, Bernard; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M; Pilarski, Robert; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rantala, Johanna; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J; Sanchez, Maria-Jose; Santella, Regina M; Sawyer, Elinor J; Schmidt, Daniel F; Schmidt, Marjanka K; Schmutzler, Rita K; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F; Sinilnikova, Olga M; Soucy, Penny; Southey, Melissa; Steinemann, Doris; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R; Teo, Soo-Hwang; Terry, Mary B; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda E; Tollenaar, Robert A E M; Tomlinson, Ian; Truong, Thérèse; Tsimiklis, Helen; Teulé, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; van Deurzen, Carolien H M; van Rensburg, Elizabeth J; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R; Yannoukakos, Drakoulis; Yao, Song; Zamora, M Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D P; Monteiro, Alvaro A N; García-Closas, Montserrat; Easton, Douglas F; Antoniou, Antonis C

2016-01-01

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci,

Oestrogen receptor α gene haplotype and postmenopausal breast cancer risk: a case control study

International Nuclear Information System (INIS)

Wedrén, Sara; Stiger, Fredrik; Persson, Ingemar; Baron, John; Weiderpass, Elisabete; Lovmar, Lovisa; Humphreys, Keith; Magnusson, Cecilia; Melhus, Håkan; Syvänen, Ann-Christine; Kindmark, Andreas; Landegren, Ulf; Fermér, Maria Lagerström

2004-01-01

Oestrogen receptor α, which mediates the effect of oestrogen in target tissues, is genetically polymorphic. Because breast cancer development is dependent on oestrogenic influence, we have investigated whether polymorphisms in the oestrogen receptor α gene (ESR1) are associated with breast cancer risk. We genotyped breast cancer cases and age-matched population controls for one microsatellite marker and four single-nucleotide polymorphisms (SNPs) in ESR1. The numbers of genotyped cases and controls for each marker were as follows: TA n , 1514 cases and 1514 controls; c.454-397C → T, 1557 cases and 1512 controls; c.454-351A → G, 1556 cases and 1512 controls; c.729C → T, 1562 cases and 1513 controls; c.975C → G, 1562 cases and 1513 controls. Using logistic regression models, we calculated odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype effects were estimated in an exploratory analysis, using expectation-maximisation algorithms for case-control study data. There were no compelling associations between single polymorphic loci and breast cancer risk. In haplotype analyses, a common haplotype of the c.454-351A → G or c.454-397C → T and c.975C → G SNPs appeared to be associated with an increased risk for ductal breast cancer: one copy of the c.454-351A → G and c.975C → G haplotype entailed an OR of 1.19 (95% CI 1.06–1.33) and two copies with an OR of 1.42 (95% CI 1.15–1.77), compared with no copies, under a model of multiplicative penetrance. The association with the c.454-397C → T and c.975C → G haplotypes was similar. Our data indicated that these haplotypes were more influential in women with a high body mass index. Adjustment for multiple comparisons rendered the associations statistically non-significant. We found suggestions of an association between common haplotypes in ESR1 and the risk for ductal breast cancer that is stronger in heavy women

Blockade of oestrogen biosynthesis in peripubertal boys: effects on lipid metabolism, insulin sensitivity, and body composition.

Science.gov (United States)

Hero, Matti; Ankarberg-Lindgren, Carina; Taskinen, Marja-Riitta; Dunkel, Leo

2006-09-01

In males, the pubertal increase in sex hormone production has been associated with proatherogenic changes in lipid and carbohydrate metabolism. Aromatase inhibitors, a novel treatment modality for some growth disorders, may significantly influence these risk factors for cardiovascular disease by suppressing oestrogen biosynthesis and stimulating gonadal androgen production. In the current study, we explored the effects of aromatase inhibition on lipid metabolism, insulin sensitivity, body composition and serum adiponectin in peripubertal boys. Prospective, double-blind, randomised, placebo-controlled clinical study. Thirty-one boys, aged 9.0-14.5 years, with idiopathic short stature were treated with the aromatase inhibitor letrozole (2.5 mg/day) or placebo for 2 years. During the treatment, the concentrations of sex hormones, IGF-I, lipids, lipoproteins and adiponectin were followed-up. The percentage of fat mass (FM) was assessed by skinfold measurements and insulin resistance by homeostasis model assessment (HOMA) index. In pubertal boys, who received letrozole, high-density lipoprotein cholesterol (HDL-C) decreased by 0.47 mmol/l (P<0.01) during the study. Simultaneously, their percentage of FM decreased from 17.0 to 10.5 (P<0.001), in an inverse relationship with serum testosterone. The concentrations of low-density lipoprotein cholesterol, triglycerides and HOMA index remained at pretreatment level in both groups. Serum adiponectin decreased similarly in letrozole- and placebo-treated pubertal boys (2.9 and 3.3 mg/l respectively). In males, aromatase inhibition reduces HDL-C and decreases relative FM after the start of puberty. The treatment does not adversely affect insulin sensitivity in lean subjects.

Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

Science.gov (United States)

Stanić, Davor; Dubois, Sydney; Chua, Hui Kheng; Tonge, Bruce; Rinehart, Nicole; Horne, Malcolm K.; Boon, Wah Chin

2014-01-01

Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, including the bed nucleus of the stria terminalis, olfactory tubercle, medial amygdaloid nucleus and medial preoptic area, with the densest distributions of EGFP-positive cell bodies in the bed nucleus and medial amygdala. Differences between male and female mice were apparent, with the density of EGFP-positive cell bodies and fibres being lower in some brain regions of female mice, including the bed nucleus and medial amygdala. EGFP-positive cell bodies in the bed nucleus, lateral septum, medial amygdala and hypothalamus co-expressed oestrogen receptor (ER) α and β, or the androgen receptor (AR), although single-labelled EGFP-positive cells were also identified. Additionally, single-labelled ERα−, ERβ- or AR-positive cell bodies often appeared to be surrounded by EGFP-immunoreactive nerve fibres/terminals. The widespread distribution of EGFP-positive cell bodies and fibres suggests that aromatase signalling is common in the mouse brain, and that locally synthesised brain oestrogens could mediate biological effects by activating pre- and post-synaptic oestrogen α and β receptors, and androgen receptors. The higher number of EGFP-positive cells in male mice may indicate that the autocrine and paracrine effects of oestrogens are more prominent in males than females. PMID:24646567

Prolactin release, oestrogens and proliferation of prolactin-secreting cells in the anterior pituitary gland of adult male rats.

Science.gov (United States)

Pérez, R L; Machiavelli, G A; Romano, M I; Burdman, J A

1986-03-01

Relationships among the release of prolactin, the effect of oestrogens and the proliferation of prolactin-secreting cells were studied under several experimental conditions. Administration of sulpiride or oestradiol released prolactin and stimulated cell proliferation in the anterior pituitary gland of adult male rats. Clomiphene completely abolished the rise in cell proliferation, but did not interfere with the sulpiride-induced release of prolactin. Treatment with oestradiol plus sulpiride significantly increased serum prolactin concentrations and the mitotic index compared with the sum of the stimulation produced by both drugs separately. Bromocriptine abolished the stimulatory effect of oestradiol on the serum prolactin concentration and on cell proliferation. In oestradiol- and/or sulpiride-treated rats, 80% of the cells in mitoses were lactotrophs. The remaining 20% did not stain with antisera against any of the pituitary hormones. The number of prolactin-secreting cells in the anterior pituitary gland significantly increased after the administration of oestradiol or sulpiride. The results demonstrate that treatment with sulpiride and/or oestradiol increases the proliferation and the number of lactotrophs in the anterior pituitary gland of the rat.

The corpus luteum of the dog: source and target of steroid hormones?

Science.gov (United States)

Papa, P C; Hoffmann, B

2011-08-01

Aim of this paper is to review our present understanding on the endocrine control of luteal function in the bitch and to add some new data generated in our laboratories in support of the hypothesis of a paracrine/autocrine role of corpus luteum (CL) derived steroid hormones. Luteal lifespan in non-pregnant dogs often exceeds that of pregnant dogs, where luteal regression terminates in a rapid luteolysis, immediately prior to parturition. In non-pregnant dogs, luteal regression occurs independently of a uterine luteolysin and in spite of increased gonadotropic support during the last third of dioestrus. The CL is the only source of progesterone (P(4)) maintaining pregnancy, and they have the capacity to synthesize oestrogens as substantiated by expression of the CYP19 (aromatase) gene observed in this study. Our data demonstrated that lutein and non-lutein cells of the canine CL express in a rather constant manner the progesterone receptor (PR) and the oestrogen receptor, classifying them as targets for an autocrine/paracrine activity of CL-derived steroids. Therefore, a functional role of P(4) within a positive loop feedback system, including StAR and 3β-hydroxysteroid dehydrogenase, has been postulated. © 2011 Blackwell Verlag GmbH.

Hormone replacement therapy and risk of non-fatal stroke

DEFF Research Database (Denmark)

Pedersen, A T; Lidegaard, O; Kreiner, S

1997-01-01

haemorrhage, 846 thromboembolic infarction, 321 transient ischaemic attack) and 3171 controls. FINDINGS: After adjustment for confounding variables and correction for the trend in sales of HRT preparations, no significant associations were detected between current use of unopposed oestrogen replacement...... influence on the risk of subarachnoid haemorrhage (1.22 [0.79-1.89]), intracerebral haemorrhage (1.17 [0.64-2.13]), or thromboembolic infarction (1.17 [0.92-1.47]). A significantly increased incidence of transient ischaemic attacks among former users of HRT and among current users of unopposed oestrogen may...... to some extent be explained by selection--HRT users being more aware of symptoms than non-users. INTERPRETATION: Unopposed oestrogen and combined oestrogen-progestagen replacement therapy have no influence on the risk of non-fatal thromboembolic or haemorrhagic stroke in women aged 45-64 years....

Investigating the role of natural phyto-oestrogens on bone health in postmenopausal women

NARCIS (Netherlands)

Valtueña, S.; Cashman, K.; Robins, S.P.; Cassidy, A.; Kardinaal, A.; Branca, F.

2003-01-01

Research on the bone effects of natural phyto-oestrogens after menopause is at a relatively early stage. Published studies are few, difficult to compare and often inconclusive, due in part to design weaknesses. Currently, many questions remain to be answered including to what extent a safe daily

[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

Science.gov (United States)

Allouche, G

2016-02-01

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses

Is immune system-related hypertension associated with ovarian hormone deficiency?

Science.gov (United States)

Sandberg, Kathryn; Ji, Hong; Einstein, Gillian; Au, April; Hay, Meredith

2016-03-01

What is the topic of this review? This review summarizes recent data on the role of ovarian hormones and sex in inflammation-related hypertension. What advances does it highlight? The adaptive immune system has recently been implicated in the development of hypertension in males but not in females. The role of the immune system in the development of hypertension in women and its relationship to ovarian hormone production are highlighted. The immune system is known to contribute to the development of high blood pressure in males. However, the role of the immune system in the development of high blood pressure in females and the role of ovarian hormones has only recently begun to be studied. In animal studies, both the sex of the host and the T cell are critical biological determinants of susceptibility and resistance to hypertension induced by angiotensin II. In women, natural menopause is known to result in significant changes in the expression of genes regulating the immune system. Likewise, in animal models, ovariectomy results in hypertension and an upregulation in T-cell tumour necrosis factor-α-related genes. Oestrogen replacement results in decreases in inflammatory genes in the brain regions involved in blood pressure regulation. Together, these studies suggest that the response of the adaptive immune system to ovarian hormone deficiency is a significant contributor to hypertension in women. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Steroid hormone and epidermal growth factor receptors in meningiomas.

Science.gov (United States)

Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

1989-11-01

A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

New once-a-month injectable contraceptives, with particular reference to Cyclofem/Cyclo-Provera.

Science.gov (United States)

Hall, P E

1998-08-01

Once-a-month injectable contraceptives containing a progestogen and an estrogen have been developed that disrupt vaginal bleeding patterns less than the widely used progestogen-only preparations. Pharmacokinetic studies were undertaken of dosages and ratios of the progestogens and the respective estrogens. In Phase III clinical trials, annual pregnancy rates were below 0.4% for Mesigyna (norethisterone enanthate/estradiol valerate, Schering AG, Berlin, Germany) and below 0.2% for Cyclofem (MPA/E2C) (medroxyprogesterone acetate/estradiol cypionate, Aplicaciones Farmaceuticas, SA, Mexico and PT Tunggal, Indonesia). More than two-thirds of women had predictable, regular cycles, and discontinuation due to bleeding-related problems occurred less than half as often as with progestogen-only injectables. With MPA/E2C, return to fertility is similar to that observed with other hormonal or intrauterine methods, and both products have little effect on lipids or hemostasis. Introductory trials of MPA/E2C in 12000 women with 100000 woman-months of experience confirmed the high efficacy of the product in routine use. The use of MPA/E2C in a non-reusable injection device, Uniject (Becton Dickinson, Franklin Lakes, NJ) is discussed. Once-a-month hormonal contraceptives have been shown to provide a safe contraceptive option for all women and an alternative for women who wish to use injectable formulations that cause less disruption in vaginal bleeding and minimal side effects.

The subtyping of primary aldosteronism by adrenal vein sampling: sequential blood sampling causes factitious lateralization.

Science.gov (United States)

Rossitto, Giacomo; Battistel, Michele; Barbiero, Giulio; Bisogni, Valeria; Maiolino, Giuseppe; Diego, Miotto; Seccia, Teresa M; Rossi, Gian Paolo

2018-02-01

The pulsatile secretion of adrenocortical hormones and a stress reaction occurring when starting adrenal vein sampling (AVS) can affect the selectivity and also the assessment of lateralization when sequential blood sampling is used. We therefore tested the hypothesis that a simulated sequential blood sampling could decrease the diagnostic accuracy of lateralization index for identification of aldosterone-producing adenoma (APA), as compared with bilaterally simultaneous AVS. In 138 consecutive patients who underwent subtyping of primary aldosteronism, we compared the results obtained simultaneously bilaterally when starting AVS (t-15) and 15 min after (t0), with those gained with a simulated sequential right-to-left AVS technique (R ⇒ L) created by combining hormonal values obtained at t-15 and at t0. The concordance between simultaneously obtained values at t-15 and t0, and between simultaneously obtained values and values gained with a sequential R ⇒ L technique, was also assessed. We found a marked interindividual variability of lateralization index values in the patients with bilaterally selective AVS at both time point. However, overall the lateralization index simultaneously determined at t0 provided a more accurate identification of APA than the simulated sequential lateralization indexR ⇒ L (P = 0.001). Moreover, regardless of which side was sampled first, the sequential AVS technique induced a sequence-dependent overestimation of lateralization index. While in APA patients the concordance between simultaneous AVS at t0 and t-15 and between simultaneous t0 and sequential technique was moderate-to-good (K = 0.55 and 0.66, respectively), in non-APA patients, it was poor (K = 0.12 and 0.13, respectively). Sequential AVS generates factitious between-sides gradients, which lower its diagnostic accuracy, likely because of the stress reaction arising upon starting AVS.

Parathyroid hormone secretion in chronic renal failure

DEFF Research Database (Denmark)

Madsen, J C; Rasmussen, A Q; Ladefoged, S D

1996-01-01

The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during....../ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...

Efficiency of different hormonal treatments for estrus synchronization in tropical Santa Inês sheep.

Science.gov (United States)

Texeira, Tarcísio Alves; da Fonseca, Jeferson Ferreira; de Souza-Fabjan, Joanna Maria Gonçalves; de Rezende Carvalheira, Luciano; de Moura Fernandes, Daniel Andrews; Brandão, Felipe Zandonadi

2016-03-01

The aim of this study was to evaluate the effect of (i) the duration of hormone treatment with progestogen sponges during the seasonal anestrus and (ii) the administration of two doses of prostaglandin at 7 days apart during the breeding season on reproductive parameters of Santa Inês ewes. In experiment 1, 32 ewes received intravaginal MAP sponges for 6 (G6 days), 9 (G9 days), or 12 (G12days) days and 75 μg D-cloprostenol i.m. and 300 IU eCG i.m. 1 day before sponge removal. In experiment 2, 23 ewes received two doses of 0.48-mg sodium cloprostenol i.m. 7 days apart. Ovarian follicular dynamic was assessed through transrectal ultrasonography. Blood samples were collected daily to determine progesterone concentrations. In experiment 1, estrus and ovulation rates did not differ (P > 0.05) among protocols and between cyclic and acyclic ewes at the beginning of the experiment. The G9 days treatment showed a lower dispersion of ovulations in relation to onset of estrus when compared to G6 days and G12 days. In experiment 2, all ewes exhibit estrus and ovulated after the second dose of prostaglandin, although ewes that were in diestrus at D0 showed subluteal concentrations of progesterone during the follicle development stage of the treatment. In conclusion, the use of progestogen device during 9 days promotes lower dispersion of ovulation when compared to its use for 6 or 12 days, and the protocol of two doses of prostaglandin 7 days apart synchronizes estrus efficiently but results in follicular development under low progesterone concentrations.

In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

International Nuclear Information System (INIS)

Rivero, Javier; Luzardo, Octavio P.; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

2015-01-01

Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

Energy Technology Data Exchange (ETDEWEB)

Rivero, Javier; Luzardo, Octavio P., E-mail: octavio.perez@ulpgc.es; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

2015-12-15

Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells.

Science.gov (United States)

Neubauer, Hans; Yang, Yang; Seeger, Harald; Fehm, Tanja; Cahill, Michael A; Tong, Xiaowen; Ruan, Xiangyan; Mueck, Alfred O

2011-08-01

Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two progestogens on MCF-7 breast cancer cells overexpressing PGRMC1. MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M). E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells. Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.

Effect of hormonal contraceptives on serum serotonin in females of reproductive age group

International Nuclear Information System (INIS)

Faryal, U.; Hajra, B.; Saqib, J.; Rashid, S.; Hassan, M.; Ali, M.A.

2016-01-01

Background: Many types of hormonal contraceptives are in use nowadays for example oral pills, emergency contraceptive pills, vaginal rings, implantable rods and injectable contraceptives (combined and progestogens only). The purpose of this study was to determine and compare serum serotonin levels in married fertile females of reproductive age group using hormonal contraceptives with non-contraceptive users. Methods: A total of 300 women were selected in the study. This cross sectional study included three groups; Group-1 (control), group-2 (combined oral contraceptive users) and group-3 (injectable contraceptive users). History and examination of subjects were recorded on proforma. Levels of serum serotonin were measured using standard ELISA kits. Results were analysed by one way anova and a p-value 0.05 percentage was taken as significant, using SPSS 16.0. Results: The mean age of the patients in group-1 was 30.4±6.1 years, group-2 was 28.9±4.9 and in group-3 was 2.5±6.8 years. For subjects in group-1, group-2 and group 3 the mean±SD concentration of serum serotonin was 160.68±53.27 ng/dl, 227.3±63.98 ng/dl and 118.19±31.32 ng/dl. A significant (p=0.00) difference was seen among three groups, i.e., group-1, group-2 and group-3. After applying Post HOC Tukey HSD, there was statistically no significant difference between group-1 and group-2 (p=0.956). Difference was seen between group-2 and group-3 (p=0.00), it was also significant between group-3 and group-1 (p=0.00). Conclusion: It was concluded that hormonal contraceptives affect the levels of serum serotonin.Background: Many types of hormonal contraceptives are in use nowadays for example oral pills, emergency contraceptive pills, vaginal rings, implantable rods and injectable contraceptives (combined and progestogens only). The purpose of this study was to determine and compare serum serotonin levels in married fertile females of reproductive age group using hormonal contraceptives with non

Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent.

Science.gov (United States)

Toogood, A A; Taylor, N F; Shalet, S M; Monson, J P

2000-01-01

The net interconversion of inactive cortisone to active cortisol by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol metabolism exhibits a sexual dimorphism with an apparently lower activity of 11betaHSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the sexual dimorphism of cortisol metabolism persists between post-menopausal, oestrogen-deficient women and elderly men. Fifteen healthy men, aged 60.8-82.0 years, and 7 healthy women, aged 62.4-87.5 years, were studied. None of the subjects was receiving steroid medication at the time of the study. All the women were post-menopausal and none was receiving sex steroid replacement therapy. 24-h urine collections were taken from each patient and assayed for steroid metabolites by gas chromatography. Body composition was determined by dual energy X-ray absorptiometry. Blood was drawn, after an overnight fast, for the determination of serum IGF-I and IGFBP1 levels. The ratio of 11-hydroxy cortisol metabolites to 11-oxo cortisol metabolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55-1.86) vs. 0.67 (0.46-0.98) (P cortisol and cortisone metabolite (Fm/Em) and total fat mass approached significance, r = - 0.39 (P = 0.07). These relationships were not apparent in the women when considered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = - 0.48, and Fm/Em and trunk fat mass, r = - 0.48 which approached significance (both P = 0.07). Serum IGFBP-1 levels were not significantly different between the two sexes. There was a significant correlation between IGFBP-1 and Fm/Em in the men, r = 0. 84 (P sexual dimorphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11beta-HSD1 gene expression during the pre

Physical growth, puberty and hormones in adolescents with Nodding Syndrome; a pilot study.

Science.gov (United States)

Piloya-Were, Theresa; Odongkara-Mpora, Beatrice; Namusoke, Hanifa; Idro, Richard

2014-11-28

Nodding syndrome is an epidemic symptomatic generalized epilepsy syndrome of unknown cause in Eastern Africa. Some patients have extreme short stature. We hypothesized that growth failure in nodding syndrome is associated with specific endocrine dysfunctions. In this pilot study, we examined the relationship between serum hormone levels and stature, bone age and sexual development. We recruited ten consecutive children, 13 years or older, with World Health Organization defined nodding syndrome and assessed physical growth, bone age, development of secondary sexual characteristics and serum hormone levels. Two children with incomplete results were excluded. Of the eight remaining, two had severe stunting (height for age Z [HAZ] scorebone age was delayed by a median 3(range 0-4) years. Serum growth hormone levels were normal in all eight but the two patients with severe stunting and one with moderate stunting had low levels of Somatomedin C (Insulin like Growth Factor [IGF1]) and/or IGF binding protein 3 (IGFBP3), mediators of growth hormone function. A linear relationship was observed between serum IGF1 level and HAZ score. With the exception of one child, all were either pre-pubertal or in early puberty (Tanner stages 1 and 2) and in the seven, levels of the gonadotrophins (luteinising and follicle stimulating hormone) and the sex hormones (testosterone/oestrogen) were all within pre-pubertal ranges or ranges of early puberty. Thyroid function, prolactin, adrenal, and parathyroid hormone levels were all normal. Patients with nodding syndrome may have dysfunctions in the pituitary growth hormone and pituitary gonadal axes that manifest as stunted growth, delayed bone age and puberty. Studies are required to determine if such endocrine dysfunction is a primary manifestation of the disease or a secondary consequence of chronic ill health and malnutrition and if so, whether targeted interventions can improve outcome.

The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise.

Science.gov (United States)

Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

2015-06-01

Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. © 2015 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

Effect of ovarian hormones on the phagocytic response of ovariectomized mares.

Science.gov (United States)

Ganjam, V K; McLeod, C; Klesius, P H; Washburn, S M; Kwapien, R; Brown, B; Fazeli, M H

1982-01-01

The reaction between ovarian hormones and experimental uterine infection (Streptococcus zooepidemicus) was investigated in 3 groups, each containing 6 ovariectomized mares. Group 1 served as controls ('anoestrus'), Group 2 mares were injected with oestrogen ('oestrus') and Group 3 with progesterone ('dioestrus') over a period of 5 weeks. All mares received an intrauterine inoculation of the bacteria 1 week after the start of hormonal treatment, and the results of the challenge were examined by endometrial biopsy and swabs once weekly. At the end of Week 1 no bacteria were recovered from the mares in Group 2. Group 1 mares were free of bacteria at the end of Week 2 but all Group 3 mares remained infected at least for the total period examined. Streptococcal phagocytosis was quantitated by chemiluminescence. Before the challenge-inoculation, phagocytosis was not significantly different in the 3 groups of mares. Bacterial cultures were negative for all three groups. However, within 48 h after infection, there was a significant increase (P less than 0.01) in phagocytosis in Group 2 and a significant suppression (P less than 0.05) in Group 3 mares. Patterns of streptococcal clearance from the uterus closely paralleled the changes in the magnitude of chemiluminescence response. The results suggest that ovarian hormonal status can modulate the phagocytic response in episodes of streptococcal-induced endometritus in mares.

In an in-vitro model using human fetal membranes, 17-α hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening.

Science.gov (United States)

Kumar, Deepak; Moore, Robert M; Mercer, Brian M; Mansour, Joseph M; Mesiano, Sam; Schatz, Frederick; Lockwood, Charles J; Moore, John J

2017-12-01

The progestogen 17-α hydroxyprogesterone caproate (17-OHPC) is 1 of only 2 agents recommended for clinical use in the prevention of spontaneous preterm delivery, and studies of its efficacy have been conflicting. We have developed an in-vitro model to study the fetal membrane weakening process that leads to rupture in preterm premature rupture of the fetal membranes (pPROM). Inflammation/infection associated with tumor necrosis factor-α (TNF-α) induction and decidual bleeding/abruption associated thrombin release are leading causes of preterm premature rupture of the fetal membranes. Both agents (TNF-α and thrombin) cause fetal membrane weakening in the model system. Furthermore, granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical intermediate for both TNF-α and thrombin-induced fetal membrane weakening. In a previous report, we demonstrated that 3 progestogens, progesterone, 17-alpha hydroxyprogesterone (17-OHP), and medroxyprogesterone acetate (MPA), each inhibit both TNF-α- and thrombin-induced fetal membrane weakening at 2 distinct points of the fetal membrane weakening pathway. Each block both the production of and the downstream action of the critical intermediate granulocyte-macrophage colony-stimulating factor. The objective of the study was to characterize the inhibitory effects of 17-OHPC on TNF-α- and thrombin-induced fetal membrane weakening in vitro. Full-thickness human fetal membrane fragments from uncomplicated term repeat cesarean deliveries were mounted in 2.5 cm Transwell inserts and cultured with/without 17-alpha hydroxyprogesterone caproate (10 -9 to 10 -7 M). After 24 hours, medium (supernatant) was removed and replaced with/without the addition of tumor necrosis factor-alpha (20 ng/mL) or thrombin (10 U/mL) or granulocyte-macrophage colony-stimulating factor (200 ng/mL). After 48 hours of culture, medium from the maternal side compartment of the model was assayed for granulocyte-macrophage colony

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

NARCIS (Netherlands)

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H; Beltran, Himisha; Fox, Archa H; Elemento, Olivier; Rubin, Mark A

2014-01-01

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers,

Antiandrogenic and antimineralocorticoid health benefits of COC containing newer progestogens: dienogest and drospirenone.

Science.gov (United States)

Regidor, Pedro-Antonio; Schindler, Adolf E

2017-10-10

Data have demonstrated that COCs, besides offering a satisfactory and safe contraception, offer a variety of non-contraceptive health benefits and therapeutic positive aspects. Many prescribes and users, however, do not realize these positive aspects especially the non-contraceptive health benefits. While the contraceptive use is the primary indication for COC use for most women, these users should be advised in regard of the non-contraceptive benefits when contraception is discussed and prescribed. Using COCs specifically for non-contraceptive indications is an off-label use in many clinical situations (only some exceptions as e.g. acne vulgaris in some countries are allowed clinical entities for the use of these drugs). Therefore, appropriate discussions with the patient regarding this fact should performed and documented by the prescribing physicians. Independent of the off-label situation, COCs containing the newer progestogens dienogest and drospirenone with their antiandrogenic and antimineralocorticoid health benefits play an important role in the management of many diseases and their use should therefore be considered by clinician's. This review will focus on the effects of these COCs on the endometrium, the skin, the fat tissue and the premenstrual syndrome.

Evolution of systemic treatment for hormone-sensitive breast cancer: from sequential use of single agents to the upfront administration of drug combinations

Directory of Open Access Journals (Sweden)

E. N. Imyanitov

2016-01-01

Full Text Available Current standards of treatment of endocrine-dependent cancers (breast cancer (BC, prostate cancer imply sequential use of endocrine therapy and cytotoxic agents: it is believed, that steroid hormone antagonists cease the division of transformed cells and therefore make them resistant to other therapeutic modalities. It is important to recognize that conceptual investigations in this field were carried out dozens of years ago, and often involved relatively non-efficient drugs, imperfect laboratory tests, etc. There are several recent examples of combined use of endocrine therapy and other compounds. The addition of docetaxel (6 cycles to androgen deprivation resulted in significant improvement of overall survival in men with metastatic prostate cancer. Clinical trial involving the combined use of exemestane and everolimus demonstrated promising results. There are ongoing studies on inhibitors of cycline-dependent kinases. Use of these drugs in the beginning of endocrine therapy may significantly delay resistance to the antagonists of estrogen signaling.

Oestrogenic activity of a textile industrial wastewater treatment plant effluent evaluated by the E-screen test and MELN gene-reporter luciferase assay

Energy Technology Data Exchange (ETDEWEB)

Schiliro, Tiziana, E-mail: tiziana.schiliro@unito.it [Department of Public Health and Microbiology, University of Torino, Via Santena 5bis, 10126 Torino (Italy); Porfido, Arianna [Department of Public Health and Microbiology, University of Torino, Via Santena 5bis, 10126 Torino (Italy); Spina, Federica; Varese, Giovanna Cristina [Department of Life Sciences and Systems Biology, University of Torino, Viale Mattioli 25, 10125 Torino (Italy); Gilli, Giorgio [Department of Public Health and Microbiology, University of Torino, Via Santena 5bis, 10126 Torino (Italy)

2012-08-15

This study quantified the biological oestrogenic activity in the effluent of a textile industrial wastewater treatment plant (IWWTP) in northwestern Italy. Samples of the IWWTP effluent were collected monthly, both before and after tertiary treatment (ozonation). After solid phase extraction, all samples were subjected to two in vitro tests of total estrogenic activity, the human breast cancer cell line (MCF-7 BUS) proliferation assay, or E-screen test, and the luciferase-transfected human breast cancer cell line (MELN) gene-reporter assay, to measure the 17{beta}-oestradiol equivalent quantity (EEQ). In the E-screen test, the mean EEQ values were 2.35 {+-} 1.68 ng/L pre-ozonation and 0.72 {+-} 0.58 ng/L post-ozonation; in the MELN gene-reporter luciferase assay, the mean EEQ values were 4.18 {+-} 3.54 ng/L pre-ozonation and 2.53 {+-} 2.48 ng/L post-ozonation. These results suggest that the post-ozonation IWWTP effluent had a lower oestrogenic activity (simple paired t-tests, p < 0.05). The average reduction of estrogenic activity of IWWTP effluent after ozonation was 67 {+-} 26% and 52 {+-} 27% as measured by E-screen test and MELN gene-reporter luciferase assay, respectively. There was a positive and significant correlation between the two tests (Rho S = 0.650, p = 0.022). This study indicates that the environmental risk is low because oestrogenic substances are deposited into the river via IWWTP at concentrations lower than those at which chronic exposure has been reported to affect the endocrine system of living organisms. -- Highlights: Black-Right-Pointing-Pointer The two in vitro tests are suited for oestrogenic activity assessment in textile WWTP. Black-Right-Pointing-Pointer There is a significant correlation between the results of the two in vitro tests. Black-Right-Pointing-Pointer The oestrogenic activity of the effluent is reduced by ozonation. Black-Right-Pointing-Pointer The input of estrogenic substances into the river via textile WWTP is low.

The potential health effects of dietary phytoestrogens

NARCIS (Netherlands)

Rietjens, Ivonne M.C.M.; Louisse, Jochem; Beekmann, Karsten

2017-01-01

Phytoestrogens are plant-derived dietary compounds with structural similarity to 17-β-oestradiol (E2), the primary female sex hormone. This structural similarity to E2 enables phytoestrogens to cause (anti)oestrogenic effects by binding to the oestrogen receptors. The aim of the present review is to

Differential effects of oestrogenic hormones on cell proliferation in the colonic crypt epithelium and in colonic carcinomata of rats.

Science.gov (United States)

Tutton, P J; Barkla, D H

1982-01-01

A number of hormones, including some steroids, have previously been shown to influence the rate of cell division in the colonic crypt epithelium and in colonic tumours. In this report the effect of oophorectomy and of treatment with ovarian hormones on cell proliferation in these tissues is compared. Colonic tumours cell proliferation was retarded following oophorectomy and this retardation was reversed by the administration of oestradiol, but not by the administration of progesterone. Oophorectomy did not retard cell proliferation in the colonic crypts. The possible significance of these findings in relation to age-dependent variations in the sex ratio for human bowel cancer is discussed.

Oestrogen receptor beta over expression in males with non-small cell lung cancer is associated with better survival

DEFF Research Database (Denmark)

Skov, Birgit Guldhammer; Sode, Birgitte M Fischer; Pappot, H.

2008-01-01

BACKGROUND: Adenocarcinoma of the lung is more frequent in females than in males and the association with smoking is less pronounced than for the other histological subtypes of lung cancer. Oestrogen induction of cell proliferation has been found in breast adenocarcinomas, and since oestrogen...... the results to gender and survival. METHODS: Paraffin embedded, histological material was collected from 104 patients (71 men and 33 women), operated in the period 1989-1992 for NSCLC (56 squamous cell carcinomas, 40 adenocarcinomas and 8 large cell carcinomas). ERalpha, ERbeta and progesterone were...... and progesterone expression for the prognosis. RESULTS: ERbeta positivity was demonstrated in 69% (72 of 104) of the tumours. There was no statistically significant correlation between ERbeta positivity and age, gender, stage, or histology. After adjusting for gender, age, stage at diagnosis and histology...

Monitoring and risk assessment for endocrine disruptors in the aquatic environment: a biomarker approach

Energy Technology Data Exchange (ETDEWEB)

Bjerregaard, P.; Korsgaard, B.; Christiansen, L.B.; Pedersen, K.L.; Christensen, L.J.; Pedersen, S.N.; Horn, P. [Odense Univ. (Denmark). Biologisk Inst.

1998-12-31

Evidence that a number of chemicals affect wildlife populations or individuals via interaction with endocrine systems has been increasing in recent years. Not all of the mechanisms of action are fully understood, but endocrine disrupting chemicals may work at various biochemical levels, e.g. affecting the synthesis of hormones, interfering with hormone transporting proteins in the blood, affecting the metabolisation of hormones or by direct effects on cellular hormone receptors. In dogwhelks Nucella lapillus tributyltin inhibits the aromatase that converts testosterone to oestrogen thereby masculinising the females (Oehlmann et al. 1996). Metabolites of polychlorinated biphenyls interfere with thyroxin transporting proteins in the blood of seals. Chemicals that induce MFO-activity may indirectly lead to altered hormone levels by increasing the metabolisation of hormones. Alkylphenols react directly with the oestrogen receptor which in turn may lead to feminisation of male organisms exposed. (orig.)

A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty

Science.gov (United States)

Arroyo, Armando; Pernasetti, Flavia; Vasilyev, Vyacheslav V.; Amato, Paula; Yen, Samuel S. C.; Mellon, Pamela L.

2010-01-01

Summary We report a 28-year-old-female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS −0.86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X-ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit-1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue. PMID:12153609

DNA polymerases in the rat pituitary gland. Effect of oestrogens and sulpiride.

Science.gov (United States)

Jahn, G A; Kalbermann, L E; Machiavelli, G; Szijan, I; Burdman, J A

1980-06-01

Changes in the activity of DNA polymerase and [3H]thymidine incorporation into the DNA of the anterior pituitary gland were studied in oestrogenized male and pregnant rats. The activities of DNA polymerases alpha and beta, extracted in Tris--HCl or in sodium phosphate buffer were characterized according to their optimum pH and sensitivity to N-ethyl-maleimide. In the Tris-soluble fraction DNA polymerase activity is almost exclusively alpha, while in the phosphate soluble fraction it is a mixture of alpha and beta. The administration of oestrogens to male rats increases [3H]thymidine incorporation and enhances the activity of DNA polymerases in the Tris-soluble fraction, while the activity of the phosphate-soluble enzyme does not change. Sulpiride administration results in a further increment of [3H]thymidine incorporation and of DNA polymerase activity in the Tris-soluble fraction. In pregnant rats sulpiride also produces an increment of DNA polymerase activity only in the Tris-soluble fraction. Thus, the activity of the Tris-soluble fraction from APG behaves as DNA polymerase alpha. This activity changes in parallel with [3H]thymidine incorporation into DNA which is an indication of cell proliferation in the gland. This is discussed with respect to a negative feedback mechanism between intracellular prolactin concentration and DNA synthesis in the APG.

New Insights on Steroid Biotechnology

DEFF Research Database (Denmark)

Fernandez-Cabezon, Lorena; Galán, Beatriz; García, José L.

