Effects of ionizing radiation and pretreatment with [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide on developing rat ovarian follicles

International Nuclear Information System (INIS)

Jarrell, J.; YoungLai, E.V.; McMahon, A.; Barr, R.; O'Connell, G.; Belbeck, L.

1987-01-01

To assess the effects of a gonadotropin-releasing hormone agonist, [D-Leu6,des-Gly10] luteinizing hormone-releasing hormone ethylamide, in ameliorating the damage caused by ionizing radiation, gonadotropin-releasing hormone agonist was administered to rats from day 22 to 37 of age in doses of 0.1, 0.4, and 1.0 microgram/day or vehicle and the rats were sacrificed on day 44 of age. There were no effects on estradiol, progesterone, luteinizing, or follicle-stimulating hormone, nor an effect on ovarian follicle numbers or development. In separate experiments, rats treated with gonadotropin-releasing hormone agonist in doses of 0.04, 0.1, 0.4, or 1.0 microgram/day were either irradiated or sham irradiated on day 30 and all groups sacrificed on day 44 of age. Irradiation produced a reduction in ovarian weight and an increase in ovarian follicular atresia. Pretreatment with the agonist prevented the reduction in ovarian weight and numbers of primordial and preantral follicles but not healthy or atretic antral follicles. Such putative radioprotection should be tested on actual reproductive performance

Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats.

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Maeng, L Y; Taha, M B; Cover, K K; Glynn, S S; Murillo, M; Lebron-Milad, K; Milad, M R

2017-08-01

Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU's effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30min prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

The estrogen myth: potential use of gonadotropin-releasing hormone agonists for the treatment of Alzheimer's disease.

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Casadesus, Gemma; Garrett, Matthew R; Webber, Kate M; Hartzler, Anthony W; Atwood, Craig S; Perry, George; Bowen, Richard L; Smith, Mark A

2006-01-01

Estrogen and other sex hormones have received a great deal of attention for their speculative role in Alzheimer's disease (AD), but at present a direct connection between estrogen and the pathogenesis of AD remains elusive and somewhat contradictory. For example, on one hand there is a large body of evidence suggesting that estrogen is neuroprotective and improves cognition, and that hormone replacement therapy (HRT) at the onset of menopause reduces the risk of developing AD decades later. However, on the other hand, studies such as the Women's Health Initiative demonstrate that HRT initiated in elderly women increases the risk of dementia. While estrogen continues to be investigated, the disparity of findings involving HRT has led many researchers to examine other hormones of the hypothalamic-pituitary-gonadal axis such as luteinising hormone (LH) and follicle-stimulating hormone. In this review, we propose that LH, rather than estrogen, is the paramount player in the pathogenesis of AD. Notably, both men and women experience a 3- to 4-fold increase in LH with aging, and LH receptors are found throughout the brain following a regional pattern remarkably similar to those neuron populations affected in AD. With respect to disease, serum LH level is increased in women with AD relative to non-diseased controls, and levels of LH in the brain are also elevated in AD. Mechanistically, we propose that elevated levels of LH may be a fundamental instigator responsible for the aberrant reactivation of the cell cycle that is seen in AD. Based on these aforementioned aspects, clinical trials underway with leuprolide acetate, a gonadotropin-releasing hormone agonist that ablates serum LH levels, hold great promise as a ready means of treatment in individuals afflicted with AD.

Growth Hormone-Releasing Hormone in Diabetes

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Leonid Evsey Fridlyand

2016-10-01

Full Text Available Growth hormone-releasing hormone (GHRH is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR has been demonstrated in different peripheral tissues and cell types including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of Type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggesting that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications.

Gonadotropin-releasing hormone agonist triggering of oocyte maturation in assisted reproductive technology cycles

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Engin Türkgeldi

2015-06-01

Full Text Available Gonadotropin-releasing hormone agonists (GnRHa have gained increasing attention in the last decade as an alternative trigger for oocyte maturation in patients at high risk for ovarian hyperstimulation syndrome (OHSS. They provide a short luteinizing hormone (LH peak that limits the production of vascular endothelial growth factor, which is the key mediator leading to increased vascular permeability, the hallmark of OHSS. Initial studies showed similar oocyte yield and embryo quality compared with conventional human chorionic gonadotropin (hCG triggering; however, lower pregnancy rates and higher miscarriage rates were alarming in GnRHa triggered groups. Therefore, two approaches have been implemented to rescue the luteal phase in fresh transfers. Intensive luteal phase support (iLPS involves administiration of high doses of progesterone and estrogen and active patient monitoring. iLPS has been shown to provide satisfactory fertilization and clinical pregnancy rates, and to be especially useful in patients with high endogenous LH levels, such as in polycystic ovary syndrome. The other method for luteal phase rescue is low-dose hCG administiration 35 hours after GnRHa trigger. Likewise, this method results in statistically similar ongoing pregnancy rates (although slightly lower than to those of hCG triggered cycles. GnRHa triggering decreased OHSS rates dramatically, however, none of the rescue methods prevent OHSS totally. Cases were reported even in patients who underwent cryopreservation and did not receive hCG. GnRH triggering induces a follicle stimulating hormone (FSH surge, similar to natural cycles. Its possible benefits have been investigated and dual triggering, GnRHa trigger accompanied by a simultaneous low-dose hCG injection, has produced promising results that urge further exploration. Last of all, GnRHa triggering is useful in fertility preservation cycles in patients with hormone sensitive tumors. In conclusion, GnRHa triggering

Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

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Steingold, K; De Ziegler, D; Cedars, M; Meldrum, D R; Lu, J K; Judd, H L; Chang, R J

1987-10-01

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic Gn

Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis

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Jose Carlos Pereira Jr.

2010-01-01

Full Text Available Data collected from medical literature indicate that dopaminergic agonists alleviate Restless Legs Syndrome symptoms while dopaminergic agonists antagonists aggravate them. Dopaminergic agonists is a physiological regulator of thyroid-stimulating hormone. Dopaminergic agonists infusion diminishes the levels of thyroid hormones, which have the ability to provoke restlessness, hyperkinetic states, tremors, and insomnia. Conditions associated with higher levels of thyroid hormones, such as pregnancy or hyperthyroidism, have a higher prevalence of Restless Legs Syndrome symptoms. Low iron levels can cause secondary Restless Legs Syndrome or aggravate symptoms of primary disease as well as diminish enzymatic activities that are involved in dopaminergic agonists production and the degradation of thyroid hormones. Moreover, as a result of low iron levels, dopaminergic agonists diminishes and thyroid hormones increase. Iron therapy improves Restless Legs Syndrome symptoms in iron deprived patients. Medical hypothesis. To discuss the theory that thyroid hormones, when not counterbalanced by dopaminergic agonists, may precipitate the signs and symptoms underpinning Restless Legs Syndrome. The main cause of Restless Legs Syndrome might be an imbalance between the dopaminergic agonists system and thyroid hormones.

Fresh versus frozen embryo transfer after gonadotropin-releasing hormone agonist trigger in gonadotropin-releasing hormone antagonist cycles among high responder women: A randomized, multi-center study

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Abbas Aflatoonian

2018-02-01

Full Text Available Background: The use of embryo cryopreservation excludes the possible detrimental effects of ovarian stimulation on the endometrium, and higher reproductive outcomes following this policy have been reported. Moreover, gonadotropin-releasing hormone agonist trigger in gonadotropin-releasing hormone (GnRH antagonist cycles as a substitute for standard human chorionic gonadotropin trigger, minimizes the risk of ovarian hyperstimulation syndrome (OHSS in fresh as well as frozen embryo transfer cycles (FET. Objective: To compare the reproductive outcomes and risk of OHSS in fresh vs frozen embryo transfer in high responder patients, undergoing in vitro fertilization triggered with a bolus of GnRH agonist. Materials and Methods: In this randomized, multi-centre study, 121 women undergoing FET and 119 women undergoing fresh ET were investigated as regards clinical pregnancy as the primary outcome and the chemical pregnancy, live birth, OHSS development, and perinatal data as secondary outcomes. Results: There were no significant differences between FET and fresh groups regarding chemical (46.4% vs. 40.2%, p=0.352, clinical (35.8% vs. 38.3%, p=0.699, and ongoing (30.3% vs. 32.7%, p=0.700 pregnancy rates, also live birth (30.3% vs. 29.9%, p=0.953, perinatal outcomes, and OHSS development (35.6% vs. 42.9%, p=0.337. No woman developed severe OHSS and no one required admission to hospital. Conclusion: Our findings suggest that GnRHa trigger followed by fresh transfer with modified luteal phase support in terms of a small human chorionic gonadotropin bolus is a good strategy to secure good live birth rates and a low risk of clinically relevant OHSS development in in vitro fertilization patients at risk of OHSS.

A neurokinin 3 receptor-selective agonist accelerates pulsatile luteinizing hormone secretion in lactating cattle.

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Nakamura, Sho; Wakabayashi, Yoshihiro; Yamamura, Takashi; Ohkura, Satoshi; Matsuyama, Shuichi

2017-07-01

Pulsatile gonadotropin-releasing hormone (GnRH) secretion, which is indispensable for follicular development, is suppressed in lactating dairy and beef cattle. Neurokinin B (NKB) neurons in the arcuate nucleus of the hypothalamus are considered to play an essential role in generating the pulsatile mode of GnRH/luteinizing hormone (LH) secretion. The present study aimed to clarify the role of NKB-neurokinin 3 receptor (NK3R) signaling in the pulsatile pattern of GnRH/gonadotropin secretion in postpartum lactating cattle. We examined the effects of the administration of an NK3R-selective agonist, senktide, on gonadotropin secretion in lactating cattle. The lactating cattle, at approximately 7 days postpartum, were intravenously infused with senktide (30 or 300 nmol/min) or vehicle for 24 h. The administration of 30 or 300 nmol/min senktide significantly increased LH pulse frequency compared to in the control group during 0-4 or 20-24 h after infusion, respectively. Moreover, LH and follicle-stimulating hormone levels were gradually increased by 300 nmol/min administration of senktide during the 0-4-h sampling period. Ultrasonography of the ovaries was performed to identify the first postpartum ovulation in senktide-administered lactating cattle. The interval from calving to first postpartum ovulation was significantly shorter in the 300 nmol/min senktide-administered group than in the control group. Taken together, these findings suggest that senktide infusion elicits an increase in LH pulse frequency that may stimulate follicular development and, in turn, induce the first postpartum ovulation in lactating cattle. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Down-regulation of parathyroid hormone (PTH) receptors in cultured bone cells is associated with agonist-specific intracellular processing of PTH-receptor complexes.

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Teitelbaum, A P; Silve, C M; Nyiredy, K O; Arnaud, C D

1986-02-01

Exposure of cultured embryonic chicken bone cells to the PTH agonists bovine (b) PTH-(1-34) and [8Nle, 18Nle, 34Tyr]bPTH-(1-34)amide [bPTH-(1-34)A] reduces the subsequent cAMP response to the hormone and decreases the specific binding of 125I-labeled PTH to these cultures. To determine whether PTH receptor down-regulation in cultured bone cells is mediated by cellular internalization of PTH-receptor complexes, we measured the uptake of [125I]bPTH-(1-34) into an acid-resistant compartment. Uptake of radioactivity into this compartment was inhibited by incubating cells at 4 C with phenylarsineoxide and unlabeled bPTH-(1-34). Tracer uptake into the acid-resistant compartment at any time was directly proportional to total cell binding at 22 C. Thus, it is likely that PTH-receptor complexes are internalized by bone cells. This mechanism may explain the loss of cell surface receptors after PTH pretreatment. To determine whether internalized PTH-receptor complexes are reinserted into the plasma membrane, we measured PTH binding and PTH stimulation of cAMP production after cells were exposed to monensin, a known inhibitor of receptor recycling. Monensin (25 microM) had no effect on PTH receptor number or affinity and did not alter PTH-stimulated cAMP accumulation. However, monensin (25 microM) incubated with cells pretreated with various concentrations of bPTH-(1-34) for 1 h potentiated the effect of the hormone to reduce subsequent [125I]bPTH-(1-34) binding and PTH-stimulated cAMP accumulation by more than 2 orders of magnitude. Chloroquine also potentiated PTH-induced down-regulation of PTH receptors. By contrast, neither agent influenced PTH binding or PTH-stimulated cAMP production in cells pretreated with the antagonist bPTH-(3-34)A. Thus, monensin potentiated PTH receptor loss only in cells pretreated with PTH agonists, indicating that antagonist-occupied receptors may be processed differently from agonist-occupied receptors in bone cells. The data further suggest

Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone

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Mo Kyung Jung

2014-12-01

Full Text Available PurposeThere is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa in central precocious puberty (CPP. We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH in girls with CPP.MethodsWe reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS for bone age (BA, and compared adult height (AH with midparental height (MPH and predicted adult height (PAH during treatment in groups received GnRHa alone (n=59 or GnRHa plus GH (n=23.ResultsIn the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm was significantly higher than the initial PAH (156.6±3.96 cm (P<0.001, and it was similar to the MPH (159.9±3.52 cm. In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm was also higher than the initial PAH (154.6±2.55 cm (P<0.001, which was similar to the MPH (158.1±3.31 cm. Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment.ConclusionIn CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.

New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

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Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

1992-10-01

The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.

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Yoshimura, Makoto; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Mineo; Tanaka, Takao

2017-09-15

Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC 50 ) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenuated muscle wasting and fat loss, and increased circulating levels of anabolic factors such as insulin and IGF-1, but not catabolic factors such as IL-6 and corticosterone. These findings suggest that Z-505 might be effective in the treatment of cachexia via the increased anabolic hormone levels stimulated by the activation of the ghrelin receptor, GHSR1a. Copyright © 2017 Elsevier B.V. All rights reserved.

Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

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Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

2015-09-01

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the

Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor

DEFF Research Database (Denmark)

Holst, Birgitte; Frimurer, Thomas M; Mokrosinski, Jacek

2008-01-01

A library of robust ghrelin receptor mutants with single substitutions at 22 positions in the main ligand-binding pocket was employed to map binding sites for six different agonists: two peptides (the 28-amino-acid octanoylated endogenous ligand ghrelin and the hexapeptide growth hormone......, and PheVI:23 on the opposing face of transmembrane domain (TM) VI. Each of the agonists was also affected selectively by specific mutations. The mutational map of the ability of L-692,429 and GHRP-6 to act as allosteric modulators by increasing ghrelin's maximal efficacy overlapped with the common....... It is concluded that although each of the ligands in addition exploits other parts of the receptor, a large, common binding site for both small-molecule agonists--including ago-allosteric modulators--and the endogenous agonist is found on the opposing faces of TM-III and -VI of the ghrelin receptor....

Genetic and non-genetic factors affecting rabbit doe sexual receptivity as estimated from one generation of divergent selection

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M. Theau.Clément

2015-09-01

Full Text Available Sexual receptivity of rabbit does at insemination greatly influences fertility and is generally induced by hormones or techniques known as “biostimulation”. Searching for more sustainable farming systems, an original alternative would be to utilise the genetic pathway to increase the does’receptivity. The purpose of the present study was to identify genetic and non-genetic factors that influence rabbit doe sexual receptivity, in the context of a divergent selection experiment over 1 generation. The experiment spanned 2 generations: the founder generation (G0 consisting of 140 rabbit does, and the G1 generation comprising 2 divergently selected lines (L and H lines with 70 does each and 2 successive batches from each generation. The selection rate of the G0 females to form the G1 lines was 24/140. The selection tests consisted of 16 to 18 successive receptivity tests at the rate of 3 tests per week. On the basis of 4716 tests from 275 females, the average receptivity was 56.6±48.2%. A batch effect and a test operator effect were revealed. The contribution of females to the total variance was 20.0%, whereas that of bucks was only 1.1%. Throughout the experiment, 18.2% of does expressed a low receptivity (< 34%, 50.7% a medium one and 33.1% a high one (>66%. Some does were frequently receptive, whereas others were rarely receptive. The repeatability of sexual receptivity was approximately 20%. The results confirmed the high variability of sexual receptivity of non-lactating rabbit does maintained without any biostimulation or hormonal treatment. A lack of selection response on receptivity was observed. Accordingly, the heritability of receptivity was estimated at 0.01±0.02 from an animal model and at 0.02±0.03 from a  sire and dam model. The heritability of the average receptivity of a doe was calculated as 0.04. In agreement with the low estimated heritability, the heritability determined was no different from zero

Beyond Reception

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This book argues that it is time to rethink reception as a traditional paradigm for understanding the relation between the ancient Greco-Roman traditions and early Judaism and Christianity. The concept of reception implies taking something from one fixed box into another, often a chronological...... intend to develop a more multi-faceted view of such precesses and to go beyond the term reception....

Investigational hormone receptor agonists as ongoing female contraception: a focus on selective progesterone receptor modulators in early clinical development.

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Nelson, Anita L

2015-01-01

As efforts are made to continue to increase the safety of contraceptive methods, those without estrogen have attracted new attention. Progestin-only options are available in many delivery systems, but most cause disturbed bleeding patterns. For gynecologic patients, selective progesterone receptor modulators (SPRMs) have been approved for medical abortion, for ovulation suppression in emergency contraception, and for the treatment of heavy menstrual bleeding due to leiomyoma. This article discusses the role of SPRMs in controlling fertility on an ongoing basis with particular emphasis on mifepristone and ulipristal acetate (UPA), since none of the other compounds has progressed out of early Phase I - II testing. It also discusses important information about the mechanisms of action and safety of these two SPRMs. Of all the investigational hormone agonist/antagonists, SPRMs have demonstrated the greatest potential as ongoing female contraceptives. They have the ability to suppress ovulation after initiation of the luteinizing hormone (LH) surge without affecting ovarian production of estrogen or inducing any significant metabolic changes. SPRMs may well be able to provide longer term contraception as oral agents, vaginal rings, and perhaps even intrauterine devices. UPA has the greatest promise. Current research needs to be expanded.