2018-01-01

Nowadays steroid manufacturing occupies a prominent place in the pharmaceutical industry with an annual global market over $10 billion. The synthesis of steroidal active pharmaceutical ingredients (APIs) such as sex hormones (estrogens, androgens, and progestogens) and corticosteroids is currentl...

The role of combined oral contraceptives in the management of acne and seborrhea.

Science.gov (United States)

del Marmol, V; Teichmann, A; Gertsen, K

2004-06-01

Acne and seborrhea (or facial oiliness) are related androgenic skin disorders which affect a high proportion of women after menarche. They can have a negative effect on psychological well-being and social life. Androgens play an important role in the pathogenesis of acne through the stimulation of sebum secretion, increasing sebaceous gland size and possibly through follicular hyperkeratinization. Conversely, estrogens decrease sebum production by suppressing gonadotropin release and androgen production and increasing sex hormone binding globulin production. One of the treatment options for these conditions is hormonal therapy, especially for women who require contraception. The effect of combined oral contraceptives in androgenic skin disorders depends on their estrogen:progestogen balance and on the antiestrogenic activity of the progestogen component. Improved understanding of what women value about oral contraceptives suggests that the choice of product should be tailored as much as possible to the individual. Several combined oral contraceptives containing new-generation progestogens (e.g. desogestrel, gestodene) or progestational antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated efficacy in the treatment of women with acne, although comparisons between trials are difficult because of differing endpoints. Seborrhea has been less well studied, but the few studies that are available show an improvement in women with this condition using combined oral contraceptives.

GnRH and prostaglandin-based synchronization protocols as alternatives to progestogen-based treatments in sheep.

Science.gov (United States)

Rekik, M; Haile, A; Abebe, A; Muluneh, D; Goshme, S; Ben Salem, I; Hilali, M El-Dine; Lassoued, N; Chanyalew, Y; Rischkowsky, B

2016-12-01

The study investigated, for cycling sheep, synchronizing protocols simultaneously to the standard "P" protocol using progestogens priming with intravaginal devices and gonadotropin. In November 2014, 90 adult Menz ewes were assigned to either the "P" protocol, "PGF" treatment where oestrus and ovulation were synchronized using two injections of prostaglandin 11 days apart or a "GnRH" treatment where the ewes had their oestrus and ovulation synchronized with GnRH (day 0)-prostaglandin (day 6)-GnRH (day 9) sequence. The ewes were naturally mated at the induced oestrus and the following 36 days. Plasma progesterone revealed that 92% of the ewes were ovulating before synchronization and all, except one, ovulated in response to the applied treatments. All "P" ewes exhibited oestrus during the 96-hr period after the end of the treatments in comparison with only 79.3% and 73.3% for "PGF" and "GnRH" ewes, respectively (p sheep after the rainy season when most animals are spontaneously cycling. © 2016 Blackwell Verlag GmbH.

Synthesis of DNA in oestrogen-induced pituitary tumurs in rats: effect of bromocriptine.

Science.gov (United States)

Kalbermann, L E; Machiavelli, G A; De Nicola, A F; Weissenberg, L S; Burdman, J A

1980-11-01

Bromocriptine increased the concentration of prolactin in oestrogen-induced tumours of the rat pituitary gland. Prolactinaemia was significantly reduced and at the same time there was a considerable decrease in the weight of the tumour, in the incorporation of tritiated thymidine into DNA and in the activity of DNA polymerase alpha. The results suggested that the intracellular content of prolactin controls cell proliferation in this experimental tumour. A hypothalamic disorder is proposed as the primary cause of these tumours.

Effects of sewage effluent and ethynyl oestradiol upon molecular markers of oestrogenic exposure, maturation and reproductive success in the sand goby (Pomatoschistus minutus, Pallas)

International Nuclear Information System (INIS)

Robinson, Craig D.; Brown, Elaine; Craft, John A.; Davies, Ian M.; Moffat, Colin F.; Pirie, David; Robertson, Fiona; Stagg, Ronald M.; Struthers, Susan

2003-01-01

Male fish in several UK estuaries are known to be exposed to oestrogenic contamination, and whilst a limited number of studies have shown that exposure to oestrogens can reduce the reproductive success of fish, the impact of environmentally relevant exposures is less clear. The aim of this study was, therefore, to investigate the effects of exposure to environmentally realistic concentrations of a sewage effluent and the synthetic oestrogen 17α-ethynyl oestradiol (EE 2 ) upon the reproductive success of a marine fish. Sand goby (Pomatoschistus minutus) were exposed for 7 months to EE 2 or a sewage effluent containing known xeno-oestrogens (alkylphenol polyethoxylates) and bred using within treatment crosses. Nominal exposure concentrations were 6 ng l -1 EE 2 , 0.3 or 0.03% v/v sewage effluent. At the end of the breeding trials, expression of hepatic zona radiata protein (Zrp) and vitellogenin (Vtg) mRNA were determined using two recently developed cDNA probes. Exposure to 6 ng l -1 EE 2 induced Zrp and Vtg mRNA expression in male and female sand goby, impaired male maturation and reproductive behaviour, reduced female fecundity and reduced egg fertility. As a consequence, fertile egg production of the EE 2 -exposed population was reduced by 90%. Exposure to sewage effluent (0.3% v/v) increased adult mortality and female Zrp and Vtg mRNA expression, but did not induce male vitellogenesis. Exposure to EE 2 and 0.3% v/v sewage effluent impaired development of the male urogenital papilla. Fish exposed to 0.03% v/v sewage effluent produced more fertile eggs than those exposed to 0.3% effluent, or those receiving no effluent. It is concluded that male vitellogenesis in an oestrogenically exposed population may be accompanied by reduced reproductive success, but that it may not be indicative of altered reproductive output in a population exposed to an industrial sewage effluent

Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women.

Science.gov (United States)

Jacobson, Melanie H; Howards, Penelope P; Darrow, Lyndsey A; Meadows, Juliana W; Kesner, James S; Spencer, Jessica B; Terrell, Metrecia L; Marcus, Michele

2018-03-08

Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E 1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). Total thyroxine (T 4 ) concentrations were positively associated with Pd3G and E 1 3G. Women with higher (vs lower) T 4 had greater luteal phase maximum Pd3G (Pd3G = 11.7 μg/mg Cr for women with high T 4 vs Pd3G = 9.5 and 8.1 μg/mg Cr for women with medium and low T 4 , respectively) and greater follicular phase maximum E 1 3G (E 1 3G = 41.7 ng/mg Cr for women with high T 4 vs E 1 3G = 34.3 and 33.7 ng/mg Cr for women with medium and low T 4 , respectively). Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease. © 2018 John Wiley & Sons Ltd.

Phyto-oestrogens in herbage and milk from cows grazing whiteclover, red clover, lucerne or chicory-rich pastures

DEFF Research Database (Denmark)

Andersen, C; Nielsen, T S; Purup, S

2009-01-01

A grazing experiment was carried out to study the concentration of phyto-oestrogens in herbage for cattle and in milk during two periods (May and June). Forty-eight Danish Holstein cows were divided into four groups with four treatment diets; white clover, red clover, lucerne and chicory-rich pas...

Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging

NARCIS (Netherlands)

Rijks, L. J.; Busemann Sokole, E.; Stabin, M. G.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

1998-01-01

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous

Parathyroid hormone secretion in chronic renal failure

DEFF Research Database (Denmark)

Madsen, J C; Rasmussen, A Q; Ladefoged, S D

1996-01-01

The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during....../ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...... of a standardized method we show that the calcium set-point is normal or slightly elevated, indicating normal parathyroid reactivity to calcium in chronic renal failure....

Parathyroid hormone secretion in chronic renal failure

DEFF Research Database (Denmark)

Madsen, J C; Rasmussen, A Q; Ladefoged, S D

1996-01-01

/ionized calcium curves were constructed, and a mean calcium set-point of 1.16 mmol/liter was estimated compared to the normal mean of about 1.13 mmol/liter. In conclusion, we demonstrate that it is important to use a standardized method to evaluate parathyroid hormone dynamics in chronic renal failure. By the use...... of a standardized method we show that the calcium set-point is normal or slightly elevated, indicating normal parathyroid reactivity to calcium in chronic renal failure.......The aim of study was to introduce and evaluate a method for quantifying the parathyroid hormone (PTH) secretion during hemodialysis in secondary hyperparathyroidism due to end-stage renal failure. We developed a method suitable for inducing sequential hypocalcemia and hypercalcemia during...

The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice.

Science.gov (United States)

Wehrle, Esther; Liedert, Astrid; Heilmann, Aline; Wehner, Tim; Bindl, Ronny; Fischer, Lena; Haffner-Luntzer, Melanie; Jakob, Franz; Schinke, Thorsten; Amling, Michael; Ignatius, Anita

2015-01-01

Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81%) and bone formation (-80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in

The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice

Directory of Open Access Journals (Sweden)

Esther Wehrle

2015-01-01

Full Text Available Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV. We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96 were either ovariectomised (OVX or sham operated (non-OVX at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine were evaluated using bending-testing, micro-computed tomography (μCT, histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (−81% and bone formation (−80% in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2 and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398% and bone formation (+637%, which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet. On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and

European Code against Cancer 4th Edition

DEFF Research Database (Denmark)

Friis, Søren; Kesminiene, Ausrele; Espina, Carolina

2015-01-01

were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self...... of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major...... health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence...

Histomorphometric analysis and immunolocalization of RANKL and OPG during the alveolar healing process in female ovariectomized rats treated with oestrogen or raloxifene.

Science.gov (United States)

Luvizuto, Eloá Rodrigues; Queiroz, Thallita Pereira; Dias, Sheila Mônica Damásio; Okamoto, Tetuo; Dornelles, Rita Cássia Menegati; Garcia, Idelmo Rangel; Okamoto, Roberta

2010-01-01

To investigate the effects of bone-resorption inhibitors (oestrogen and raloxifene) on the RANKL/OPG balance during the chronology of the alveolar healing process in ovariectomized (OVX) rats by means of immunocolocalization and histomorphometric analysis. One hundred sixty female Wistar rats at 70 days of age were either OVX or sham-operated and divided into four groups: sham, OVX/Oil, OVX with E(2) replacement (17beta-estradiol, 400 microg/month), OVX with RLX treatment (1mg/kg bw/day). The 60-day treatment started 8 days after ovariectomy. The incisors were extracted to allow analysis of 7, 14, 21, 28 and 42 days of wound healing. After obtaining the histological samples, slides were stained with hematoxylin and eosin or subjected to immunocolocalization reaction for RANKL and OPG. Results were quantitatively evaluated. Histomorphometric analysis showed that the sham group presented the highest and OVX/Oil group the lowest mean bone formation value in the post-extraction period. The immunocolocalization analysis showed a larger increase in bone turnover at 7 postoperative days in OVX/Oil and sham groups and decreasing bone turnover in the other periods. The OVX/Oil group showed a large decrease in bone turnover at 14 postoperative days, a period demonstrated by mild cellular activity. OVX/E(2) and sham groups showed a decreased bone turnover at 28 postoperative days while OVX/RLX group showed a decreased bone turnover at 21 postoperative days. On the 42nd postoperative day, sham and OVX/RLX groups showed an established alveolar bone healing process. Ovariectomy delays the alveolar healing process and interferes with bone turnover through the balance between RANKL and OPG. Oestrogen replacement or raloxifene treatment did not totally recover the oestrogen-deficient state. However raloxifene treatment showed more satisfactory results than oestrogen replacement. Copyright 2009 Elsevier Ltd. All rights reserved.

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African Journals Online (AJOL)

Pl“()(lll.lCli0U of testosterone uml oestrogen is controlled by the jiiitttitory release ol' the leiiteitnsing hormones (Lil). 'l'l'ie administration of testosterone and oestrogen or their. analogues, suppresses the release of Lt! by a negative feedback mechanism. The ii'iechanism of the hot flushes is wtiiclezit'2 although it is known to ...

EFFECT OF HORMONAL CONTRACEPTIVES ON SERUM SEROTONIN IN FEMALES OF REPRODUCTIVE AGE GROUP.

Science.gov (United States)

Faryal, Uzma; Rashid, Shazia; Hajra, Bibi; Hassan, Mukhtiar; Saqib, Javeria; Ali, Muhammad Afaq

2016-01-01

Many types of hormonal contraceptives are in use nowadays for example oral pills, emergency contraceptive pills, vaginal rings, implantable rods and injectable contraceptives (combined and progestogens only). The purpose of this study was to determine and compare serum serotonin levels in married fertile females of reproductive age group using hormonal contraceptives with non-contraceptive users. A total of 300 women were selected in the study. This cross sectional study included three groups; Group-1 (control), group-2 (combined oral contraceptive users) and group-3 (injectable contraceptive users). History and examination of subjects were recorded on pro forma. Levels of serum serotonin were measured using standard ELISA kits. Results were analysed by one way ANOVA and a p-value 0.05% was taken as significant, using SPSS 16.0. The mean age of the patients in group-1 was 30.4 ± 6.1 years, group-2 was 28.9 ± 4.9 and in group-3 was 2.5 ± 6.8 years. For subjects in group-1, group-2 and group 3 the mean ± SD concentration of serum serotonin was 160.68 ± 53.27 ng/dl, 227.3 ± 63.98 ng/dl and 118.19 ± 31.32 ng/dl. A significant (p = 0.00) difference was seen among three groups, i.e., group-1, group-2 and group-3. After applying Post HOC Tukey's HSD, there was statistically no significant difference between group-1 and group-2 (p = 0.956). Difference was seen between group-2 and group-3 (p = 0.00), it was also significant between group-3 and group-1 (p = 0.00). It was concluded that hormonal contraceptives affect the levels of serum serotonin.

Hypogonadism in a male-to-female transsexual with super obesity.

Science.gov (United States)

Ayanian, S; Irwig, M S

2013-08-01

The global obesity epidemic is having a profound impact on the health of populations. From a reproductive standpoint, obesity has been associated with infertility and hypogonadism. We present the case of a 29-year-old male-to-female transsexual with super obesity (body mass index >50) who was found to have profound hypogonadism with total and free testosterone levels in the normal female reference range. There is virtually no literature on the hormonal sequelae of obesity in transsexual people. The patient was prescribed an aromatase inhibitor, letrozole 2.5 mg twice daily for 2 weeks, to determine the role of oestrogen in the hypogonadism. The aromatase inhibitor reduced the serum oestradiol concentration from 125 to 6.9 pm. There were dramatic corresponding rises in total testosterone (2.8 to 10.7 nm), luteinising hormone (4.1 to 20.5 mIU ml(-1) ) and follicle stimulating hormone (1.8 to 15.3 mIU ml(-1) ). This diagnostic test demonstrated the important role of oestrogen in mediating the hypogonadism. After the testing, the patient was started on oestrogen therapy after a careful discussion of the benefits versus risks of oestrogen therapy. We anticipate that similar cases of hypogonadism in male-to-female transsexuals will likely become more common in an era of increased obesity rates. © 2012 Blackwell Verlag GmbH.

Sexual dimorphism and oestrogen regulation of KCNE3 expression modulates the functional properties of KCNQ1 K channels.

LENUS (Irish Health Repository)

Alzamora, Rodrigo

2012-02-01

The KCNQ1 potassium channel associates with various KCNE ancillary subunits that drastically affect channel gating and pharmacology. Co-assembly with KCNE3 produces a current with nearly instantaneous activation, some time-dependent activation at very positive potentials, a linear current-voltage relationship and a 10-fold higher sensitivity to chromanol 293B. KCNQ1:KCNE3 channels are expressed in colonic crypts and mediate basolateral K(+) recycling required for Cl(-) secretion. We have previously reported the female-specific anti-secretory effects of oestrogen via KCNQ1:KCNE3 channel inhibition in colonic crypts. This study was designed to determine whether sex and oestrogen regulate the expression and function of KCNQ1 and KCNE3 in rat distal colon. Colonic crypts were isolated from Sprague-Dawley rats and used for whole-cell patch-clamp and to extract total RNA and protein. Sheets of epithelium were used for short-circuit current recordings. KCNE1 and KCNE3 mRNA and protein abundance were significantly higher in male than female crypts. No expression of KCNE2 was found and no difference was observed in KCNQ1 expression between male and female (at oestrus) colonic crypts. Male crypts showed a 2.2-fold higher level of association of KCNQ1 and KCNE3 compared to female cells. In female colonic crypts, KCNQ1 and KCNE3 protein expression fluctuated throughout the oestrous cycle and 17beta-oestradiol (E2 10 nM) produced a rapid (<15 min) dissociation of KCNQ1 and KCNE3 in female crypts only. Whole-cell K(+) currents showed a linear current-voltage relationship in male crypts, while K(+) currents in colonic crypts isolated from females displayed voltage-dependent outward rectification. Currents in isolated male crypts and epithelial sheets were 10-fold more sensitive to specific KCNQ1 inhibitors, such as chromanol 293B and HMR-1556, than in female. The effect of E2 on K(+) currents mediated by KCNQ1 with or without different beta-subunits was assayed from current

Hormonal priming, induction of ovulation and in-vitro fertilization of the endangered Wyoming toad (Bufo baxteri

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Seratt Jessica

2006-06-01

Full Text Available Abstract The endangered Wyoming toad (Bufo baxteri is the subject of an extensive captive breeding and reintroduction program. Wyoming toads in captivity rarely ovulate spontaneously and hormonal induction is used to ovulate females or to stimulate spermiation in males. With hormonal induction, ovulation is unreliable and egg numbers are low. The sequential administration of anovulatory doses of hormones (priming has increased egg numbers and quality in both anurans and fish. Consequently, we tested the efficacy of a combination of human Chorionic Gonadotrophin (hCG and Luteinizing Hormone Releasing Hormone analogue (LHRHa administered as one dose, or two or three sequential doses to Bufo baxteri on egg numbers, fertilization and early embryo development. Spawning toads deposited eggs into Simplified Amphibian Ringers (SAR solution to enable controlled in-vitro fertilization (IVF with sperm from hormonally induced male toads. Unprimed females receiving a single mixed normally ovulatory dose of 500 IU hCG plus 4 micrograms of LHRHa produced no eggs. Whereas females primed with this dose and an anovulatory dose (100 IU hCG and 0.8 micrograms of LHRHa of the same hormones, or primed only with an anovulatory dose, spawned after then receiving an ovulatory dose. Higher total egg numbers were produced with two primings than with one priming. Moreover, two primings produced significantly more eggs from each individual female than one priming. The cleavage rate of eggs was not found to differ between one or two primings. Nevertheless, embryo development with eggs from two primings gave a significantly greater percentage neurulation and swim-up than those from one priming. Of the male toads receiving a single dose of 300 IU hCG, 80% produced spermic urine with the greatest sperm concentration 7 hours post-administration (PA. However, peak sperm motility (95% was achieved at 5 hours PA and remained relatively constant until declining 20 hours PA. In

Sequential treatment with basic fibroblast growth factor and parathyroid hormone restores lost cancellous bone mass and strength in the proximal tibia of aged ovariectomized rats

DEFF Research Database (Denmark)

Wronski, T.J.; Ratkus, A.M.; Thomsen, Jesper Skovhus

2001-01-01

This study was designed to determine whether sequential treatment with basic fibroblast growth factor (bFGF) and parathyroid hormone (PTH) can restore lost cancellous bone mass and strength at a severely osteopenic skeletal site in aged ovariectomized (OVX) rats. Female Sprague-Dawley rats were...... intravenously (iv) daily with bFGF for 14 days at a dose of 200 microg/kg body weight. At the end of bFGF treatment, one group was killed whereas the other group was subjected to 8 weeks of treatment with synthetic human PTH 1-34 [hPTH(1-34)] consisting of subcutaneous (sc) injections 5 days/week at a dose...... of 80 microg/kg. Another group of OVX rats was treated iv with vehicle for 2 weeks followed by treatment with PTH alone for 8 weeks. Other groups of sham-operated control rats and OVX rats were treated iv and sc with vehicle alone. The right proximal tibia from each rat was processed undecalcified...

Terapia hormonal y calidad del hueso Hormone therapy and bone quality

Directory of Open Access Journals (Sweden)

2005-08-01

Full Text Available La osteoporosis se reconoce como uno de los problemas de salud de la población femenina posmenopáusica, y la terapia hormonal de reemplazo (THR como una de las medidas terapéuticas efectivas para evitar la fractura. Nos propusimos mostrar la experiencia acumulada en relación con el efecto de la terapia hormonal de reemplazo sobre la calidad del hueso. En un estudio retrospectivo realizado en 42 mujeres con edades entre 40 y 59 años que asistieron a la Clínica de Climaterio y Osteoporosis y a la consulta multidisciplinaria de climaterio del Hospital Ginecoobstétrico “Ramón González Coro” entre enero de 1997 y diciembre del año 2003, se determinó la calidad ósea mediante absorciometría dual de rayos X en región lumbar (L2-L4 o por ultrasonido del calcáneo (USCAL y recibieron tratamiento continuado con terapia estrogénica (E o con estrógenos progestagenos (EP durante no menos de un año (n = 30. Las mujeres que no pudieron recibir THR fueron agrupadas y evaluadas como grupo control (n =12. Durante el tiempo de observación promedio de 2 años, las mujeres que recibieron THR mejoraron su calidad ósea en el 16,8 %, mientras que las del grupo control empeoraron en el 8 % de los casos. Estos resultados iniciales, aunque son modestos, muestran la utilidad de la THR para mejorar la calidad del hueso y la necesidad de continuar estudios que permitan definir en nuestro medio la persistencia de la mejoría ósea, así como la magnitud de la osteoporosis posmenopáusica.Osteoporosis is recognized as one of the health problems of the female postmenopausic population and the replacement hormone therapy (RHT as one of the effective therapeutical measures to prevent fracture. We proposed ourselves to show the experience accumulated in relation to the effect of the replacement hormone therapy on the bone quality. In a retrospective study conducted among 42 women aged 30-59 that attended the Climacteric and Osteoporosis Clinic and the

Submaximal doses of ghrelin do not inhibit gonadotrophin levels but stimulate prolactin secretion in postmenopausal women.

Science.gov (United States)

Messini, Christina I; Malandri, Maria; Anifandis, George; Dafopoulos, Konstantinos; Georgoulias, Panagiotis; Sveronis, Georgios; Garas, Antonios; Daponte, Alexandros; Messinis, Ioannis E

2017-07-01

An inhibitory effect of ghrelin on gonadotrophin secretion has been reported in normally menstruating women possibly modulated by endogenous oestrogen. The aim of this study was to examine the effect of ghrelin on gonadotrophin and prolactin (PRL) secretion in oestrogen-deprived postmenopausal women. Prospective intervention study. Ten healthy postmenopausal volunteer women were studied during two 15-days periods of oestrogen treatment (A and B) a month apart. Four experiments (Exp) were performed in total, two on day 1 (Exp 1A and Exp 1B) and two on day 15 (Exp 15A and Exp 15B) of the two periods. The women received in Exp 1A and in Exp 15A two iv injections of ghrelin (0.15 μg/kg at time 0 minute and 0.30 μg/kg at time 90 minutes) and in Exp1B and in Exp 15B normal saline (2 mL), respectively. Blood samples were taken at -15, 0, 30, 60, 90, 120, 150 and 180 minutes. After oestrogen treatment, late follicular phase serum oestradiol levels were attained on day 15 of periods A and B. Ghrelin administration did not affect serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), whereas it increased significantly those of growth hormone (GH) and PRL. In Exp 15A, serum PRL increment in response to ghrelin (area under the curve, net increment) was significantly greater than in Exp 1A (Pghrelin administration affects neither FSH nor LH levels but stimulates PRL secretion, that is amplified by exogenous oestrogen administration. © 2017 John Wiley & Sons Ltd.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-08-15

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

The use of hormonal treatments to improve reproductive performance of anestrous beef cattle in tropical climates.

Science.gov (United States)

Baruselli, P S; Reis, E L; Marques, M O; Nasser, L F; Bó, G A

2004-07-01

Most of the world's bovine herd is found in tropical regions. Bos indicus predominates, due to their adaptation to the climate and management conditions. Anestrous is the main factor that negatively affects reproductive performance of animals bred in these regions of the globe. Several factors affect postpartum anestrous, including suckling and maternal-offspring bond, and pre- and postpartum nutritional status. The short duration of estrus and the tendency to show estrus during the night, greatly affect the efficiency of artificial insemination (AI) programs in B. indicus cattle managed in tropical areas. Several restricted suckling or weaning procedures (temporary or permanent), and hormonal treatments have been used to induce ovulation and cyclicity in postpartum cows. Most hormonal treatments are based on progesterone/progestogen (P4) releasing devices associated with estradiol benzoate (EB), or a combination of GnRH/PGF(2alpha)/GnRH (Ovsynch). Treatments with GnRH/PGF(2alpha)/GnRH has presented inconsistent results, probably due to the variable number of cows in anestrous. Treatments using P4 devices and EB have resulted in apparently more consistent results than Ovsynch programs in B. indicus cattle; however, pregnancy rates are low in herds presenting high anestrous rates and moderate to low body condition. The addition of an eCG treatment at the time of device removal, which increased plasma progesterone concentrations and pregnancy rates in anestrous postpartum suckled B. indicus cows, may be useful to improve reproductive performance of beef cattle in tropical climates.

Menstrual phase-related differences in the pulsatility index on the central retinal artery suggest an oestrogen vasodilatation effect that antagonizes with progesterone.

Science.gov (United States)

Viana, Luiz Carlos; Faria, Marcos; Pettersen, Heverton; Sampaio, Marcos; Geber, Selmo

2011-03-01

The actual effect of steroid hormones on cerebral microcirculation is still controversial. Therefore, the aim of our study was to investigate vascular flow variations in the central retinal artery that may exist during the ovulatory menstrual cycle. A total of 34 healthy women were included in this observational, longitudinal, and prospective study. All participants were submitted to dopplerfluxometric evaluation of the eyes in order to study the pulsatility index (PI) of the central retinal arteries, during four phases of the menstrual cycle: early follicular, mid follicular, periovulatory, and mid luteal phases. Subjects' ages ranged from 14 to 47 years old (mean: 29.7 ± 10.1) and PI did not differ among age groups. The PI of the central retinal artery was different among the four phases of the menstrual cycle. PI showed a significant decrease from early follicular phase (1.72) to mid follicular phase (1.57) (p = 0.037), and was similar during periovulatory phase (1.56) and significantly increased in mid luteal phase (1.70). After that it returned to the values observed in the early follicular phase. Our results suggest the existence of an oestrogen vasodilatation effect on the central retinal artery that is menstrual phase-related and antagonized by progesterone.

Steroid Hormone Vitamin D: Implications for Cardiovascular Disease.

Science.gov (United States)

Demer, Linda L; Hsu, Jeffrey J; Tintut, Yin

2018-05-25

Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations. © 2018 American Heart Association, Inc.

Hormonalna terapia okresu menopauzy – spojrzenie okiem hipertensjologa

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Anna Posadzy-Małaczyńska

2011-04-01

Full Text Available The results of experimental studies and clinical observations from the last two decades indicate the beneficialimpact of oestrogens on the cardiovascular system. However, later published large randomized clinical trials(WHI, HERS did not confirm the benefits of hormonal substitution in primary as well as secondary preventionof cardiovascular diseases in women. Thus it was concluded that the studies should be designed and interpretedin a different way. The reasons for these discrepancies are probably the different effects of oestrogens onthe healthy and atherosclerotically changed coronary arteries. We cannot expect that the oestrogens, even inlong-term treatment, would reverse the process in an already changed artery wall, which was progressing foryears. The time of the start of hormone replacement after the occurrence of menopause may also be significant.The WHI clinical trial, which was by the opponents considered as proof of the lack of benefits of this therapyin primary prevention, concerned a population of women who had been after the menopause for many years.

In vivo oestrogenic modulation of Egr1 and Pitx1 gene expression in female rat pituitary gland.

Science.gov (United States)

Gajewska, Alina; Herman, Andrzej P; Wolińska-Witort, Ewa; Kochman, Kazimierz; Zwierzchowski, Lech

2014-12-01

EGR1 and PITX1 are transcription factors required for gonadotroph cell Lhb promoter activation. To determine changes in Egr1 and Pitx1 mRNA levels in central and peripheral pituitary stimulations, an in vivo model based on i.c.v. pulsatile (1 pulse/0.5 h over 2 h) GnRH agonist (1.5 nM buserelin) or antagonist (2 nM antide) microinjections was used. The microinjections were given to ovariectomised and 17β-oestradiol (E2) (3×20 μg), ERA (ESR1) agonist propyl pyrazole triol (PPT) (3×0.5 mg), ERB (ESR2) agonist diarylpropionitrile (DPN) (3×0.5 mg) s.c. pre-treated rats 30 min after last pulse anterior pituitaries were excised. Relative mRNA expression was determined by quantitative RT-PCR (qRT-PCR). Results revealed a gene-specific response for GnRH and/or oestrogenic stimulations in vivo. Buserelin pulses enhanced Egr1 expression by 66% in ovariectomised rats, whereas the oestradiol-supplemented+i.c.v. NaCl-microinjected group showed a 50% increase in Egr1 mRNA expression. The oestrogenic signal was transmitted via ERA (ESR1) and ERB (ESR2) activation as administration of PPT and DPN resulted in 97 and 62%, respectively, elevation in Egr1 mRNA expression. A synergistic action of GnRH agonist and 17β-oestradiol (E2) stimulation of the Egr1 gene transcription in vivo were found. GnRHR activity did not affect Pitx1 mRNA expression; regardless of NaCl, buserelin or antide i.c.v. pulses, s.c. oestrogenic supplementation (with E2, PPT or DPN) consistently decreased (by -46, -48 and -41% respectively) the Pitx1 mRNA in the anterior pituitary gland. Orchestrated Egr1 and Pitx1 activities depending on specific central and peripheral regulatory inputs could be responsible for physiologically variable Lhb gene promoter activation in vivo. © 2014 Society for Endocrinology.

Evaluation of the association of vitamin D deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome.

Science.gov (United States)

Velija-Ašimi, Zelija

2014-02-01

To evaluate the association of vitamin D (VD) deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome (PCOS). Of the total of 140 women, thirty obese and thirty nonobese, aged 20-40 years, were included in the study. Inclusion criteria were the women with normal level of thyroid-stimulating hormone (TSH), prolactin (PRL), parathyroid hormone (PTH), and calcium, and those who had not received any medication or VD supplementation within the last 6 months. Serum 25- hydroxyvitamin D (25(OH)D), C-reactive protein (CRP), lipid profile, fasting serum glucose, basal insulin, homeostasis model analysis of insulin resistance (HOMA-IR) index, follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen, total testosterone, dehidroepiandrostendion-sulphat (DHEA-S), androstendione, and sex hormone binding globulin (SHBG) were determined at follicular phase. Body mass index (BMI), weight, waist, lipids, and CRP were significantly higher in obese than in non-obese PCOS women (p=0.000). Meanwhile, insulin and HOMA-IR were also higher in the obese PCOS (p less than 0.000), and so was the fasting glucose (p=0.004). Furthermore, obese PCOS showed significantly higher level of LH (p=0.012), but lower level of progesterone (p=0.001) and androstendione (p=0.006) than in non-obese PCOS. In total 68% of PCOS women had VD deficiency but without significant difference among groups according to BMI. There was no association of VD deficiency with gonadotropins and sex hormones except SHBG. Insulin resistance was a better independent risk factor for the presence of vitamin D deficiency than SHBG. The insulin resistance and vitamin D deficiency significantly predicted the obesity risk in PCOS women.

Radioimmunological oestrogen and progesterone measurement in the serum and ovaries of pseudogravid female rats after PMS and HCG treatment

International Nuclear Information System (INIS)

Hauck, P.

1978-01-01

Infantile female rats were made pseudogravid with PMS-HCG (according to Karg). Two bioassays were employed to investigate the effects of HCG on the ovaries; the HCG was injected subactaneously in the back of the animals in varying doses and at various intervals after the initial PMS administration. As specific parameters, oestrogen and progesterone levels in serum and ovary homogenate were determined radioimmunologically. The first animal experiment showed that the ovaries of pseudogravid animals had reached maximum sensitivity for corpus luteum production after HCG administration between 50 and 70 hours after PMS administration. In the second animal experiment with repeated HCG stimulus in the luteal phase, it was found that the corpus luteum of the rat ovary is apparently unable to synthesize oestrogens. In contrast, progesteron synthesis received maximum stimulation already with the lowest dose administered (3 IE HCG). The experiments clearly showed a dependence on HCG dose and the time which the test substance is allowed to take effect. (orig./AJ) 891 AJ/orig.- 892 KN [de

Menopause and postmenopausal hormone therapy and risk of hearing loss.

Science.gov (United States)

Curhan, Sharon G; Eliassen, A Heather; Eavey, Roland D; Wang, Molin; Lin, Brian M; Curhan, Gary C

2017-09-01

Menopause may be a risk factor for hearing loss, and postmenopausal hormone therapy (HT) has been proposed to slow hearing decline; however, there are no large prospective studies. We prospectively examined the independent relations between menopause and postmenopausal HT and risk of self-reported hearing loss. Prospective cohort study among 80,972 women in the Nurses' Health Study II, baseline age 27 to 44 years, followed from 1991 to 2013. Baseline and updated information was obtained from detailed validated biennial questionnaires. Cox proportional-hazards regression models were used to examine independent associations between menopausal status and postmenopausal HT and risk of hearing loss. After 1,410,928 person-years of follow-up, 18,558 cases of hearing loss were reported. There was no significant overall association between menopausal status, natural or surgical, and risk of hearing loss. Older age at natural menopause was associated with higher risk. The multivariable-adjusted relative risk of hearing loss among women who underwent natural menopause at age 50+ years compared with those aged less than 50 years was 1.10 (95% confidence interval [CI] 1.03, 1.17). Among postmenopausal women, oral HT (estrogen therapy or estrogen plus progestogen therapy) was associated with higher risk of hearing loss, and longer duration of use was associated with higher risk (P trend menopause and longer duration of postmenopausal HT are associated with higher risk of hearing loss.

Circulating sex hormones and gene expression of subcutaneous adipose tissue oestrogen and alpha-adrenergic receptors in HIV-lipodystrophy: implications for fat distribution

DEFF Research Database (Denmark)

Andersen, Ove; Pedersen, Steen B; Svenstrup, Birgit

2007-01-01

in lipodystrophic patients compared to nonlipodystrophic patients, whereas luteinizing hormone, follicle-stimulating hormone and prolactin were similar and normal in both study groups. Ratio of subcutaneous to total abdominal fat mass, limb fat, and insulin sensitivity, which were all decreased in lipodystrophic...... patients, correlated positively with both plasma oestradiol and testosterone (n = 31). Glycerol concentration during clamp (a marker of lipolysis) correlated inversely with expression of alpha2A-adrenergic-receptor, ratio of subcutaneous to total abdominal fat mass, and limb fat, respectively. Expression......OBJECTIVE: Circulating oestradiol and testosterone, which have been shown to increase in human immunodeficiency virus (HIV)-infected patients following highly active antiretroviral therapy (HAART), may influence fat distribution and insulin sensitivity. Oestradiol increases subcutaneous adipose...

Environmental chemical exposures and breast cancer

Directory of Open Access Journals (Sweden)

E. Stanley

2016-02-01

Full Text Available As a hormone-sensitive condition with no single identifiable cause, breast cancer is a major health problem. It is characterized by a wide range of contributing factors and exposures occurring in different combinations and strengths across a lifetime that may be amplified during periods of enhanced developmental susceptibility and impacted by reproductive patterns and behaviours. The vast majority of cases are oestrogen-receptor positive and occur in women with no family history of the disease suggesting that modifiable risk factors are involved. A substantial body of evidence now links oestrogen-positive breast cancer with environmental exposures. Synthetic chemicals capable of oestrogen mimicry are characteristic of industrial development and have been individually and extensively assessed as risk factors for oestrogen-sensitive cancers. Existing breast cancer risk assessment tools do not take such factors into account. In the absence of consensus on causation and in order to better understand the problem of escalating incidence globally, an expanded, integrated approach broadening the inquiry into individual susceptibility breast cancer is proposed. Applying systems thinking to existing data on oestrogen-modulating environmental exposures and other oestrogenic factors characteristic of Westernisation and their interactions in the exposure, encompassing social, behavioural, environmental, hormonal and genetic factors, can assist in understanding cancer risks and the pursuit of prevention strategies. A new conceptual framework based on a broader understanding of the “system” that underlies the development of breast cancer over a period of many years, incorporating the factors known to contribute to breast cancer risk, could provide a new platform from which government and regulators can promulgate enhanced and more effective prevention strategies.

The Effect of Tamoxifen Administration and γ-Irradiation on Thyroid Hormones Levels in Rats Bearing Mammary Tumours

International Nuclear Information System (INIS)

Abdelgawad, M.R.