Alpha 2-adrenoceptor blockade, pituitary-adrenal hormones, and agonistic interactions in rats.

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Haller, J; Barna, I; Kovács, J L

1994-08-01

The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. Alpha 2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an alpha 2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different alpha 2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the alpha 2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.

Organization and activation of sexual and agonistic behavior in the leopard gecko, Eublepharis macularius.

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Rhen, T; Crews, D

2000-04-01

Gonadal sex is determined by the temperature experienced during incubation in the leopard gecko (Eublepharis macularius). Furthermore, both factors, incubation temperature and gonadal sex, influence adult sexual and agonistic behavior in this species. Yet it is unclear whether such differences in behavior are irreversibly organized during development or are mediated by differences in hormone levels in adulthood. To address this question, we gonadectomized adult females and males generated from a female-biased (30 degrees C) and a male-biased (32.5 degrees C) incubation temperature and treated them with equivalent levels of various sex steroids. We found that 17beta-estradiol (E(2)) activated sexual receptivity in females but not males, suggesting an organized sex difference in behavioral sensitivity to E(2). There were also organized and activated sex differences in attractivity to stimulus males. Although females were more attractive than males when treated with E(2), both sexes were equally unattractive when treated with dihydrotestosterone (DHT) or testosterone (T). Likewise, sex differences in aggressive and submissive behavior were organized and activated. Attacks on stimulus males were activated by T in males but not in females. In contrast, hormones did not influence flight behavior in males but did affect female submissiveness. Overall, males also evoked more attacks by stimulus males than did females. Nevertheless, females and males treated with androgens evoked more attacks than animals of the same sex that were treated with cholesterol or E(2). Incubation temperature had some weak effects on certain behaviors and no effect on others. This suggests that temperature effects in gonadally intact geckos may be due primarily to differences in circulating levels of hormones in adulthood. We conclude that gonadal sex has both organizational and activational effects on various behaviors in the leopard gecko. Copyright 2000 S. Karger AG, Basel

Potent agonists of growth hormone-releasing hormone. Part I.

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Zarandi, M; Serfozo, P; Zsigo, J; Bokser, L; Janaky, T; Olsen, D B; Bajusz, S; Schally, A V

1992-03-01

Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) in position 29 have been synthesized by the solid phase method, purified, and tested in vitro and in vivo. The majority of the analogs contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N-MeTyr1. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27, and/or 28. Compared to the natural sequence of GH-RH(1-29)NH2, [Dat1,Ala15]GH-RH(1-28)Agm (MZ-3-191) and [D-Ala2,Ala15]GH-RH(1-28)Agm (MZ-3-201) were 8.2 and 7.1 times more potent in vitro, respectively. These two peptides contained Met27. Their Nle27 analogs, [Dat1,Ala15,Nle27]GH-RH(1-28)Agm(MZ-2-51), prepared previously (9), and [D-Ala2,Ala15,Nle28]GH-RH(1-28)Agm(MZ-3-195) showed relative in vitro potencies of 10.5 and 2.4, respectively. These data indicate that replacement of Met27 by Nle27 enhanced the GH-releasing activity of the analog when the molecule contained Dat1-Ala2 residues at the N-terminus, but peptides containing Tyr1-D-Ala2 in addition to Nle27 showed decreased potencies. Replacement of Ser28 with Asp in multi-substituted analogs of GH-RH(1-28)Agm resulted in a decrease in in vitro potencies compared to the parent compound. Thus, the Ser28-containing MZ-2-51, and [Dat1,Ala15,D-Lys21,Nle27]GH-RH(1-28)Agm, its Asp28 homolog (MZ-3-149), possessed relative activities of 10.5 and 5.6, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists.

Science.gov (United States)

Liu, Tao; Zhang, Yong; Liu, Yan; Wang, Ying; Jia, Haiqun; Kang, Mingchao; Luo, Xiaozhou; Caballero, Dawna; Gonzalez, Jose; Sherwood, Lance; Nunez, Vanessa; Wang, Danling; Woods, Ashley; Schultz, Peter G; Wang, Feng

2015-02-03

On the basis of the 3D structure of a bovine antibody with a well-folded, ultralong complementarity-determining region (CDR), we have developed a versatile approach for generating human or humanized antibody agonists with excellent pharmacological properties. Using human growth hormone (hGH) and human leptin (hLeptin) as model proteins, we have demonstrated that functional human antibody CDR fusions can be efficiently engineered by grafting the native hormones into different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR fusion proteins were expressed in good yields in mammalian cells and retain comparable in vitro biological activity to the native hormones. Pharmacological studies in rodents indicated a 20- to 100-fold increase in plasma circulating half-life for these antibody agonists and significantly extended in vivo activities in the GH-deficient rat model and leptin-deficient obese mouse model for the hGH and hLeptin antibody fusions, respectively. These results illustrate the utility of antibody CDR fusions as a general and versatile strategy for generating long-acting protein therapeutics.

Effects of hormones on platelet aggregation.

Science.gov (United States)

Farré, Antonio López; Modrego, Javier; Zamorano-León, José J

2014-04-01

Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

Characterization of 12 GnRH peptide agonists - a kinetic perspective.

Science.gov (United States)

Nederpelt, Indira; Georgi, Victoria; Schiele, Felix; Nowak-Reppel, Katrin; Fernández-Montalván, Amaury E; IJzerman, Adriaan P; Heitman, Laura H

2016-01-01

Drug-target residence time is an important, yet often overlooked, parameter in drug discovery. Multiple studies have proposed an increased residence time to be beneficial for improved drug efficacy and/or longer duration of action. Currently, there are many drugs on the market targeting the gonadotropin-releasing hormone (GnRH) receptor for the treatment of hormone-dependent diseases. Surprisingly, the kinetic receptor-binding parameters of these analogues have not yet been reported. Therefore, this project focused on determining the receptor-binding kinetics of 12 GnRH peptide agonists, including many marketed drugs. A novel radioligand-binding competition association assay was developed and optimized for the human GnRH receptor with the use of a radiolabelled peptide agonist, [(125) I]-triptorelin. In addition to radioligand-binding studies, a homogeneous time-resolved FRET Tag-lite™ method was developed as an alternative assay for the same purpose. Two novel competition association assays were successfully developed and applied to determine the kinetic receptor-binding characteristics of 12 high-affinity GnRH peptide agonists. Results obtained from both methods were highly correlated. Interestingly, the binding kinetics of the peptide agonists were more divergent than their affinities with residence times ranging from 5.6 min (goserelin) to 125 min (deslorelin). Our research provides new insights by incorporating kinetic, next to equilibrium, binding parameters in current research and development that can potentially improve future drug discovery targeting the GnRH receptor. © 2015 The British Pharmacological Society.

GnRH agonist versus GnRH antagonist in in vitro fertilization and embryo transfer (IVF/ET

Directory of Open Access Journals (Sweden)

Depalo Raffaella

2012-04-01

Full Text Available Abstract Several protocols are actually available for in Vitro Fertilization and Embryo Transfer. The review summarizes the main differences and the clinic characteristics of the protocols in use with GnRH agonists and GnRH antagonists by emphasizing the major outcomes and hormonal changes associated with each protocol. The majority of randomized clinical trials clearly shows that in “in Vitro” Fertilization and Embryo Transfer, the combination of exogenous Gonadotropin plus a Gonadotropin Releasing Hormone (GnRH agonist, which is able to suppress pituitary FSH and LH secretion, is associated with increased pregnancy rate as compared with the use of gonadotropins without a GnRH agonist. Protocols with GnRH antagonists are effective in preventing a premature rise of LH and induce a shorter and more cost-effective ovarian stimulation compared to the long agonist protocol. However, a different synchronization of follicular recruitment and growth occurs with GnRH agonists than with GnRH antagonists. Future developments have to be focused on timing of the administration of GnRH antagonists, by giving a great attention to new strategies of stimulation in patients in which radio-chemotherapy cycles are needed.

MELATONIN DAN MELATONIN RECEPTOR AGONIST SEBAGAI PENANGANAN INSOMNIA PRIMER KRONIS

Directory of Open Access Journals (Sweden)

Ni Luh Putu Ayu Maha Iswari

2013-04-01

Full Text Available Melatonin is a hormone that has an important role in the mechanism of sleep. Hypnotic effects of melatonin and melatonin receptor agonist are mediated via MT1 and MT2 receptors, especially in circadian rhythm pacemaker, suprachiasmatic nucleus, which is worked on the hypothalamic sleep switch. This mechanism is quite different with the GABAergic drugs such as benzodiazepine. Agonist melatonin triggers the initiation of sleep and normalize circadian rhythms so that makes it easier to maintain sleep. The main disadvantage of melatonin in helping sleep maintenance on primary insomnia is that the half life is very short. The solution to this problem is the use of prolonged-release melatonin and melatonin receptor agonist agents such as ramelteon. Melatoninergic agonist does not cause withdrawal effects, dependence, as well as cognitive and psychomotor disorders as often happens on the use of benzodiazepine.  

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone

International Nuclear Information System (INIS)

Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

1989-01-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer and prostate cancer cell lines in vitro. Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides

Different gonadotropin releasing hormone agonist doses for the final oocyte maturation in high-responder patients undergoing in vitro fertilization/intra-cytoplasmic sperm injection

Directory of Open Access Journals (Sweden)

Emre Goksan Pabuccu

2015-01-01

Full Text Available Context: Efficacy of gonadotropin releasing hormone agonists (GnRH-a for ovulation in high-responders. Aims: The aim of the current study is to compare the impact of different GnRH-a doses for the final oocyte maturation on cycle outcomes and ovarian hyperstimulation syndrome (OHSS rates in high-responder patients undergoing ovarian stimulation. Settings And Designs: Electronic medical records of a private in vitro fertilization center, a retrospective analysis. Subjects and Methods: A total of 77 high-responder cases were detected receiving GnRH-a. Group I consisted of 38 patients who received 1 mg of agonist and Group II consisted of 39 patients who received 2 mg of agonist. Statistical Analysis: In order to compare groups, Student′s t-test, Mann-Whitney U-test, Pearson′s Chi-square test or Fisher′s exact test were used where appropriate. A P < 0.05 was considered as statistically significant. Result: Number of retrieved oocytes (17.5 vs. 15.0, P = 0.510, implantation rates (46% vs. 55.1%, P = 0.419 and clinical pregnancy rates (42.1% vs. 38.5%, P = 0.744 were similar among groups. There were no mild or severe OHSS cases detected in Group I. Only 1 mild OHSS case was detected in Group II. Conclusion: A volume of 1 or 2 mg leuprolide acetate yields similar outcomes when used for the final oocyte maturation in high-responder patients.

Induction of ovulation by a potent, orally active, low molecular weight agonist (Org 43553) of the luteinizing hormone receptor.

Science.gov (United States)

van de Lagemaat, R; Timmers, C M; Kelder, J; van Koppen, C; Mosselman, S; Hanssen, R G J M

2009-03-01

In assisted reproductive technology, human chorionic gonadotrophin (hCG) is administered subcutaneously for the induction of oocyte maturation and ovulation. Our efforts to develop orally bioavailable luteinizing hormone (LH) receptor agonists have led to the discovery of Org 43553, a low molecular weight (LMW) LH receptor (LH-R) agonist. Org 43553 was tested in vitro and in vivo in pre-clinical pharmacological models to demonstrate efficacy and oral availability. Org 43553 is a potent stimulator of the human LH-R in vitro (EC(50) 3.7 nM). In primary mouse Leydig cells, Org 43553 stimulated testosterone production. Pharmacokinetic analyses showed high oral bioavailability in rats (79%) and dogs (44%) with a shorter half-life compared with hCG (3.4 versus 5.6 h in the rat). Ovulation induction by Org 43553 was demonstrated in immature mice as well as in cyclic rats after single-dose oral administration (50 mg/kg). The ovulated oocytes were of good quality as demonstrated by successful fertilization and implantation of normal embryos. In male rats, testosterone production was substantially induced after oral administration. Org 43553 is the first LMW LH-R mimetic with demonstrated in vivo efficacy upon oral administration and could therefore replace subcutaneously administered hCG. The elimination half-life of Org 43553 is substantially shorter than hCG, which could potentially represent a clinical benefit in reducing the risk of ovarian hyperstimulation syndrome (OHSS).

Predicting Volleyball Serve-Reception

NARCIS (Netherlands)

Paulo, Ana; Zaal, Frank T J M; Fonseca, Sofia; Araujo, Duarte

2016-01-01

Serve and serve-reception performance have predicted success in volleyball. Given the impact of serve-reception on the game, we aimed at understanding what it is in the serve and receiver's actions that determines the selection of the type of pass used in serve-reception and its efficacy. Four

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6.

Science.gov (United States)

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-08-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel6]LH-RH (SB-05) and [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,Arg5,D-Mel6,D-Ala10++ +]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells.

Highly potent analogues of luteinizing hormone-releasing hormone containing D-phenylalanine nitrogen mustard in position 6

International Nuclear Information System (INIS)

Bajusz, S.; Janaky, T.; Csernus, V.J.; Bokser, L.; Fekete, M.; Srkalovic, G.; Redding, T.W.; Schally, A.V.

1989-01-01

The nitrogen mustard derivatives of 4-phenylbutyric acid and L-phenylalanine, called chlorambucil (Chl) and melphalan (Mel), respectively, have been incorporated into several peptide hormones, including luteinizing hormone-releasing hormone (LH-RH). The alkylating analogues of LH-RH were prepared by linking Chl, as an N-acyl moiety, to the complete amino acid sequence of agonistic and antagonistic analogues. These compounds, in particular the antagonistic analogues, showed much lower potency than their congeners carrying other acyl groups. To obtain highly potent alkylating analogues of LH-RH, the D enantiomer of Mel was incorporated into position 6 of the native hormone and some of its antagonistic analogues. Of the peptides prepared, [D-Mel 6 ]LH-RH (SB-05) and [Ac-D-Nal(2) 1 ,D-Phe(pCl) 2 ,D-Pal(3) 3 ,Arg 5 ,D-Mel 6 ,D-Ala 10 ]LH-RH [SB-86, where Nal(2) is 3-(2-naphthyl)alanine and Pal(3) is 3-(3-pyridyl)alanine] possessed the expected high agonistic and antagonistic activities, respectively, and also showed high affinities for the membrane receptors of rat pituitary cells, human breast cancer cells, human prostate cancer cells, and rat Dunning R-3327 prostate tumor cells. These two analogues exerted cytotoxic effects on human and rat mammary cancer cells in vitro. Thus these two D-Mel 6 analogues seem to be particularly suitable for the study of how alkylating analogues of LH-RH could interfere with intracellular events in certain cancer cells

Growth hormone releasing hormone (GHRH) signaling modulates intermittent hypoxia-induced oxidative stress and cognitive deficits in mouse.

Science.gov (United States)

Nair, Deepti; Ramesh, Vijay; Li, Richard C; Schally, Andrew V; Gozal, David

2013-11-01

Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea (OSA), leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in adult mice. In both patients and murine models of OSA, the disease is associated with suppression of growth hormone (GH) secretion, which is actively involved in the growth, development, and function of the central nervous system (CNS). Recent work showed that exogenous GH therapy attenuated neurocognitive deficits elicited by IH during sleep in rats. Here, we show that administration of the Growth Hormone Releasing Hormone (GHRH) agonist JI-34 attenuates IH-induced neurocognitive deficits, anxiety, and depression in mice along with reduction in oxidative stress markers such as MDA and 8-hydroxydeoxyguanosine, and increases in hypoxia inducible factor-1α DNA binding and up-regulation of insulin growth factor-1 and erythropoietin expression. In contrast, treatment with a GHRH antagonist (MIA-602) during intermittent hypoxia did not affect any of the IH-induced deleterious effects in mice. Thus, exogenous GHRH administered as the formulation of a GHRH agonist may provide a viable therapeutic intervention to protect IH-vulnerable brain regions from OSA-associated neurocognitive dysfunction. Sleep apnea, characterized by chronic intermittent hypoxia (IH), is associated with substantial cognitive and behavioral deficits. Here, we show that administration of a GHRH agonist (JI-34) reduces oxidative stress, increases both HIF-1α nuclear binding and downstream expression of IGF1 and erythropoietin (EPO) in hippocampus and cortex, and markedly attenuates water maze performance deficits in mice exposed to intermittent hypoxia during sleep. © 2013 International Society for Neurochemistry.

Ecdysone Agonist: New Insecticides with Novel Mode of Action

Directory of Open Access Journals (Sweden)

Y. Andi Trisyono

2002-12-01

Full Text Available Development of insect resistance to insecticide has been the major driving force for the development of new insecticides. Awareness and demand from public for more environmentally friendly insecticides have contributed in shifting the trend from using broad spectrum to selective insecticides. As a result, scientists have looked for new target sites beyond the nervous system. Insect growth regulators (IGRs are more selective insecticides than conventional insecticides, and ecdysone agonists are the newest IGRs being commercialized, e.g. tebufenozide, methoxyfenozide, and halofenozide. Ecdysone agonists bind to the ecdysteroid receptors, and they act similarly to the molting hormone 20-hydroxyecdysone. The binding provides larvae or nymphs with a signal to enter a premature and lethal molting cycle. In addition, the ecdysone agonists cause a reduction in the number of eggs laid by female insects. The ecdysone agonists are being developed as selective biorational insecticides. Tebufenozide and methoxyfenozide are used to control lepidopteran insect pests, whereas halofenozide is being used to control coleopteran insect pests. Their selectivity is due to differences in the binding affinity between these compounds to the receptors in insects from different orders. The selectivity of these compounds makes them candidates to be used in combinations with other control strategies to develop integrated pest management programs in agricultural ecosystems. Key words: new insecticides, selectivity, ecdysone agonists

Does Gonadotropin Releasing Hormone Agonists plus add-back therapy bring an aurora to orthodontic treatment?