2013-01-01

Breast Cancer is the most common malignancy among women in most developed and developing regions of the world, in female, tamoxifen acting as an oestrogen antagonist on the breast. Thyroid hormones can stimulate the proliferation in vitro of certain tumor cell lines. The aim of the present study is to evaluate the effect of tamoxifen and/ or irradiation treatment on thyroid hormones in rats' mammary tumours. Forty-two female Sprague-Dawely rats randomly divided into seven groups' proliferation (6 rats each). Control group, normal rats supplemented with tamoxifen for 3 weeks, normal rats exposed to a single dose 3Gy γ-rays, rats treated with Dimethylbenz (a) anthracene (DMBA) dissolved in corn oil (30ppm) sc and followed for 6 months until breast cancer occurrence, breast cancer bearing rats supplemented with tamoxifen for 3 weeks twice a day, breast cancer bearing rats exposed to a single dose 3Gy γ-rays, breast cancer bearing rats exposed to a single dose 3Gy γ-rays and supplemented with tamoxifen for 3 weeks twice a day. At the end of the experiment, mammary tumours and control rats were sacrificed after 3 weeks from different treatments and serum thyroid hormones and estradiol (E2) levels were assayed using commercial kits. Results show T4 and E2 levels not triiodothyronine (T3) were altered in different experimental groups. It could be concluded that γ-irradiation promote the expression of neoplastic potential by affecting both E2 and thyroid hormones and tamoxifen may alter the thyroid hormones. Tamoxifen administration and γ-irradiation may have worth effects on thyroxin (T4) and E2 levels. It is recommended to further studies towards the bystander effect of γ-rays exposure and tamoxifen treatment on the tissue culture and molecular biology scale.

Multiresidue analysis of oestrogenic compounds in cow, goat, sheep and human milk using core-shell polydopamine coated magnetic nanoparticles as extraction sorbent in micro-dispersive solid-phase extraction followed by ultra-high-performance liquid chromatography tandem mass spectrometry.

Science.gov (United States)

Socas-Rodríguez, Bárbara; Hernández-Borges, Javier; Herrera-Herrera, Antonio V; Rodríguez-Delgado, Miguel Ángel

2018-03-01

In this work, the suitability of Fe 3 O 4 nanoparticles coated with polydopamine was evaluated as sorbent for the extraction of a group of 21 compounds with oestrogenic activity including seven phytoestrogens, six mycotoxins as well as four synthetic and four natural oestrogens from different types of milk, including sheep milk, in which the evaluation of oestrogenic compounds have never been developed before. Extraction was carried out using magnetic micro-dispersive solid-phase extraction after a previous deproteinisation step. Separation, determination and quantification of the target analytes were achieved by ultra-high-performance liquid chromatography coupled to triple quadrupole-tandem mass spectrometry. The methodology was validated for five milk samples using 17β-estradiol-2,4,16,16,17-d 5 as internal standard for natural and synthetic oestrogens, β-zearalanol-10,10,11,12,12-d 5 for mycotoxins and prunetin for phytoestrogens. Recovery values ranged from 70 to 120% for the five types of matrices with relative standard deviation values lower than 18%. Limits of quantification of the method were in the range 0.55-11.8 μg L -1 for all samples. Graphical abstract General scheme of the multiresidue analysis of oestrogenic compounds in milk using core-shell polydopamine coated magnetic nanoparticles as extraction sorbent in μ-dSPE.

Time-dependent integrity during storage of natural surface water samples for the trace analysis of pharmaceutical products, feminizing hormones and pesticides

Directory of Open Access Journals (Sweden)

Prévost Michèle

2010-04-01

Full Text Available Abstract Monitoring and analysis of trace contaminants such as pharmaceuticals and pesticides require the preservation of the samples before they can be quantified using the appropriate analytical methods. Our objective is to determine the sample shelf life to insure proper quantification of ultratrace contaminants. To this end, we tested the stability of a variety of pharmaceutical products including caffeine, natural steroids, and selected pesticides under refrigerated storage conditions. The analysis was performed using multi-residue methods using an on-line solid-phase extraction combined with liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS in the selected reaction monitoring mode. After 21 days of storage, no significant difference in the recoveries was observed compared to day 0 for pharmaceutical products, while for pesticides, significant losses occurred for DIA and simazine after 10 days (14% and 17% reduction respectively and a statistically significant decrease in the recovery was noted for cyanazine (78% disappearance. However, the estrogen and progestogen steroids were unstable during storage. The disappearance rates obtained after 21 days of storage vary from 63 to 72% for the feminizing hormones. Overall, pharmaceuticals and pesticides seem to be stable for refrigerated storage for up to about 10 days (except cyanazine and steroidal hormones can be quite sensitive to degradation and should not be stored for more than a few days.

Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

DEFF Research Database (Denmark)

Cassidy, A.; Albertazzi, P.; Nielsen, I. L.

2006-01-01

or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were...... to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus...... on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health....

Episodic nature of the delta 4-ene and delta 5-ene steroidogenic pathways and their relationship to the adreno-gonadal axis in stallions.

Science.gov (United States)

Ganjam, V K

1979-01-01

Changes in the daily secretory patterns of testosterone and other 17 beta-hydroxyandrogen, total oestrogens and total corticoids were investigated in 7 stallions. Pulsatile fluctuations in plasma hormone levels were found in the serial blood samples collected hourly for 24 h in all animals. The plasma profiles indicated that corticoids, oestrogens and androgens were secreted episodically at all times in stallions. A significant correlation was observed between the precursor and products of delta 4-ene and delta 5-ene pathways and in inverse correlation (r = -0.68; P less than 0.01) was observed between total androgens and total corticoids. The significance of these episodic fluctuations of the major steroid hormones are discussed.

Inverse antagonist activities of parabens on human oestrogen-related receptor γ (ERRγ): In vitro and in silico studies

International Nuclear Information System (INIS)

Zhang, Zhaobin; Sun, Libei; Hu, Ying; Jiao, Jian; Hu, Jianying

2013-01-01

Parabens are p-hydroxybenzoic acid esters that have been used extensively as preservatives in foods, cosmetics, drugs and toiletries. These intact esters are commonly detected in human breast cancer tissues and other human samples, thus arousing concern about the involvement of parabens in human breast cancer. In this study, an in vitro nuclear receptor coactivator recruiting assay was developed and used to evaluate the binding activities of parabens, salicylates and benzoates via antagonist competitive binding on the human oestrogen-related receptor γ (ERRγ), which is known as both a diagnostic biomarker and a treatment target of breast cancer. The results showed that all of the test parabens (methyl-, ethyl-, propyl-, butyl- and benzylparaben) possessed clear inverse antagonist activities on ERRγ, with a lowest observed effect level (LOEL) of 10 −7 M and the 50% relative effective concentrations (REC50) varying from 3.09 × 10 −7 to 5.88 × 10 −7 M, whereas the salicylates possessed much lower activities and the benzoates showed no obvious activity. In silico molecular docking analyses showed that parabens fitted well into the active site of ERRγ, with hydrogen bonds forming between the p-hydroxyl group of parabens and the Glu275/Arg316 of ERRγ. As the paraben levels reported in breast cancer tissues are commonly higher than the LOELs observed in this study, parabens may play some role via ERRγ in the carcinogenesis of human breast cancer. In addition, parabens may have significant effects on breast cancer patients who are taking tamoxifen, as ERRγ is regarded as a treatment target for tamoxifen. - Highlights: • An oestrogen-related receptor γ coactivator recruiting assay was developed. • Strong binding activities of parabens with oestrogen-related receptor γ were found. • The paraben levels reported in breast cancer tissues were higher than their LOELs. • Parabens may play some role via ERRγ in the carcinogenesis of human breast cancer. �

Hormone-receptor expression and ovarian cancer survival

DEFF Research Database (Denmark)

Sieh, Weiva; Köbel, Martin; Longacre, Teri A

2013-01-01

Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated ...

Glucoregulatory function of thyroid hormones: role of pancreatic hormones

International Nuclear Information System (INIS)

Mueller, M.J.B.; Burger, A.G.; Ferrannini, E.; Jequier, E.; Acheson, K.J.

1989-01-01

Glucose metabolism was investigated in humans before and 14 days after 300 micrograms L-thyroxine (T4)/day using a sequential clamp protocol during short-term somatostatin infusion (500 micrograms/h, 0-6 h) at euglycemia (0-2.5 h), at 165 mg/dl (2.5-6 h), and during insulin infusion (1.0 mU.kg-1.min-1, 4.5-6 h). T4 treatment increased plasma T4 (+96%) and 3,5,3'-triiodothyronine (T3, +50%), energy expenditure (+8%), glucose turnover (+32%), and glucose oxidation (Glucox +87%) but decreased thyroid-stimulating hormone (-96%) and nonoxidative glucose metabolism (Glucnonox, -30%) at unchanged lipid oxidation (Lipox). During somatostatin and euglycemia glucose production (Ra, -67%) and disposal (Rd, -28%) both decreased in euthyroid subjects but remained at -22% and -5%, respectively, after T4 treatment. Glucox (control, -20%; +T4, -25%) fell and Lipox increased (control, +42%; +T4, +45%) in both groups, whereas Glucnonox decreased before (-36%) but increased after T4 (+57%). During somatostatin infusion and hyperglycemia Rd (control, +144%; +T4, +84%) and Glucnonox (control, +326%; +T4, +233%) increased, whereas Glucox and Lipox remained unchanged. Insulin further increased Rd (+76%), Glucox (+155%), and Glucnonox (+50%) but decreased Ra (-43%) and Lipox (-43%). All these effects were enhanced by T4 (Rd, +38%; Glucox, +45%; Glucnonox, +35%; Ra, +40%; Lipox, +11%). Our data provide evidence that, in humans, T3 stimulates Ra and Rd, which is in part independent of pancreatic hormones

Use and discontinuation of hormone replacement therapy in women with myocardial infarction: a nationwide study

DEFF Research Database (Denmark)

Bretler, Ditte-Marie; Hansen, P. R.; Abildstrom, S. Z.

2011-01-01

of HRT were vaginal oestrogen and oral oestrogen alone (46.6% and 28.7%, respectively). The percentage of women who continued HRT during the first year after discharge was 85.0% in the period 2000-2002 and had decreased to 79.6% in the period 2003-2005. Vaginal oestrogen use was associated with overall...... pharmacies. Characteristics associated with HRT use at time of MI and subsequent HRT discontinuation were analysed by multivariable logistic regression. RESULTS In the study period, 34 778 women were discharged after MI. Of these, 3979 (11.4%) received HRT at the time of MI and their most used categories...... The majority of women experiencing an MI during ongoing HRT continued HRT after discharge and this pattern of HRT use did not change markedly after 2002....

Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with pubertal gynaecomastia

DEFF Research Database (Denmark)

Mieritz, Mikkel G; Sorensen, Kaspar; Aksglaede, Lise

2014-01-01

OBJECTIVE: Pubertal gynaecomastia is a very common condition. Although the underlying aetiology is poorly understood, it is generally accepted that excess of oestrogens and deficit of androgens are involved in the pathogenesis. Furthermore, adiposity as well as the GH/IGF-I axis may play a role....... In this study, we elucidate the association of adiposity and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), testosterone, oestrogen, IGF-I and IGFBP-3 with the presence of pubertal gynaecomastia in a large cohort of healthy boys. PATIENTS: A total...... of 501 healthy Danish school boys (aged 6·1-19·8 year) from the COPENHAGEN Puberty Study. MEASUREMENTS: Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated, and the presence of gynaecomastia was assessed. Body fat percentage was calculated by means of four skin folds and impedance...

HORMONE LEVELS IN THE PERIPHERAL BLOOD OF THE ...

African Journals Online (AJOL)

, 1972. Plasma oestrogen and progesterone levels after mating, and during late pregnancy and post partum in cows . Endocrinologt, 90, 1336. MARION, G.B. & GIER, H.T., 1968. Factors affecting bovine ovarian activity after parturition. J. Anim.

Intake of whole grain products and risk of breast cancer by hormone receptor status and histology among postmenopausal women

DEFF Research Database (Denmark)

Egeberg, Rikke; Olsen, Anja; Loft, Steffen

2009-01-01

No clear relationship between whole grain products and risk of breast cancer has been established. In a large prospective cohort study, we investigated the association between intake of whole grain products and risk of breast cancer by tumour receptor status [oestrogen receptor (ER......) and progesterone receptor (PR)] and tumour histology (ductal/lobular). It was further investigated whether the association differed by use of hormone replacement therapy (HRT). The study included 25,278 postmenopausal women participating in the Danish Diet, Cancer and Health cohort study (1993-1997). During a mean...... follow-up time of 9.6 years, 978 breast cancer cases were diagnosed. Associations between intake of whole grain products and the breast cancer rate were analysed using Cox's regression model. A higher intake of whole grain products was not associated with a lower risk of breast cancer. Per an increment...

Tritium-labelled steroids, their preparation and application for the determination and location of steroid tissular hormone receptors

International Nuclear Information System (INIS)

Jouquey, Alain; Raynaud, J.P.

1977-01-01

A product is prepared by the action of tritiated methanol on 11β-hydroxy-estra-4,9-dien-3,17-dione, the action of an aromatisation agent on the (11β)-11-methoxy- 3 H 3 -estra-4,9-dien-3,17-dione formed and the action of an ethynylation agent on the resulting (11β)-3-hydroxy-11-methoxy- 3 H 3 -estra-1,3,5(10)-trien-17-one giving (11β, 17α)-11-methoxy- 3 H 3 -19-norpregna-1,3,5(10)-trien-20-yne-3,17 diol, the free hydroxyl function or functions of this product may be etherified or esterified as the case may be. The tritiated methanol acts in the presence of perchloric acid. The aromatisation agent is palladium hydroxide and the operation is carried out in methanol. The ethynylation agent is acetylene and the reaction takes place in the presence of sodium t-amylate in toluene. This product allows the study and determination of the estrogen specific receptor present in the tissue cells of target organs for the action of estrogens: uterus, vagina, hypophysis, hypothalamus and tumours, of the breast and prostate for example, in both animals and man. Not being fixed by the plasma proteins binding such hormones as testosterone and estradiol in women the product is an ideal indicator of the tissular estrogen receptor with which it forms a complex of strong affinity and great stability, especially since it interacts with the tissular receptors of no other steroid hormone groups (glucocorticoids, androgen or progestogen mineralocorticosteroids) [fr

Cytotoxic effects of the synthetic oestrogens and androgens on Balb/c 3T3 and HepG2 cells

Directory of Open Access Journals (Sweden)

Minta Maria

2014-12-01

Full Text Available The aim of the study was to test and compare the cytotoxic potential of two synthetic oestrogens: diethylstilboestrol (DES and ethinyloestradiol (EE2 and two androgens: testosterone propionate (TP and trenbolone (TREN on two cell lines. The fibroblast cell line Balb/c 3T3 and the hepatoma cell line HepG2 were selected. To get more insight into the mode of toxic action, four methods were used, which evaluated different biochemical endpoints: mitochondrial activity (3-(4,5-dimethylthiazol-2-yl- 2,5-diphenyltetrazolium bromide reduction assay, lysosomal activity (neutral red uptake assay, total protein content, and lactate dehydrogenase release. Cytotoxicity was assessed after 24, 48, and 72 h exposure to eight concentrations ranging from 0.78 to 100 μg/mL. Concentration- and time- dependent effects were observed. Depending on the line and assay used, half maximal effective concentration after 72 h (EC50-72h values ranged as follows: DES 1-13.7 μg/mL (Balb/c 3T3 and 3.7-5.2 μg/mL (HepG2; EE2 2.1-14.3 μg/mL (Balb/c 3T3 and 1.8-7.8 μg/mL (HepG2; TP-14.9-17.5 μg/mL (Balb/c 3T3, and 63.9- 100 μg/mL (HepG2; and TREN 11.3-31.4 μg/mL (Balb/c 3T3 and 12.5-59.4 μg/mL (HepG2. The results revealed that oestrogens were more toxic than androgens and the most affected endpoint was mitochondrial activity. In contrast to oestrogens, for which EC50-72h values were similar in both lines and by all assays used, Balb/c 3T3 cells were more sensitive than HepG2 cells to TP.

Menopausal hormone therapy and new-onset diabetes in the French Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) cohort.

Science.gov (United States)

de Lauzon-Guillain, B; Fournier, A; Fabre, A; Simon, N; Mesrine, S; Boutron-Ruault, M-C; Balkau, B; Clavel-Chapelon, F

2009-10-01

Two US randomised trials found a lower incidence of type 2 diabetes in women treated by menopausal hormone therapy (MHT) with oral conjugated equine oestrogen combined with medroxyprogesterone acetate. The purpose of this study was to evaluate the influence of various MHTs, according to their formulation and route of administration, on new-onset diabetes in a cohort of postmenopausal French women. The association between MHT use and new-onset diabetes was investigated by Cox regression analysis in 63,624 postmenopausal women in the prospective French cohort of the Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N). Cases of diabetes were identified through self-reporting or drug-reimbursement record linkage, and further validated. 1,220 new-onset diabetes cases were validated. We observed a lower risk of new-onset diabetes among women who had ever used MHT (HR 0.82 [95% CI 0.72-0.93]), compared with those who had never used MHT. Adjustment for BMI during follow-up (rather than according to baseline BMI) did not substantially modify this association. An oral route of oestrogen administration was associated with a greater decrease in diabetes risk than a cutaneous route (HR 0.68 [95% CI 0.55-0.85] vs 0.87 [95% CI 0.75-1.00], p for homogeneity = 0.028). We were not able to show significant differences between the progestagens used in combined MHT. Use of MHT appeared to be associated with a lower risk of new-onset diabetes. This relationship was not mediated by changes in BMI. Further studies are needed to confirm the stronger effect of oral administration of oestrogen compared with cutaneous administration.

Sequential Power-Dependence Theory

NARCIS (Netherlands)

Buskens, Vincent; Rijt, Arnout van de

2008-01-01

Existing methods for predicting resource divisions in laboratory exchange networks do not take into account the sequential nature of the experimental setting. We extend network exchange theory by considering sequential exchange. We prove that Sequential Power-Dependence Theory—unlike

Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women

DEFF Research Database (Denmark)

Petersen, K R; Sidelmann, Johannes Jakobsen; Skouby, S O

1993-01-01

OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles of treat......OBJECTIVE: The purpose of this study was to examine key variables in the regulation of coagulation and fibrinolysis during intake of low-dose oral contraceptives containing newly developed progestogens. STUDY DESIGN: Thirty-four healthy young women were allocated to 12 consecutive cycles...... and concentration of plasminogen activator inhibitor. Thrombin-antithrombin III complexes and fibrin degradation products were unchanged, signifying no effect of hormonal intake on the degree of activation of the coagulation system or the efficacy of fibrinolysis. CONCLUSION: The overall dynamic balance between...

Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

Science.gov (United States)

Shek, L L; Godolphin, W; Spinelli, J J

1987-12-01

The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation.

Radiometrical, hormonal and biological correlates of skeletal growth in the female rat from birth to senescence.

Science.gov (United States)

del Pozo, Emilio; Janner, Marco; Mackenzie, Andrew R; Arampatzis, Spyridon; Dixon, Arnold K; Perrelet, Romain; Ruch, Walter; Lippuner, Kurt; Zapf, Juergen; Lamberts, Steven W; Mullis, Primus E

2014-01-01

We investigated the skeletal growth profile of female rats from birth to senescence (100weeks) on the basis of sequential radiometrical, hormonal and biochemical parameters. Weaning rats entered the study which was divided into two sections: a) sequential measurements of vertebral and tibial growths and bone mineral density (BMD), estimation of mineral content of the entire skeleton (BMC) and chemical analysis of vertebral Ca; and b) determination of basal and pulsatile growth hormone (rGH), insulin-like growth hormone (IGF-I), estradiol (E2), parathyroid hormone (PTH), osteocalcin (OC) and urinary d-pyridinoline (dp) throughout the experimental period. Vertebral and tibial growths ceased at week 25 whereas BMD and BMC as well as total vertebral Ca exhibited a peak bone mass at week 40. rGH pulsatile profiles were significantly higher in younger animals coinciding with the period of active growth and IGF-I peaked at 7weeks, slowly declining thereafter and stabilizing after week 60. OC and dp closely paralleled IGF-I coinciding with the period of enhanced skeletal growth, remaining thereafter in the low range indicative of reduced bone turnover. E2 increased during reproductive life but the lower values subsequently recorded were still in the physiological range, strongly suggesting a protective role of this steroid on bone remodeling. PTH followed a similar profile to E2, but the significance of this after completion of growth remains unclear. Mechanisms governing skeletal growth in the female rat appear similar to those in humans. Bone progression and attainment of peak bone mass are under simultaneous control of rGH, IGF-I and calciotropic hormones and are modulated by E2. This steroid seems to protect the skeleton from resorption before senescence whereas the role of PTH in this context remains uncertain. Copyright © 2014. Published by Elsevier Ltd.

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

Science.gov (United States)

Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

2015-01-01

Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib

Hormone action. Part I. Peptide hormones

International Nuclear Information System (INIS)

Birnbaumer, L.; O'Malley, B.W.

1985-01-01

The major sections of this book on the hormonal action of peptide hormones cover receptor assays, identification of receptor proteins, methods for identification of internalized hormones and hormone receptors, preparation of hormonally responsive cells and cell hybrids, purification of membrane receptors and related techniques, assays of hormonal effects and related functions, and antibodies in hormone action

Sex steroids and neurogenesis.

Science.gov (United States)

Heberden, Christine

2017-10-01

The brain has long been known as a dimorphic organ and as a target of sex steroids. It is also a site for their synthesis. Sex steroids in numerous ways can modify cerebral physiology, and along with many processes adult neurogenesis is also modulated by sex steroids. This review will focus on the effects of the main steroids, estrogens, androgens and progestogens, and unveil some aspects of their partly disclosed mechanisms of actions. Gonadal steroids act on different steps of neurogenesis: cell proliferation seems to be increased by estrogens only, while androgens and progestogens favor neuronal renewal by increasing cell survival; differentiation is a common target. Aging is characterized by a cognitive deficiency, paralleled by a decrease in the rate of neuronal renewal and in the levels of circulating gonadal hormones. Therefore, the effects of gonadal hormones on the aging brain are important to consider. The review will also be expanded to related molecules which are agonists to the nuclear receptors. Sex steroids can modify adult neuronal renewal and the extensive knowledge of their actions on neurogenesis is essential, as it can be a leading pathway to therapeutic perspectives. Copyright © 2017 Elsevier Inc. All rights reserved.

Vaginal mucus from ewes treated with progestogen sponges affects quality of ram spermatozoa.

Science.gov (United States)

Manes, Jorgelina; Ríos, Glenda; Fiorentino, María Andrea; Ungerfeld, Rodolfo

2016-03-15

The use of intravaginal sponges (IS) to synchronize estrous onset in ewes provokes vaginitis, an increase in the vaginal bacterial load, and growth of bacterial species that are not present during spontaneous estrous behavior. The objective of the study was to compare the functional sperm parameters after incubating it with mucus collected from the vagina of ewes during spontaneous estrus or estrous synchronized with IS. Pooled spermatozoa were co-incubated with: (1) vaginal mucus collected from ewes in spontaneous estrus; (2) vaginal mucus collected from ewes in estrus pretreated with progestogen-impregnated IS; (3) synthetic mucus; and (4) medium without mucus as a control group. Sperm samples were evaluated after incubating it for 30 and 90 minutes. The number of colony-forming units (CFUs/mL), pH, and osmolality were greater in the mucus collected from ewes treated with IS than from those untreated (P = 0.046; P ewes treated with IS than in the other three treatments both, 30 and 90 minutes after incubation (P = 0.0009 and P ewes treated with IS had a lower percentage of sperm with intact plasma membrane than all the other treatments (P ewes treated with IS than in the other three treatments (P ewes during their spontaneous estrus (P = 0.0005). The lowest percentages of sperm with acrosome damage were observed in sperm incubated with mucus collected from sheep in spontaneous estrus for 30 and 90 minutes (P ewes treated with IS than in the other three groups (P = 0.0005). The functionality and the viability of ram sperm is negatively affected by the cervical mucus of ewes pretreated with progestagen-impregnated IS used in estrous synchronization treatments. This may partially explain the decrease in conception rate obtained with treatments with IS. Copyright © 2016 Elsevier Inc. All rights reserved.

Radiations - induced disorders in ovarian function

International Nuclear Information System (INIS)

Saleh, S.; Roushdy, H.M.; Abdel-Aziz, M.T.; Eldenshary, A.E.; Abdel-Khalek, A.; Ramadan, L.A.

1988-01-01

The effect of whole body gamma radiation exposure (7.5 and 6.5 Gy) on the secretory activity and the structure of the ovaries was investigated. The parameters studied were serum levels of oestrogen, progesterone, Lh and FSH, beside histopathological studies of the ovaries of femaler rats. These were measured on the next day after radiation exposure and then after one two oestrus cycles. Whole body gamma - irradiation of females rats at two levels of exposure progressively decreased the level of oestrogen and progesterone while increased the level of LH and FSH as compared with the control. moreover, the changes in the ovaries were demonstrated in the histopathological investigation. Keywords: Radiation exposure - ovarian function - hormone radioimmunoassay - oestrogen - progesterone - LH - FSH

Progesterone in Breast Cancer Angiogenesis

OpenAIRE

Botelho, Monica C.; Soares, Raquel; Alves, Helena

2015-01-01

The involvement of steroid hormones in breast carcinogenesis is well established. Recent evidence suggests that angiogenesis can be regulated by hormones. Both oestrogen and progesterone have been implicated in the angiogenic process of hormone-dependent cancers, such as breast cancer. Vascular Endothelial Growth Factor (VEGF) is a growth factor involved in angiogenesis in breast cancer that is up-regulated by estrogens. In our study we evaluated the role of progesterone in the expression of ...

The menstrual cycle and the skin.

Science.gov (United States)

Raghunath, R S; Venables, Z C; Millington, G W M

2015-03-01

Perimenstrual exacerbations of dermatoses are commonly recognized, yet our knowledge of the underlying pathophysiological mechanisms remains imperfect. Research into the effects of oestrogen on the skin has provided evidence to suggest that oestrogen is associated with increases in skin thickness and dermal water content, improved barrier function, and enhanced wound healing. Research into the effects of progesterone suggests that the presence of various dermatoses correlates with peak levels of progesterone. Dermatoses that are exacerbated perimenstrually include acne, psoriasis, atopic eczema and irritant dermatitis, and possibly also erythema multiforme. Exacerbations occur at the peak levels of progesterone in the menstrual cycle. Underlying mechanisms include reduced immune and barrier functions as a result of cyclical fluctuations in oestrogen and/or progesterone. Autoimmune progesterone and oestrogen dermatitis are the best-characterized examples of perimenstrual cutaneous reactions to hormones produced during the menstrual cycle. In this review, we describe the current understanding of the menstrual cycle, and its effect on the skin and cutaneous disorders. © 2015 British Association of Dermatologists.

GENETICS OF BREAST CANCER AND HORMONE REPLACEMENT THERAPY

Directory of Open Access Journals (Sweden)

Ksenija Geršak

2008-12-01

The findings of pharmacogenomic studies about polymorphisms in oestrogen synthesizingand metabolizing genes could have an important clinical value: before prescribing HRT,we would offer women genetic counselling and define their genotype. Thus, we would beable to organize an individualized postmenopausal period for each woman accordingly

Systematic review of hormone replacement therapy in the infertile man

Directory of Open Access Journals (Sweden)

Amr El Meliegy

2018-03-01

Full Text Available Objectives: To highlight alternative treatment options other than exogenous testosterone administration for hypogonadal men with concomitant infertility or who wish to preserve their fertility potential, as testosterone replacement therapy (TRT inhibits spermatogenesis, representing a problem for hypogonadal men of reproductive age. Materials and methods: We performed a comprehensive literature review for the years 1978–2017 via PubMed. Also abstracts from major urological/surgical conferences were reviewed. Review was consistent with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA criteria. We used Medical Subject Heading terms for the search including ‘testosterone replacement therapy’ or ‘TRT’ and ‘male infertility’. Results: In all, 91 manuscripts were screened and the final number used for the review was 56. All studies included were performed in adults, were written in English and had an abstract available. Conclusions: Exogenous testosterone inhibits spermatogenesis. Hypogonadal men wanting to preserve their fertility and at the same time benefiting from TRT effects can be prescribed selective oestrogen receptor modulators or testosterone plus low-dose human chorionic gonadotrophin (hCG. Patients treated for infertility with hypogonadotrophic hypogonadism can be prescribed hCG alone at first followed by or in combination from the start with follicle-stimulating hormone preparations. Keywords: Gonadotrophins, Hypogonadism, Infertility, Systematic review, Testosterone therapy

The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

International Nuclear Information System (INIS)

Wang, Chao; Luo, Fei; Zhou, Ying; Du, Xiaoling; Shi, Jiandang; Zhao, Xiaoling; Xu, Yong; Zhu, Yan; Hong, Wei; Zhang, Ju

2016-01-01

Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.

The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

Energy Technology Data Exchange (ETDEWEB)

Wang, Chao [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China); Luo, Fei [Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211 (China); Zhou, Ying; Du, Xiaoling; Shi, Jiandang; Zhao, Xiaoling [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China); Xu, Yong [Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211 (China); Zhu, Yan [Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193 (China); Hong, Wei, E-mail: hongwei@tijmu.edu.cn [Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070 (China); Zhang, Ju, E-mail: zhangju@nankai.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China)

2016-07-15

Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.

Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial.

Science.gov (United States)

Johnston, Stephen Rd; Kilburn, Lucy S; Ellis, Paul; Dodwell, David; Cameron, David; Hayward, Larry; Im, Young-Hyuck; Braybrooke, Jeremy P; Brunt, A Murray; Cheung, Kwok-Leung; Jyothirmayi, Rema; Robinson, Anne; Wardley, Andrew M; Wheatley, Duncan; Howell, Anthony; Coombes, Gill; Sergenson, Nicole; Sin, Hui-Jung; Folkerd, Elizabeth; Dowsett, Mitch; Bliss, Judith M

2013-09-01

The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation. In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 mg intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratification was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea). Between March 26, 2004, and Aug 6, 2010, 723 patients underwent randomisation: 243 were assigned to receive fulvestrant plus anastrozole, 231 to fulvestrant plus placebo, and 249 to exemestane. Median PFS was 4·4 months (95% CI 3·4-5·4) in patients assigned to

Risks and benefits of hormone therapy: has medical dogma now been overturned?

Science.gov (United States)

Shapiro, S; de Villiers, T J; Pines, A; Sturdee, D W; Baber, R J; Panay, N; Stevenson, J C; Mueck, A O; Burger, H G

2014-06-01

In an integrated overview of the benefits and risks of menopausal hormone therapy (HT), the Women's Health Initiative (WHI) investigators have claimed that their 'findings … do not support use of this therapy for chronic disease prevention'. In an accompanying editorial, it was claimed that 'the WHI overturned medical dogma regarding menopausal [HT]'. To evaluate those claims. Epidemiological criteria of causation were applied to the evidence. A 'global index' purporting to summarize the overall benefit versus the risk of HT was not valid, and it was biased. For coronary heart disease, an increased risk in users of estrogen plus progestogen (E + P), previously reported by the WHI, was not confirmed. The WHI study did not establish that E+ P increases the risk of breast cancer; the findings suggest that unopposed estrogen therapy (ET) does not increase the risk, and may even reduce it. The findings for stroke and pulmonary embolism were compatible with an increased risk, and among E+ P users there were credible reductions in the risk of colorectal and endometrial cancer. For E+ P and ET users, there were credible reductions in the risk of hip fracture. Under 'worst case' and 'best case' assumptions, the changes in the incidence of the outcomes attributable to HT were minor. Over-interpretation and misrepresentation of the WHI findings have damaged the health and well-being of menopausal women by convincing them and their health professionals that the risks of HT outweigh the benefits.

The 2012 Hormone Therapy Position Statement of The North American Menopause Society

Science.gov (United States)

2012-01-01

Objective This position statement aimed to update the evidence-based position statement published by The North American Menopause Society (NAMS) in 2010 regarding recommendations for hormone therapy (HT) for postmenopausal women. This updated position statement further distinguishes the emerging differences in the therapeutic benefit-risk ratio between estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) at various ages and time intervals since menopause onset. Methods An Advisory Panel of expert clinicians and researchers in the field of women’s health was enlisted to review the 2010 NAMS position statement, evaluate new evidence, and reach consensus on recommendations. The Panel’s recommendations were reviewed and approved by the NAMS Board of Trustees as an official NAMS position statement. Results Current evidence supports the use of HT for perimenopausal and postmenopausal women when the balance of potential benefits and risks is favorable for the individual woman. This position statement reviews the effects of ET and EPT on many aspects of women’s health and recognizes the greater safety profile associated with ET. Conclusions Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms and to prevent osteoporosis in women at high risk of fracture. The more favorable benefit-risk ratio for ET allows more flexibility in extending the duration of use compared with EPT, where the earlier appearance of increased breast cancer risk precludes a recommendation for use beyond 3 to 5 years. PMID:22367731

Modelling sequentially scored item responses

NARCIS (Netherlands)

Akkermans, W.

2000-01-01

The sequential model can be used to describe the variable resulting from a sequential scoring process. In this paper two more item response models are investigated with respect to their suitability for sequential scoring: the partial credit model and the graded response model. The investigation is

ORIGINAL ARTICLES Potential for medical error: Incorrectly ...

African Journals Online (AJOL)

Drugs that affect thyroid hormone transport. Oestrogen. Tamoxifen. Heroin. Methadone. Androgens. Glucocorticoids. Salicylates. Anabolic steroids. Drugs that increase hepatic metabolism of T4 and T3. Phenobarbitol. Rifampicin. Phenytoin. Carbamazepine. Decreased T4 5'-deiodinase activity. Amiodarone. Glucocorticoids.

The safety and tolerance of phytotherapies in menopausal medicine – a review of the literature

Directory of Open Access Journals (Sweden)

Piotr Czuczwar

2017-04-01

Full Text Available Phytoestrogens are polyphenol, non-steroidal substances of plant origin, resembling 17-estradiol in structure. These substances can act as either agonists or antagonists of oestrogen receptors  and . Phytoestrogens are widely used to alleviate menopausal symptoms, such as hot flushes and night sweats. Most of the currently available products of plant origin registered to soften climacteric symptoms consist of extracts obtained from soy, red clover, or black cohosh. Non-hormonal phytotherapy is a new alternative for patients suffering from menopausal symptoms. Active ingredients such as PI 82-GC FEM extract do not show any direct hormonal mechanisms of action typical for oestrogens and phytoestrogens. There are concerns about the safety and tolerability of phytoestrogens. In this review we summarise the current literature regarding the clinical aspect of safety and tolerance of different phytotherapies used to relieve menopausal symptoms.

Multi-agent sequential hypothesis testing

KAUST Repository

Kim, Kwang-Ki K.

2014-12-15

This paper considers multi-agent sequential hypothesis testing and presents a framework for strategic learning in sequential games with explicit consideration of both temporal and spatial coordination. The associated Bayes risk functions explicitly incorporate costs of taking private/public measurements, costs of time-difference and disagreement in actions of agents, and costs of false declaration/choices in the sequential hypothesis testing. The corresponding sequential decision processes have well-defined value functions with respect to (a) the belief states for the case of conditional independent private noisy measurements that are also assumed to be independent identically distributed over time, and (b) the information states for the case of correlated private noisy measurements. A sequential investment game of strategic coordination and delay is also discussed as an application of the proposed strategic learning rules.

Analytical method for the determination of trace levels of steroid hormones and corticosteroids in soil, based on PLE/SPE/LC-MS/MS.

Science.gov (United States)

Gineys, N; Giroud, B; Vulliet, E

2010-07-01

The aim of this study was to develop an efficient, sensitive and reliable analytical method for the determination of traces of steroid hormones (including oestrogen, androgens and progestagens) and corticosteroids in soil. A method of sample preparation involving pressurized liquid extraction (PLE) and solid-phase extraction (SPE) was developed for the determination of six steroids and five corticosteroids in soils, followed by analysis by liquid chromatography-tandem mass spectrometry. The conditions employed for PLE involved acetone/methanol (50:50) as the extracting solvent, a temperature of 80 degrees C, two cycles and a static time of 5 min. The extraction was followed by a SPE clean-up based on a polymeric phase. With use of protocol, a residual matrix effect was, however, highlighted. The limit of detection in soil was 0.08-0.89 ng/g for steroids and 0.09-2.84 ng/g for corticosteroids.

EFFECT TN EWES OF OESTROGEN PRIMING AND GnRH ON LH ...

African Journals Online (AJOL)

Cyclicvariationsintheincreasedresponsivenessof thepituitaryto luteinizing hormone-releasing hormone ( LH RH) induced by LHRH . Endocrinology 9l , 13. COPPINGS, R.J. & MALVEN, P.V.. 1976. Biphasic effect of oestradiol on LH release mechanisms.