Directory of Open Access Journals (Sweden)

Jiang Lingyong

2012-01-01

Full Text Available Introduction: Obviously, long therapy time of orthodontic treatment and a number of its adverse effects, such as pain, root resorption, enamel demineralization, periodontal disease, are the main reasons of complaints from patients. It is the first thing for an orthodontist to shorten the period of treatment and decrease the complications of orthodontic treatment as much as possible. The Hypothesis: We hypothesis Gonadotropin Releasing Hormone Agonists (GnRHa and add-back therapy can create the "therapeutic window", namely, the appropriate estrogen level and assuage the adverse effects of estrogen deficiency which should be avoided as much as possible. Evaluation of the Hypothesis: It is generally acknowledged that estrogen has direct regulating role in bone metabolism by acting on osteoblasts and osteoclasts. Estrogen deficiency can increase the rate of orthodontic tooth movement and also bring about some adverse effects. The appropriate estrogen level, which we call the "therapeutic window" in orthodontic treatment, can speed up the orthodontic tooth movement and eliminate the adverse effects as far as possible. GnRHa can be the maker of estrogen deficiency; meanwhile, add-back therapy can remove the adverse effects by estrogen deficiency. So, we believe that GnRHa plus add-back therapy could be a new adjuvant method of orthodontic treatment and be good for orthodontists and patients.

Reception research 2.0

DEFF Research Database (Denmark)

Mathieu, David

Some might argue that reception analysis is a remnant of the past in an age where “people formerly known as the audience” (Rosen, 2006) are producing and circulating content on a diversity of interactive and participatory media platforms. Far from being the case, reception research must continue......, which appears increasingly complex, multi-formed and integrated to the audience. The original dimensions of Schrøder’s model need to be looked at with reference to both reception and circulation (Jenkins et al., 2013), and to the network that binds participatory media culture. It appears that with media...... 2.0, phenomena which traditionally fell under the labels of interpretation or reception are increasingly taking part in the media text itself. As audiences become textual matters, they contribute to set a new agenda for media research....

Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits

Science.gov (United States)

Bielohuby, Maximilian; Zarkesh-Esfahani, Sayyed Hamid; Manolopoulou, Jenny; Wirthgen, Elisa; Walpurgis, Katja; Toghiany Khorasgani, Mohaddeseh; Aghili, Zahra Sadat; Wilkinson, Ian Robert; Hoeflich, Andreas; Thevis, Mario; Ross, Richard J.; Bidlingmaier, Martin

2014-01-01

The development of new growth hormone (GH) agonists and growth hormone antagonists (GHAs) requires animal models for pre-clinical testing. Ideally, the effects of treatment are monitored using the same pharmacodynamic marker that is later used in clinical practice. However, intact rodents are of limited value for this purpose because serum IGF-I, the most sensitive pharmacodynamic marker for the action of GH in humans, shows no response to treatment with recombinant human GH and there is little evidence for the effects of GHAs, except when administered at very high doses or when overexpressed. As an alternative, more suitable model, we explored pharmacodynamic markers of GH action in intact rabbits. We performed the first validation of an IGF-I assay for the analysis of rabbit serum and tested precision, sensitivity, linearity and recovery using an automated human IGF-I assay (IDS-iSYS). Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant. For a subset of samples, we used LC-MS/MS to measure IGF-I, and quantitative western ligand blot to analyze IGF-binding proteins (IGFBPs). Although recovery of recombinant rabbit IGF-I was only 50% in the human IGF-I assay, our results show that the sensitivity, precision (1.7–3.3% coefficient of variation) and linearity (90.4–105.6%) were excellent in rabbit samples. As expected, sex, age and genetic background were major determinants of IGF-I concentration in rabbits. IGF-I and IGFBP-2 levels increased after single and multiple injections of recombinant human GH (IGF-I: 286±22 versus 434±26 ng/ml; PIGF-I levels from the fourth injection onwards (PIGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on sex, age and genetic background. Unlike in rodents, the IGF-I response to treatment with recombinant human GH or a GHA closely mimics the

Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep.

Science.gov (United States)

Nuruddin, Syed; Krogenæs, Anette; Brynildsrud, Ola Brønstad; Verhaegen, Steven; Evans, Neil P; Robinson, Jane E; Haraldsen, Ira Ronit Hebold; Ropstad, Erik

2013-12-01

The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright �

Gonadotropin Releasing Hormone Agonists or Antagonists for Preimplantation Genetic Diagnosis (PGD)? A Prospective Randomised Trial.

Science.gov (United States)

Verpoest, Willem; De Vos, Anick; De Rycke, Martine; Parikh, Shruti; Staessen, Catherine; Tournaye, Herman; De Vos, Michel; Vloeberghs, Veerle; Blockeel, Christophe

2017-11-10

The use of GnRH analogue medication is essential in reproductive medicine to avoid premature ovulation by pituitary suppression for the duration of ovarian stimulation by gonadotrophins. The type of pituitary suppression by either GnRH agonist analogues versus GnRH antagonist analogues may result in different embryological hence clinical results. Preimplantation genetic diagnosis is a subtype of IVF in which embryos are created for genetic diagnosis of hereditary disorders in order to avoid genetically affected children. Embryological quality hence ovarian stimulation in preimplantation genetic diagnosis is crucial as genetic selection will reduce the number of available embryos to a fraction of the total. The aim of this study was to assess the efficiency of GnRH antagonist versus GnRH agonist treatment for pituitary suppression in ovarian stimulation for PGD, by proxy of number and quality of embryos at cleavage stage available for biopsy. We conducted a prospective randomised controlled trial comparing pituitary suppression by GnRH antagonist versus GnRH agonist in ovarian stimulation for PGD. The primary outcome measure was the number of embryos of sufficient quality for biopsy at cleavage stage. Secondary outcome parameters were the number of blastocysts available of top quality, and clinical pregnancy rate. There was no difference in number of oocytes retrieved, embryos at cleavage stage available for biopsy or embryo quality. The clinical pregnancy rate was higher in the GnRH agonist group; however the sample size was insufficient to allow conclusions. The use of GnRH agonist versus antagonist treatment does not result in differences in a number of oocytes, embryos or embryo quality in ovarian stimulation for preimplantation genetic diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Serum level of hormone and metabolites in pregnant rabbit does

Directory of Open Access Journals (Sweden)

Gabriele Brecchia

2010-01-01

Full Text Available The aims of this study were to compare the hormones and metabolites serum levels and the reproductive performances of nulliparous (n=100 and primiparous pregnant does submitted to artificial insemination (AI 11 days post-partum. On the day of AI, all the does were weighed and the sexual receptivity was evaluated. The kits were weaned at 26 day. Blood samples were collect by punc- ture of the marginal ear vein from one day before AI until few days before the kindling and assayed for hormones and metabolites. The higher sexual receptivity and the fertility in nulliparous than in primiparous does confirmed the negative effect of lactation. Nulliparous does showed higher blood con- centration of leptine than primiparous, and in both the groups such level lowered during pregnancy, probably reflecting the reduction of the fat reserve. The insuline level increased during pregnancy in either groups as a consequence of the growing of the foetuses. In nulliparous does the cortisol, NEFA and T3 concentrations were higher than primiparous does. The glucose levels were similar in both the groups probably due to the homeostatic mechanisms controlling the glycemia. Hormonal and metabo- lite analyses represent a good tool for understanding the physiological mechanisms required to meet higher reproductive performance.

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

Science.gov (United States)

Park, Jina; Kim, Jae Hyun

2017-03-01

Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP. Patient group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment. No statistical difference in BMI z -score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z -scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z -scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

Receptive processer og IT

DEFF Research Database (Denmark)

Ambjørn, Lone

2002-01-01

Sproglæringsteoretisk værktøj til udvikling af IT-støttede materialer og programmer inden for sproglig reception......Sproglæringsteoretisk værktøj til udvikling af IT-støttede materialer og programmer inden for sproglig reception...

Invocation Receptivity in Female of Rabbit

Directory of Open Access Journals (Sweden)

Martin Fik

2017-05-01

Full Text Available The target of this work was verified effect of transport females in the car for advance state of receptivity in young females broiler rabbits. We used nulliparous females of broiler hybrid HYCOLE (age 4-5 months, weight 3.5-3.8 kg. Experiment was realizated twice. First in half of November (31 females, second in half of February (32 females. Females was layed individually in boxes. After they were transported by car 1 hour (50 km. Before and after experiment we detected state of receptivity in females with coloration of vulva. The state of receptivity was determited from 1 for 4 colour of vulva. ( 1 – anemic coloration of vulva, 2- pink, 3 – red, 4- violet. We detected positive state of transport, on the receptivity. In November before transport was average of receptivity 1.87, after transport 2.25. The state of receptivity will be improve in 12 females (38.71 %. Improve from 1 to 2 was detected in 4 females, from 2 to 3 in 8 females. Improved from 2 to 4 , or from 3 to 4 wasn´t noticed in this group. The state of receptivity wasn´t changed in 19 females (61.29 %. In the state of receptivity 1 stayed 2 females, in the state 2 stayed 15 females, in the state 3 stayed 2 females and in the state 4 wasn´t any female. In February after the end of experiment, state of receptivity was improved with transport in the car from 2.19 to 2.65. The state of receptivity was improved in 13 females  (40.63 %.  Improve from 1 to 2 we detected in 1 female, from 2 to 3 we detected in 8 females, from 2 to 4 we detected in 2 females, from 3 to 4 in 2 females. In 19 females (59.38% we don´t noticed change state of receptivity. In the state of receptivity 1 were 2 females, in 2 were 11 females, in 3 were 5 females, in 4 was 1 female.

Gonadotropin-releasing hormone agonist trigger in oocyte donors co-treated with a gonadotropin-releasing hormone antagonist

DEFF Research Database (Denmark)

Vuong, T. N. L.; Ho, M. T.; Ha, T. D.

2016-01-01

-35 years, body mass index [BMI] hormone level >1.25 ng/mL, and antral follicle count >= 6). Intervention(s): Ovulation trigger with 0.2, 0.3, or 0.4 mg triptorelin in a GnRH antagonist cycle. Main Outcome Measure(s): The primary end point was number of metaphase II oocytes...... to number of metaphase II oocytes (16.0 +/- 8.5, 15.9 +/- 7.8, and 14.7 +/- 8.4, respectively), embryos (13.2 +/- 7.8, 11.7 +/- 6.9, 11.8 +/- 7.0), and number of top-quality embryos (3.8 +/- 2.9, 3.6 +/- 3.0, 4.1 +/- 3.0). Luteinizing hormone levels at 24 hours and 36 hours after trigger was significantly...

Measuring receptive collocational competence across proficiency ...

African Journals Online (AJOL)

The present study investigates (i) English as Foreign Language (EFL) learners' receptive collocational knowledge growth in relation to their linguistic proficiency level; (ii) how much receptive collocational knowledge is acquired as linguistic proficiency develops; and (iii) the extent to which receptive knowledge of ...

Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

Directory of Open Access Journals (Sweden)

Yiyi Sun

Full Text Available Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (--arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: a SWOT analysis.

Science.gov (United States)

Engmann, Lawrence; Benadiva, Claudio; Humaidan, Peter

2016-03-01

Gonadotrophin releasing hormone agonist (GnRHa) trigger is effective in the induction of oocyte maturation and prevention of ovarian hyperstimulation syndrome during IVF treatment. This trigger concept, however, results in early corpora lutea demise and consequently luteal phase dysfunction and impaired endometrial receptivity. The aim of this strenghths, weaknesses, opportunities and threats analysis was to summarize the progress made over the past 15 years to optimize ongoing pregnancy rates after GnRHa trigger. The advantages and potential drawbacks of this type of triggering are reviewed. The current approach to the management of GnRHa trigger in autologous cycles is based on the peak serum oestradiol level or follicle number and aims at a fresh embryo transfer or a segmentation approach with elective cryopreservation policy. We recommend intensive luteal support with transdermal oestradiol and intramuscular progesterone alone if peak serum oestradiol is 4000 or more pg/ml after GnRHa trigger or dual trigger with GnRHa and HCG 1000 IU if peak serum oestradiol is less than 4000 pg/mL. On the contrary, we recommend HCG 1500 IU 35 h after GnRHa trigger if there are less than 25 follicles, or freeze all oocytes or embryos if there are over 25 follicles. Copyright © 2015. Published by Elsevier Ltd.

EFFECT OF POST-MATING GNRH TREATMET ON SERUM PROGESTERONE, LUTEINIZING HORMONE LEVELS, DURATION OF ESTROUS CYCLE AND PREGNANCY RATES IN COWS

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H. YILDIZ, E. KAYGUSUZOĞLU, M. KAYA1 AND M. ÇENESIZ1

2009-07-01

Full Text Available Pregnancy rate, estrous cycle lenght, serum progesterone and luteinizing hormone (LH concentrations were determined in gonadotropin releasing hormone (GnRH; 10.5 μg synthetic gonadotrophin releasing hormone agonist, receptal administered cows on day 12 post-mating (n=9 compared to control cows (n=8. Their oestrous cycles were synchronised by intramuscular administration of prostaglandin F2 alpha (its analog, cloprostenol twice at 11 days interval. Estrous exhibited cows were mated naturally. Blood samples were collected every two days from all animals. Serum progesterone and LH concentrations were measured by ELISA method. GnRH administration significantly increased serum LH concentration which reached peak levels 2-3 h after treatment. However, serum progesterone concentration was not affected. There were no differences in mean progesterone concentrations on days 12 to 24 post-mating between GnRH administrated and control pregnant cows. However, in non pregnant animals, progesterone concentrations on days 16 in the treated group were lower than control group (P<0.01. Pregnancy diagnosis in animals made by B-mode ultrasonography between the 30th and 35th day showed that 77.7% of treated cows were pregnant compared to 50% in control group. Duration of the estrous cycle in the non-pregnant animals was not affected by the treatment (control, 21.3 ± 0.8 days; treated, 22.5 ± 0.5 days. In conclusion, this study supports the use of GnRH on day 12 post-mating as a method for enhancing pregnancy rates in lactating dairy cattle.

Bruce X Longwood television reception survey

International Nuclear Information System (INIS)

Hatanaka, G.K.

1992-01-01

Property owners living close to a proposed 500-kV transmission line route in Ontario expressed concerns that the line would affect their television reception. To give a reasonable evaluation of the impact of the transmission line, tests were conducted before and after installation of the line in which the possibility of active or passive interference to reception was assessed. Measurements were made of signal strength and ambient noise, and television reception was also recorded on videotape. Possible transmission line effects due to radiated noise, signal reduction, and ghosts are analyzed. The analysis of signal and noise conditions, and the assessment of videotaped reception, provide reasonable evidence that the line has had negligible impact on the television reception along the line route. 13 refs., 18 figs., 12 tabs

PARTIAL AGONISTS, FULL AGONISTS, ANTAGONISTS - DILEMMAS OF DEFINITION

NARCIS (Netherlands)

HOYER, D; BODDEKE, HWGM

The absence of selective antagonists makes receptor characterization difficult, and largely dependent on the use of agonists. However, there has been considerable debate as to whether certain drugs acting at G protein-coupled receptors are better described as agonists, partial agonists or

Suppression of interleukin-6-induced C-reactive protein expression by FXR agonists

International Nuclear Information System (INIS)

Zhang Songwen; Liu Qiangyuan; Wang Juan; Harnish, Douglas C.

2009-01-01

C-reactive protein (CRP), a human acute-phase protein, is a risk factor for future cardiovascular events and exerts direct pro-inflammatory and pro-atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily, plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver, whereas no effect was observed in FXR knockout mice. These data provide new evidence for direct anti-inflammatory properties of FXR.

PERCEPTION OF THE MOLTING HORMONE 20-HYDROXECDYSONE BY HOMARUS AMERICANUS: LOCALIZATION OF STEROID RECEPTORS AND EFFECT ON BEHAVIOR

Science.gov (United States)

There is growing evidence that hormones, when released from an animal into the environment, act as chemical signals to other organisms. There is also evidence to suggest that hormones are released by lobsters during sexual and agonistic encounters to signal conspecifics. The go...

Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.

Science.gov (United States)

Janáky, T; Juhász, A; Bajusz, S; Csernus, V; Srkalovic, G; Bokser, L; Milovanovic, S; Redding, T W; Rékási, Z; Nagy, A

1992-02-01

In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic radicals including an alkylating nitrogen mustard derivative of D-phenylalanine (D-melphalan), reactive cyclopropane, anthraquinone derivatives [2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N delta-(2,3-diaminopropionyl)-D-ornithine were used as carriers for one or two cytotoxic moieties. The enhanced biological activities produced by the incorporation of D amino acids into position 6 of the agonistic analogues were further increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with 10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues showed high affinities for the membrane receptors of human breast cancer cells, while the receptor binding affinities of peptides containing two cytotoxic side chains were lower. Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,D-Lys6,D-Ala10] LH-RH [where Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N epsilon-(2,3-diaminopropionyl)-D-Lys6,D-Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3) is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds. The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited [3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell lines

Hormonal fluctuations during the estrous cycle modulate Heme Oxygenase-1 expression in the uterus

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Maria Laura Zenclussen

2014-03-01

Full Text Available Deletion of the Heme Oxygenase-1 (Hmox1 locus in mice results in intrauterine lethality. The expression of the heme catabolyzing enzyme encoded by this gene, namely HO 1, is required to successfully support reproductive events. We have previously observed that HO-1 acts at several key events in reproduction ensuring pregnancy. HO-1 defines ovulation, positively influences implantation and placentation and ensures fetal growth and survival. Here, we embarked on a study aimed to determine whether hormonal changes during the estrous cycle in the mouse define HO-1 expression, thus influencing receptivity. We analyzed the serum levels of progesterone and estrogen by ELISA and HO-1 mRNA expression in uterus by real time RT-PCR at the metestrus, proestrus, estrus and diestrus phases of the estrous cycle. Further, we studied the HO-1 protein expression by Western Blot upon hormone addition to cultured uterine AN3 cells. We observed that HO-1 variations in uterine tissue correlated to changes in hormonal levels at different phases of the estrus cycle. In vitro, HO-1 protein levels in AN3 cells augmented after the addition of physiological concentrations of progesterone and estradiol, which confirmed our in vivo observations. Our data suggest an important role for hormones in HO-1 regulation in uterus that has a significant impact in receptivity and later on blastocyst implantation.