Sequential charged particle reaction

International Nuclear Information System (INIS)

Hori, Jun-ichi; Ochiai, Kentaro; Sato, Satoshi; Yamauchi, Michinori; Nishitani, Takeo

2004-01-01

The effective cross sections for producing the sequential reaction products in F82H, pure vanadium and LiF with respect to the 14.9-MeV neutron were obtained and compared with the estimation ones. Since the sequential reactions depend on the secondary charged particles behavior, the effective cross sections are corresponding to the target nuclei and the material composition. The effective cross sections were also estimated by using the EAF-libraries and compared with the experimental ones. There were large discrepancies between estimated and experimental values. Additionally, we showed the contribution of the sequential reaction on the induced activity and dose rate in the boundary region with water. From the present study, it has been clarified that the sequential reactions are of great importance to evaluate the dose rates around the surface of cooling pipe and the activated corrosion products. (author)

Progesterone Only Contraception

African Journals Online (AJOL)

argues further that the physiological effect of oestrogen in oral contraceptives on .... release of LH and FSH, exactly the same mechaniSm as that of the combined ... each the size of a matchstick, which contain levonorgestrel. The hormone is ...

Risk Factors for Breast Cancer, Including Occupational Exposures

Directory of Open Access Journals (Sweden)

Elisabete Weiderpass

2011-03-01

Full Text Available The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr. For breast cancer the following substances have been classified as “carcinogenic to humans” (Group 1: alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure. Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification “probably carcinogenic to humans” (Group 2A includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women.

Missed pills: frequency, reasons, consequences and solutions.

Science.gov (United States)

Chabbert-Buffet, Nathalie; Jamin, Christian; Lete, Iñaki; Lobo, Paloma; Nappi, Rossella E; Pintiaux, Axelle; Häusler, Günther; Fiala, Christian

2017-06-01

Oral hormonal contraception is an effective contraceptive method as long as regular daily intake is maintained. However, a daily routine is a constraint for many women and can lead to missed pills, pill discontinuation and/or unintended pregnancy. This article describes the frequency of inconsistent use, the consequences, the risk factors and the possible solutions. The article comprises a narrative review of the literature. Forgetting one to three pills per cycle is a frequent problem among 15-51% of users, generally adolescents. The reasons for this are age, inability to establish a routine, pill unavailability, side effects, loss of motivation and lack of involvement in the initial decision to use oral contraceptives. The consequences are 'escape ovulations' and, possibly, unintended pregnancy. Solutions are either to use a long-acting method or, for women who prefer to take oral contraceptives, use a continuous or long-cycle regimen to reduce the risks of follicular development and thus the likelihood of ovulation and unintended pregnancy. A progestogen with a long half-life can increase ovarian suppression. For women deciding to use oral contraceptives, a shortened or eliminated hormone-free interval and a progestogen with a long half-life may be an option to reduce the negative consequences of missed oral contraceptive pills.

Eyewitness confidence in simultaneous and sequential lineups: a criterion shift account for sequential mistaken identification overconfidence.

Science.gov (United States)

Dobolyi, David G; Dodson, Chad S

2013-12-01

Confidence judgments for eyewitness identifications play an integral role in determining guilt during legal proceedings. Past research has shown that confidence in positive identifications is strongly associated with accuracy. Using a standard lineup recognition paradigm, we investigated accuracy using signal detection and ROC analyses, along with the tendency to choose a face with both simultaneous and sequential lineups. We replicated past findings of reduced rates of choosing with sequential as compared to simultaneous lineups, but notably found an accuracy advantage in favor of simultaneous lineups. Moreover, our analysis of the confidence-accuracy relationship revealed two key findings. First, we observed a sequential mistaken identification overconfidence effect: despite an overall reduction in false alarms, confidence for false alarms that did occur was higher with sequential lineups than with simultaneous lineups, with no differences in confidence for correct identifications. This sequential mistaken identification overconfidence effect is an expected byproduct of the use of a more conservative identification criterion with sequential than with simultaneous lineups. Second, we found a steady drop in confidence for mistaken identifications (i.e., foil identifications and false alarms) from the first to the last face in sequential lineups, whereas confidence in and accuracy of correct identifications remained relatively stable. Overall, we observed that sequential lineups are both less accurate and produce higher confidence false identifications than do simultaneous lineups. Given the increasing prominence of sequential lineups in our legal system, our data argue for increased scrutiny and possibly a wholesale reevaluation of this lineup format. PsycINFO Database Record (c) 2013 APA, all rights reserved.

A randomised study comparing the effect on ovarian activity of a progestogen-only pill (POP) containing desogestrel and a new POP containing drospirenone in a 24/4 regimen

DEFF Research Database (Denmark)

Duijkers, Ingrid J M; Heger-Mahn, Doris; Drouin, Dominique

2015-01-01

OBJECTIVES: Progestogen-only pills (POPs) are safer with respect to cardiovascular risks than contraceptives containing estrogens. Despite the increased contraceptive efficacy of a desogestrel-only pill compared with a traditional POP, POPs are still not widely used due to an unpredictable bleeding...... pattern. A new POP containing 4 mg drospirenone has been developed with a 24/4 intake regimen which may improve the bleeding pattern. The objectives of this study were to investigate ovulation inhibition with the new drospirenone-only pill in comparison with the desogestrel-only pill and, in addition......, to assess the effects on cervical mucus permeability and bleeding. METHODS: Sixty-four healthy volunteers with proven ovulatory cycles were randomised and treated with either the drospirenone-only or the desogestrel-only pill during two 28-day cycles. Follicular diameter, endometrial thickness, and serum...

Occurrence and removal of emerging contaminants in wastewaters

OpenAIRE

Janna, Hussein

2011-01-01

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University. Over the past decade, the occurrence and removal of emerging contaminants in the environment has received much attention. Both natural and synthetic progestogens, which are hormones, and also benzotriazoles are two examples of such emerging contaminants. Sewage treatment works are recognised as one of the main routes of these compounds to the environment. Low concentrations (nanograms per lit...

Hormone assay

International Nuclear Information System (INIS)

Eisentraut, A.M.

1977-01-01

An improved radioimmunoassay is described for measuring total triiodothyronine or total thyroxine levels in a sample of serum containing free endogenous thyroid hormone and endogenous thyroid hormone bound to thyroid hormone binding protein. The thyroid hormone is released from the protein by adding hydrochloric acid to the serum. The pH of the separated thyroid hormone and thyroid hormone binding protein is raised in the absence of a blocking agent without interference from the endogenous protein. 125 I-labelled thyroid hormone and thyroid hormone antibodies are added to the mixture, allowing the labelled and unlabelled thyroid hormone and the thyroid hormone antibody to bind competitively. This results in free thyroid hormone being separated from antibody bound thyroid hormone and thus the unknown quantity of thyroid hormone may be determined. A thyroid hormone test assay kit is described for this radioimmunoassay. It provides a 'single tube' assay which does not require blocking agents for endogenous protein interference nor an external solid phase sorption step for the separation of bound and free hormone after the competitive binding step; it also requires a minimum number of manipulative steps. Examples of the assay are given to illustrate the reproducibility, linearity and specificity of the assay. (UK)

Standard and Low-dose Hormone Therapy for Postmenopausal Women—Focus on the Breast

Directory of Open Access Journals (Sweden)

Peng-Hui Wang

2007-06-01

Full Text Available Menopause occurs naturally when the ovary ceases folliculogenesis, or artificially by surgical and/or medical ablation of the ovarian function. Menopause is a hypoestrogenic state, which may adversely affect estrogen target tissues, such as the brain, skeleton and skin, as well as the cardiovascular and genitourinary systems, with resultant frequency and severity of climacteric symptoms. The climacteric symptoms, however, vary significantly among women. For decades, hormone therapy (HT has been the mainstay and is considered the most effective for managing menopausal symptoms. The prolonged use of either single estrogen therapy or a combination therapy of estrogen and progestogen (EPT might be associated with a slightly increased risk of breast cancer and many resultant adverse events, such as coronary heart disease, stroke and venous thromboembolism. Perhaps because the clear benefits are limited to these end points of HT in treating menopausal women, the relatively significant adverse event profiles of these women may not be enough to trigger primary care physicians to be more aggressive than they have been to date in treating climacteric symptoms of postmenopausal women. However, severe climacteric symptoms really disturb the woman's life. Some epidemiologic studies have shown that the increased risk for breast cancer after 5 years of combined EPT is similar in magnitude to other lifestyle variables, such as 10-year delayed menopause, fewer pregnancies and reduced breastfeeding, postmenopausal obesity, excessive alcohol or cigarette use, and lack of regular exercise. Furthermore, elevated serum concentrations of either endogenous or exogenous (replaced by HT sex hormone in either pre- or postmenopausal women are associated with an increased risk of breast cancer. Finally, the increased breast cancer risk diminishes soon after discontinuing hormones, and largely disappears by 5 years after cessation. Taken together, low-dose conventional HT

Remarks on sequential designs in risk assessment

International Nuclear Information System (INIS)

Seidenfeld, T.

1982-01-01

The special merits of sequential designs are reviewed in light of particular challenges that attend risk assessment for human population. The kinds of ''statistical inference'' are distinguished and the problem of design which is pursued is the clash between Neyman-Pearson and Bayesian programs of sequential design. The value of sequential designs is discussed and the Neyman-Pearson vs. Bayesian sequential designs are probed in particular. Finally, warnings with sequential designs are considered, especially in relation to utilitarianism

Oligoadenylate synthetase 1 (OAS1 expression in human breast and prostate cancer cases, and its regulation by sex steroid hormones

Directory of Open Access Journals (Sweden)

Cláudio Jorge Maia

2016-06-01

Full Text Available Oligoadenylate synthetase 1 (OAS1 is an interferon-induced protein characterised by its capacity to catalyse the synthesis of 2ʹ-5ʹ-linked oligomers of adenosine from adenosine triphosphate (2-5A. The 2-5A binds to a latent Ribonuclease L (RNase L, which subsequently dimerises into its active form and may play an important role in the control of cell growth, differentiation and apoptosis. Previously, our research group identified OAS1 as a differentially-expressed gene in breast and prostate cancer cell lines when compared to normal cells. This study evaluates: i the expression of OAS1 in human breast and prostate cancer specimens; and ii the effect of sex steroid hormones in regulating the expression of OAS1 in breast (MCF-7 and prostate (LNCaP cancer cell lines. The obtained results showed that OAS1 expression was down-regulated in human infiltrative ductal carcinoma of breast, adenocarcinoma of prostate, and benign prostate hyperplasia, both at mRNA and protein level. In addition, OAS1 expression was negatively correlated with the progression of breast and prostate cancer. With regards to the regulation of OAS1 gene, it was demonstrated that 17β-estradiol (E2 down-regulates OAS1 gene in MCF-7 cell lines, an effect that seems to be dependent on the activation of oestrogen receptor (ER. On the other hand, 5α-dihydrotestosterone (DHT treatment showed no effect on the expression of OAS1 in LNCaP cell lines. The lower levels of OAS1 in breast and prostate cancer cases indicated that the OAS1/RNaseL apoptotic pathway may be compromised in breast and prostate tumours. Moreover, the present findings suggested that this effect may be enhanced by oestrogen in ER-positive breast cancers.

Sequential lineup laps and eyewitness accuracy.

Science.gov (United States)

Steblay, Nancy K; Dietrich, Hannah L; Ryan, Shannon L; Raczynski, Jeanette L; James, Kali A

2011-08-01

Police practice of double-blind sequential lineups prompts a question about the efficacy of repeated viewings (laps) of the sequential lineup. Two laboratory experiments confirmed the presence of a sequential lap effect: an increase in witness lineup picks from first to second lap, when the culprit was a stranger. The second lap produced more errors than correct identifications. In Experiment 2, lineup diagnosticity was significantly higher for sequential lineup procedures that employed a single versus double laps. Witnesses who elected to view a second lap made significantly more errors than witnesses who chose to stop after one lap or those who were required to view two laps. Witnesses with prior exposure to the culprit did not exhibit a sequential lap effect.

Robustness of the Sequential Lineup Advantage

Science.gov (United States)

Gronlund, Scott D.; Carlson, Curt A.; Dailey, Sarah B.; Goodsell, Charles A.

2009-01-01

A growing movement in the United States and around the world involves promoting the advantages of conducting an eyewitness lineup in a sequential manner. We conducted a large study (N = 2,529) that included 24 comparisons of sequential versus simultaneous lineups. A liberal statistical criterion revealed only 2 significant sequential lineup…

Sex change strategy and the aromatase genes.

Science.gov (United States)

Gardner, L; Anderson, T; Place, A R; Dixon, B; Elizur, A

2005-04-01

Sequential hermaphroditism is a common reproductive strategy in many teleosts. Steroid production is known to mediate both the natural and induced sex change, yet beyond this the physiology directing this process has received little attention. Cytochrome P450 aromatase is a key enzyme in the hormonal pathway catalysing the conversion of sex steroids, androgens to oestrogens, and thus is highly relevant to the process of sex change. This study reports the isolation of cDNA sequences for aromatase isoforms CYP19A1 and CYP19A2 from teleost species representing three forms of sexual hermaphroditism: Lates calcarifer (protandry), Cromileptes altivelis (protogyny), and Gobiodon histrio (bi-directional). Deduced amino acid analysis of these isoforms with other reported isoforms from gonochoristic (single sex) teleosts revealed 56-95% identity within the same isoform while only 48-65% identity between isoforms irrespective of species and sexual strategy. Phylogenetic analysis supported this result separating sequences into isoform exclusive clades in spite of species apparent evolutionary distance. Furthermore, this study isolates 5' flanking regions of all above genes and describes putative cis-acting elements therein. Elements identified include steroidogenic factor 1 binding site (SF-1), oestrogen response element (ERE), progesterone response element (PRE), androgen response element (ARE), glucocorticoid response elements (GRE), peroxisome proliferator-activated receptor alpha/retinoid X receptor alpha heterodimer responsive element (PPARalpha/RXRalpha), nuclear factor kappabeta (NF-kappabeta), SOX 5, SOX 9, and Wilms tumor suppressor (WTI). A hypothetical in vivo model was constructed for both isoforms highlighting potential roles of these putative cis-acting elements with reference to normal function and sexual hermaphroditism.

Multi-agent sequential hypothesis testing

KAUST Repository

Kim, Kwang-Ki K.; Shamma, Jeff S.

2014-01-01

incorporate costs of taking private/public measurements, costs of time-difference and disagreement in actions of agents, and costs of false declaration/choices in the sequential hypothesis testing. The corresponding sequential decision processes have well

Sequential stochastic optimization

CERN Document Server

Cairoli, Renzo

1996-01-01

Sequential Stochastic Optimization provides mathematicians and applied researchers with a well-developed framework in which stochastic optimization problems can be formulated and solved. Offering much material that is either new or has never before appeared in book form, it lucidly presents a unified theory of optimal stopping and optimal sequential control of stochastic processes. This book has been carefully organized so that little prior knowledge of the subject is assumed; its only prerequisites are a standard graduate course in probability theory and some familiarity with discrete-paramet

Exploring the sequential lineup advantage using WITNESS.

Science.gov (United States)

Goodsell, Charles A; Gronlund, Scott D; Carlson, Curt A

2010-12-01

Advocates claim that the sequential lineup is an improvement over simultaneous lineup procedures, but no formal (quantitatively specified) explanation exists for why it is better. The computational model WITNESS (Clark, Appl Cogn Psychol 17:629-654, 2003) was used to develop theoretical explanations for the sequential lineup advantage. In its current form, WITNESS produced a sequential advantage only by pairing conservative sequential choosing with liberal simultaneous choosing. However, this combination failed to approximate four extant experiments that exhibited large sequential advantages. Two of these experiments became the focus of our efforts because the data were uncontaminated by likely suspect position effects. Decision-based and memory-based modifications to WITNESS approximated the data and produced a sequential advantage. The next step is to evaluate the proposed explanations and modify public policy recommendations accordingly.

In vitro screening for endocrine disruptive activity in selected South African harbours and river mouths

CSIR Research Space (South Africa)

Truter, JC

2015-12-01

Full Text Available . Moreover, levels of the female hormone 17ß-(o)estradiol (E2) were determined in all samples, as well as a selection of hydrocarbons in the eThekwini samples. A high proportion of samples collected from eThekwini were oestrogenic, whereas none from Port...

Sequential and simultaneous choices: testing the diet selection and sequential choice models.

Science.gov (United States)

Freidin, Esteban; Aw, Justine; Kacelnik, Alex

2009-03-01

We investigate simultaneous and sequential choices in starlings, using Charnov's Diet Choice Model (DCM) and Shapiro, Siller and Kacelnik's Sequential Choice Model (SCM) to integrate function and mechanism. During a training phase, starlings encountered one food-related option per trial (A, B or R) in random sequence and with equal probability. A and B delivered food rewards after programmed delays (shorter for A), while R ('rejection') moved directly to the next trial without reward. In this phase we measured latencies to respond. In a later, choice, phase, birds encountered the pairs A-B, A-R and B-R, the first implementing a simultaneous choice and the second and third sequential choices. The DCM predicts when R should be chosen to maximize intake rate, and SCM uses latencies of the training phase to predict choices between any pair of options in the choice phase. The predictions of both models coincided, and both successfully predicted the birds' preferences. The DCM does not deal with partial preferences, while the SCM does, and experimental results were strongly correlated to this model's predictions. We believe that the SCM may expose a very general mechanism of animal choice, and that its wider domain of success reflects the greater ecological significance of sequential over simultaneous choices.

Calcium status in premenopausal and post menopausal women

International Nuclear Information System (INIS)

Qureshi, H.J.; Hussain, G.; Bashir, M.U.; Latif, N.; Riaz, Z.

2010-01-01

Background: In postmenopausal women, the two major causes of bone loss are oestrogen deficiency after menopause and age related processes. Bone turnover increases to high levels and oestrogen deficiency may induce calcium loss by indirect effects on extra skeletal calcium homeostasis. Objective of this study was to evaluate calcium status in pre-menopausal and postmenopausal women. Methods: This cross sectional study was carried out in 34 premenopausal women and 33 postmenopausal women, in Department of Physiology, Services Institute of Medical Sciences, Lahore. Height and weight of each woman were taken to find out the body mass index (BMI). Serum calcium, parathyroid hormone and calcitonin levels of each subject were determined. Results: Premenopausal women were obese (BMI>30 Kg/m/sup 2/) while postmenopausal women were overweight (BMI>25 Kg/m/sup 2/). Serum calcium levels were significantly lower in postmenopausal women than in pre-menopausal women, while serum parathyroid hormone levels were significantly higher in postmenopausal woman. Serum calcitonin level was not significantly different in the two groups. Conclusion: Postmenopausal women are calcium deficient and have increased bone turnover as indicated by increased serum parathyroid hormone levels. (author)

Sequential memory: Binding dynamics

Science.gov (United States)

Afraimovich, Valentin; Gong, Xue; Rabinovich, Mikhail

2015-10-01

Temporal order memories are critical for everyday animal and human functioning. Experiments and our own experience show that the binding or association of various features of an event together and the maintaining of multimodality events in sequential order are the key components of any sequential memories—episodic, semantic, working, etc. We study a robustness of binding sequential dynamics based on our previously introduced model in the form of generalized Lotka-Volterra equations. In the phase space of the model, there exists a multi-dimensional binding heteroclinic network consisting of saddle equilibrium points and heteroclinic trajectories joining them. We prove here the robustness of the binding sequential dynamics, i.e., the feasibility phenomenon for coupled heteroclinic networks: for each collection of successive heteroclinic trajectories inside the unified networks, there is an open set of initial points such that the trajectory going through each of them follows the prescribed collection staying in a small neighborhood of it. We show also that the symbolic complexity function of the system restricted to this neighborhood is a polynomial of degree L - 1, where L is the number of modalities.

The effects of female sex steroids on the development of autoimmune thyroiditis in thymectomized and irradiated rats

International Nuclear Information System (INIS)

Ahmed, S.A.; Young, P.R.; Penhale, W.J.

1983-01-01

Female PVG/c strain rats are more susceptible to induction of autoimmune thyroiditis initiated by thymectomy and irradiation (Tx-X) than similarly treated males. Pre-pubertal ovariectomy further augmented susceptibility. Administration of oestrogen or progesterone to groups of 4 weeks old ovariectomized Tx-X animals over a period of 15 weeks significantly altered induction of this condition. Oestrogen administered repeatedly at dose levels of 1 μg and 10 μg/100 g body weight resulted in partial suppression of thyroiditis with a corresponding change in the incidence of antibodies to thyroglobulin. Oestrogen administered by a single implantation had a suppressive effect on the development of autoimmunity in ovariectomized Tx-X females. Oestrogen given by either of these procedures also reduced the incidence of thyroiditis and autoantibody induction in orchidectomized male Tx-X rats. In contrast, repeated administration of progesterone at a dose of 250 mg and 1,500 μg/100 g body weight appeared to augment levels of autoimmunity. It is concluded that the differential susceptibility to the induction of autoimmunity by thymectomy and irradiation is the direct consequence of sex hormonal influences. The higher incidence of the disease in the female would appear to be determined by the balance between the activity of oestrogen and progesterone which would further appear to have antagonistic influences in this particular situation. (UK)

Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

Energy Technology Data Exchange (ETDEWEB)

Farquharson, M J [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St W Hamilton, Ontario, L8S 4L8 (Canada); Al-Ebraheem, A [Department of Radiography, City Community and Health Sciences, City University, London, EC1V 0HB (United Kingdom); Geraki, K [Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxon, OX11 0DE (United Kingdom); Leek, R; Jubb, A; Harris, A L [Cancer Research UK, Oxford Cancer Centre, Molecular Oncology Laboratories, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, 0X3 9DS (United Kingdom)], E-mail: farquhm@mcmaster.ca

2009-07-07

Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01)

Zinc presence in invasive ductal carcinoma of the breast and its correlation with oestrogen receptor status

International Nuclear Information System (INIS)

Farquharson, M J; Al-Ebraheem, A; Geraki, K; Leek, R; Jubb, A; Harris, A L

2009-01-01

Zinc is known to play an important role in many cellular processes, and the levels of zinc are controlled by specific transporters from the ZIP (SLC39A) influx transporter group and the ZnT (SLC30A) efflux transporter group. The distribution of zinc was measured in 59 samples of invasive ductal carcinoma of breast using synchrotron radiation micro probe x-ray fluorescence facilities. The samples were formalin fixed paraffin embedded tissue micro arrays (TMAs) enabling a high throughput of samples and allowing us to correlate the distribution of trace metals with tumour cell distribution and, for the first time, important biological variables. The samples were divided into two classes, 34 oestrogen receptor positive (ER+ve) and 25 oestrogen receptor negative (ER-ve) based on quantitative immunohistochemistry assessment. The overall levels of zinc (i.e. in tumour and surrounding tissue) in the ER+ve samples were on average 60% higher than those in the ER-ve samples. The zinc levels were higher in the ER+ve tumour areas compared to the ER-ve tumour areas with the mean levels in the ER+ve samples being approximately 80% higher than the mean ER-ve levels. However, the non-tumour tissue regions of the samples contained on average the same levels of zinc in both types of breast cancers. The relative levels of zinc in tumour areas of the tissue were compared with levels in areas of non-tumour surrounding tissue. There was a significant increase in zinc in the tumour regions of the ER+ve samples compared to the surrounding regions (P < 0.001) and a non-significant increase in the ER-ve samples. When comparing the increase in zinc in the tumour regions expressed as a percentage of the surrounding non-tumour tissue zinc level in the same sample, a significant difference between the ER+ve and ER-ve samples was found (P < 0.01).

Role of Oestrogen α Receptors in Sociosexual Behaviour in Female Rats Housed in a Seminatural Environment.

Science.gov (United States)

Snoeren, E M S; Antonio-Cabrera, E; Spiteri, T; Musatov, S; Ogawa, S; Pfaff, D W; Ågmo, A

2015-11-01

The present study investigated the role of oestrogen receptor (ER)α in the ventromedial nucleus of the hypothalamus (VMN), the preoptic area (POA), the medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in sociosexual behaviour in female rats. This was conducted in two sets of experiments, with the VMN and POA investigated in the first set, and the MePD and BNST in the second set. The VMN and POA received intense projections from the MePD and BNST. We used a short hairpin RNA encoded within an adeno-associated viral vector directed against the gene for ERα to reduce the number of ERα in the VMN or POA (first set of experiments) or in the BNST or MePD (second set of experiments) in female rats. The rats were housed in groups of four ovariectomised females and three males in a seminatural environment for 8 days. Compared with traditional test set-ups, the seminatural environment provides an arena in which the rats can express their full behavioural repertoire, which allowed us to investigate multiple aspects of social and sexual behaviour in groups of rats. Behavioural observation was performed after oestrogen and progesterone injections. A reduction of ERα expression in the VMN or POA diminished the display of paracopulatory behaviours and lordosis responses compared to controls, whereas the lordosis quotient remained unaffected. This suggests that ERα in the VMN and POA play an important role in intrinsic sexual motivation. The reduction in ERα did not affect the social behaviour of the females, although the males sniffed and pursued the females with reduced ERα less than the controls. This suggests that the ERα in the VMN and POA is involved in the regulation of sexual attractiveness of females. The ERα in the MePD and BNST, on the other hand, plays no role in sociosexual behaviour. © 2015 British Society for Neuroendocrinology.

Sequential Probability Ration Tests : Conservative and Robust

NARCIS (Netherlands)

Kleijnen, J.P.C.; Shi, Wen

2017-01-01

In practice, most computers generate simulation outputs sequentially, so it is attractive to analyze these outputs through sequential statistical methods such as sequential probability ratio tests (SPRTs). We investigate several SPRTs for choosing between two hypothesized values for the mean output

Cyclic changes in hormones, carbohydrates and indole metabolism in cervical mucus of normal, fertilizing cows and the relationship with non-fertility.

Science.gov (United States)

Zaaijer, D; van der Horst, C J

1983-01-01

In the cervical mucus of 'normal' cows the cholesterol content was very low at D--0; at D + 12 it was about fifty times as high; then it decreased to about half its value at D + 17 and then to the low value at D--0. Usually small amounts of oestrogen, testosterone, pregnanedione and progesterone were found at D--0; on D + 12 more pregnanedione was found and less oestrogen, while at D + 17 more oestrogen occurred and less pregnanedione. The fructose and glucose content was very low at D--0; then it increased until D + 12, when glucose was dominant, while at D + 17 it had decreased and rather large amounts of glucuronic acid and of sorbitol occurred. On D + 12 a blue fluorescing indole metabolite was sometimes found. Deviations from these patterns, were found particularly in the winter months, and coincided with lowered fertility. Indole metabolism was stronger in the winter months than in the summer months and occurred more in cows than in heifers.

Influence of chronic alcoholism and oestrogen deficiency on the variation of stoichiometry of hydroxyapatite within alveolar bone crest of rats.

Science.gov (United States)

Marchini, Adriana M P S; Deco, Camila P; Lodi, Karina B; Marchini, Leonardo; Santo, Ana M E; Rocha, Rosilene F

2012-10-01

Previous findings suggest that chronic alcoholism and oestrogenic deficiency may affect bones in general (including alveolar bone) and increase individuals' susceptibility to the development of periodontal disease. The aim of this study was to assess possible alterations in the chemical composition of alveolar bone in rats subjected to chronic alcoholism, oestrogen deficiency or both. Fifty-four rats were initially divided into two groups: ovariectomized (Ovx), and Sham operated (Sham). A month after surgery, the groups were sub-divided and received the following dietary intervention for eight weeks: 20% alcohol, isocaloric diet and ad libitum diet. Samples of the mandible, in the alveolar bone crest region, were analyzed to verify possible changes in the stoichiometric composition of bone hydroxyapatite, by measuring the relationship between the concentration of calcium and phosphorus (Ca/P ratios), using micro X-ray fluorescence spectrometry. The ad libitum groups presented the highest average values of Ca/P ratios, while the groups with dietary restrictions presented the smallest average values. The Ovx ad libitum group presented the highest values of Ca/P ratios (2.03 ± 0.04). However, these values were not considered statistically different (p>0.05) from the Sham ad libitum group (2.01 ± 0.01). The Ovx alcohol group presented lower values for Ca/P ratios (1.92 ± 0.06), being the only group statistically different (palcohol consumption at 20% significantly changed the stoichiometry composition of hydroxyapatite in the alveolar bone crest, leading to a reduction in Ca/P ratios. Copyright © 2012 Elsevier Ltd. All rights reserved.

Influence of hormone substitution therapy on postmenopausal uterus; Einfluss einer Hormonsubstitution auf den postmenopausalen Uterus

Energy Technology Data Exchange (ETDEWEB)

Otte, A.; Ruedisueli, A.; Goetze, M.; Leibundgut, U.; Mueller-Brand, J. [Inst. fuer Nuklearmedizin, Kantonsspital, Universitaetskliniken, Basel (Switzerland); Nitzsche, E.U. [Abt. Nuklearmedizin, Radiologische Universitaetsklinik, Freiburg (Germany)

1997-12-01

In a 58-year-old postmenopausal woman blood flow and blood pool images of bone scintigraphy showed a focus of increased activity in the right pelvic region. Computed tomography and ultrasound exhibited no abnormalities in the abdomen; especially the uterus and ovaries were normal. Careful anamnestic evaluation revealed that the patient received a long-term peroral estrogen/gestagen replacement therapy for the prevention of osteoporosis, but did not have menstruation-like bleedings for the last twelve months of therapy. At time of admission, the patient was on day 25 of hormone replacement therapy, and the uterus wash, therefore, in a premenstrual stage. Hence, despite cessation of bleedings in postmenopausal women, one should think of hormone replacement therapy as an explanation for vascular pelvic tumors seen by the first two phases of bone scintigraphy, before further diagnostic steps are undertaken. (orig.) [Deutsch] Bei der Skelettszintigraphie einer 58jaehrigen postmenopausalen Frau erkannte man in der Perfusions- und Blood-pool-Phase einen unklaren Fokus erhoehter Aktivitaet im rechten Becken. Computertomographie und Sonographie des Abdomens, insbesondere des Uterus und der Ovarien, waren unauffaellig. Nach eingehender anamnestischer Befragung stellte sich heraus, dass die Patientin unter einer mehrjaehrigen peroralen Oestrogen-/Gestagen-Hormonsubstitutionstherapie zur Osteoporose-Prophylaxe stand, jedoch seit den letzten zwoelf Monaten der Therapie ueber keine menstruationsaehnlichen Abbruchblutungen mehr berichten konnte. Bei ihrer Zuweisung befand sich die Patientin am 25. Tag der Hormonsubstitutionstherapie und ihr Uterus somit in einem praemenstruellen Stadium. Trotz Ausbleibens der Blutung bei postmenopausalen Frauen sollte somit an die Moeglichkeit der Hormonsubstitution gedacht und danach gefragt werden, wenn in den ersten beiden Phasen der Skelettszintigraphie eine unklare, gut vaskularisierte Struktur im kleinen Becken gefunden wird, bevor weitere

Sequential lineup presentation: Patterns and policy

OpenAIRE

Lindsay, R C L; Mansour, Jamal K; Beaudry, J L; Leach, A-M; Bertrand, M I

2009-01-01

Sequential lineups were offered as an alternative to the traditional simultaneous lineup. Sequential lineups reduce incorrect lineup selections; however, the accompanying loss of correct identifications has resulted in controversy regarding adoption of the technique. We discuss the procedure and research relevant to (1) the pattern of results found using sequential versus simultaneous lineups; (2) reasons (theory) for differences in witness responses; (3) two methodological issues; and (4) im...

Dose-dependent effects of exogenous gonadotrophins on the ...

African Journals Online (AJOL)

We compared the serwn levels of oestrogen and progesterone and the endometrial morphology of normal pregnant rats at 5,5 days' gestation with those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-stimulating hormone (FSH) and hwnan chorionic gonadotrophin (HCG).

Ozone oxidation of oestrogenic active substances in wastewater and drinking water.

Science.gov (United States)

Baig, S; Hansmann, G; Paolini, B

2008-01-01

Ozone oxidation is proven to be an effective solution for the degradation of selected oestrogenic active substances detected in secondary wastewaters such as beta-oestradiol, oestrone, oestriol, 17-alpha-ethinyloestradiol, mestranol, daidzeine, beta-sitosterol, bisphenol A, norethisterone, 4-tert-octylphenol and 4-iso-nonylphenol, up to their limit of detection. The matrix-effect of wastewater was investigated performing ozone experiments under batch mode and continuous mode using drinking water and a wastewater issued from a local plant both spiked with the non-detected substances. The results obtained indicate that the wastewater matrix greatly affects the kinetics of ozone reaction with these substances but does not really change the related reactivity scale. The ozone dose corresponding to the full conversion of target EDCs consequently increases as their oxidation takes place competing with reactions of background pollutants represented by the COD and DOC content. However, a usual dose close to 12 mg/L was found sufficient to provide high degradation yields for all substances studied while 35% of COD was removed. This is a contribution to the numerous current works focused on technologies able to improve the quality of water discharged from wastewater treatment plants, both considering conventional parameters and emerging contaminants. IWA Publishing 2008.

Sequential Product of Quantum Effects: An Overview

Science.gov (United States)

Gudder, Stan

2010-12-01

This article presents an overview for the theory of sequential products of quantum effects. We first summarize some of the highlights of this relatively recent field of investigation and then provide some new results. We begin by discussing sequential effect algebras which are effect algebras endowed with a sequential product satisfying certain basic conditions. We then consider sequential products of (discrete) quantum measurements. We next treat transition effect matrices (TEMs) and their associated sequential product. A TEM is a matrix whose entries are effects and whose rows form quantum measurements. We show that TEMs can be employed for the study of quantum Markov chains. Finally, we prove some new results concerning TEMs and vector densities.

Response rates to oestrogen treatment in perimenopausal women

DEFF Research Database (Denmark)

Rejnmark, Lars; Vestergaard, Peter; Tofteng, C.L.

2004-01-01

OBJECTIVE: To characterise women with no response or with a good response to hormone replacement therapy (HRT), evaluated by change in bone mineral density (BMD). Design: Nested case-control study within a comprehensive cohort study. SUBJECTS AND METHODS: In the Danish Osteoporosis Prevention Study...

Optimal Sequential Rules for Computer-Based Instruction.

Science.gov (United States)

Vos, Hans J.

1998-01-01

Formulates sequential rules for adapting the appropriate amount of instruction to learning needs in the context of computer-based instruction. Topics include Bayesian decision theory, threshold and linear-utility structure, psychometric model, optimal sequential number of test questions, and an empirical example of sequential instructional…

Determination of oestrogen hormones in raw and treated water ...

African Journals Online (AJOL)

use, via sewage treatment plants. If these compounds are not eliminated by wastewater treatment plants, they can then be discharged to rivers and lakes which are used as sources for drinking water production. Therefore, the presence of such organic contaminants may have a negative impact on the quality of drinking ...

Effects of ovarian steroids upon responses mediated by adrenoceptors in separated layers of the myometrium and in the costo-uterine muscle of the guinea-pig

Science.gov (United States)

Hartley, Margaret L.; Pennefather, Jocelyn N.; Story, Margot E.

1983-01-01

1 This study describes the effects of ovarian steroid hormones upon the responses to adrenoceptor agonists of isolated myometrium, separated into its longitudinal and circular layers, and of costo-uterine muscle from guinea-pigs. The preparations were field-stimulated at 100 s intervals, and the adrenoceptor agonists phenylephrine and isoprenaline produced enhancement or inhibition of the evoked contractions. 2 Isoprenaline produced propranolol-sensitive inhibitory effects in longitudinal and circular myometrium and costo-uterine muscle preparations from animals from all experimental groups: i.e. from nonsteroid-treated animals (ovariectomized and intact); intact animals treated with either oestrogen or progesterone alone; ovariectomized animals treated with oestrogen; ovariectomized and intact animals treated with progesterone following oestrogen priming; and from animals 1-4 days post-partum. Longitudinal myometrial preparations from progesterone-treated oestrogen-primed and from post-partum animals were most sensitive to this agonist. 3 Phenylephrine produced phentolamine-sensitive excitatory effects in circular myometrial and costo-uterine muscle preparations from animals from all the experimental groups. In contrast, propranolol-sensitive inhibitory responses to phenylephrine occurred in longitudinal myometrial preparations taken from animals treated with progesterone following oestrogen priming, and from post-partum animals. Longitudinal myometrium from animals from the remaining experimental groups exhibited phentolamine-sensitive excitatory responses to phenylephrine. 4 The basis for the selective effect upon the longitudinal myometrium of exposure to progesterone following a period of oestrogen priming, is discussed. The results described are consistent with the possibility that in the longitudinal layer of guinea-pig uterus exposed to progesterone following oestrogen priming there is an increase in the proportion of β-adrenoceptors in this layer. This

Positron emission tomography of tumour [{sup 18}F]fluoroestradiol uptake in patients with acquired hormone-resistant metastatic breast cancer prior to oestradiol therapy

Energy Technology Data Exchange (ETDEWEB)

Kruchten, Michel van; Schroeder, Carolien P.; Vries, Elisabeth G.E. de; Hospers, Geke A.P. [University of Groningen, Department of Medical Oncology, University Medical Centre Groningen (Netherlands); Glaudemans, Andor W.J.M.; Vries, Erik F.J. de [University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen (Netherlands)

2015-10-15

Whereas anti-oestrogen therapy is widely applied to treat oestrogen receptor (ER) positive breast cancer, paradoxically, oestrogens can also induce tumour regression. Up-regulation of ER expression is a marker for oestrogen hypersensitivity. We, therefore, performed an exploratory study to evaluate positron emission tomography (PET) with the tracer 16α-[{sup 18}F]fluoro-17β-oestradiol ({sup 18}F-FES) as potential marker to select breast cancer patients for oestradiol therapy. Eligible patients had acquired endocrine-resistant metastatic breast cancer that progressed after ≥2 lines of endocrine therapy. All patients had prior ER-positive histology. Treatment consisted of oestradiol 2 mg, three times daily, orally. Patients underwent {sup 18}F-FES-PET/CT imaging at baseline. Tumour {sup 18}F-FES-uptake was quantified for a maximum of 20 lesions and expressed as maximum standardised uptake value (SUV{sub max}). CT-scan was repeated every 3 months to evaluate treatment response. Clinical benefit was defined as time to radiologic or clinical progression ≥24 weeks. {sup 18}F-FES uptake, quantified for 255 lesions in 19 patients, varied greatly between lesions (median 2.8; range 0.6-24.3) and between patients (median 2.5; range 1.1-15.5). Seven (37 %) patients experienced clinical benefit of oestrogen therapy, eight progressed (PD), and four were non-evaluable due to side effects. The positive and negative predictive value (PPV/NPV) of {sup 18}F-FES-PET for response to treatment were 60 % (95 % CI: 31-83 %) and 80 % (95 % CI: 38-96 %), respectively, using SUV{sub max} >1.5. {sup 18}F-FES-PET may aid identification of patients with acquired antihormone resistant breast cancer that are unlikely to benefit from oestradiol therapy. (orig.)

Quantum Inequalities and Sequential Measurements

International Nuclear Information System (INIS)

Candelpergher, B.; Grandouz, T.; Rubinx, J.L.

2011-01-01

In this article, the peculiar context of sequential measurements is chosen in order to analyze the quantum specificity in the two most famous examples of Heisenberg and Bell inequalities: Results are found at some interesting variance with customary textbook materials, where the context of initial state re-initialization is described. A key-point of the analysis is the possibility of defining Joint Probability Distributions for sequential random variables associated to quantum operators. Within the sequential context, it is shown that Joint Probability Distributions can be defined in situations where not all of the quantum operators (corresponding to random variables) do commute two by two. (authors)

Bulletin of Animal Health and Production in Africa - Vol 65, No 2 (2017)

African Journals Online (AJOL)

Localization of oestrogen hormone receptors in the reproductive tract of giant African land snail (Archachatina marginata) and potential role of Mucuna pruriens on level of expression · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. J A Abiona, O L Adeiga, M O Onagbesan, 221- ...

The treatment of severe premenstrual syndrome with goserelin with and without 'add-back' estrogen therapy: a placebo-controlled study.

Science.gov (United States)

Leather, A T; Studd, J W; Watson, N R; Holland, E F

1999-02-01

The study aimed to determine if the addition of daily low-dose oral estrogen with a cyclical progestogen given to young women using a depot gonadotropin-releasing hormone (GnRH) analog implant for the treatment of their premenstrual syndrome (PMS) would affect the clinical outcome. In a double-blind placebo-controlled study in a specialist premenstrual syndrome clinic setting, 60 women aged between 20 and 45 years were randomized to one of three treatment groups: Group A (placebo implant four weekly + placebo tablets daily), Group B (goserelin 3.6 mg implant four weekly + estradiol valerate 2 mg daily with norethisterone 5 mg from days 21-28 of a 28-day cycle) or Group C (goserelin 3.6 mg implant four weekly + placebo tablets daily). Differences between PMS scores at 2, 4 and 6 months were compared with pretreatment values. There was a significant improvement in PMS scores in Group C (Zoladex + placebo) after 2, 4 and 6 months of treatment when compared to pretreatment values and Group A (placebo + placebo). The addition of a low-dose oral estrogen with a cyclical progestogen to GnRH analog treatment (Group B) resulted in a less dramatic response when compared to pretreatment values and no significant improvement when compared to Group A (placebo + placebo) at 2, 4 and 6 months of treatment. The addition of a low-dose oral estrogen with a cyclical progestogen to depot GnRH analog therapy in the treatment of PMS reduces the clinical response.

Risk of venous thrombosis in users of hormonal contraceptives in German gynaecological practices: a patient database analysis.

Science.gov (United States)

Ziller, M; Ziller, V; Haas, G; Rex, J; Kostev, K

2014-02-01

Recent studies showed differences in the risk of venous thrombosis between different combined hormonal contraceptives. Database studies comprising large cohorts can add relevant aspects from daily clinical practice. The purpose of this study was to evaluate different progestogen in combination with ethinylestradiol on the risk of venous thrombosis in Germany. Computerized data from 68,168 contraceptive users in gynecological practices throughout Germany (Disease Analyzer Database) were analyzed. The adjusted odds ratios for risk of thrombosis were estimated in users of different oral contraceptive (OC) formulations relative to users of levonorgestrel-containing preparations. In total, 38 (0.06 %) of the 68,168 contraceptive users had a recorded diagnosis of thrombosis within 365 days after the initial prescription. The adjusted risk was 1.95 for desogestrel (95 % CI 0.52-7.29), 2.97 for dienogest (95 % CI 0.96-9.24), 1.57 for drospirenone (95 % CI 0.46-5.38), 2.54 for chlormadinone (95 % CI 0.72-9.04), and 3.24 for norgestimate (95 % CI 0.59-17.75) compared to levonorgestrel. None of those findings reached statistical significance. The maximum absolute increase versus levonorgestrel was 6 cases per 10,000 women (n.s.). The study shows the low incidence rates of thrombosis in OC users. Since there is no significant difference, this study does not confirm an increased risk but shows only a tendency for this risk of third- and fourth-generation OC versus levonorgestrel-containing products.

Sequential Generalized Transforms on Function Space

Directory of Open Access Journals (Sweden)

Jae Gil Choi

2013-01-01

Full Text Available We define two sequential transforms on a function space Ca,b[0,T] induced by generalized Brownian motion process. We then establish the existence of the sequential transforms for functionals in a Banach algebra of functionals on Ca,b[0,T]. We also establish that any one of these transforms acts like an inverse transform of the other transform. Finally, we give some remarks about certain relations between our sequential transforms and other well-known transforms on Ca,b[0,T].

Forced Sequence Sequential Decoding

DEFF Research Database (Denmark)

Jensen, Ole Riis; Paaske, Erik

1998-01-01

We describe a new concatenated decoding scheme based on iterations between an inner sequentially decoded convolutional code of rate R=1/4 and memory M=23, and block interleaved outer Reed-Solomon (RS) codes with nonuniform profile. With this scheme decoding with good performance is possible as low...... as Eb/N0=0.6 dB, which is about 1.25 dB below the signal-to-noise ratio (SNR) that marks the cutoff rate for the full system. Accounting for about 0.45 dB due to the outer codes, sequential decoding takes place at about 1.7 dB below the SNR cutoff rate for the convolutional code. This is possible since...... the iteration process provides the sequential decoders with side information that allows a smaller average load and minimizes the probability of computational overflow. Analytical results for the probability that the first RS word is decoded after C computations are presented. These results are supported...

Sequential probability ratio controllers for safeguards radiation monitors

International Nuclear Information System (INIS)

Fehlau, P.E.; Coop, K.L.; Nixon, K.V.

1984-01-01

Sequential hypothesis tests applied to nuclear safeguards accounting methods make the methods more sensitive to detecting diversion. The sequential tests also improve transient signal detection in safeguards radiation monitors. This paper describes three microprocessor control units with sequential probability-ratio tests for detecting transient increases in radiation intensity. The control units are designed for three specific applications: low-intensity monitoring with Poisson probability ratios, higher intensity gamma-ray monitoring where fixed counting intervals are shortened by sequential testing, and monitoring moving traffic where the sequential technique responds to variable-duration signals. The fixed-interval controller shortens a customary 50-s monitoring time to an average of 18 s, making the monitoring delay less bothersome. The controller for monitoring moving vehicles benefits from the sequential technique by maintaining more than half its sensitivity when the normal passage speed doubles

The influence of certain environmental factors on the sexual development and reproductive ability of Karakul sheep

International Nuclear Information System (INIS)

Faure, A.S.

1986-01-01

An investigation conducted on the influence of season of birth on sexual development, reproduction and luteinizing hormone of karakul sheep is described. The influence of season of birth on testosterone and semen properties of rams as well as nutrition and exogenous oestrogen of ewes are discussed. A radioimmunology technique was used for the determination of testosterone concentration of karakul rams. A Radioimmunology technique was also used for the determination of the plasma concentration of oestrogen and progesterone of ewe lambs. Results obtained, provided sufficient evidence that the Karakul sheep can reproduce successfully early in life which is desirable to enhance reproduction. It also emphasised the importance of optimal nutrition to promote sexual development and reproduction

Influence of certain environmental factors on the sexual development and reproductive ability of Karakul sheep. Die invloed van sekere omgewingsfakfore op die geslagsontwikkeling en reproduksievermoe van Karakoelskape

Energy Technology Data Exchange (ETDEWEB)

Faure, A S

1986-01-01

An investigation conducted on the influence of season of birth on sexual development, reproduction and luteinizing hormone of Karakul sheep is described. The influence of season of birth on testosterone and semen properties of rams as well as nutrition and exogenous oestrogen of ewes are discussed. A radioimmunology technique was used for the determination of testosterone concentration of Karakul rams. A radioimmunology technique was also used for the determination of the plasma concentration of oestrogen and progesterone of ewe lambs. Results obtained, provided sufficient evidence that the Karakul sheep can reproduce successfully early in life which is desirable to enhance reproduction. It also emphasised the importance of optimal nutrition to promote sexual development and reproduction.

Biased lineups: sequential presentation reduces the problem.

Science.gov (United States)

Lindsay, R C; Lea, J A; Nosworthy, G J; Fulford, J A; Hector, J; LeVan, V; Seabrook, C

1991-12-01

Biased lineups have been shown to increase significantly false, but not correct, identification rates (Lindsay, Wallbridge, & Drennan, 1987; Lindsay & Wells, 1980; Malpass & Devine, 1981). Lindsay and Wells (1985) found that sequential lineup presentation reduced false identification rates, presumably by reducing reliance on relative judgment processes. Five staged-crime experiments were conducted to examine the effect of lineup biases and sequential presentation on eyewitness recognition accuracy. Sequential lineup presentation significantly reduced false identification rates from fair lineups as well as from lineups biased with regard to foil similarity, instructions, or witness attire, and from lineups biased in all of these ways. The results support recommendations that police present lineups sequentially.

Insulin-like growth factors I and II in healthy women with and without established osteoporosis

DEFF Research Database (Denmark)

Ravn, Pernille; Spencer, E M; Christiansen, C

1995-01-01

-controlled treatment with continuous estrogen/progestogen, anabolic steroids, salmon calcitonin or placebo and the IGFs were measured every 6 months. Women less than 35 years of age had 29% higher levels of IGF-I (p ....05) was seen in the nandrolone decanoate-treated group. The same tendency was seen for hormone replacement therapy, although it was not significant. In conclusion, the serum level of IGF-I is high in young women, when peak bone mass is attained, and low in postmenopausal women with established osteoporosis....

Contraceptives as possible risk factors for postpartum depression: A retrospective study of the food and drug administration adverse event reporting system, 2004-2015.

Science.gov (United States)

Horibe, Megumi; Hane, Yuuki; Abe, Junko; Matsui, Toshinobu; Kato, Yamato; Ueda, Natsumi; Sasaoka, Sayaka; Motooka, Yumi; Hatahira, Haruna; Hasegawa, Shiori; Kinosada, Yasutomi; Hara, Hideaki; Nakamura, Mitsuhiro

2018-04-01

Postpartum depression is a mood disorder that commonly affects women during the early postpartum period. The objective of this study was to analyse the association of postpartum depression with drugs (including contraceptive devices and implants) with spontaneously reported adverse events reported in the US Food and Drug Administration Adverse Event Reporting System database. Retrospective study. Reports of postpartum depression events between 2004-2015 were analysed with a reporting odds ratio (ROR) algorithm. The Medical Dictionary for Regulatory Activities was used to identify postpartum depression. The reporting odds ratios (95% confidence intervals, CI) of levonorgestrel (an intrauterine device with progestogen), etonogestrel (a hormonal contraceptive implant), sertraline and drospirenone (an oral contraceptive) were 12.5 (8.7-18.0), 14.0 (8.5-22.8), 12.2 (6.5-23.1) and 5.4 (2.7-10.9) respectively. Among the drugs in the US Food and Drug Administration Adverse Event Reporting System database, the use of contraceptives or an intrauterine device with progestogen might convey risk for postpartum depression.

Lineup composition, suspect position, and the sequential lineup advantage.

Science.gov (United States)

Carlson, Curt A; Gronlund, Scott D; Clark, Steven E

2008-06-01

N. M. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001) argued that sequential lineups reduce the likelihood of mistaken eyewitness identification. Experiment 1 replicated the design of R. C. L. Lindsay and G. L. Wells (1985), the first study to show the sequential lineup advantage. However, the innocent suspect was chosen at a lower rate in the simultaneous lineup, and no sequential lineup advantage was found. This led the authors to hypothesize that protection from a sequential lineup might emerge only when an innocent suspect stands out from the other lineup members. In Experiment 2, participants viewed a simultaneous or sequential lineup with either the guilty suspect or 1 of 3 innocent suspects. Lineup fairness was varied to influence the degree to which a suspect stood out. A sequential lineup advantage was found only for the unfair lineups. Additional analyses of suspect position in the sequential lineups showed an increase in the diagnosticity of suspect identifications as the suspect was placed later in the sequential lineup. These results suggest that the sequential lineup advantage is dependent on lineup composition and suspect position. (c) 2008 APA, all rights reserved

Sexual dimorphism in medulloblastoma features.

Science.gov (United States)

Zannoni, Gian Franco; Ciucci, Alessandra; Marucci, Gianluca; Travaglia, Daniele; Stigliano, Egidio; Foschini, Maria Pia; Scambia, Giovanni; Gallo, Daniela

2016-03-01

Male sex is a risk factor for medulloblastoma (MB), and is also a negative predictor for clinical outcome. The aim of this study was to assess sex differences in tumour biological features and hormone receptor profiles in a cohort of MB patients. Sixty-four MBs and five normal cerebella were included in the study. Cell proliferation (Ki67), apoptosis (cleaved caspase-3) and microvessel density (CD31) were evaluated in tumours by immunohistochemistry. Tissues were analysed for oestrogen receptor (ER)α, ERβ1, ERβ2, ERβ5 and androgen receptor (AR) expression. The results demonstrated sex-specific features in MBs, with tumours from females showing a higher apoptosis/proliferation ratio and less tumour vascularization than tumours from males. MBs were negative for ERα and AR, but expressed ERβ isoforms at similar levels between the sexes. Altogether, these findings indicate that signalling mechanisms that control cell turnover and angiogenesis operate more efficiently in females than in males. The lack of sex differences in the hormone receptor profiles suggests that circulating oestrogens could be the major determinants of the sexual dimorphism observed in MB features. Here, we provide molecular support for epidemiological data showing sex differences in MB incidence and outcome, completely defining the hormone receptor profile of the tumours. © 2015 John Wiley & Sons Ltd.

Tradable permit allocations and sequential choice

Energy Technology Data Exchange (ETDEWEB)

MacKenzie, Ian A. [Centre for Economic Research, ETH Zuerich, Zurichbergstrasse 18, 8092 Zuerich (Switzerland)

2011-01-15

This paper investigates initial allocation choices in an international tradable pollution permit market. For two sovereign governments, we compare allocation choices that are either simultaneously or sequentially announced. We show sequential allocation announcements result in higher (lower) aggregate emissions when announcements are strategic substitutes (complements). Whether allocation announcements are strategic substitutes or complements depends on the relationship between the follower's damage function and governments' abatement costs. When the marginal damage function is relatively steep (flat), allocation announcements are strategic substitutes (complements). For quadratic abatement costs and damages, sequential announcements provide a higher level of aggregate emissions. (author)

Hormones

Science.gov (United States)

Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

Applying the minimax principle to sequential mastery testing

NARCIS (Netherlands)

Vos, Hendrik J.

2002-01-01

The purpose of this paper is to derive optimal rules for sequential mastery tests. In a sequential mastery test, the decision is to classify a subject as a master, a nonmaster, or to continue sampling and administering another random item. The framework of minimax sequential decision theory (minimum

Classical and sequential limit analysis revisited

Science.gov (United States)

Leblond, Jean-Baptiste; Kondo, Djimédo; Morin, Léo; Remmal, Almahdi

2018-04-01

Classical limit analysis applies to ideal plastic materials, and within a linearized geometrical framework implying small displacements and strains. Sequential limit analysis was proposed as a heuristic extension to materials exhibiting strain hardening, and within a fully general geometrical framework involving large displacements and strains. The purpose of this paper is to study and clearly state the precise conditions permitting such an extension. This is done by comparing the evolution equations of the full elastic-plastic problem, the equations of classical limit analysis, and those of sequential limit analysis. The main conclusion is that, whereas classical limit analysis applies to materials exhibiting elasticity - in the absence of hardening and within a linearized geometrical framework -, sequential limit analysis, to be applicable, strictly prohibits the presence of elasticity - although it tolerates strain hardening and large displacements and strains. For a given mechanical situation, the relevance of sequential limit analysis therefore essentially depends upon the importance of the elastic-plastic coupling in the specific case considered.

Simultaneous versus sequential penetrating keratoplasty and cataract surgery.

Science.gov (United States)

Hayashi, Ken; Hayashi, Hideyuki

2006-10-01

To compare the surgical outcomes of simultaneous penetrating keratoplasty and cataract surgery with those of sequential surgery. Thirty-nine eyes of 39 patients scheduled for simultaneous keratoplasty and cataract surgery and 23 eyes of 23 patients scheduled for sequential keratoplasty and secondary phacoemulsification surgery were recruited. Refractive error, regular and irregular corneal astigmatism determined by Fourier analysis, and endothelial cell loss were studied at 1 week and 3, 6, and 12 months after combined surgery in the simultaneous surgery group or after subsequent phacoemulsification surgery in the sequential surgery group. At 3 and more months after surgery, mean refractive error was significantly greater in the simultaneous surgery group than in the sequential surgery group, although no difference was seen at 1 week. The refractive error at 12 months was within 2 D of that targeted in 15 eyes (39%) in the simultaneous surgery group and within 2 D in 16 eyes (70%) in the sequential surgery group; the incidence was significantly greater in the sequential group (P = 0.0344). The regular and irregular astigmatism was not significantly different between the groups at 3 and more months after surgery. No significant difference was also found in the percentage of endothelial cell loss between the groups. Although corneal astigmatism and endothelial cell loss were not different, refractive error from target refraction was greater after simultaneous keratoplasty and cataract surgery than after sequential surgery, indicating a better outcome after sequential surgery than after simultaneous surgery.

Parasitism by Cuscuta pentagona sequentially induces JA and SA defence pathways in tomato.

Science.gov (United States)

Runyon, Justin B; Mescher, Mark C; Felton, Gary W; De Moraes, Consuelo M

2010-02-01

While plant responses to herbivores and pathogens are well characterized, responses to attack by other plants remain largely unexplored. We measured phytohormones and C(18) fatty acids in tomato attacked by the parasitic plant Cuscuta pentagona, and used transgenic and mutant plants to explore the roles of the defence-related phytohormones salicylic acid (SA) and jasmonic acid (JA). Parasite attachment to 10-day-old tomato plants elicited few biochemical changes, but a second attachment 10 d later elicited a 60-fold increase in JA, a 30-fold increase in SA and a hypersensitive-like response (HLR). Host age also influenced the response: neither Cuscuta seedlings nor established vines elicited a HLR in 10-day-old hosts, but both did in 20-day-old hosts. Parasites grew larger on hosts deficient in SA (NahG) or insensitive to JA [jasmonic acid-insensitive1 (jai1)], suggesting that both phytohormones mediate effective defences. Moreover, amounts of JA peaked 12 h before SA, indicating that defences may be coordinated via sequential induction of these hormones. Parasitism also induced increases in free linolenic and linoleic acids and abscisic acid. These findings provide the first documentation of plant hormonal signalling induced by a parasitic plant and show that tomato responses to C. pentagona display characteristics similar to both herbivore- and pathogen-induced responses.

Enhanced screening efficiency for endocrine-disrupting chemicals in milk and powdered milk using UPLC/QTOF-MS by the introduction of dansyl chloride derivatisation.

Science.gov (United States)

Wang, He-Xing; Zhou, Ying; Jiang, Qing-Wu

2013-01-01

This study developed and validated a sensitive analytical method for simultaneous screening of four classes of endocrine-disrupting chemicals (i.e. progestogens, androgens, oestrogens and phenols) in milk and powdered milk using ultra-performance liquid chromatography (UPLC) coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry (QTOF-MS). Dansylation of oestrogens and phenols enhanced the ionisation efficiency and shifted the ionisation mode from negative to positive, which allowed for the simultaneous analysis of four EDCs in one chromatographic run. An efficient sample pre-treatment minimised the matrix effects. The mass errors for the precursor and product ions for 26 target compounds varied between -2.8 and 2.3 mDa; and the limits of detection (signal-to-noise ratio = 3) for milk and powdered milk were less than 0.04 µg l(-1) and 0.10 µg kg(-1), respectively. The proposed method was successfully used to analyse multiple types of real samples, including normal temperature whole milk, infant formula and whole powdered milk. In 11 samples, two target compounds, progesterone and androstenedione, were detected. The progesterone concentrations ranged from 8.1 to 12.7 µg l(-1) in milk, and from 1.2 to 32.0 µg kg(-1) in infant formulas and whole powdered milks. The androstenedione concentrations varied from 0.39 to 0.79 µg l(-1) in milks, and from 0.29 to 1.2 µg kg(-1) in infant formulas and whole powdered milks. Two post-target compounds, one isomer of oestriol and 5α-dihydroprogesterone, were tentatively identified by post-target analysis in two of 11 real samples.

Trial Sequential Methods for Meta-Analysis

Science.gov (United States)

Kulinskaya, Elena; Wood, John

2014-01-01

Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

Sequentially pulsed traveling wave accelerator

Science.gov (United States)

Caporaso, George J [Livermore, CA; Nelson, Scott D [Patterson, CA; Poole, Brian R [Tracy, CA

2009-08-18

A sequentially pulsed traveling wave compact accelerator having two or more pulse forming lines each with a switch for producing a short acceleration pulse along a short length of a beam tube, and a trigger mechanism for sequentially triggering the switches so that a traveling axial electric field is produced along the beam tube in synchronism with an axially traversing pulsed beam of charged particles to serially impart energy to the particle beam.

Exaggerated gonadotropin response to luteinizing hormone-releasing hormone in amenorrheic runners.

Science.gov (United States)

Yahiro, J; Glass, A R; Fears, W B; Ferguson, E W; Vigersky, R A

1987-03-01

Most studies of exercise-induced amenorrhea have compared amenorrheic athletes (usually runners) with sedentary control subjects. Such comparisons will identify hormonal changes that develop as a result of exercise training but cannot determine which of these changes play a role in causing amenorrhea. To obviate this problem, we assessed reproductive hormone status in a group of five amenorrheic runners and compared them to a group of six eumenorrheic runners matched for body fatness, training intensity, and exercise performance. Compared to the eumenorrheic runners, the amenorrheic runners had lower serum estradiol concentrations, similar basal serum luteinizing hormone and follicle-stimulating hormone concentrations, and exaggerated responses of serum gonadotropins after administration of luteinizing hormone-releasing hormone (100 micrograms intravenous bolus). Serum prolactin levels, both basally and after thyrotropin-releasing hormone administration (500 micrograms intravenous bolus) or treadmill exercise, was similar in the two groups, as were serum thyroid function tests (including thyrotropin response to thyrotropin-releasing hormone). Changes in serum cortisol levels after short-term treadmill exercise were similar in both groups, and serum testosterone levels increased after exercise only in the eumenorrheic group. In neither group did such exercise change serum luteinizing hormone, follicle-stimulating hormone, or thyrotropin levels. We concluded that exercise-induced amenorrhea is not solely related to the development of increased prolactin output after exercise training. The exaggerated gonadotropin response to luteinizing hormone-releasing hormone seen in amenorrheic runners in comparison with matched eumenorrheic runners is consistent with a hypothalamic etiology for the menstrual dysfunction, analogous to that previously described in "stress-induced" or "psychogenic" amenorrhea.

Overnight Levels of Luteinizing Hormone, Follicle-Stimulating Hormone and Growth Hormone before and during Gonadotropin-Releasing Hormone Analogue Treatment in Short Boys Born Small for Gestational Age

NARCIS (Netherlands)

van der Kaay, Danielle C. M.; de Jong, Frank H.; Rose, Susan R.; Odink, Roelof J. H.; Bakker-van Waarde, Willie M.; Sulkers, Eric J.; Hokken-Koelega, Anita C. S.

2009-01-01

Aims: To evaluate if 3 months of gonadotropin-releasing hormone analogue (GnRHa) treatment results in sufficient suppression of pubertal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) profile patterns in short pubertal small for gestational age (SGA) boys. To compare growth hormone

Role of obestatin on growth hormone secretion: An in vitro approach

International Nuclear Information System (INIS)

Pazos, Yolanda; Alvarez, Carlos J.P.; Camina, Jesus P.; Al-Massadi, Omar; Seoane, Luisa M.; Casanueva, Felipe F.

2009-01-01

Obestatin, the ghrelin-associated peptide, showed to activate MAPK signaling with no effect on Akt nor cell proliferating activity in rat tumor somatotroph cells (growth cells, GC). A sequential analysis of the obestatin transmembrane signaling pathway indicated a route involving the consecutive activation of G i , PI3k, novel PKCε, and Src for ERK1/2 activation. Furthermore, obestatin treatment triggers growth hormone (GH) release in the first 30 min, being more acute at 15 min. At 1 h, obestatin treated cells showed the same levels in GH secretion than controls. Added to this functionality, obestatin was secreted by GC cells. Based on the capacity to stimulate GH release from somatotroph cells, obestatin may act directly in the pituitary through an autocrine/paracrine mechanism.

Role of obestatin on growth hormone secretion: An in vitro approach

Energy Technology Data Exchange (ETDEWEB)

Pazos, Yolanda [Area de Endocrinologia Molecular y Celular, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela (Spain); CIBER Fisiopatologia de la Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III (Spain); Alvarez, Carlos J.P. [Area de Endocrinologia Molecular y Celular, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela (Spain); CIBER Fisiopatologia de la Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III (Spain); Universidad de Santiago de Compostela (USC), Santiago de Compostela (Spain); Camina, Jesus P. [Area de Endocrinologia Molecular y Celular, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela (Spain); CIBER Fisiopatologia de la Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III (Spain); Al-Massadi, Omar [Area de Endocrinologia Molecular y Celular, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela (Spain); CIBER Fisiopatologia de la Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III (Spain); Universidad de Santiago de Compostela (USC), Santiago de Compostela (Spain); Seoane, Luisa M. [Area de Endocrinologia Molecular y Celular, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela (Spain); CIBER Fisiopatologia de la Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III (Spain); Casanueva, Felipe F. [Area de Endocrinologia Molecular y Celular, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela (Spain); CIBER Fisiopatologia de la Obesidad y Nutricion (CB06/03), Instituto de Salud Carlos III (Spain); Universidad de Santiago de Compostela (USC), Santiago de Compostela (Spain)

2009-12-25

Obestatin, the ghrelin-associated peptide, showed to activate MAPK signaling with no effect on Akt nor cell proliferating activity in rat tumor somatotroph cells (growth cells, GC). A sequential analysis of the obestatin transmembrane signaling pathway indicated a route involving the consecutive activation of G{sub i}, PI3k, novel PKC{epsilon}, and Src for ERK1/2 activation. Furthermore, obestatin treatment triggers growth hormone (GH) release in the first 30 min, being more acute at 15 min. At 1 h, obestatin treated cells showed the same levels in GH secretion than controls. Added to this functionality, obestatin was secreted by GC cells. Based on the capacity to stimulate GH release from somatotroph cells, obestatin may act directly in the pituitary through an autocrine/paracrine mechanism.

The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

Science.gov (United States)

Root, A W; Shulman, D; Root, J; Diamond, F

1986-01-01

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

The 2017 hormone therapy position statement of The North American Menopause Society.

Science.gov (United States)

2017-07-01

The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS) updates the 2012 Hormone Therapy Position Statement of The North American Menopause Society and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2012 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees.Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT.For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture. For women who initiate HT more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS or bone loss, with shared decision making and periodic reevaluation. For bothersome GSM symptoms not

An Efficient System Based On Closed Sequential Patterns for Web Recommendations

OpenAIRE

Utpala Niranjan; R.B.V. Subramanyam; V-Khana

2010-01-01

Sequential pattern mining, since its introduction has received considerable attention among the researchers with broad applications. The sequential pattern algorithms generally face problems when mining long sequential patterns or while using very low support threshold. One possible solution of such problems is by mining the closed sequential patterns, which is a condensed representation of sequential patterns. Recently, several researchers have utilized the sequential pattern discovery for d...

The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer

Science.gov (United States)

Chakravarty, Dimple; Sboner, Andrea; Nair, Sujit S.; Giannopoulou, Eugenia; Li, Ruohan; Hennig, Sven; Mosquera, Juan Miguel; Pauwels, Jonathan; Park, Kyung; Kossai, Myriam; MacDonald, Theresa Y.; Fontugne, Jacqueline; Erho, Nicholas; Vergara, Ismael A.; Ghadessi, Mercedeh; Davicioni, Elai; Jenkins, Robert B.; Palanisamy, Nallasivam; Chen, Zhengming; Nakagawa, Shinichi; Hirose, Tetsuro; Bander, Neil H.; Beltran, Himisha; Fox, Archa H.; Elemento, Olivier; Rubin, Mark A.

2014-01-01

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical cohorts also revealed that NEAT1 expression is associated with prostate cancer progression. Prostate cancer cells expressing high levels of NEAT1 were recalcitrant to androgen or AR antagonists. Finally, we provide evidence that NEAT1 drives oncogenic growth by altering the epigenetic landscape of target gene promoters to favour transcription. PMID:25415230

Integration of inorganic and isotopic geochemistry with endocrine disruption activity assays to assess risks to water resources near unconventional oil and gas development in Garfield County, CO.

Science.gov (United States)

Harkness, J.; Kassotis, C.; Cornelius, J.; Nagel, S.; Vengosh, A.

2016-12-01

The rise of hydraulic fracturing in the United States has sparked a debate about the impact of oil and gas development on the quality of water resources. Wastewater associated with hydraulic fracturing includes injection fluid that is a mixture of sand, freshwater and synthetic organic chemicals, flowback water that is a mixture of injection fluid and formation brine, and produced water that is primarily brine. The fluids range in salinity and chemical composition that can have different environmental impacts. We analyzed the inorganic and isotope geochemistry of 58 surface and groundwater samples near and away from unconventional oil and gas operations (UOG), along with hormonal profiles via bioassays. Cl (0.12 to 198 mg/L), Na (1.2 to 518 mg/L) and Sr (1.4 to 2410 ug/L) were higher in both groundwater and surface water near UOG wells. Four surface waters and one groundwater had Br/Cl indicative of brine contamination (>1.5x10-3). Three of the SW samples also had 87Sr/86Sr ratios similar to values found in produced or flowback water (0.7118 and 0.7158, respectively) from the Williams-Fork formation and elevated compared to background ratios (0.71062 to 0.7115). Increased progestogenic activity was observed in groundwater near UOG operations and inncreased estrogenic, androgenic, progestogenic, anti-androgenic, anti-progestogenic, and anti-glucocorticoid activities in surface water near UOG operations. The association of increased EDCs with inorganic and isotopic indicators of UOG wastewater provides evidence for possible environmental and health impacts from drilling activity.

Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

DEFF Research Database (Denmark)

Hubina, Erika; Mersebach, Henriette; Rasmussen, Ase Krogh

2004-01-01

We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes.......We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes....

Region-specific expression and hormonal regulation of the first exon variants of rat prolactin receptor mRNA in rat brain and anterior pituitary gland.

Science.gov (United States)

Nogami, H; Hoshino, R; Ogasawara, K; Miyamoto, S; Hisano, S

2007-08-01

Recent studies have revealed the occurrence of five first exon variants of the rat prolactin receptor mRNA, suggesting that multiple promoters direct prolactin receptor transcription in response to different regulatory factors. In the present study, regional expression of these first exon variants, as well as two prolactin receptor subtypes generated by alternative splicing, was examined in the brains and anterior pituitary glands of female rats. Expression of the long-form was detected in the choroid plexus, hypothalamus, hippocampus, cerebral cortex and anterior pituitary gland, whereas the short form was detected only in the choroid plexus. E1-3 mRNA, a first exon variant, was detected in the choroid plexus, hypothalamus, and anterior pituitary gland, whereas E1-4 was detected only in the choroid plexus. Other variants were not detectable by the polymerase chain reaction protocol employed in this study. Ovariectomy increased the short form in the choroid plexus and the E1-3 expression in the choroid plexus and pituitary gland, but changes in the long-form and E1-4 expression were minimal. Replacement of oestrogens and prolactin suggest that oestrogens down-regulate E1-3 expression in the choroid plexus and pituitary gland, and that the negative effect of oestrogen is mediated by prolactin in the pituitary gland. The present results revealed the region-specific promoter usage in prolactin receptor mRNA transcription, as well as the involvement of oestrogens in the regulation of E1-3 mRNA expression in the brain and pituitary gland.

Discrimination between sequential and simultaneous virtual channels with electrical hearing.

Science.gov (United States)

Landsberger, David; Galvin, John J

2011-09-01

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation modes. For sequential VCs, the interpulse interval (IPI) varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud, loudness-balanced levels at a 250 pulse per second per electrode (ppse) stimulation rate. On average, CI subjects were able to reliably discriminate between sequential and simultaneous VCs. While there was no significant effect of IPI or stimulation mode on VC discrimination, some subjects exhibited better VC discrimination with BP + 1 stimulation. Subjects' discrimination between sequential and simultaneous VCs was correlated with electrode discrimination, suggesting that spatial selectivity may influence perception of sequential VCs. To maintain equal loudness, sequential VC amplitudes were nearly double those of simultaneous VCs, presumably resulting in a broader spread of excitation. These results suggest that perceptual differences between simultaneous and sequential VCs might be explained by differences in the spread of excitation. © 2011 Acoustical Society of America

Sequential versus simultaneous market delineation

DEFF Research Database (Denmark)

Haldrup, Niels; Møllgaard, Peter; Kastberg Nielsen, Claus

2005-01-01

and geographical markets. Using a unique data setfor prices of Norwegian and Scottish salmon, we propose a methodologyfor simultaneous market delineation and we demonstrate that comparedto a sequential approach conclusions will be reversed.JEL: C3, K21, L41, Q22Keywords: Relevant market, econometric delineation......Delineation of the relevant market forms a pivotal part of most antitrustcases. The standard approach is sequential. First the product marketis delineated, then the geographical market is defined. Demand andsupply substitution in both the product dimension and the geographicaldimension...

Impact of hormone therapy on quality of life after menopause.

Science.gov (United States)

Utian, Wulf H; Woods, Nancy Fugate

2013-10-01

Given the complexity of the literature on quality of life (QOL) and hormone therapy (HT) among women in the menopausal transition and postmenopause, the purposes of this integrative review were to (1) define QOL as a multidimensional construct; (2) review validated instruments for measurement of QOL; (3) review results of HT and QOL clinical trials that have used validated instruments; and (4) assess the effectiveness of HT on QOL, including health-related QOL (HRQOL), menopause-specific QOL (MSQOL), and global QOL (GQOL). The literature on HT and QOL was searched for definitions of QOL and validated instruments for measuring QOL, and the results were summarized. The purposes of this integrative review were to evaluate the effects of HT on HRQOL, differentiating the effects of HT on GQOL, HRQOL, and MSQOL. As a basis for this review, we searched for published controlled clinical trials in which the effects of HT on QOL were studied using validated QOL instruments, in particular menopause-specific validated instruments. Clear definitions are elucidated. Validated instruments for the measurements of HRQOL, GQOL, and MSQOL are summarized, and the necessity of their incorporation into future research and clinical practice is emphasized. The published effects on QOL of estrogens and progestogens administered to symptomatic and nonsymptomatic women in the menopausal transition and beyond are reviewed. The impact of various health state-related symptoms on HRQOL and GQOL is now an integral component of contemporary health care. Effects of HT include GQOL and HRQOL and should be menopause-specific. There is clearly a need for further studies on menopause and menopause-related therapies using appropriate and validated instruments. Literature review shows that HT provides a significant benefit for MSQOL in midlife women, mainly through relief of symptoms, but treatment also may result in a global increase in sense of well-being (GQOL). HRQOL benefits are contingent on

Disease expression in women with hereditary angioedema

DEFF Research Database (Denmark)

Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle

2008-01-01

OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT p......-sensitive phenotype for some patients. CONCLUSION: The course of angioedema in women with C1 inhibitor deficiency is affected by physiologic hormonal changes; consequently, physicians should take these into account when advising on management.......OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...... project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills...