Experience modulates both aromatase activity and the sensitivity of agonistic behaviour to testosterone in black-headed gulls

NARCIS (Netherlands)

Ros, Albert F. H.; Franco, Aldina M. A.; Groothuis, Ton G. G.

2009-01-01

In young black-headed gulls (Larus ridibundus), exposure to testosterone increases the sensitivity of agonistic behaviour to a subsequent exposure to this hormone. The aim of this paper is twofold: to analyze whether social experience, gained during testosterone exposure, mediates this increase in

Pre-stimulation parameters predicting live birth after IVF in the long GnRH agonist protocol

DEFF Research Database (Denmark)

Pettersson, Göran; Andersen, Anders Nyboe; Broberg, Per

2010-01-01

This retrospective study aimed to identify novel pre-stimulation parameters associated with live birth in IVF and to develop a model for prediction of the chances of live birth at an early phase of the treatment cycle. Data were collected from a randomized trial in couples with unexplained...... infertility, tubal factor, mild male factor or other reason for infertility. All women (n=731) had undergone an IVF cycle (no intracytoplasmic sperm injection) after stimulation with human menopausal gonadotrophin or follicle-stimulating hormone following the long gonadotrophin-releasing hormone agonist...

Pre-stimulation parameters predicting live birth after IVF in the long GnRH agonist protocol

DEFF Research Database (Denmark)

Pettersson, Göran; Andersen, Anders Nyboe; Broberg, Per

2010-01-01

infertility, tubal factor, mild male factor or other reason for infertility. All women (n=731) had undergone an IVF cycle (no intracytoplasmic sperm injection) after stimulation with human menopausal gonadotrophin or follicle-stimulating hormone following the long gonadotrophin-releasing hormone agonist......This retrospective study aimed to identify novel pre-stimulation parameters associated with live birth in IVF and to develop a model for prediction of the chances of live birth at an early phase of the treatment cycle. Data were collected from a randomized trial in couples with unexplained...

A computational theory of visual receptive fields.

Science.gov (United States)

Lindeberg, Tony

2013-12-01

A receptive field constitutes a region in the visual field where a visual cell or a visual operator responds to visual stimuli. This paper presents a theory for what types of receptive field profiles can be regarded as natural for an idealized vision system, given a set of structural requirements on the first stages of visual processing that reflect symmetry properties of the surrounding world. These symmetry properties include (i) covariance properties under scale changes, affine image deformations, and Galilean transformations of space-time as occur for real-world image data as well as specific requirements of (ii) temporal causality implying that the future cannot be accessed and (iii) a time-recursive updating mechanism of a limited temporal buffer of the past as is necessary for a genuine real-time system. Fundamental structural requirements are also imposed to ensure (iv) mutual consistency and a proper handling of internal representations at different spatial and temporal scales. It is shown how a set of families of idealized receptive field profiles can be derived by necessity regarding spatial, spatio-chromatic, and spatio-temporal receptive fields in terms of Gaussian kernels, Gaussian derivatives, or closely related operators. Such image filters have been successfully used as a basis for expressing a large number of visual operations in computer vision, regarding feature detection, feature classification, motion estimation, object recognition, spatio-temporal recognition, and shape estimation. Hence, the associated so-called scale-space theory constitutes a both theoretically well-founded and general framework for expressing visual operations. There are very close similarities between receptive field profiles predicted from this scale-space theory and receptive field profiles found by cell recordings in biological vision. Among the family of receptive field profiles derived by necessity from the assumptions, idealized models with very good qualitative

Six-month gonadotropin releasing hormone (GnRH agonist depots provide efficacy, safety, convenience, and comfort

Directory of Open Access Journals (Sweden)

Phillips JM

2011-07-01

Full Text Available E David Crawford, Jason M PhillipsUniversity of Colorado Health Sciences Center, Aurora, CO, USAAbstract: Two different 6-month GnRH agonist depot formulations approved for palliative treatment of advanced and metastatic prostate cancer in the United States – leuprolide acetate 45 mg and triptorelinpalmoate 22.5 mg – provide patients with efficacy and safety comparable to those of existing 1-, 3-, and 4-month GnRH agonist depots. However, the 6-month formulations can increase patient convenience, comfort, and compliance by reducing the number of physician visits and injections required. At the conclusion of their pivotal trials, the 6-month formulations demonstrated efficacy rates in achieving chemical castration (serum testosterone #50 ng/dL that ranged between 93% and 99%. As with existing GnRH agonist depot formulations, hot flashes represented the most common adverse event reported in trials of 6-month leuprolide acetate or triptorelin. As such, these products may prove useful not only for their labeled indication, but also as adjuncts to other treatments such as radical prostatectomy, radiotherapy, and chemotherapy. We recommend further research, including head-to-head trials between the 6-month GnRH depots, to refine our understanding of these products.Keywords: prostate cancer, leuprorelin, leuprolide, triptorelin, 6-month depot, testosterone

Effects of irradiation and adrenal cortex disfunction on ovarial-hormonal status of mature female rats

International Nuclear Information System (INIS)

Konoplya, E.F.; Banetskaya, N.V.; Sechko, L.K.; Pavlenko, V.S.; Popov, E.G.

2003-01-01

It was shown that development of glucocorticoid disfunction in mature rats (made by series of 10 mg/kg body wt subcutaneous corticosterone injections, during I month) essentially increased radiosensitivity of female reproductive organs. Additionally in the experimental conditions after external g-irradiation (1.0 Gy) development of atrophic processes in follicular apparatus of ovary caused severe ovarial disorders (polycystosis, fibrosis). Simultaneously degree of hormonal misregulations and upsets for systems of hormone reception in female sex tissues is aggravating. (authors)

Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

Science.gov (United States)

Varamini, Pegah; Rafiee, Amirreza; Giddam, Ashwini Kumar; Mansfeld, Friederike M; Steyn, Frederik; Toth, Istvan

2017-10-26

Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy. They possess improved stability as compared to the natural GnRH, yet they suffer from a poor pharmacokinetic profile. To address this, we used a GnRH peptide-modified dendrimer platform with and without lipidation strategy. Dendrimers were synthesized on a polylysine core and bore either native GnRH (1, 2, and 5) or lipid-modified GnRH (3 and 4). Compound 3, which bore a lipidic moiety in a branched tetramer structure, showed approximately 10-fold higher permeability and metabolic stability and 39 times higher antitumor activity against hormone-resistant prostate cancer cells (DU145) relative to triptorelin. In gonadotropin-release experiments, dendrimer 3 was shown to be the most potent construct. Dendrimer 3 showed similar luteinizing hormone (LH)-release activity to triptorelin in mice. Our findings indicate that dendrimer 3 is a promising analog with higher potency for the treatment of hormone-resistant prostate cancer than the currently available GnRH agonists.

Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the invasiveness of endometrial cancer cells through the GnRH-I receptor and mitogen-activated protein kinase (MAPK)-dependent activation of matrix metalloproteinase (MMP)-2

International Nuclear Information System (INIS)

Wu, Hsien-Ming; Wang, Hsin-Shih; Huang, Hong-Yuan; Lai, Chyong-Huey; Lee, Chyi-Long; Soong, Yung-Kuei; Leung, Peter CK

2013-01-01

More than 25% of patients diagnosed with endometrial carcinoma have an invasive primary cancer accompanied by metastases. Gonadotropin-releasing hormone (GnRH) plays an important role in reproduction. In mammals, expression of GnRH-II is higher than GnRH-I in reproductive tissues. Here, we examined the effect of a GnRH-II agonist on the motility of endometrial cancer cells and its mechanism of action in endometrial cancer therapy. Immunoblotting and immunohistochemistry (IHC) were used to determine the expression of the GnRH-I receptor protein in human endometrial cancer. The activity of MMP-2 in the conditioned medium was determined by gelatin zymography. Cell motility was assessed by invasion and migration assay. GnRH-I receptor si-RNA was applied to knockdown GnRH-I receptor. The GnRH-I receptor was expressed in the endometrial cancer cells. The GnRH-II agonist promoted cell motility in a dose-dependent manner. The GnRH-II agonist induced the phosphorylation of ERK1/2 and JNK, and the phosphorylation was abolished by ERK1/2 inhibitor (U0126) and the JNK inhibitor (SP600125). Cell motility promoted by GnRH-II agonist was suppressed in cells that were pretreated with U0126 and SP600125. Moreover, U0126 and SP600125 abolished the GnRH-II agonist-induced activation of MMP-2. The inhibition of MMP-2 with MMP-2 inhibitor (OA-Hy) suppressed the increase in cell motility in response to the GnRH-II agonist. Enhanced cell motility mediated by GnRH-II agonist was also suppressed by the knockdown of the endogenous GnRH-I receptor using siRNA. Our study indicates that GnRH-II agonist promoted cell motility of endometrial cancer cells through the GnRH-I receptor via the phosphorylation of ERK1/2 and JNK, and the subsequent, MAPK-dependent activation of MMP-2. Our findings represent a new concept regarding the mechanism of GnRH-II-induced cell motility in endometrial cancer cells and suggest the possibility of exploring GnRH-II as a potential therapeutic target for the