Bioidentical Hormones and Menopause

Science.gov (United States)

... Endocrinologist Search Featured Resource Menopause Map™ View Bioidentical Hormones January 2012 Download PDFs English Espanol Editors Howard ... take HT for symptom relief. What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

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

Science.gov (United States)

Manickum, Thavrin; John, Wilson

2015-07-01

The availability of national test centers to offer a routine service for analysis and quantitation of some selected steroid hormones [natural estrogens (17-β-estradiol, E2; estrone, E1; estriol, E3), synthetic estrogen (17-α-ethinylestradiol, EE2), androgen (testosterone), and progestogen (progesterone)] in wastewater matrix was investigated; corresponding internationally used chemical- and immuno-analytical test methods were reviewed. The enzyme-linked immunosorbent assay (ELISA) (immuno-analytical technique) was also assessed for its suitability as a routine test method to quantitate the levels of these hormones at a sewage/wastewater treatment plant (WTP) (Darvill, Pietermaritzburg, South Africa), over a 2-year period. The method performance and other relevant characteristics of the immuno-analytical ELISA method were compared to the conventional chemical-analytical methodology, like gas/liquid chromatography-mass spectrometry (GC/LC-MS), and GC-LC/tandem mass spectrometry (MSMS), for quantitation of the steroid hormones in wastewater and environmental waters. The national immuno-analytical ELISA technique was found to be sensitive (LOQ 5 ng/L, LOD 0.2-5 ng/L), accurate (mean recovery 96%), precise (RSD 7-10%), and cost-effective for screening and quantitation of these steroid hormones in wastewater and environmental water matrix. A survey of the most current international literature indicates a fairly equal use of the LC-MS/MS, GC-MS/MS (chemical-analytical), and ELISA (immuno-analytical) test methods for screening and quantitation of the target steroid hormones in both water and wastewater matrix. Internationally, the observed sensitivity, based on LOQ (ng/L), for the steroid estrogens E1, E2, EE2, is, in decreasing order: LC-MSMS (0.08-9.54) > GC-MS (1) > ELISA (5) (chemical-analytical > immuno-analytical). At the national level, the routine, unoptimized chemical-analytical LC-MSMS method was found to lack the required sensitivity for meeting environmental

Group-sequential analysis may allow for early trial termination

DEFF Research Database (Denmark)

Gerke, Oke; Vilstrup, Mie H; Halekoh, Ulrich

2017-01-01

BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT mea......BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG...

Sequential logic analysis and synthesis

CERN Document Server

Cavanagh, Joseph

2007-01-01

Until now, there was no single resource for actual digital system design. Using both basic and advanced concepts, Sequential Logic: Analysis and Synthesis offers a thorough exposition of the analysis and synthesis of both synchronous and asynchronous sequential machines. With 25 years of experience in designing computing equipment, the author stresses the practical design of state machines. He clearly delineates each step of the structured and rigorous design principles that can be applied to practical applications. The book begins by reviewing the analysis of combinatorial logic and Boolean a

Use of hormone replacement therapy in the Hong Kong public health sector after the Women's Health Initiative trial.

Science.gov (United States)

Leung, K Y; Ling, Matina; Tang, G W K

2005-01-01

To determine the impact of Women Health Initiative (WHI) trial on the use of hormone replacement therapy (HRT) in the Hong Kong public health sector. The central prescription database of the Hospital Authority was used to describe the half-yearly trend in the use of HRT between July 2000 and December 2003. The data of hysterectomy was retrieved from another clinical database. Before the publication of the WHI trial in July 2002, conjugated equine estrogens (CEE) and its related products dominated HRT prescribing. Relative to the first half of 2002, there was an immediate and substantial decline by 43.5% in the prescriptions of combined CEE/progestogen products and a modest decline by 22.4% in the prescriptions of CEE-alone therapy in the second half of 2002. In the first half of 2003, a decline in the prescriptions of all HRT preparations except raloxifene was observed. However, in the second half of 2003, there were no more declines in overall HRT users. Relative to the first half of 2002, the decline in the overall HRT users in the first half of 2003 was more than 46% in women aged 50-69. The decline was greater in women with a history of hysterectomy (60.3%) than women without (38.6%), but was similar between gynaecology specialty (41.7%) and non-gynaecology specialty (43.9%). Similar to the U.S., an immediate and substantial decline in the use of CEE and its related products was observed in Hong Kong after the publication of the WHI trial.

Structural Consistency, Consistency, and Sequential Rationality.

OpenAIRE

Kreps, David M; Ramey, Garey

1987-01-01

Sequential equilibria comprise consistent beliefs and a sequentially ra tional strategy profile. Consistent beliefs are limits of Bayes ratio nal beliefs for sequences of strategies that approach the equilibrium strategy. Beliefs are structurally consistent if they are rationaliz ed by some single conjecture concerning opponents' strategies. Consis tent beliefs are not necessarily structurally consistent, notwithstan ding a claim by Kreps and Robert Wilson (1982). Moreover, the spirit of stru...

HORMONETHERAPY IN MARE

Directory of Open Access Journals (Sweden)

A. L. M. Marinho

2015-06-01

Full Text Available When compared with other domestic animals the equine species is that present the minors reproductive indices. Besides some parameters of estrous cycle are variable to we consider each mare individually, what hinders the reproductive handling, these females respond the alterations of seasonality, this fact limits in reproduction its potential. Therefore, the uses of innovative reproductive biotechnologies and hormonal protocols have shown indispensable for the producers who wish to increase the reproductive rate of this species. Hormontherapy has shown great efficiency in handling the estrous cycle of these females. Thus, this literature review aimed to perform an update regarding hormonal protocols used in the equine species. Dealt with the main hormones used to control the estrous cycle of mares, as prostaglandin F2a (PGF2α, estrogens, progestogens, human chorionic gonadotropin (hCG, the gonadotropin-releasing hormone (GnRH, equine pituitary extract (EPE, the purified equine follicle stimulating hormone (eFSH and oxytocin. It became evident that the knowledge of hormontherapy applied in equine reproduction is of utmost importance, allowing higher profitability by improving the reproductive efficiency of animals of high genetic value, generating benefits for both the professional as to the owner

Effects of antiandrogenic progestins, chlormadinone and cyproterone acetate, and the estrogen 17α-ethinylestradiol (EE2), and their mixtures: Transactivation with human and rainbowfish hormone receptors and transcriptional effects in zebrafish (Danio rerio) eleuthero-embryos

Energy Technology Data Exchange (ETDEWEB)

Siegenthaler, Patricia Franziska [University of Applied Sciences and Arts Northwestern Switzerland (FHNW), School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Bain, Peter [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Land and Water Flagship, PMB2, Glen Osmond, 5064 South Australia (Australia); Riva, Francesco [IRCCS – Istituto di Ricerche Farmacologiche “Mario Negri”, Environmental Biomarkers Unit, Department of Environmental Health Sciences, Via La Masa 19, I-20156 Milan (Italy); Fent, Karl, E-mail: karl.fent@fhnw.ch [University of Applied Sciences and Arts Northwestern Switzerland (FHNW), School of Life Sciences, Gründenstrasse 40, CH-4132 Muttenz (Switzerland); Swiss Federal Institute of Technology (ETH Zürich), Institute of Biogeochemistry and Pollution Dynamics, Department of Environmental System Sciences, CH-8092 Zürich (Switzerland)

2017-01-15

Highlights: • Agonistic and antagonistic activity of CMA and CPA were assessed in vitro. • CMA and CPA showed different interaction with human and fish receptors. • No progestogenic but antiandrogenic and antiglucocorticoid activity occurred in fish. • CMA and CPA showed transcriptional changes in zebrafish embryos. • Binary mixtures of the progestins with EE2 were assessed in vitro and in vivo. - Abstract: Synthetic progestins act as endocrine disrupters in fish but their risk to the environment is not sufficiently known. Here, we focused on an unexplored antiandrogenic progestin, chlormadinone acetate (CMA), and the antiandrogenic progestin cyproterone acetate (CPA). The aim was to evaluate whether their in vitro interaction with human and rainbowfish (Melanotaenia fluviatilis) sex hormone receptors is similar. Furthermore, we investigated their activity in zebrafish (Danio rerio) eleuthero-embryos. First, we studied agonistic and antagonistic activities of CMA, CPA, and 17α-ethinylestradiol (EE2), in recombinant yeast expressing either the human progesterone (PGR), androgen (AR), or estrogen receptor. The same compounds were also investigated in vitro in a stable transfection cell system expressing rainbowfish nuclear steroid receptors. For human receptors, both progestins exhibited progestogenic, androgenic and antiestrogenic activity with no antiandrogenic or estrogenic activity. In contrast, interactions with rainbowfish receptors showed no progestogenic, but antiandrogenic, antiglucocorticoid, and some antiestrogenic activity. Thus, interaction with and transactivation of human and rainbowfish PGR and AR were distinctly different. Second, we analyzed transcriptional alterations in zebrafish eleuthero‐embryos at 96 and 144 h post fertilization after exposure to CPA, CMA, EE2, and binary mixtures of CMA and CPA with EE2, mimicking the use in oral contraceptives. CMA led to slight down-regulation of the ar transcript, while CPA down-regulated ar

Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea.

Science.gov (United States)

Carmina, Enrico; Fruzzetti, Franca; Lobo, Roger A

2016-06-01

Functional hypothalamic amenorrhea is a disorder characterized by cessation of menstrual cycles in the absence of organic disease. In most patients, it occurs in adult life after a stressful event and may be related to a condition of mild chronic energy deprivation. The endocrine pattern is characterized by low estrogen levels with an absent response to a progestogen challenge test and low-normal gonadotropin levels. A few studies have shown that some of these women may have some features of polycystic ovary syndrome; these features include an increased androgen response to gonadotropins, increased anti-Mullerian hormone levels, and altered ovarian morphology or increased ovarian size. These findings suggest a link between these 2 completely different disorders: functional hypothalamic amenorrhea and polycystic ovary syndrome. The importance of the possible coexistence of these disorders in some women is important for follow-up of these women and in their treatment if they desire to become pregnant. To determine whether a subgroup of well-characterized women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Retrospective analysis of women with functional hypothalamic amenorrhea. Forty consecutive patients and 28 normal age-matched control patients were studied. Blood was obtained for serum anti-Mullerian hormone, androgens, and other hormone levels and all women had ovarian ultrasonographic measurements. In the entire group of women with functional hypothalamic amenorrhea, anti-Mullerian hormone and ovarian volume were greater than in control patients. In 13 patients (32.5%), anti-Mullerian hormone was elevated (>4.7 ng/mL, levels consistent with polycystic ovary syndrome) and in this group, ovarian volume was significantly greater than in the remaining patients with functional hypothalamic amenorrhea. Four of the 13 women with functional hypothalamic amenorrhea who had elevated anti-Mullerian hormone levels (10%), also

Hormones and absence epilepsy

NARCIS (Netherlands)

Luijtelaar, E.L.J.M. van; Tolmacheva, E.A.; Budziszewska, B.; Stein, J.

2017-01-01

Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime,

Adult height in Turner syndrome girls after long-term growth hormone treatment Talla adulta en pacientes con síndrome de Turner tratadas con hormona de crecimiento a largo plazo

Directory of Open Access Journals (Sweden)

Analía Morín

2009-10-01

Full Text Available We studied the adult height (AH outcome, and factors likely to influence it, in Turner Syndrome (TS girls treated with growth hormone (GH. A total of 25 TS girls treated with GH were compared with 10 TS girls not treated with GH. The percentage of girls who achieved normal third percentile was determined. Projected AH (PAH was calculated according to height standard deviation score (HSDS at the beginning of the treatment. Gain in height was determined as: AH - pretreatment PAH. The percentage of girls who achieved target range (midparental height±2 SD was determined. Multiple linear regression models were fitted on baseline variables- chronological age (CA, midparental height (MPH and HSDS; and treatment variablesduration of oestrogen-free GH therapy and duration of GH therapy+oestrogens. As for baseline data: median CA was 13.0 years (5.6-15.8. Mean HSDS was 0.25±1.1 SDS. PAH was 139.2±5.6 cm. MPH was 160.0±5.0 cm. As for follow up data: Median CA at onset oestrogens was 15.1 years (13.2-16.6. Median duration of GH therapy was 3.8 years (2.1-10.3. Median oestrogen-free GH period was 2.0 years (0.7-7.8, and median GH+oestrogens period, 1.8 years (1.0-3.2. Adult height: Mean AH was 150.4±7.0 cm in treated patients and 140.8±7.2 cm in the group not treated with GH (p=0.001. Fourteen (56% girls achieved normal third percentile compared with an initially predicted 1 (4%. Gain in height was 11.2±3.7 cm. Thirteen (59% girls reached an AH within target range. HSDS at the beginning of the treatment was the variable most strongly related to AH and duration of oestrogen-free GH period was the variable most strongly related to gain in height.Se estudió la talla adulta (TA y los factores que pudieran influenciarla en niñas con síndrome de Turner (ST tratadas con hormona de crecimiento (HC. Se compararon 25 pacientes con ST tratadas con HC y 10 niñas no tratadas. Se determinó: el porcentaje de niñas que alcanzó el tercer percentilo de la curva

Generalized infimum and sequential product of quantum effects

International Nuclear Information System (INIS)

Li Yuan; Sun Xiuhong; Chen Zhengli

2007-01-01

The quantum effects for a physical system can be described by the set E(H) of positive operators on a complex Hilbert space H that are bounded above by the identity operator I. For A, B(set-membership sign)E(H), the operation of sequential product A(convolution sign)B=A 1/2 BA 1/2 was proposed as a model for sequential quantum measurements. A nice investigation of properties of the sequential product has been carried over [Gudder, S. and Nagy, G., 'Sequential quantum measurements', J. Math. Phys. 42, 5212 (2001)]. In this note, we extend some results of this reference. In particular, a gap in the proof of Theorem 3.2 in this reference is overcome. In addition, some properties of generalized infimum A sqcap B are studied

Oestrogene mimetic isoflavones’ pharmacokinetics and pharmacodynamics

Directory of Open Access Journals (Sweden)

Anca Dragomirescu,

2008-12-01

Full Text Available Genisteine is the most abundant and the most studied estrogen-mimetic izoflavone. It's chemical formula is 4',5,7 – trihidroxyisoflavone. It has also estrogen-modulated properties by its binding ability to the beta type estrogen receptor. Genisteine presents the following farmacodinamic effects: antiaterogen effect, prevention of estrogen-dependent cancers, especially breast cancer, prevention of skin aging body, osteoprogen effect, prevention of osteoporosis at the menopauses women. Despite all these real benefits, there are also many adverse effects, registered both in humans and animals. Thus, the sheep feeding with some Fabaceae species, containing estrogen-mimetic isoflavones were stopped their reproductive function(isoflavones acted as an oral contraceptive. In humans, phytoestroges influence is still under evaluation, being suspected effects such as cerebral involution - via abusive apoptosis - or disturbance in hormonal status, in male children. All these are added to already known allergies, caused by soy proteins.

Negative regulation of parathyroid hormone-related protein expression by steroid hormones

International Nuclear Information System (INIS)

Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

2011-01-01

Highlights: → Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. → Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. → Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1β in Rats.

Science.gov (United States)

Brito, H O; Radulski, D R; Wilhelms, D B; Stojakovic, A; Brito, L M O; Engblom, D; Franco, C R C; Zampronio, A R

2016-10-01

There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50 μg/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2 mg/kg, i.p. 30 min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E 2 (PGE 2 ). In addition, OVX rats were hyper-responsive to PGE 2 injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE 2 , the febrile response induced by i.c.v. injection of interleukin (IL)-1β was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-1α were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF-α and MIP-1α. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE 2 . © 2016 British Society for Neuroendocrinology.

Sequential analysis in neonatal research-systematic review.

Science.gov (United States)

Lava, Sebastiano A G; Elie, Valéry; Ha, Phuong Thi Viet; Jacqz-Aigrain, Evelyne

2018-05-01

As more new drugs are discovered, traditional designs come at their limits. Ten years after the adoption of the European Paediatric Regulation, we performed a systematic review on the US National Library of Medicine and Excerpta Medica database of sequential trials involving newborns. Out of 326 identified scientific reports, 21 trials were included. They enrolled 2832 patients, of whom 2099 were analyzed: the median number of neonates included per trial was 48 (IQR 22-87), median gestational age was 28.7 (IQR 27.9-30.9) weeks. Eighteen trials used sequential techniques to determine sample size, while 3 used continual reassessment methods for dose-finding. In 16 studies reporting sufficient data, the sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674) with respect to a traditional trial. When the number of neonates finally included in the analysis was considered, the difference became significant: 35 (57%) patients (IQR 10 to 136.5, p = 0.0033). Sequential trial designs have not been frequently used in Neonatology. They might potentially be able to reduce the number of patients in drug trials, although this is not always the case. What is known: • In evaluating rare diseases in fragile populations, traditional designs come at their limits. About 20% of pediatric trials are discontinued, mainly because of recruitment problems. What is new: • Sequential trials involving newborns were infrequently used and only a few (n = 21) are available for analysis. • The sequential design allowed to non-significantly reduce the number of enrolled neonates by a median of 24 (31%) patients (IQR - 4.75 to 136.5, p = 0.0674).

Group-sequential analysis may allow for early trial termination

DEFF Research Database (Denmark)

Gerke, Oke; Vilstrup, Mie H; Halekoh, Ulrich

2017-01-01

BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG-PET/CT mea......BACKGROUND: Group-sequential testing is widely used in pivotal therapeutic, but rarely in diagnostic research, although it may save studies, time, and costs. The purpose of this paper was to demonstrate a group-sequential analysis strategy in an intra-observer study on quantitative FDG...... assumed to be normally distributed, and sequential one-sided hypothesis tests on the population standard deviation of the differences against a hypothesised value of 1.5 were performed, employing an alpha spending function. The fixed-sample analysis (N = 45) was compared with the group-sequential analysis...... strategies comprising one (at N = 23), two (at N = 15, 30), or three interim analyses (at N = 11, 23, 34), respectively, which were defined post hoc. RESULTS: When performing interim analyses with one third and two thirds of patients, sufficient agreement could be concluded after the first interim analysis...

Efficacy of chemotherapy after hormone therapy for hormone receptor-positive metastatic breast cancer.

Science.gov (United States)

Mori, Ryutaro; Nagao, Yasuko

2014-01-01

According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor-positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy-effective and hormone therapy-ineffective cases. Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2-positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy-ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy. The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of

Comparison of ablation centration after bilateral sequential versus simultaneous LASIK.

Science.gov (United States)

Lin, Jane-Ming; Tsai, Yi-Yu

2005-01-01

To compare ablation centration after bilateral sequential and simultaneous myopic LASIK. A retrospective randomized case series was performed of 670 eyes of 335 consecutive patients who had undergone either bilateral sequential (group 1) or simultaneous (group 2) myopic LASIK between July 2000 and July 2001 at the China Medical University Hospital, Taichung, Taiwan. The ablation centrations of the first and second eyes in the two groups were compared 3 months postoperatively. Of 670 eyes, 274 eyes (137 patients) comprised the sequential group and 396 eyes (198 patients) comprised the simultaneous group. Three months post-operatively, 220 eyes of 110 patients (80%) in the sequential group and 236 eyes of 118 patients (60%) in the simultaneous group provided topographic data for centration analysis. For the first eyes, mean decentration was 0.39 +/- 0.26 mm in the sequential group and 0.41 +/- 0.19 mm in the simultaneous group (P = .30). For the second eyes, mean decentration was 0.28 +/- 0.23 mm in the sequential group and 0.30 +/- 0.21 mm in the simultaneous group (P = .36). Decentration in the second eyes significantly improved in both groups (group 1, P = .02; group 2, P sequential group and 0.32 +/- 0.18 mm in the simultaneous group (P = .33). The difference of ablation center angles between the first and second eyes was 43.2 sequential group and 45.1 +/- 50.8 degrees in the simultaneous group (P = .42). Simultaneous bilateral LASIK is comparable to sequential surgery in ablation centration.

A Survey of Multi-Objective Sequential Decision-Making

NARCIS (Netherlands)

Roijers, D.M.; Vamplew, P.; Whiteson, S.; Dazeley, R.

2013-01-01

Sequential decision-making problems with multiple objectives arise naturally in practice and pose unique challenges for research in decision-theoretic planning and learning, which has largely focused on single-objective settings. This article surveys algorithms designed for sequential

Interactions between the thyroid hormones and the hormones of the growth hormone axis.

Science.gov (United States)

Laron, Zvi

2003-12-01

The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.

Sequential lineups: shift in criterion or decision strategy?

Science.gov (United States)

Gronlund, Scott D

2004-04-01

R. C. L. Lindsay and G. L. Wells (1985) argued that a sequential lineup enhanced discriminability because it elicited use of an absolute decision strategy. E. B. Ebbesen and H. D. Flowe (2002) argued that a sequential lineup led witnesses to adopt a more conservative response criterion, thereby affecting bias, not discriminability. Height was encoded as absolute (e.g., 6 ft [1.83 m] tall) or relative (e.g., taller than). If a sequential lineup elicited an absolute decision strategy, the principle of transfer-appropriate processing predicted that performance should be best when height was encoded absolutely. Conversely, if a simultaneous lineup elicited a relative decision strategy, performance should be best when height was encoded relatively. The predicted interaction was observed, providing direct evidence for the decision strategies explanation of what happens when witnesses view a sequential lineup.

Plurihormonal pituitary adenoma immunoreactive for thyroid-stimulating hormone, growth hormone, follicle-stimulating hormone, and prolactin.

Science.gov (United States)

Luk, Cynthia T; Kovacs, Kalman; Rotondo, Fabio; Horvath, Eva; Cusimano, Michael; Booth, Gillian L

2012-01-01

To describe the case of a patient with an unusual plurihormonal pituitary adenoma with immunoreactivity for thyroid-stimulating hormone (TSH), growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. We report the clinical, laboratory, imaging, and pathology findings of a patient symptomatic from a plurihormonal pituitary adenoma and describe her outcome after surgical treatment. A 60-year-old woman presented to the emergency department with headaches, blurry vision, fatigue, palpitations, sweaty hands, and weight loss. Her medical history was notable for hyperthyroidism, treated intermittently with methimazole. Magnetic resonance imaging disclosed a pituitary macroadenoma (2.3 by 2.2 by 2.0 cm), and preoperative blood studies revealed elevated levels of TSH at 6.11 mIU/L, free thyroxine at 3.6 ng/dL, and free triiodothyronine at 6.0 pg/mL. She underwent an uncomplicated transsphenoidal resection of the pituitary adenoma. Immunostaining of tumor tissue demonstrated positivity for not only TSH but also growth hormone, follicle-stimulating hormone, prolactin, and α-subunit. The Ki-67 index of the tumor was estimated at 2% to 5%, and DNA repair enzyme O6-methylguanine-DNA methyltransferase immunostaining was mostly negative. Electron microscopy showed the ultrastructural phenotype of a glycoprotein-producing adenoma. Postoperatively, her symptoms and hyperthyroidism resolved. Thyrotropin-secreting pituitary adenomas are rare. Furthermore, recent reports suggest that 31% to 36% of adenomas may show evidence of secretion of multiple pituitary hormones. This case emphasizes the importance of considering pituitary causes of thyrotoxicosis and summarizes the clinical and pathology findings in a patient with a plurihormonal pituitary adenoma.

How to Read the Tractatus Sequentially

Directory of Open Access Journals (Sweden)

Tim Kraft

2016-11-01

Full Text Available One of the unconventional features of Wittgenstein’s Tractatus Logico-Philosophicus is its use of an elaborated and detailed numbering system. Recently, Bazzocchi, Hacker und Kuusela have argued that the numbering system means that the Tractatus must be read and interpreted not as a sequentially ordered book, but as a text with a two-dimensional, tree-like structure. Apart from being able to explain how the Tractatus was composed, the tree reading allegedly solves exegetical issues both on the local (e. g. how 4.02 fits into the series of remarks surrounding it and the global level (e. g. relation between ontology and picture theory, solipsism and the eye analogy, resolute and irresolute readings. This paper defends the sequential reading against the tree reading. After presenting the challenges generated by the numbering system and the two accounts as attempts to solve them, it is argued that Wittgenstein’s own explanation of the numbering system, anaphoric references within the Tractatus and the exegetical issues mentioned above do not favour the tree reading, but a version of the sequential reading. This reading maintains that the remarks of the Tractatus form a sequential chain: The role of the numbers is to indicate how remarks on different levels are interconnected to form a concise, surveyable and unified whole.

Effect of PREDICT on chemotherapy/trastuzumab recommendations in HER2-positive patients with early-stage breast cancer

OpenAIRE

DOWN, SUE K.; LUCAS, OLIVIA; BENSON, JOHN R.; WISHART, GORDON C.

2014-01-01

PREDICT is an online prognostication tool for early-stage breast cancer, which incorporates human epidermal growth factor 2 (HER2) status and stratifies absolute treatment benefits for hormone therapy, chemotherapy and trastuzumab. The present study compared historical multidisciplinary team (MDT) decisions regarding adjuvant treatment with PREDICT estimates, to determine whether certain patients are being over- or undertreated, particularly when stratified by age and oestrogen-receptor (ER) ...

Effects of repeated potassium iodide administration on genes involved in synthesis and secretion of thyroid hormone in adult male rat.

Science.gov (United States)

Lebsir, Dalila; Manens, Line; Grison, Stephane; Lestaevel, Philippe; Ebrahimian, Teni; Suhard, David; Phan, Guillaume; Dublineau, Isabelle; Tack, Karine; Benderitter, Marc; Pech, Annick; Jourdain, Jean-Rene; Souidi, Maâmar

2018-02-26

A single dose of potassium iodide (KI) is recommended to reduce the risk of thyroid cancer during nuclear accidents. However in case of prolonged radioiodine exposure, more than one dose of KI may be necessary. This work aims to evaluate the potential toxic effect of repeated administration of KI. Adult Wistar rats received an optimal dose of KI 1 mg/kg over a period of 1, 4 or 8 days. hormonal status (TSH, FT4) of treated rats was unaffected. Contrariwise, a sequential Wolff-Chaikoff effect was observed, resulting in a prompt decrease of NIS and MCT8 mRNA expression (-58% and -26% respectively), followed by a delayed decrease of TPO mRNA expression (-33%) in conjunction with a stimulation of PDS mRNA expression (+62%). we show for the first time that repeated administration of KI at 1 mg/kg/24h doesn't cause modification of thyroid hormones level, but leads to a reversible modification of the expression of genes involved in the synthesis and secretion of thyroid hormones. Copyright © 2018 Elsevier B.V. All rights reserved.

A minimax procedure in the context of sequential mastery testing

NARCIS (Netherlands)

Vos, Hendrik J.

1999-01-01

The purpose of this paper is to derive optimal rules for sequential mastery tests. In a sequential mastery test, the decision is to classify a subject as a master or a nonmaster, or to continue sampling and administering another random test item. The framework of minimax sequential decision theory

HERBAL SUPPLEMENTS: CAUSE FOR CONCERN?

Directory of Open Access Journals (Sweden)

Paolo Borrione

2008-12-01

mouse liver, heart and muscles, and act on lipids methabolism, reduce glucagon-induced hyperglycaemia, and enhance glucose utilization by tissues. The mechanism involved seems to be an increase of tissue sensitivity to insulin (Bathori and Pongracz, 2005. PhytooestrogensPhytooestrogens are biologically active plant substances with a chemical structure similar to oestradiol. This structural similarity accounts for their ability to bind to oestrogen receptors, and exert various oestrogenic or anti-oestrogenic effects. There are three main classes of phytooestrogens: isoflavones, coumestans, and lignans. Most of the phytooestrogens have a higher affinity to oestrogen receptor beta than alpha. The former is strongly expressed in the ovary, uterus, brain, bladder, testis, prostate, bone, cardiovascular system, and lungs. Expression of oestrogen receptor beta appears to occur at different sites in the brain than oestrogen receptor alpha. (Setchell and Cassidy, 1999 The oestrogenic effect of phytooestrogens produces reproductive disturbances in sheep, and a phytooestrogen-rich diet is associated with a lower risk of breast and prostate cancer, and of cardiovascular disease (Adlercreutz, 1990. In vitro, phytooestrogens exert both proliferative (oestrogenic and antiproliferative (antioestrogenic effects in human cell lines (Wang et al., 1996. In humans, isoflavones increase the length of the follicular phase, with suppression of the midcycle surges of FSH and LH. Some dietary phytooestrogens can produce mild oestrogenic effects in postmenopausal women, including oestrogen- like effects on vaginal cytology and reductions in hot flushes, and oestrogen-like activity on bone and lipid metabolism (Cassidy et al., 1994. Isoflavones demonstrate anticarcinogenetic activity, inhibiting angiogenesis and cell progression, inhibiting aromatase enzyme, and stimulating sex hormone binding globulin synthesis (Messina et al. , 2006. Most of the phytooestrogens-based preparations freely

Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165

International Nuclear Information System (INIS)

Atkinson, Charlotte; Warren, Ruth ML; Sala, Evis; Dowsett, Mitch; Dunning, Alison M; Healey, Catherine S; Runswick, Shirley; Day, Nicholas E; Bingham, Sheila A

2004-01-01

Isoflavones are hypothesized to protect against breast cancer, but it is not clear whether they act as oestrogens or anti-oestrogens in breast tissue. Our aim was to determine the effects of taking a red clover-derived isoflavone supplement daily for 1 year on mammographic breast density. Effects on oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), lymphocyte tyrosine kinase activity and menopausal symptoms were also assessed. A total of 205 women (age range 49–65 years) with Wolfe P2 or DY mammographic breast patterns were randomly assigned to receive either a red clover-derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein) or placebo. Change in mammographic breast density, serum oestradiol, FSH, LH, menopausal symptoms and lymphocyte tyrosine kinase activity from baseline to 12 months were assessed. A total of 177 women completed the trial. Mammographic breast density decreased in both groups but the difference between the treatment and placebo was not statistically significant. There was a significant interaction between treatment group and oestrogen receptor (ESR1) PvuII polymorphism for the change in estimated percentage breast density (mean ± standard deviation): TT isoflavone 1.4 ± 12.3% and TT placebo -9.6 ± 14.2%; CT isoflavone -5.2 ± 12.0% and CT placebo -2.8 ± 10.3%; and CC isoflavone -3.4 ± 9.7% and CC placebo -1.1 ± 9.5%. There were no statistically significant treatment effects on oestradiol, FSH, or LH (assessed only in postmenopausal women), or on lymphocyte tyrosine kinase activity. Baseline levels of menopausal symptoms were low, and there were no statistically significant treatment effects on frequency of hot flushes or other menopausal symptoms. In contrast to studies showing that conventional hormone replacement therapies increase mammographic breast density, the isoflavone supplement did not increase mammographic breast density in this population of women

Multichannel, sequential or combined X-ray spectrometry

International Nuclear Information System (INIS)

Florestan, J.

1979-01-01

X-ray spectrometer qualities and defects are evaluated for sequential and multichannel categories. Multichannel X-ray spectrometer has time-coherency advantage and its results could be more reproducible; on the other hand some spatial incoherency limits low percentage and traces applications, specially when backgrounds are very variable. In this last case, sequential X-ray spectrometer would find again great usefulness [fr

Induction of simultaneous and sequential malolactic fermentation in durian wine.

Science.gov (United States)

Taniasuri, Fransisca; Lee, Pin-Rou; Liu, Shao-Quan

2016-08-02

This study represented for the first time the impact of malolactic fermentation (MLF) induced by Oenococcus oeni and its inoculation strategies (simultaneous vs. sequential) on the fermentation performance as well as aroma compound profile of durian wine. There was no negative impact of simultaneous inoculation of O. oeni and Saccharomyces cerevisiae on the growth and fermentation kinetics of S. cerevisiae as compared to sequential fermentation. Simultaneous MLF did not lead to an excessive increase in volatile acidity as compared to sequential MLF. The kinetic changes of organic acids (i.e. malic, lactic, succinic, acetic and α-ketoglutaric acids) varied with simultaneous and sequential MLF relative to yeast alone. MLF, regardless of inoculation mode, resulted in higher production of fermentation-derived volatiles as compared to control (alcoholic fermentation only), including esters, volatile fatty acids, and terpenes, except for higher alcohols. Most indigenous volatile sulphur compounds in durian were decreased to trace levels with little differences among the control, simultaneous and sequential MLF. Among the different wines, the wine with simultaneous MLF had higher concentrations of terpenes and acetate esters while sequential MLF had increased concentrations of medium- and long-chain ethyl esters. Relative to alcoholic fermentation only, both simultaneous and sequential MLF reduced acetaldehyde substantially with sequential MLF being more effective. These findings illustrate that MLF is an effective and novel way of modulating the volatile and aroma compound profile of durian wine. Copyright © 2016 Elsevier B.V. All rights reserved.

Sequential Banking.

OpenAIRE

Bizer, David S; DeMarzo, Peter M

1992-01-01

The authors study environments in which agents may borrow sequentially from more than one leader. Although debt is prioritized, additional lending imposes an externality on prior debt because, with moral hazard, the probability of repayment of prior loans decreases. Equilibrium interest rates are higher than they would be if borrowers could commit to borrow from at most one bank. Even though the loan terms are less favorable than they would be under commitment, the indebtedness of borrowers i...

Equivalence between quantum simultaneous games and quantum sequential games

OpenAIRE

Kobayashi, Naoki

2007-01-01

A framework for discussing relationships between different types of games is proposed. Within the framework, quantum simultaneous games, finite quantum simultaneous games, quantum sequential games, and finite quantum sequential games are defined. In addition, a notion of equivalence between two games is defined. Finally, the following three theorems are shown: (1) For any quantum simultaneous game G, there exists a quantum sequential game equivalent to G. (2) For any finite quantum simultaneo...

Accounting for Heterogeneous Returns in Sequential Schooling Decisions

NARCIS (Netherlands)

Zamarro, G.

2006-01-01

This paper presents a method for estimating returns to schooling that takes into account that returns may be heterogeneous among agents and that educational decisions are made sequentially.A sequential decision model is interesting because it explicitly considers that the level of education of each

Simultaneous Versus Sequential Ptosis and Strabismus Surgery in Children.

Science.gov (United States)

Revere, Karen E; Binenbaum, Gil; Li, Jonathan; Mills, Monte D; Katowitz, William R; Katowitz, James A

The authors sought to compare the clinical outcomes of simultaneous versus sequential ptosis and strabismus surgery in children. Retrospective, single-center cohort study of children requiring both ptosis and strabismus surgery on the same eye. Simultaneous surgeries were performed during a single anesthetic event; sequential surgeries were performed at least 7 weeks apart. Outcomes were ptosis surgery success (margin reflex distance 1 ≥ 2 mm, good eyelid contour, and good eyelid crease); strabismus surgery success (ocular alignment within 10 prism diopters of orthophoria and/or improved head position); surgical complications; and reoperations. Fifty-six children were studied, 38 had simultaneous surgery and 18 sequential. Strabismus surgery was performed first in 38/38 simultaneous and 6/18 sequential cases. Mean age at first surgery was 64 months, with mean follow up 27 months. A total of 75% of children had congenital ptosis; 64% had comitant strabismus. A majority of ptosis surgeries were frontalis sling (59%) or Fasanella-Servat (30%) procedures. There were no significant differences between simultaneous and sequential groups with regards to surgical success rates, complications, or reoperations (all p > 0.28). In the first comparative study of simultaneous versus sequential ptosis and strabismus surgery, no advantage for sequential surgery was seen. Despite a theoretical risk of postoperative eyelid malposition or complications when surgeries were performed in a combined manner, the rate of such outcomes was not increased with simultaneous surgeries. Performing ptosis and strabismus surgery together appears to be clinically effective and safe, and reduces anesthesia exposure during childhood.

Forced Sequence Sequential Decoding

DEFF Research Database (Denmark)

Jensen, Ole Riis

In this thesis we describe a new concatenated decoding scheme based on iterations between an inner sequentially decoded convolutional code of rate R=1/4 and memory M=23, and block interleaved outer Reed-Solomon codes with non-uniform profile. With this scheme decoding with good performance...... is possible as low as Eb/No=0.6 dB, which is about 1.7 dB below the signal-to-noise ratio that marks the cut-off rate for the convolutional code. This is possible since the iteration process provides the sequential decoders with side information that allows a smaller average load and minimizes the probability...... of computational overflow. Analytical results for the probability that the first Reed-Solomon word is decoded after C computations are presented. This is supported by simulation results that are also extended to other parameters....

Hormonal changes in secondary impotence

International Nuclear Information System (INIS)

Salama, F.M.; El-Shabrawy, N.O.; Nosseir, S.A.; Abo El-Azayem, Naglaa.

1985-01-01

Impotence is one of the problems which is still obscure both in its aetiology and treatment. The present study deals with the possible hormonal changes in cases of secondary infertility. The study involved 25 patients diagnosed as secondary impotence. Hormonal assay was performed for the following hormones: 1. Prolaction hormone. 2. Luteinising hormone (L.H.). 3. Testosterone. 4. Follicle stimulating hormone (F.S.H.). The assay was carried out by radioimmunoassay using double antibody technique. Results are discussed

Reading Remediation Based on Sequential and Simultaneous Processing.

Science.gov (United States)

Gunnison, Judy; And Others

1982-01-01

The theory postulating a dichotomy between sequential and simultaneous processing is reviewed and its implications for remediating reading problems are reviewed. Research is cited on sequential-simultaneous processing for early and advanced reading. A list of remedial strategies based on the processing dichotomy addresses decoding and lexical…

The influence of selenium, vitamin E, and oestrogen on the development of tumours in mice exposed to 90Sr

International Nuclear Information System (INIS)

Bierke, P.

1994-01-01

The primary object of this experiment was to evaluate the potential role of the antioxidants, selenium and vitamin E, in the anti-tumour defence of mice internally irradiated with 90 Sr. Comparison in terms of neoplastic response was made between mice kept on a selenium and vitamin E deficient diet and mice given the same deficient diet but administered selenium and/or vitamin E in a controlled manner. The influence of simultaneous oestrogen treatment, known to promote radiogenic osteosarcoma induction, was also investigated. Non-irradiated mice were used as controls. Results are presented as crude and actuarial tumour incidence. No significant difference in tumour yield or actuarial tumour incidence was found when the differently treated mouse groups were compared, and accordingly no support was gained for the theory that the antioxidants selenium and vitamin E constitute a critical part of the complex defence system against neoplasms. (orig.)

Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles

DEFF Research Database (Denmark)

Arce, Joan-Carles; La Marca, Antonio; Mirner Klein, Bjarke

2013-01-01

To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol....

[Customization of hormonal contraception].

Science.gov (United States)

DE Leo, Vincenzo; Cianci, Antonio; DI Carlo, Costantino; Cappelli, Valentina; Fruzzetti, Franca

2018-02-01

In the last few years new oral contraceptives have been marketed showing a better safety profile for women. They are the result of important changes made to the old compounds. As far as the estrogenic component, with the aim of decreasing side effects, the dose of ethinyl estradiol has been reduced and synthetic estrogens have been replaced by natural estradiol, further improving the safety profile. Also the progestin component in the last years has been changed in terms of dose, endocrine and metabolic characteristics. Levonorgestrel is an androgenic progestin, but now there is the possibility of choosing progestins without androgenic effect (gestodene and desogestrel) or progestins with antiandrogenic effect (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate), very useful in patients with hyperandrogenism. Some of these progestins, like Drospirenone, represented the real held contributing, because of its antimineralcorticoid action, to reduce an important side effect like fluid retention; moreover there is the possibility to choose products with high progestogen effect on endometrium (dienogest, nomegestrole acetate), resulting very effective in women with abnormal uterine bleedings. Also the regimens of administration have been changed, by shortening or eliminating the tablet-free period; in this way the women may avoid premenstrual symptoms. The oral is not the only route of administration, but today there are alternative routes like transdermal, transvaginal, intrauterine and subcutaneous, reducing gastro-intestinal interferences and possible mistakes in pill intake.

Gastrointestinal hormones and their targets

DEFF Research Database (Denmark)

Rehfeld, Jens F.

2014-01-01

Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone producing organ in the body. Modern biology makes...... it feasible to conceive the hormones under five headings: The structural homology groups a majority of the hormones into nine families, each of which is assumed to originate from one ancestral gene. The individual hormone gene often has multiple phenotypes due to alternative splicing, tandem organization......, or differentiated maturation of the prohormone. By a combination of these mechanisms, more than 100 different hormonally active peptides are released from the gut. Gut hormone genes are also widely expressed in cells outside the gut, some only in extraintestinal endocrine cells and neurons but others also in other...

Missed hormonal contraceptives: new recommendations.

Science.gov (United States)

Guilbert, Edith; Black, Amanda; Dunn, Sheila; Senikas, Vyta

2008-11-01

To provide evidence-based guidance for women and their health care providers on the management of missed or delayed hormonal contraceptive doses in order to prevent unintended pregnancy. Medline, PubMed, and the Cochrane Database were searched for articles published in English, from 1974 to 2007, about hormonal contraceptive methods that are available in Canada and that may be missed or delayed. Relevant publications and position papers from appropriate reproductive health and family planning organizations were also reviewed. The quality of evidence is rated using the criteria developed by the Canadian Task Force on Preventive Health Care. This committee opinion will help health care providers offer clear information to women who have not been adherent in using hormonal contraception with the purpose of preventing unintended pregnancy. The Society of Obstetricians and Gynaecologists of Canada. SUMMARY STATEMENTS: 1. Instructions for what women should do when they miss hormonal contraception have been complex and women do not understand them correctly. (I) 2. The highest risk of ovulation occurs when the hormone-free interval is prolonged for more than seven days, either by delaying the start of combined hormonal contraceptives or by missing active hormone doses during the first or third weeks of combined oral contraceptives. (II) Ovulation rarely occurs after seven consecutive days of combined oral contraceptive use. (II) RECOMMENDATIONS: 1. Health care providers should give clear, simple instructions, both written and oral, on missed hormonal contraceptive pills as part of contraceptive counselling. (III-A) 2. Health care providers should provide women with telephone/electronic resources for reference in the event of missed or delayed hormonal contraceptives. (III-A) 3. In order to avoid an increased risk of unintended pregnancy, the hormone-free interval should not exceed seven days in combined hormonal contraceptive users. (II-A) 4. Back-up contraception should

C-quence: a tool for analyzing qualitative sequential data.

Science.gov (United States)

Duncan, Starkey; Collier, Nicholson T

2002-02-01

C-quence is a software application that matches sequential patterns of qualitative data specified by the user and calculates the rate of occurrence of these patterns in a data set. Although it was designed to facilitate analyses of face-to-face interaction, it is applicable to any data set involving categorical data and sequential information. C-quence queries are constructed using a graphical user interface. The program does not limit the complexity of the sequential patterns specified by the user.

Chronic food restriction and the circadian rhythms of pituitary-adrenal hormones, growth hormone and thyroid-stimulating hormone.

Science.gov (United States)

Armario, A; Montero, J L; Jolin, T

1987-01-01

Adult male Sprague-Dawley rats were subjected to food restriction so that they ate 65% of food ingested by control rats. While control rats had free access to food over the 24-hour period, food-restricted rats were provided with food daily at 10 a.m. The experimental period lasted for 34 days. On day 35, rats from both experimental groups were killed at 08.00, 11.00, 14.00, 24.00 and 02.00 h. Food restriction modified the circadian rhythms of ACTH and corticosterone. In addition, total circulating corticosterone throughout the day was higher in food-restricted than in control rats. In contrast, food restriction resulted in depressed secretion of thyroid-stimulating hormone and growth hormone. The results indicate that time of food availability entrained circadian corticosterone rhythm but not thyroid-stimulating hormone and growth hormone rhythms.

Endocrine disruption of courtship behaviour and reproduction in zebrafish (Danio rerio)

DEFF Research Database (Denmark)

Broch-Lips, Mia Gina Gruwier

2011-01-01

of the reversibility of hormonally induced shifts in sex ratio of zebrafish. In the first part of this study zebrafish were exposed to three different environmentally relevant concentrations of the synthetic oestrogen17α-ethinylestradiol (EE2) from egg stage to sexual maturity. Secondary sexual characteristics...... as fertilizing the spawned eggs. It was further demonstrated that the exposure to TB led to irreversible masculinisation of zebrafish which is in contrast with the partial reversibility of oestrogen induced sex change. During my investigations leading to this thesis it became apparent that sexual behaviour...... courtship behaviour have only been scarcely investigated. The aim of this project was to learn more about the effects of EDCS on the courtship behaviour and reproduction in zebrafish as well as investigating the reversibility of observed effects. I furthermore observed some interesting aspects...

Top-down attention affects sequential regularity representation in the human visual system.

Science.gov (United States)

Kimura, Motohiro; Widmann, Andreas; Schröger, Erich

2010-08-01

Recent neuroscience studies using visual mismatch negativity (visual MMN), an event-related brain potential (ERP) index of memory-mismatch processes in the visual sensory system, have shown that although sequential regularities embedded in successive visual stimuli can be automatically represented in the visual sensory system, an existence of sequential regularity itself does not guarantee that the sequential regularity will be automatically represented. In the present study, we investigated the effects of top-down attention on sequential regularity representation in the visual sensory system. Our results showed that a sequential regularity (SSSSD) embedded in a modified oddball sequence where infrequent deviant (D) and frequent standard stimuli (S) differing in luminance were regularly presented (SSSSDSSSSDSSSSD...) was represented in the visual sensory system only when participants attended the sequential regularity in luminance, but not when participants ignored the stimuli or simply attended the dimension of luminance per se. This suggests that top-down attention affects sequential regularity representation in the visual sensory system and that top-down attention is a prerequisite for particular sequential regularities to be represented. Copyright 2010 Elsevier B.V. All rights reserved.

Gut hormones and gastric bypass

DEFF Research Database (Denmark)

Holst, Jens J.

2016-01-01

Gut hormone secretion in response to nutrient ingestion appears to depend on membrane proteins expressed by the enteroendocrine cells. These include transporters (glucose and amino acid transporters), and, in this case, hormone secretion depends on metabolic and electrophysiological events elicited...... that determines hormone responses. It follows that operations that change intestinal exposure to and absorption of nutrients, such as gastric bypass operations, also change hormone secretion. This results in exaggerated increases in the secretion of particularly the distal small intestinal hormones, GLP-1, GLP-2......, oxyntomodulin, neurotensin and peptide YY (PYY). However, some proximal hormones also show changes probably reflecting that the distribution of these hormones is not restricted to the bypassed segments of the gut. Thus, cholecystokinin responses are increased, whereas gastric inhibitory polypeptide responses...

Adult growth hormone deficiency

Directory of Open Access Journals (Sweden)

Vishal Gupta

2011-01-01

Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

Mining compressing sequential problems

NARCIS (Netherlands)

Hoang, T.L.; Mörchen, F.; Fradkin, D.; Calders, T.G.K.

2012-01-01

Compression based pattern mining has been successfully applied to many data mining tasks. We propose an approach based on the minimum description length principle to extract sequential patterns that compress a database of sequences well. We show that mining compressing patterns is NP-Hard and

Fast sequential Monte Carlo methods for counting and optimization

CERN Document Server

Rubinstein, Reuven Y; Vaisman, Radislav

2013-01-01

A comprehensive account of the theory and application of Monte Carlo methods Based on years of research in efficient Monte Carlo methods for estimation of rare-event probabilities, counting problems, and combinatorial optimization, Fast Sequential Monte Carlo Methods for Counting and Optimization is a complete illustration of fast sequential Monte Carlo techniques. The book provides an accessible overview of current work in the field of Monte Carlo methods, specifically sequential Monte Carlo techniques, for solving abstract counting and optimization problems. Written by authorities in the

Computing sequential equilibria for two-player games

DEFF Research Database (Denmark)

Miltersen, Peter Bro

2006-01-01

Koller, Megiddo and von Stengel showed how to efficiently compute minimax strategies for two-player extensive-form zero-sum games with imperfect information but perfect recall using linear programming and avoiding conversion to normal form. Their algorithm has been used by AI researchers...... for constructing prescriptive strategies for concrete, often fairly large games. Koller and Pfeffer pointed out that the strategies obtained by the algorithm are not necessarily sequentially rational and that this deficiency is often problematic for the practical applications. We show how to remove this deficiency...... by modifying the linear programs constructed by Koller, Megiddo and von Stengel so that pairs of strategies forming a sequential equilibrium are computed. In particular, we show that a sequential equilibrium for a two-player zero-sum game with imperfect information but perfect recall can be found in polynomial...

Computing Sequential Equilibria for Two-Player Games

DEFF Research Database (Denmark)

Miltersen, Peter Bro; Sørensen, Troels Bjerre

2006-01-01

Koller, Megiddo and von Stengel showed how to efficiently compute minimax strategies for two-player extensive-form zero-sum games with imperfect information but perfect recall using linear programming and avoiding conversion to normal form. Koller and Pfeffer pointed out that the strategies...... obtained by the algorithm are not necessarily sequentially rational and that this deficiency is often problematic for the practical applications. We show how to remove this deficiency by modifying the linear programs constructed by Koller, Megiddo and von Stengel so that pairs of strategies forming...... a sequential equilibrium are computed. In particular, we show that a sequential equilibrium for a two-player zero-sum game with imperfect information but perfect recall can be found in polynomial time. In addition, the equilibrium we find is normal-form perfect. Our technique generalizes to general-sum games...

Examination of androgen- and estrogen concentrations in the blood of male dogs with and without perineal hernia

International Nuclear Information System (INIS)

Pemsel, K.

1985-10-01

Concentrations of dehydroepiandrosterone, androstendione and testosterone were measured in the blood of male dogs by radioimmunoassay. Mean values were 0.67 - 1.51 ng/ml DHA, 1.06 -1.30 ng/ml AD, 1.52 - 1.92 ng/ml T and 22 - 25 pg/ml total oestrogens. The hypothesis that a hormonal unbalance is an important etiological factor in hermia perinealis of dogs could not be corroborated. (P.W.)

Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

Science.gov (United States)

Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

2018-01-01

Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

Science.gov (United States)

Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

2005-04-01

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

Sensitivity Analysis in Sequential Decision Models.

Science.gov (United States)

Chen, Qiushi; Ayer, Turgay; Chhatwal, Jagpreet

2017-02-01

Sequential decision problems are frequently encountered in medical decision making, which are commonly solved using Markov decision processes (MDPs). Modeling guidelines recommend conducting sensitivity analyses in decision-analytic models to assess the robustness of the model results against the uncertainty in model parameters. However, standard methods of conducting sensitivity analyses cannot be directly applied to sequential decision problems because this would require evaluating all possible decision sequences, typically in the order of trillions, which is not practically feasible. As a result, most MDP-based modeling studies do not examine confidence in their recommended policies. In this study, we provide an approach to estimate uncertainty and confidence in the results of sequential decision models. First, we provide a probabilistic univariate method to identify the most sensitive parameters in MDPs. Second, we present a probabilistic multivariate approach to estimate the overall confidence in the recommended optimal policy considering joint uncertainty in the model parameters. We provide a graphical representation, which we call a policy acceptability curve, to summarize the confidence in the optimal policy by incorporating stakeholders' willingness to accept the base case policy. For a cost-effectiveness analysis, we provide an approach to construct a cost-effectiveness acceptability frontier, which shows the most cost-effective policy as well as the confidence in that for a given willingness to pay threshold. We demonstrate our approach using a simple MDP case study. We developed a method to conduct sensitivity analysis in sequential decision models, which could increase the credibility of these models among stakeholders.

The sequential structure of brain activation predicts skill.

Science.gov (United States)

Anderson, John R; Bothell, Daniel; Fincham, Jon M; Moon, Jungaa

2016-01-29

In an fMRI study, participants were trained to play a complex video game. They were scanned early and then again after substantial practice. While better players showed greater activation in one region (right dorsal striatum) their relative skill was better diagnosed by considering the sequential structure of whole brain activation. Using a cognitive model that played this game, we extracted a characterization of the mental states that are involved in playing a game and the statistical structure of the transitions among these states. There was a strong correspondence between this measure of sequential structure and the skill of different players. Using multi-voxel pattern analysis, it was possible to recognize, with relatively high accuracy, the cognitive states participants were in during particular scans. We used the sequential structure of these activation-recognized states to predict the skill of individual players. These findings indicate that important features about information-processing strategies can be identified from a model-based analysis of the sequential structure of brain activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

A one-sided sequential test

Energy Technology Data Exchange (ETDEWEB)

Racz, A.; Lux, I. [Hungarian Academy of Sciences, Budapest (Hungary). Atomic Energy Research Inst.

1996-04-16

The applicability of the classical sequential probability ratio testing (SPRT) for early failure detection problems is limited by the fact that there is an extra time delay between the occurrence of the failure and its first recognition. Chien and Adams developed a method to minimize this time for the case when the problem can be formulated as testing the mean value of a Gaussian signal. In our paper we propose a procedure that can be applied for both mean and variance testing and that minimizes the time delay. The method is based on a special parametrization of the classical SPRT. The one-sided sequential tests (OSST) can reproduce the results of the Chien-Adams test when applied for mean values. (author).

Mining Emerging Sequential Patterns for Activity Recognition in Body Sensor Networks

DEFF Research Database (Denmark)

Gu, Tao; Wang, Liang; Chen, Hanhua

2010-01-01

Body Sensor Networks oer many applications in healthcare, well-being and entertainment. One of the emerging applications is recognizing activities of daily living. In this paper, we introduce a novel knowledge pattern named Emerging Sequential Pattern (ESP)|a sequential pattern that discovers...... signicant class dierences|to recognize both simple (i.e., sequential) and complex (i.e., interleaved and concurrent) activities. Based on ESPs, we build our complex activity models directly upon the sequential model to recognize both activity types. We conduct comprehensive empirical studies to evaluate...

Discrimination between sequential and simultaneous virtual channels with electrical hearing

OpenAIRE

Landsberger, David; Galvin, John J.

2011-01-01

In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent electrodes can produce intermediate pitch percepts between those of the component electrodes. However, it is unclear whether simultaneous and sequential virtual channels (VCs) can be discriminated. In this study, CI users were asked to discriminate simultaneous and sequential VCs; discrimination was measured for monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and focused stimulation mode...

Pituitary mammosomatotroph adenomas develop in old mice transgenic for growth hormone-releasing hormone

DEFF Research Database (Denmark)

Asa, S L; Kovacs, K; Stefaneanu, L

1990-01-01

It has been shown that mice transgenic for human growth hormone-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs and mammosomatotrophs, cells capable of producing both growth hormone and prolactin, by 8 months of age. We now report for the first time that old GRH-transgenic...

A model for evaluating steroids acting at the hypothalamus-pituitary axis using radioimmunoassay and related procedures

International Nuclear Information System (INIS)

Spona, J.; Bieglmayer, Ch.; Schroeder, R.; Poeckl, E.

1978-01-01

The relative affinity constants for binding of estrone (E 1 ), estriol (E 3 ), 17β-estradiol(E 2 ) and 17α-ethinyl-17β-estradiol(EE 2 ) to cytosol estrogen-receptors of rat hypothalamus and pituitary were estimated by a radioligand-receptor assay procedure. The relative affinity constants in the hypothalamic system were 6.5x10 -10 M for E 2 , 1x10 -9 M for EE 2 and 2x10 -8 M for E 1 and E 3 . The affinity constants were 1x10 -9 M for E 2 and E 3 and 7x10 -9 M for E 1 and E 3 when pituitary cytosol samples were used. Some discrepancies between biological activity and affinity for the estrogen-receptor were noted. These may be due to differences in the metabolism and cellular uptake of the estrogens. The radioligand-receptor assay procedure may be useful in evaluating the action of estrogens and anti-estrogens acting at the hypothalamic and pituitary level. Sedimentation patterns of cytosol samples labelled with the estrogens used in this study revealed, upon ultracentrifugation, protein moieties sedimenting in the 8 S region. The potency of progesterone and D-Norgestrel to modulate the release of LH and FSH stimulated by luteinizing hormone-releasing hormone (LH-RH) in castrated female rats was found to correlate well with the biological activity of the progestogens. It is concluded that the radioligand-receptor assay procedure for estrogens and the in-vivo model for the evaluation of the central action of progestogens may be valuable tools for testing new steroids to be used in oral contraceptives. (author)

Menopause and Hormones

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... Consumer Information by Audience For Women Menopause and Hormones: Common Questions Share Tweet Linkedin Pin it More ... reproduction and distribution. Learn More about Menopause and Hormones Menopause--Medicines to Help You Links to other ...

Hybrid Computerized Adaptive Testing: From Group Sequential Design to Fully Sequential Design

Science.gov (United States)

Wang, Shiyu; Lin, Haiyan; Chang, Hua-Hua; Douglas, Jeff

2016-01-01

Computerized adaptive testing (CAT) and multistage testing (MST) have become two of the most popular modes in large-scale computer-based sequential testing. Though most designs of CAT and MST exhibit strength and weakness in recent large-scale implementations, there is no simple answer to the question of which design is better because different…

Sequential dependencies in magnitude scaling of loudness

DEFF Research Database (Denmark)

Joshi, Suyash Narendra; Jesteadt, Walt

2013-01-01

Ten normally hearing listeners used a programmable sone-potentiometer knob to adjust the level of a 1000-Hz sinusoid to match the loudness of numbers presented to them in a magnitude production task. Three different power-law exponents (0.15, 0.30, and 0.60) and a log-law with equal steps in d......B were used to program the sone-potentiometer. The knob settings systematically influenced the form of the loudness function. Time series analysis was used to assess the sequential dependencies in the data, which increased with increasing exponent and were greatest for the log-law. It would be possible......, therefore, to choose knob properties that minimized these dependencies. When the sequential dependencies were removed from the data, the slope of the loudness functions did not change, but the variability decreased. Sequential dependencies were only present when the level of the tone on the previous trial...

Visual short-term memory for sequential arrays.

Science.gov (United States)

Kumar, Arjun; Jiang, Yuhong

2005-04-01

The capacity of visual short-term memory (VSTM) for a single visual display has been investigated in past research, but VSTM for multiple sequential arrays has been explored only recently. In this study, we investigate the capacity of VSTM across two sequential arrays separated by a variable stimulus onset asynchrony (SOA). VSTM for spatial locations (Experiment 1), colors (Experiments 2-4), orientations (Experiments 3 and 4), and conjunction of color and orientation (Experiment 4) were tested, with the SOA across the two sequential arrays varying from 100 to 1,500 msec. We find that VSTM for the trailing array is much better than VSTM for the leading array, but when averaged across the two arrays VSTM has a constant capacity independent of the SOA. We suggest that multiple displays compete for retention in VSTM and that separating information into two temporally discrete groups does not enhance the overall capacity of VSTM.

Thyroid Hormone Treatment

Science.gov (United States)

... THYROID HORMONES? Desiccated ( dried and powdered ) animal thyroid ( Armour ®), now mainly obtained from pigs, was the most ... hormone can increase the risk or heart rhythm problems and bone loss making the use of thyroxine ...

The target-to-foils shift in simultaneous and sequential lineups.

Science.gov (United States)

Clark, Steven E; Davey, Sherrie L

2005-04-01

A theoretical cornerstone in eyewitness identification research is the proposition that witnesses, in making decisions from standard simultaneous lineups, make relative judgments. The present research considers two sources of support for this proposal. An experiment by G. L. Wells (1993) showed that if the target is removed from a lineup, witnesses shift their responses to pick foils, rather than rejecting the lineups, a result we will term a target-to-foils shift. Additional empirical support is provided by results from sequential lineups which typically show higher accuracy than simultaneous lineups, presumably because of a decrease in the use of relative judgments in making identification decisions. The combination of these two lines of research suggests that the target-to-foils shift should be reduced in sequential lineups relative to simultaneous lineups. Results of two experiments showed an overall advantage for sequential lineups, but also showed a target-to-foils shift equal in size for simultaneous and sequential lineups. Additional analyses indicated that the target-to-foils shift in sequential lineups was moderated in part by an order effect and was produced with (Experiment 2) or without (Experiment 1) a shift in decision criterion. This complex pattern of results suggests that more work is needed to understand the processes which underlie decisions in simultaneous and sequential lineups.

Characterisation of monoclonal antibodies for human luteinising hormone, and mapping of antigenic determinants on the hormone

International Nuclear Information System (INIS)

Soos, M.; Siddle, K.

1983-01-01

Twelve mouse monoclonal antibodies for human luteinising hormone were produced. The affinities varied from 4 X 10 7 to 1 X 10 10 l/mol. The specificity of each antibody was assessed by determining the relative reactivities with luteinising hormone, thyroid stimulating hormone, follicle stimulating hormone and chorionic gonadotrophin. Six antibodies bound to the α-subunit as shown by similar reactivity with all hormones, and the remainder to the β-subunit as shown by specificity for luteinising hormone. This latter group of antibodies cross-reacted only weakly with thyroid stimulating hormone (approximately 10%) and follicle stimulating hormone (approximately 3%). Three of these antibodies also showed low reactivity towards chorionic gonadotrophin (<10%), though the others did not (80-300%). The ability of different antibodies to bind simultaneously to luteinising hormone was examined and it was shown that several distinct antigenic determinants existed on both subunits. The characterisation of monoclonal binding sites is discussed in relation to the use of antibodies in two-site immunoradiometric assays. (Auth.)

Heart, lipids and hormones

Directory of Open Access Journals (Sweden)

Peter Wolf

2017-05-01

Full Text Available Cardiovascular disease is the leading cause of death in general population. Besides well-known risk factors such as hypertension, impaired glucose tolerance and dyslipidemia, growing evidence suggests that hormonal changes in various endocrine diseases also impact the cardiac morphology and function. Recent studies highlight the importance of ectopic intracellular myocardial and pericardial lipid deposition, since even slight changes of these fat depots are associated with alterations in cardiac performance. In this review, we overview the effects of hormones, including insulin, thyroid hormones, growth hormone and cortisol, on heart function, focusing on their impact on myocardial lipid metabolism, cardiac substrate utilization and ectopic lipid deposition, in order to highlight the important role of even subtle hormonal changes for heart function in various endocrine and metabolic diseases.

Dynamics-based sequential memory: Winnerless competition of patterns

International Nuclear Information System (INIS)

Seliger, Philip; Tsimring, Lev S.; Rabinovich, Mikhail I.

2003-01-01

We introduce a biologically motivated dynamical principle of sequential memory which is based on winnerless competition (WLC) of event images. This mechanism is implemented in a two-layer neural model of sequential spatial memory. We present the learning dynamics which leads to the formation of a WLC network. After learning, the system is capable of associative retrieval of prerecorded sequences of patterns

Sequential, progressive, equal-power, reflective beam-splitter arrays

Science.gov (United States)

Manhart, Paul K.

2017-11-01

The equations to calculate equal-power reflectivity of a sequential series of beam splitters is presented. Non-sequential optical design examples are offered for uniform illumination using diode lasers. Objects created using Boolean operators and Swept Surfaces can create objects capable of reflecting light into predefined elevation and azimuth angles. Analysis of the illumination patterns for the array are also presented.

Basal ganglia and cortical networks for sequential ordering and rhythm of complex movements

Directory of Open Access Journals (Sweden)

Jeffery G. Bednark

2015-07-01

Full Text Available Voluntary actions require the concurrent engagement and coordinated control of complex temporal (e.g. rhythm and ordinal motor processes. Using high-resolution functional magnetic resonance imaging (fMRI and multi-voxel pattern analysis (MVPA, we sought to determine the degree to which these complex motor processes are dissociable in basal ganglia and cortical networks. We employed three different finger-tapping tasks that differed in the demand on the sequential temporal rhythm or sequential ordering of submovements. Our results demonstrate that sequential rhythm and sequential order tasks were partially dissociable based on activation differences. The sequential rhythm task activated a widespread network centered around the SMA and basal-ganglia regions including the dorsomedial putamen and caudate nucleus, while the sequential order task preferentially activated a fronto-parietal network. There was also extensive overlap between sequential rhythm and sequential order tasks, with both tasks commonly activating bilateral premotor, supplementary motor, and superior/inferior parietal cortical regions, as well as regions of the caudate/putamen of the basal ganglia and the ventro-lateral thalamus. Importantly, within the cortical regions that were active for both complex movements, MVPA could accurately classify different patterns of activation for the sequential rhythm and sequential order tasks. In the basal ganglia, however, overlapping activation for the sequential rhythm and sequential order tasks, which was found in classic motor circuits of the putamen and ventro-lateral thalamus, could not be accurately differentiated by MVPA. Overall, our results highlight the convergent architecture of the motor system, where complex motor information that is spatially distributed in the cortex converges into a more compact representation in the basal ganglia.

The sequential price of anarchy for atomic congestion games

NARCIS (Netherlands)

de Jong, Jasper; Uetz, Marc Jochen; Liu, Tie-Yan; Qi, Qi; Ye, Yinyu

2014-01-01

In situations without central coordination, the price of anarchy relates the quality of any Nash equilibrium to the quality of a global optimum. Instead of assuming that all players choose their actions simultaneously, we consider games where players choose their actions sequentially. The sequential

Botanical modulation of menopausal symptoms: Mechanisms of action?

Science.gov (United States)

Hajirahimkhan, Atieh; Dietz, Birgit M.; Bolton, Judy L.

2013-01-01

Menopausal women suffer from a variety of symptoms, including hot flashes and night sweats which can affect quality of life. Although hormone therapy (HT) has been the treatment of choice for relieving these symptoms, HT has been associated with increased breast cancer risk leading many women to search for natural, efficacious, and safe alternatives such as botanical supplements. Data from clinical trials suggesting that botanicals have efficacy for menopausal symptom relief, have been controversial and several mechanisms of action have been proposed including estrogenic, progestogenic, and serotonergic pathways. Plant extracts with potential estrogenic activities include soy, red clover, kudzu, hops, licorice, rhubarb, yam, and chasteberry. Botanicals with reported progestogenic activities are red clover, hops, yam, and chasteberry. Serotonergic mechanisms have also been proposed since women taking antidepressants often report reduction in hot flashes and night sweats. Black cohosh, kudzu, kava, licorice, and dong quai all either have reported 5-HT7 ligands or inhibit serotonin re-uptake, therefore have potential serotonergic activities. Understanding the mechanisms of action of these natural remedies used for women’s health, could lead to more efficacious formulations and to the isolation of active components which have the potential of becoming effective medications in the future. PMID:23408273

Menopause and cardiovascular disease: the evidence.

Science.gov (United States)

Rosano, G M C; Vitale, C; Marazzi, G; Volterrani, M

2007-02-01

Menopause is a risk factor for cardiovascular disease (CVD) because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism. The menopause compounds many traditional CVD risk factors, including changes in body fat distribution from a gynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction and vascular inflammation. Many CVD risk factors have different impacts in men and women. In postmenopausal women, treatment of arterial hypertension and glucose intolerance should be priorities. Observational studies and randomized clinical trials suggest that hormone replacement therapy (HRT) started soon after the menopause may confer cardiovascular benefit. In contrast to other synthetic progestogens used in continuous combined HRTs, the unique progestogen drospirenone has antialdosterone properties. Drospirenone can therefore counteract the water- and sodium-retaining effects of the estrogen component of HRT via the renin-angiotensin-aldosterone system, which may otherwise result in weight gain and raised blood pressure. As a continuous combined HRT with 17beta-estradiol, drospirenone has been shown to significantly reduce blood pressure in postmenopausal women with elevated blood pressure, but not in normotensive women. Therefore, in addition to relieving climacteric symptoms, drospirenone/17beta-estradiol may offer further benefits in postmenopausal women, such as improved CVD risk profile.

Hereditary angioedema in women

Directory of Open Access Journals (Sweden)

Bouillet Laurence

2010-07-01

Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

Native Frames: Disentangling Sequential from Concerted Three-Body Fragmentation

Science.gov (United States)

Rajput, Jyoti; Severt, T.; Berry, Ben; Jochim, Bethany; Feizollah, Peyman; Kaderiya, Balram; Zohrabi, M.; Ablikim, U.; Ziaee, Farzaneh; Raju P., Kanaka; Rolles, D.; Rudenko, A.; Carnes, K. D.; Esry, B. D.; Ben-Itzhak, I.

2018-03-01

A key question concerning the three-body fragmentation of polyatomic molecules is the distinction of sequential and concerted mechanisms, i.e., the stepwise or simultaneous cleavage of bonds. Using laser-driven fragmentation of OCS into O++C++S+ and employing coincidence momentum imaging, we demonstrate a novel method that enables the clear separation of sequential and concerted breakup. The separation is accomplished by analyzing the three-body fragmentation in the native frame associated with each step and taking advantage of the rotation of the intermediate molecular fragment, CO2 + or CS2 + , before its unimolecular dissociation. This native-frame method works for any projectile (electrons, ions, or photons), provides details on each step of the sequential breakup, and enables the retrieval of the relevant spectra for sequential and concerted breakup separately. Specifically, this allows the determination of the branching ratio of all these processes in OCS3 + breakup. Moreover, we find that the first step of sequential breakup is tightly aligned along the laser polarization and identify the likely electronic states of the intermediate dication that undergo unimolecular dissociation in the second step. Finally, the separated concerted breakup spectra show clearly that the central carbon atom is preferentially ejected perpendicular to the laser field.

A nonpeptidyl growth hormone secretagogue.

Science.gov (United States)

Smith, R G; Cheng, K; Schoen, W R; Pong, S S; Hickey, G; Jacks, T; Butler, B; Chan, W W; Chaung, L Y; Judith, F

1993-06-11

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5 -yl) (1,1'-biphenyl)-4-yl]methyl)-1H-1-benzazepin-3(R)-yl)-butanamid e (L-692,429) has been identified. L-692,429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.

Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

Science.gov (United States)

Warren, W B; Gurewitsch, E D; Goland, R S

1995-02-01

We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

An update on cystic ovarian degeneration in cattle.

Science.gov (United States)

Peter, A T

2004-02-01

Cystic ovarian degeneration (COD) is considered to be one of the most important causes of reproductive failure in cattle. There is a severe economic loss to dairy industry because COD increases days-open in the postpartum period and the culling rates. The disease process is a consequence of a mature follicle that fails to ovulate at the appointed time of ovulation in the oestrous cycle. This anovulatory follicular structure either regresses or persists as a follicular or luteal cyst depending upon its structural/functional characteristics. The cells lining the follicular cyst synthesize oestrogen that, in certain instances, forces the animal to exhibit clinical signs of nymphomania. Besides oestrogen production, as per recent findings, they are also capable of secreting varying amount of progesterone which may dictate their fate. The animals that carry a luteal cyst may tend to be in anoestrus as the higher amount of progesterone secreted by this luteinized structure may change the pattern of gonadotrophins' secretion. Present findings suggest that perturbation of the hypothalamo-hypophyseal-ovarian (HHO) axis, due to many exogenous and endogenous factors, as the cause for anovulation. For example, it has been suggested that lack of hypothalamic or hypophyseal response to the positive feedback effect of oestrogens that are secreted by the dominant follicle as one of the many causes. The non-physiological changes that occur in the receptor expression of the HHO axis for the hormones involved in maturation, deviation, dominance and ovulation of the follicle may be yet another cause. The changes that occur at the cellular and molecular level in the ovary (in response to the factors mentioned above) that contribute to anovulation remain to be documented. This approach would allow us to completely understand the disease process. Hitherto, hormonal preparations that release luteinizing hormone from the anterior pituitary or have luteinizing hormone-like action are used

Campbell and moment measures for finite sequential spatial processes

NARCIS (Netherlands)

M.N.M. van Lieshout (Marie-Colette)

2006-01-01

textabstractWe define moment and Campbell measures for sequential spatial processes, prove a Campbell-Mecke theorem, and relate the results to their counterparts in the theory of point processes. In particular, we show that any finite sequential spatial process model can be derived as the vector

Sequential Dependencies in Driving

Science.gov (United States)

Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

2012-01-01

The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

Thyroid Hormone Receptor Mutations in Cancer and Resistance to Thyroid Hormone: Perspective and Prognosis

Directory of Open Access Journals (Sweden)

Meghan D. Rosen

2011-01-01

Full Text Available Thyroid hormone, operating through its receptors, plays crucial roles in the control of normal human physiology and development; deviations from the norm can give rise to disease. Clinical endocrinologists often must confront and correct the consequences of inappropriately high or low thyroid hormone synthesis. Although more rare, disruptions in thyroid hormone endocrinology due to aberrations in the receptor also have severe medical consequences. This review will focus on the afflictions that are caused by, or are closely associated with, mutated thyroid hormone receptors. These include Resistance to Thyroid Hormone Syndrome, erythroleukemia, hepatocellular carcinoma, renal clear cell carcinoma, and thyroid cancer. We will describe current views on the molecular bases of these diseases, and what distinguishes the neoplastic from the non-neoplastic. We will also touch on studies that implicate alterations in receptor expression, and thyroid hormone levels, in certain oncogenic processes.

Research on parallel algorithm for sequential pattern mining

Science.gov (United States)

Zhou, Lijuan; Qin, Bai; Wang, Yu; Hao, Zhongxiao

2008-03-01

Sequential pattern mining is the mining of frequent sequences related to time or other orders from the sequence database. Its initial motivation is to discover the laws of customer purchasing in a time section by finding the frequent sequences. In recent years, sequential pattern mining has become an important direction of data mining, and its application field has not been confined to the business database and has extended to new data sources such as Web and advanced science fields such as DNA analysis. The data of sequential pattern mining has characteristics as follows: mass data amount and distributed storage. Most existing sequential pattern mining algorithms haven't considered the above-mentioned characteristics synthetically. According to the traits mentioned above and combining the parallel theory, this paper puts forward a new distributed parallel algorithm SPP(Sequential Pattern Parallel). The algorithm abides by the principal of pattern reduction and utilizes the divide-and-conquer strategy for parallelization. The first parallel task is to construct frequent item sets applying frequent concept and search space partition theory and the second task is to structure frequent sequences using the depth-first search method at each processor. The algorithm only needs to access the database twice and doesn't generate the candidated sequences, which abates the access time and improves the mining efficiency. Based on the random data generation procedure and different information structure designed, this paper simulated the SPP algorithm in a concrete parallel environment and implemented the AprioriAll algorithm. The experiments demonstrate that compared with AprioriAll, the SPP algorithm had excellent speedup factor and efficiency.

2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy.

Science.gov (United States)

Li, Jingmei; Lindström, Linda S; Foo, Jia N; Rafiq, Sajjad; Schmidt, Marjanka K; Pharoah, Paul D P; Michailidou, Kyriaki; Dennis, Joe; Bolla, Manjeet K; Wang, Qin; Van 't Veer, Laura J; Cornelissen, Sten; Rutgers, Emiel; Southey, Melissa C; Apicella, Carmel; Dite, Gillian S; Hopper, John L; Fasching, Peter A; Haeberle, Lothar; Ekici, Arif B; Beckmann, Matthias W; Blomqvist, Carl; Muranen, Taru A; Aittomäki, Kristiina; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M; Kataja, Vesa; Chenevix-Trench, Georgia; Phillips, Kelly-Anne; McLachlan, Sue-Anne; Lambrechts, Diether; Thienpont, Bernard; Smeets, Ann; Wildiers, Hans; Chang-Claude, Jenny; Flesch-Janys, Dieter; Seibold, Petra; Rudolph, Anja; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Kristensen, Vessela; Alnæs, Grethe I Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Tchatchou, Sandrine; Devilee, Peter; Tollenaar, Robert; Seynaeve, Caroline; Hooning, Maartje; Kriege, Mieke; Hollestelle, Antoinette; van den Ouweland, Ans; Li, Yi; Hamann, Ute; Torres, Diana; Ulmer, Hans U; Rüdiger, Thomas; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Chen, Shou-Tung; Teo, Soo Hwang; Taib, Nur Aishah Mohd; Har Yip, Cheng; Fuang Ho, Gwo; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Maishman, Tom; Tapper, William J; Dunning, Alison; Shah, Mitul; Luben, Robert; Brown, Judith; Khor, Chiea Chuen; Eccles, Diana M; Nevanlinna, Heli; Easton, Douglas; Humphreys, Keith; Liu, Jianjun; Hall, Per; Czene, Kamila

2014-06-17

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

Radioimmunoassay of polypeptide hormones and enzymes

International Nuclear Information System (INIS)

Felber, J.P.

1974-01-01

General principles of radioimmunoassay are reviewed. Detailed procedures are reviewed for the following hormones: insulin, pituitary hormones, gonadotropins, parathyroid hormone, ACTH, glucagon, gastrin, and peptide hormones. Radioimmunoassay of enzymes is also discussed. (U.S.)

Aging changes in hormone production

Science.gov (United States)

... this page: //medlineplus.gov/ency/article/004000.htm Aging changes in hormone production To use the sharing ... that produce hormones are controlled by other hormones. Aging also changes this process. For example, an endocrine ...

The "multiple hormone deficiency" theory of aging: is human senescence caused mainly by multiple hormone deficiencies?

Science.gov (United States)

Hertoghe, T

2005-12-01

In the human body, the productions, levels and cell receptors of most hormones progressively decline with age, gradually putting the body into various states of endocrine deficiency. The circadian cycles of these hormones also change, sometimes profoundly, with time. In aging individuals, the well-balanced endocrine system can fall into a chaotic condition with losses, phase-advancements, phase delays, unpredictable irregularities of nycthemeral hormone cycles, in particular in very old or sick individuals. The desynchronization makes hormone activities peak at the wrong times and become inefficient, and in certain cases health threatening. The occurrence of multiple hormone deficits and spilling through desynchronization may constitute the major causes of human senescence, and they are treatable causes. Several arguments can be put forward to support the view that senescence is mainly a multiple hormone deficiency syndrome: First, many if not most of the signs, symptoms and diseases (including cardiovascular diseases, cancer, obesity, diabetes, osteoporosis, dementia) of senescence are similar to physical consequences of hormone deficiencies and may be caused by hormone deficiencies. Second, most of the presumed causes of senescence such as excessive free radical formation, glycation, cross-linking of proteins, imbalanced apoptosis system, accumulation of waste products, failure of repair systems, deficient immune system, may be caused or favored by hormone deficiencies. Even genetic causes such as limits to cell proliferation (such as the Hayflick limit of cell division), poor gene polymorphisms, premature telomere shortening and activation of possible genetic "dead programs" may have links with hormone deficiencies, being either the consequence, the cause, or the major favoring factor of hormone deficiencies. Third, well-dosed and -balanced hormone supplements may slow down or stop the progression of signs, symptoms, or diseases of senescence and may often

Prolactin levels during short- and long-term cross-sex hormone treatment: an observational study in transgender persons.

Science.gov (United States)

Nota, N M; Dekker, M J H J; Klaver, M; Wiepjes, C M; van Trotsenburg, M A; Heijboer, A C; den Heijer, M

2017-08-01

The cause of prolactin alterations in transgender persons is often assigned to oestrogens, but the precise cause and time course during different phases of cross-sex hormone treatment (CHT) remain unclear. In this study, we prospectively examined prolactin levels in 55 female-to-males (FtMs) and 61 male-to-females (MtFs) during the first year of CHT. Because long-term prolactin data were not available in this population, we studied these levels in a retrospective population of 25 FtMs and 38 MtFs who underwent gonadectomy. FtMs were treated with testosterone and MtFs with estradiol, with or without the anti-androgen cyproterone acetate (CPA) (after gonadectomy CPA is cessated). During the first year of CHT, prolactin decreased with 25% (95CI: -33%, -12%) in FtMs and increased with 193% (95CI: 156%, 219%) in MtFs. Eighteen MtFs developed hyperprolactinemia (≥0.6 IU L -1 ). In the retrospective population, post-gonadectomy levels in FtMs were lower than baseline levels (-39%; 95CI: -51%, -20%) while in MtFs post-gonadectomy levels and baseline levels were comparable (-6%; 95CI: -24%, 15%). No hyperprolactinemia was found after gonadectomy. In conclusion, in FtMs, prolactin decreased consistently during CHT and in MtFs, prolactin increased during pre-surgical CHT but normalised after gonadectomy. It is likely that CPA induces increasing prolactin levels in MtFs. © 2016 Blackwell Verlag GmbH.

Venous and arterial thrombo-embolic complications of hormonal treatment in a male-to-female transgender patient.

LENUS (Irish Health Repository)

Mullins, G M

2012-02-03

We present a male-to-female (MTF) transgender patient admitted with a pulmonary embolism. The patient had been treated with high-dose oestrogens since the age of 16. Following a prolonged period of hypotension, our patient sustained cerebral border zone infarcts. There was evidence of bilateral carotid stenosis on Doppler ultrasound. We discuss the treatment and vascular complications of gender dysphoria.

Kinetics of thyroid hormones

International Nuclear Information System (INIS)

Inada, Mitsuo; Nishikawa, Mitsushige; Naito, Kimikazu; Ishii, Hitoshi; Tanaka, Kiyoshi

1980-01-01

Kinetics of thyroid hormones were outlined, and recent progress in metabolism of these hormones was also described. Recently, not only T 4 and T 3 but also rT 3 , 3,3'-T 2 , 3',5'-T 2 , and 3,5-T 2 can be measured by RIA. To clarify metabolic pathways of these hormones, metabolic clearance rate and production rate of these hormones were calculated. As single-compartment analysis was insufficient to clarify disappearance curves of thyroid hormones in blood such as T 3 and T 2 of which metabolic speed was so fast, multi-compartment analysis or non-compartment analysis were also performed. Thyroid hormones seemed to be measured more precisely by constant infusion method. At the first step of T 4 metabolism, T 3 was formed by 5'-monodeiodination of T 4 , and rT 3 was formed by 5-monodeiodination of T 4 . As metabolic pathways of T 3 and rT 3 , conversion of them to 3,3'-T 2 or to 3',5'-T 2 and 3,5-T 2 was supposed. This subject will be an interesting research theme in future. (Tsunoda, M.)

Plants altering hormonal milieu: A review

Directory of Open Access Journals (Sweden)

Prashant Tiwari

2017-02-01

Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

Plants altering hormonal milieu: A review

Directory of Open Access Journals (Sweden)

Prashant Tiwari

2017-01-01

Full Text Available The aim of the present review article is to investigate the herbs which can alter the levels of hormones like Follicle stimulating hormone, Prolactin, Growth hormone, Insulin, Thyroxine, Estrogen, Progesterone, Testosterone, and Relaxin etc. Hormones are chemical signal agents produced by different endocrine glands for regulating our biological functions. The glands like pituitary, thyroid, adrenal, ovaries in women and testes in men all secrete a number of hormones with different actions. However, when these hormones are perfectly balanced then people become healthy and fit. But several factors like pathophysiological as well as biochemical changes, disease conditions, changes in the atmosphere, changes in the body, diet changes etc. may result in imbalance of various hormones that produce undesirable symptoms and disorders. As medicinal plants have their importance since ancient time, people have been using it in various ways as a source of medicine for regulation of hormonal imbalance. Moreover, it is observed that certain herbs have a balancing effect on hormones and have great impact on well-being of the people. So, considering these facts we expect that the article provides an overview on medicinal plants with potential of altering hormone level.

Thyroid Hormone, Cancer, and Apoptosis.

Science.gov (United States)

Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

2016-06-13

Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Concordance of self-reported hormonal contraceptive use and presence of exogenous hormones in serum among African women.

Science.gov (United States)

Pyra, Maria; Lingappa, Jairam R; Heffron, Renee; Erikson, David W; Blue, Steven W; Patel, Rena C; Nanda, Kavita; Rees, Helen; Mugo, Nelly R; Davis, Nicole L; Kourtis, Athena P; Baeten, Jared M

2018-04-01

Studies that rely on self-report to investigate the relationship between hormonal contraceptive use and HIV acquisition and transmission, as well as other health outcomes, could have compromised results due to misreporting. We determined the frequency of misreported hormonal contraceptive use among African women with and at risk for HIV. We tested 1102 archived serum samples from 664 African women who had participated in prospective HIV prevention studies. Using a novel high-performance liquid chromatography-mass spectrometry assay, we quantified exogenous hormones for injectables (medroxyprogesterone acetate or norethisterone), oral contraceptives (OC) (levonorgestrel or ethinyl estradiol) and implants (levonorgestrel or etonogestrel) and compared them to self-reported use. Among women reporting hormonal contraceptive use, 258/358 (72%) of samples were fully concordant with self-report, as were 642/744 (86%) of samples from women reporting no hormonal contraceptive use. However, 42/253 (17%) of samples from women reporting injectable use, 41/66 (62%) of samples from self-reported OC users and 3/39 (8%) of samples from self-reported implant users had no quantifiable hormones. Among self-reported nonusers, 102/744 (14%) had ≥1 hormone present. Concordance between self-reported method and exogenous hormones did not differ by HIV status. Among African women with and at risk for HIV, testing of exogenous hormones revealed agreement with self-reported contraceptive use for most women. However, unexpected exogenous hormones were identified among self-reported hormonal contraceptive users and nonusers, and an important fraction of women reporting hormonal contraceptive use had no hormones detected; absence of oral contraceptive hormones could be due, at least in part, to samples taken during the hormone-free interval. Misreporting of hormonal contraceptive use could lead to biased results in observational studies of the relationship between contraceptive use and health

Framework for sequential approximate optimization

NARCIS (Netherlands)

Jacobs, J.H.; Etman, L.F.P.; Keulen, van F.; Rooda, J.E.

2004-01-01

An object-oriented framework for Sequential Approximate Optimization (SAO) isproposed. The framework aims to provide an open environment for thespecification and implementation of SAO strategies. The framework is based onthe Python programming language and contains a toolbox of Python

A Survey of Multi-Objective Sequential Decision-Making

OpenAIRE

Roijers, D.M.; Vamplew, P.; Whiteson, S.; Dazeley, R.

2013-01-01

Sequential decision-making problems with multiple objectives arise naturally in practice and pose unique challenges for research in decision-theoretic planning and learning, which has largely focused on single-objective settings. This article surveys algorithms designed for sequential decision-making problems with multiple objectives. Though there is a growing body of literature on this subject, little of it makes explicit under what circumstances special methods are needed to solve multi-obj...

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations

Science.gov (United States)

Qin, Fangjun; Jiang, Sai; Zha, Feng

2018-01-01

In this paper, a sequential multiplicative extended Kalman filter (SMEKF) is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms. PMID:29751538

A Sequential Multiplicative Extended Kalman Filter for Attitude Estimation Using Vector Observations

Directory of Open Access Journals (Sweden)

Fangjun Qin

2018-05-01

Full Text Available In this paper, a sequential multiplicative extended Kalman filter (SMEKF is proposed for attitude estimation using vector observations. In the proposed SMEKF, each of the vector observations is processed sequentially to update the attitude, which can make the measurement model linearization more accurate for the next vector observation. This is the main difference to Murrell’s variation of the MEKF, which does not update the attitude estimate during the sequential procedure. Meanwhile, the covariance is updated after all the vector observations have been processed, which is used to account for the special characteristics of the reset operation necessary for the attitude update. This is the main difference to the traditional sequential EKF, which updates the state covariance at each step of the sequential procedure. The numerical simulation study demonstrates that the proposed SMEKF has more consistent and accurate performance in a wide range of initial estimate errors compared to the MEKF and its traditional sequential forms.

Asynchronous Operators of Sequential Logic Venjunction & Sequention

CERN Document Server

Vasyukevich, Vadim

2011-01-01

This book is dedicated to new mathematical instruments assigned for logical modeling of the memory of digital devices. The case in point is logic-dynamical operation named venjunction and venjunctive function as well as sequention and sequentional function. Venjunction and sequention operate within the framework of sequential logic. In a form of the corresponding equations, they organically fit analytical expressions of Boolean algebra. Thus, a sort of symbiosis is formed using elements of asynchronous sequential logic on the one hand and combinational logic on the other hand. So, asynchronous

Hormones and the blood-brain barrier.

Science.gov (United States)

Hampl, Richard; Bičíková, Marie; Sosvorová, Lucie

2015-03-01

Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

Hormonal control of euryhalinity

Science.gov (United States)

Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

2013-01-01

Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

Human visual system automatically encodes sequential regularities of discrete events.

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Kimura, Motohiro; Schröger, Erich; Czigler, István; Ohira, Hideki

2010-06-01

For our adaptive behavior in a dynamically changing environment, an essential task of the brain is to automatically encode sequential regularities inherent in the environment into a memory representation. Recent studies in neuroscience have suggested that sequential regularities embedded in discrete sensory events are automatically encoded into a memory representation at the level of the sensory system. This notion is largely supported by evidence from investigations using auditory mismatch negativity (auditory MMN), an event-related brain potential (ERP) correlate of an automatic memory-mismatch process in the auditory sensory system. However, it is still largely unclear whether or not this notion can be generalized to other sensory modalities. The purpose of the present study was to investigate the contribution of the visual sensory system to the automatic encoding of sequential regularities using visual mismatch negativity (visual MMN), an ERP correlate of an automatic memory-mismatch process in the visual sensory system. To this end, we conducted a sequential analysis of visual MMN in an oddball sequence consisting of infrequent deviant and frequent standard stimuli, and tested whether the underlying memory representation of visual MMN generation contains only a sensory memory trace of standard stimuli (trace-mismatch hypothesis) or whether it also contains sequential regularities extracted from the repetitive standard sequence (regularity-violation hypothesis). The results showed that visual MMN was elicited by first deviant (deviant stimuli following at least one standard stimulus), second deviant (deviant stimuli immediately following first deviant), and first standard (standard stimuli immediately following first deviant), but not by second standard (standard stimuli immediately following first standard). These results are consistent with the regularity-violation hypothesis, suggesting that the visual sensory system automatically encodes sequential

A Bayesian Theory of Sequential Causal Learning and Abstract Transfer.

Science.gov (United States)

Lu, Hongjing; Rojas, Randall R; Beckers, Tom; Yuille, Alan L

2016-03-01

Two key research issues in the field of causal learning are how people acquire causal knowledge when observing data that are presented sequentially, and the level of abstraction at which learning takes place. Does sequential causal learning solely involve the acquisition of specific cause-effect links, or do learners also acquire knowledge about abstract causal constraints? Recent empirical studies have revealed that experience with one set of causal cues can dramatically alter subsequent learning and performance with entirely different cues, suggesting that learning involves abstract transfer, and such transfer effects involve sequential presentation of distinct sets of causal cues. It has been demonstrated that pre-training (or even post-training) can modulate classic causal learning phenomena such as forward and backward blocking. To account for these effects, we propose a Bayesian theory of sequential causal learning. The theory assumes that humans are able to consider and use several alternative causal generative models, each instantiating a different causal integration rule. Model selection is used to decide which integration rule to use in a given learning environment in order to infer causal knowledge from sequential data. Detailed computer simulations demonstrate that humans rely on the abstract characteristics of outcome variables (e.g., binary vs. continuous) to select a causal integration rule, which in turn alters causal learning in a variety of blocking and overshadowing paradigms. When the nature of the outcome variable is ambiguous, humans select the model that yields the best fit with the recent environment, and then apply it to subsequent learning tasks. Based on sequential patterns of cue-outcome co-occurrence, the theory can account for a range of phenomena in sequential causal learning, including various blocking effects, primacy effects in some experimental conditions, and apparently abstract transfer of causal knowledge. Copyright © 2015

Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: an exploratory analysis of TEXT and SOFT.

Science.gov (United States)

Regan, M M; Walley, B A; Francis, P A; Fleming, G F; Láng, I; Gómez, H L; Colleoni, M; Tondini, C; Pinotti, G; Salim, M; Spazzapan, S; Parmar, V; Ruhstaller, T; Abdi, E A; Gelber, R D; Coates, A S; Goldhirsch, A; Pagani, O

2017-09-01

Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFS-containing adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n = 1242) versus sequentially post-chemotherapy in SOFT (n = 630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR = 1.11, 95% CI 0.72-1.72; P = 0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup <40 years, neither

Impact of Diagrams on Recalling Sequential Elements in Expository Texts.

Science.gov (United States)

Guri-Rozenblit, Sarah

1988-01-01

Examines the instructional effectiveness of abstract diagrams on recall of sequential relations in social science textbooks. Concludes that diagrams assist significantly the recall of sequential relations in a text and decrease significantly the rate of order mistakes. (RS)

Quantum Probability Zero-One Law for Sequential Terminal Events

Science.gov (United States)

Rehder, Wulf

1980-07-01

On the basis of the Jauch-Piron quantum probability calculus a zero-one law for sequential terminal events is proven, and the significance of certain crucial axioms in the quantum probability calculus is discussed. The result shows that the Jauch-Piron set of axioms is appropriate for the non-Boolean algebra of sequential events.

A path-level exact parallelization strategy for sequential simulation

Science.gov (United States)

Peredo, Oscar F.; Baeza, Daniel; Ortiz, Julián M.; Herrero, José R.

2018-01-01

Sequential Simulation is a well known method in geostatistical modelling. Following the Bayesian approach for simulation of conditionally dependent random events, Sequential Indicator Simulation (SIS) method draws simulated values for K categories (categorical case) or classes defined by K different thresholds (continuous case). Similarly, Sequential Gaussian Simulation (SGS) method draws simulated values from a multivariate Gaussian field. In this work, a path-level approach to parallelize SIS and SGS methods is presented. A first stage of re-arrangement of the simulation path is performed, followed by a second stage of parallel simulation for non-conflicting nodes. A key advantage of the proposed parallelization method is to generate identical realizations as with the original non-parallelized methods. Case studies are presented using two sequential simulation codes from GSLIB: SISIM and SGSIM. Execution time and speedup results are shown for large-scale domains, with many categories and maximum kriging neighbours in each case, achieving high speedup results in the best scenarios using 16 threads of execution in a single machine.

Oestrogen and progesterone receptor assays in breast tumours. The Prince Henry's Hospital experience, 1983-1990.

Science.gov (United States)

Pearce, P T; Myles, K M; Funder, J W

1993-08-16

To present and analyse the results of eight years of experience (1983-1990) in breast tumour receptor analysis. All female primary breast tumour samples received (4683) were analysed for seasonal variation, patient age, relative risk index, oestrogen receptor (ER) and progesterone receptor (PR) status, ER and PR status as a function of age, ER and PR levels as a function of age, and ER and PR levels as a function of month of analysis. The assays were done at the Medical Research Centre, Prince Henry's Hospital, Melbourne, as a non-profit service to surgeons, oncologists and pathologists. The numbers of samples referred for assay increased progressively each year, from 473 in 1983 to 1097 in 1990, but the receptor status (ER +/-, PR +/-) appeared not to vary from year to year. ER+PR+ tumours were the most common in all age groups, steadily increasing from between 50% and 60% in premenopausal women to 70% or more in those aged over 80. In postmenopausal women, levels of ER in ER+ tumours were three times those in premenopausal women; PR levels in PR+ tumours, however, were bimodal, with higher levels in the age groups 35-49 and 70-89 years than in women aged 50-69 years. No significant seasonal variation was seen, and the overall patterns of receptor status are similar to those seen in Northern hemisphere studies.

Concatenated coding system with iterated sequential inner decoding

DEFF Research Database (Denmark)

Jensen, Ole Riis; Paaske, Erik

1995-01-01

We describe a concatenated coding system with iterated sequential inner decoding. The system uses convolutional codes of very long constraint length and operates on iterations between an inner Fano decoder and an outer Reed-Solomon decoder......We describe a concatenated coding system with iterated sequential inner decoding. The system uses convolutional codes of very long constraint length and operates on iterations between an inner Fano decoder and an outer Reed-Solomon decoder...

Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

Directory of Open Access Journals (Sweden)

Claudia eBarth

2015-02-01

Full Text Available Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo.

Lineup Composition, Suspect Position, and the Sequential Lineup Advantage

Science.gov (United States)

Carlson, Curt A.; Gronlund, Scott D.; Clark, Steven E.

2008-01-01

N. M. Steblay, J. Dysart, S. Fulero, and R. C. L. Lindsay (2001) argued that sequential lineups reduce the likelihood of mistaken eyewitness identification. Experiment 1 replicated the design of R. C. L. Lindsay and G. L. Wells (1985), the first study to show the sequential lineup advantage. However, the innocent suspect was chosen at a lower rate…

Trial Sequential Analysis in systematic reviews with meta-analysis

Directory of Open Access Journals (Sweden)

Jørn Wetterslev

2017-03-01

Full Text Available Abstract Background Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors and too many false negative conclusions (type II errors. Methods We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. Results The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D2 measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in

Heat accumulation during sequential cortical bone drilling.

Science.gov (United States)

Palmisano, Andrew C; Tai, Bruce L; Belmont, Barry; Irwin, Todd A; Shih, Albert; Holmes, James R

2016-03-01

Significant research exists regarding heat production during single-hole bone drilling. No published data exist regarding repetitive sequential drilling. This study elucidates the phenomenon of heat accumulation for sequential drilling with both Kirschner wires (K wires) and standard two-flute twist drills. It was hypothesized that cumulative heat would result in a higher temperature with each subsequent drill pass. Nine holes in a 3 × 3 array were drilled sequentially on moistened cadaveric tibia bone kept at body temperature (about 37 °C). Four thermocouples were placed at the center of four adjacent holes and 2 mm below the surface. A battery-driven hand drill guided by a servo-controlled motion system was used. Six samples were drilled with each tool (2.0 mm K wire and 2.0 and 2.5 mm standard drills). K wire drilling increased temperature from 5 °C at the first hole to 20 °C at holes 6 through 9. A similar trend was found in standard drills with less significant increments. The maximum temperatures of both tools increased from drill sizes was found to be insignificant (P > 0.05). In conclusion, heat accumulated during sequential drilling, with size difference being insignificant. K wire produced more heat than its twist-drill counterparts. This study has demonstrated the heat accumulation phenomenon and its significant effect on temperature. Maximizing the drilling field and reducing the number of drill passes may decrease bone injury. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

A common polymorphism of the growth hormone receptor is associated with increased responsiveness to growth hormone.

Science.gov (United States)

Dos Santos, Christine; Essioux, Laurent; Teinturier, Cécile; Tauber, Maïté; Goffin, Vincent; Bougnères, Pierre

2004-07-01

Growth hormone is used to increase height in short children who are not deficient in growth hormone, but its efficacy varies largely across individuals. The genetic factors responsible for this variation are entirely unknown. In two cohorts of short children treated with growth hormone, we found that an isoform of the growth hormone receptor gene that lacks exon 3 (d3-GHR) was associated with 1.7 to 2 times more growth acceleration induced by growth hormone than the full-length isoform (P < 0.0001). In transfection experiments, the transduction of growth hormone signaling through d3-GHR homo- or heterodimers was approximately 30% higher than through full-length GHR homodimers (P < 0.0001). One-half of Europeans are hetero- or homozygous with respect to the allele encoding the d3-GHR isoform, which is dominant over the full-length isoform. These observations suggest that the polymorphism in exon 3 of GHR is important in growth hormone pharmacogenetics.

Cost-effectiveness of simultaneous versus sequential surgery in head and neck reconstruction.

Science.gov (United States)

Wong, Kevin K; Enepekides, Danny J; Higgins, Kevin M

2011-02-01

To determine whether simultaneous (ablation and reconstruction overlaps by two teams) head and neck reconstruction is cost effective compared to sequentially (ablation followed by reconstruction) performed surgery. Case-controlled study. Tertiary care hospital. Oncology patients undergoing free flap reconstruction of the head and neck. A match paired comparison study was performed with a retrospective chart review examining the total time of surgery for sequential and simultaneous surgery. Nine patients were selected for both the sequential and simultaneous groups. Sequential head and neck reconstruction patients were pair matched with patients who had undergone similar oncologic ablative or reconstructive procedures performed in a simultaneous fashion. A detailed cost analysis using the microcosting method was then undertaken looking at the direct costs of the surgeons, anesthesiologist, operating room, and nursing. On average, simultaneous surgery required 3 hours 15 minutes less operating time, leading to a cost savings of approximately $1200/case when compared to sequential surgery. This represents approximately a 15% reduction in the cost of the entire operation. Simultaneous head and neck reconstruction is more cost effective when compared to sequential surgery.

Dihydroazulene photoswitch operating in sequential tunneling regime

DEFF Research Database (Denmark)

Broman, Søren Lindbæk; Lara-Avila, Samuel; Thisted, Christine Lindbjerg

2012-01-01

to electrodes so that the electron transport goes by sequential tunneling. To assure weak coupling, the DHA switching kernel is modified by incorporating p-MeSC6H4 end-groups. Molecules are prepared by Suzuki cross-couplings on suitable halogenated derivatives of DHA. The synthesis presents an expansion of our......, incorporating a p-MeSC6H4 anchoring group in one end, has been placed in a silver nanogap. Conductance measurements justify that transport through both DHA (high resistivity) and VHF (low resistivity) forms goes by sequential tunneling. The switching is fairly reversible and reenterable; after more than 20 ON...

BIOTECHNOLOGY OF RECOMBINANT HORMONES IN DOPING

Directory of Open Access Journals (Sweden)

Biljana Vitošević

2011-09-01

Full Text Available Recombinant DNA technology has allowed rapid progress in creating biosynthetic gene products for the treatment of many diseases. In this way it can produce large amounts of hormone, which is intended for the treatment of many pathological conditions. Recombinant hormones that are commonly used are insulin, growth hormone and erythropoietin. Precisely because of the availability of these recombinant hormones, it started their abuse by athletes. Experiments in animal models confirmed the potential effects of some of these hormones in increasing physical abilities, which attracted the attention of athletes who push the limits of their competitive capability by such manipulation. The risks of the use of recombinant hormones in doping include serious consequences for the health of athletes. Methods of detection of endogenous hormones from recombined based on the use of a monoclonal antibodies, capillary zone electrophoresis and protein biomarkers

A Trust-region-based Sequential Quadratic Programming Algorithm

DEFF Research Database (Denmark)

Henriksen, Lars Christian; Poulsen, Niels Kjølstad

This technical note documents the trust-region-based sequential quadratic programming algorithm used in other works by the authors. The algorithm seeks to minimize a convex nonlinear cost function subject to linear inequalty constraints and nonlinear equality constraints.......This technical note documents the trust-region-based sequential quadratic programming algorithm used in other works by the authors. The algorithm seeks to minimize a convex nonlinear cost function subject to linear inequalty constraints and nonlinear equality constraints....

Sequential search leads to faster, more efficient fragment-based de novo protein structure prediction.

Science.gov (United States)

de Oliveira, Saulo H P; Law, Eleanor C; Shi, Jiye; Deane, Charlotte M

2018-04-01

Most current de novo structure prediction methods randomly sample protein conformations and thus require large amounts of computational resource. Here, we consider a sequential sampling strategy, building on ideas from recent experimental work which shows that many proteins fold cotranslationally. We have investigated whether a pseudo-greedy search approach, which begins sequentially from one of the termini, can improve the performance and accuracy of de novo protein structure prediction. We observed that our sequential approach converges when fewer than 20 000 decoys have been produced, fewer than commonly expected. Using our software, SAINT2, we also compared the run time and quality of models produced in a sequential fashion against a standard, non-sequential approach. Sequential prediction produces an individual decoy 1.5-2.5 times faster than non-sequential prediction. When considering the quality of the best model, sequential prediction led to a better model being produced for 31 out of 41 soluble protein validation cases and for 18 out of 24 transmembrane protein cases. Correct models (TM-Score > 0.5) were produced for 29 of these cases by the sequential mode and for only 22 by the non-sequential mode. Our comparison reveals that a sequential search strategy can be used to drastically reduce computational time of de novo protein structure prediction and improve accuracy. Data are available for download from: http://opig.stats.ox.ac.uk/resources. SAINT2 is available for download from: https://github.com/sauloho/SAINT2. saulo.deoliveira@dtc.ox.ac.uk. Supplementary data are available at Bioinformatics online.

Gastrointestinal hormone research - with a Scandinavian annotation

DEFF Research Database (Denmark)

Rehfeld, Jens F

2015-01-01

Gastrointestinal hormones are peptides released from neuroendocrine cells in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gut, which makes it the largest hormone-producing organ in the body. Modern biology makes it feasible to conceive the hormones...... as a blood-borne hormone, a neurotransmitter, a local growth factor or a fertility factor. The targets of gastrointestinal hormones are specific G-protein-coupled receptors that are expressed in the cell membranes also outside the digestive tract. Thus, gut hormones not only regulate digestive functions...

[Hormones and hair growth].

Science.gov (United States)

Trüeb, R M

2010-06-01

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

An uncommon cause of anaemia: Sheehan's syndrome.

Science.gov (United States)

Melchardt, Thomas; Namberger, Konrad; Weiss, Lukas; Egle, Alexander; Faber, Viktoria; Greil, Richard

2010-12-01

Ischemic pituitary necrosis due to severe postpartum haemorrhage called Sheehan's syndrome is a rare cause of hypopituitarism in the western world, but much more common in developing countries. A 45-year-old female patient being a war refugee from Chechnya with severe anaemia and fatigue was diagnosed at our outpatient department with Sheehan's syndrome after severe postpartum haemorrhage and emergency hysterectomy 15 years ago. Panhypopituitarism was adequately treated with substitution of hydrocortisone, thyroxine and transdermal oestrogen which resulted in haemoglobin increase to nearly normal levels and symptoms improved immediately. Severe anaemia caused by panhypopituitarism shows the importance of the hormonal system for erythropoiesis. Clinical and basic scientific evidence indicates thyroidal hormones to be the main cause.

Heterogeneity of protein hormones

Energy Technology Data Exchange (ETDEWEB)

Rosselin, G; Bataille, D; Laburthe, M; Duran-Garcia, S [Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Saint-Antoine, 75 - Paris (France)

1975-12-01

Radioimmunoassay measures antigenic determinants of hormonal molecules in the plasmas and tissues. These estimations carried out after fractionation in biological fluids, have revealed several immunological forms of the same hormone. The main problem is in the relationship of the various immunoreactive forms to the same hormonal sequence. The similar immunoreactive forms of high molecular weight usually have low biological activity and suggest the presence of prohormone; the suggestion of prohormonal nature depends on the chronology of the incorporation of labelled leucine and enzymatic transformation of prohormone with low biological into active hormone. The forms with high molecular weight and similar immunological activity may be of another nature. Thus, it has been shown that the biosynthetic nature of a compound such as big big insulin in the rat is doubtful owing to the absence of specific incorporation of labelled leucine into the immunoprecipitate of this fraction. The significance of low molecular weight form is still little known. An example of these forms is supplied by the existence of an alpha sub-unit of gonadotrophin present in the plasma of menopausal women. The interest of analytical methods by radio-receptor, simulation of cyclase activity in the identification of biological activity of immunoreactive forms, is discussed in relation to immunological forms ofenteroglucagon. An unusual aspect of the evolutive and adaptative character of hormonal heterogeneity is given by the gastro-intestinal hormones.

Hormonal effects in newborns

Science.gov (United States)

... page: //medlineplus.gov/ency/article/001911.htm Hormonal effects in newborns To use the sharing features on this page, please enable JavaScript. Hormonal effects in newborns occur because in the womb, babies ...

Antidiuretic hormone blood test

Science.gov (United States)

... medlineplus.gov/ency/article/003702.htm Antidiuretic hormone blood test To use the sharing features on this page, please enable JavaScript. Antidiuretic blood test measures the level of antidiuretic hormone (ADH) in ...

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

International Nuclear Information System (INIS)

Li Jinmei; Wang Xuefeng; Xi Zhiqin; Gong Yun; Liu Fengying; Sun Jijun; Wu Yuan; Luan Guoming; Wang Yuping; Li Yunlin; Zhang Jianguo; Lu Yong; Li Hongwei

2006-01-01

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in the temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures

Synthetic Aperture Sequential Beamforming

DEFF Research Database (Denmark)

Kortbek, Jacob; Jensen, Jørgen Arendt; Gammelmark, Kim Løkke

2008-01-01

A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective is to im......A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective...... is to improve and obtain a more range independent lateral resolution compared to conventional dynamic receive focusing (DRF) without compromising frame rate. SASB is a two-stage procedure using two separate beamformers. First a set of Bmode image lines using a single focal point in both transmit and receive...... is stored. The second stage applies the focused image lines from the first stage as input data. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The performance of SASB with a static image object is compared with DRF...

Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

Directory of Open Access Journals (Sweden)

Peng Xue

2013-01-01

Full Text Available Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

Growth hormone stimulation test

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... this page: //medlineplus.gov/ency/article/003377.htm Growth hormone stimulation test To use the sharing features on this page, please enable JavaScript. The growth hormone (GH) stimulation test measures the ability of ...

Evaluation Using Sequential Trials Methods.

Science.gov (United States)

Cohen, Mark E.; Ralls, Stephen A.

1986-01-01

Although dental school faculty as well as practitioners are interested in evaluating products and procedures used in clinical practice, research design and statistical analysis can sometimes pose problems. Sequential trials methods provide an analytical structure that is both easy to use and statistically valid. (Author/MLW)

Attack Trees with Sequential Conjunction

NARCIS (Netherlands)

Jhawar, Ravi; Kordy, Barbara; Mauw, Sjouke; Radomirović, Sasa; Trujillo-Rasua, Rolando

2015-01-01

We provide the first formal foundation of SAND attack trees which are a popular extension of the well-known attack trees. The SAND at- tack tree formalism increases the expressivity of attack trees by intro- ducing the sequential conjunctive operator SAND. This operator enables the modeling of