Hormone Use for Therapeutic Amenorrhea and Contraception During Hematopoietic Cell Transplantation

Science.gov (United States)

Chang, Katherine; Merideth, Melissa A.; Stratton, Pamela

2015-01-01

There is a growing population of women who have or will undergo hematopoietic stem cell transplant for a variety of malignant and benign conditions. Gynecologists play an important role in addressing the gynecologic and reproductive health concerns for these women throughout the transplant process. As women undergo cell transplantation, they should avoid becoming pregnant and are at risk of uterine bleeding. Thus, counseling about and implementing hormonal treatments such as gonadotropin-releasing hormone agonists, combined hormonal contraceptives, and progestin-only methods help to achieve therapeutic amenorrhea and can serve as contraception during the peritransplant period. In this commentary, we summarize the timing, risks and benefits of the hormonal options just prior, during and for the year after hematopoietic stem cell transplantation. PMID:26348182

Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging.

Science.gov (United States)

Smith, Roy G; Sun, Yuxiang; Jiang, Hong; Albarran-Zeckler, Rosie; Timchenko, Nikolai

2007-11-01

Administration of an orally active agonist (MK-0677) of the growth hormone secretagogue receptor (GHS-R1a) to elderly subjects restored the amplitude of endogenous episodic growth hormone (GH) release to that of young adults. Functional benefits include increased lean mass and bone density and modest improvements in strength. In old mice, a similar agonist partially restored function to the thymus and reduced tumor cell growth and metastasis. Treatment of old mice with the endogenous GHS-R1a agonist ghrelin restored a young liver phenotype. The mechanism involves inhibition of cyclin D3:cdk4/cdk6 activity and increased protein phosphatase-2A (PP2A) activity in liver nuclei, which stabilizes the dephosphorylated form of the transcription factor C/EBPalpha preventing the age-dependent formation of the C/EBPalpha-Rb-E2F4-Brm nuclear complex. By inhibiting formation of this complex, repression of E2F target genes is de-repressed and C/EBPalpha regulated expression of Pepck, a regulator of gluconeogenesis, is normalized, thereby restoring a young liver phenotype. In the brain, aging is associated with decline in dopamine function. We investigated the potential neuromodulatory role of GHS-R1a on dopamine action. Neurons were identified in the hippocampus, cortex, substantia nigra, and ventral tegmental areas that coexpressed GHS-R1a and dopamine receptor subtype-1 (D1R). Cell culture studies showed that, in the presence of ghrelin and dopamine, GHS-R and D1R form heterodimers, which modified G-protein signal transduction resulting in amplification of dopamine signaling. We speculate that aging is associated with deficient endogenous ghrelin signaling that can be rescued by intervention with GHS-R1a agonists to improve quality of life and maintain independence.

THE INFLUENCE OF INSECT JUVENILE HORMONE AGONISTTS ON METAMORPHOSIS AND REPRODUCTION IN ESTUARINE CRUSTACEANS

Science.gov (United States)

Comparative developmental and reproductive studies were performed on several species of estuarine crustaceans in response to three juvenile hormone agonists (JHAs) (methoprene, fenoxycarb, and pyriproxyfen). Larval development of the grass shrimp, Palaemonetes pugio, was greater ...

Central auditory neurons have composite receptive fields.

Science.gov (United States)

Kozlov, Andrei S; Gentner, Timothy Q

2016-02-02

High-level neurons processing complex, behaviorally relevant signals are sensitive to conjunctions of features. Characterizing the receptive fields of such neurons is difficult with standard statistical tools, however, and the principles governing their organization remain poorly understood. Here, we demonstrate multiple distinct receptive-field features in individual high-level auditory neurons in a songbird, European starling, in response to natural vocal signals (songs). We then show that receptive fields with similar characteristics can be reproduced by an unsupervised neural network trained to represent starling songs with a single learning rule that enforces sparseness and divisive normalization. We conclude that central auditory neurons have composite receptive fields that can arise through a combination of sparseness and normalization in neural circuits. Our results, along with descriptions of random, discontinuous receptive fields in the central olfactory neurons in mammals and insects, suggest general principles of neural computation across sensory systems and animal classes.

Glutamate receptor agonists

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart

2011-01-01

The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients.

Science.gov (United States)

Morote, Juan; Comas, Imma; Ferrer, Roser; Planas, Jacques; Celma, Anna; Regis, Lucas

2017-10-22

Luteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists. Serum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients "on LH-RH agonists", 303 "off LH-RH agonist" in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion "no LH-RH agonist" who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on "LH-RH agonists" and 19 "off LH-RH agonists", serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS). The area under the curve (AUC) to distinguish patients "on versus off LH-RH agonists" was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients "on LH-RH agonists" was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients "on versus off LH-RH agonists" was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method. Serum LH is more accurate than serum testosterone regardless the method, to distinguish patients "on versus off LH-RH agonists". The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.

TEACHING COMMUNICATIVE TRANSLATION: AN ACTIVE RECEPTION ANALYSIS BETWEEN THE TRANSLATION AND READER’S RECEPTION

Directory of Open Access Journals (Sweden)

Venny Eka Meidasari

2014-06-01

Full Text Available Literary theory sees reception theory from the reader response that emphasizes the reader’s reception of a literary text. It is generally called audience reception in the analysis of communications models. In literary studies, reception theory originated from the work of Hans-Robert Jauss in the late 1960s. Communication only means that the original message will be clearly sent in its equivalent context to the target receptor. Similarly, the main role of translators is to send the message across without any form of distortion or emphasis. It is delivering the genuine context of the message to the language that the active receptor understands. A single mistake in a context translation can result to offensive message that can eventually lead to misunderstandings between active receptors. This paper proposes on the role of translator as the mediator between a writer of the original text and the active target language receptors of translated version in the course of communication which definitely affects the process and result of translation practice. It also reveals the emphasis on the creation text of the translation theories originated from the strategic communication theories, which hopefully leads to a dream of the most equivalence between the text and the translated version.

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

Science.gov (United States)

Phumsatitpong, Chayarndorn; Moenter, Suzanne M

2018-01-01

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

Internalization and recycling of receptor-bound gonadotropin-releasing hormone agonist in pituitary gonadotropes

International Nuclear Information System (INIS)

Schvartz, I.; Hazum, E.

1987-01-01

The fate of cell surface gonadotropin-releasing hormone (GnRH) receptors on pituitary cells was studied utilizing lysosomotropic agents and monensin. Labeling of pituitary cells with a photoreactive GnRH derivative, [azidobenzoyl-D-Lys6]GnRH, revealed a specific band of Mr = 60,000. When photoaffinity-labeled cells were exposed to trypsin immediately after completion of the binding, the radioactivity incorporated into the Mr = 60,000 band decreased, with a concomitant appearance of a proteolytic fragment (Mr = 45,000). This fragment reflects cell surface receptors. Following GnRH binding, the hormone-receptor complexes underwent internalization, partial degradation, and recycling. The process of hormone-receptor complex degradation was substantially prevented by lysosomotropic agents, such as chloroquine and methylamine, or the proton ionophore, monensin. Chloroquine and monensin, however, did not affect receptor recycling, since the tryptic fragment of Mr = 45,000 was evident after treatment with these agents. This suggests that recycling of GnRH receptors in gonadotropes occurs whether or not the internal environment is acidic. Based on these findings, we propose a model describing the intracellular pathway of GnRH receptors

Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.

Science.gov (United States)

Ferrari, Silvia Martina; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro; Fallahi, Poupak

2016-01-01

Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.

A Novel Non-Peptidic Agonist of the Ghrelin Receptor with Orexigenic Activity In vivo

Science.gov (United States)

Pastor-Cavada, Elena; Pardo, Leticia M.; Kandil, Dalia; Torres-Fuentes, Cristina; Clarke, Sarah L.; Shaban, Hamdy; McGlacken, Gerard P.; Schellekens, Harriet

2016-11-01

Loss of appetite in the medically ill and ageing populations is a major health problem and a significant symptom in cachexia syndromes, which is the loss of muscle and fat mass. Ghrelin is a gut-derived hormone which can stimulate appetite. Herein we describe a novel, simple, non-peptidic, 2-pyridone which acts as a selective agonist for the ghrelin receptor (GHS-R1a). The small 2-pyridone demonstrated clear agonistic activity in both transfected human cells and mouse hypothalamic cells with endogenous GHS-R1a receptor expression. In vivo tests with the hit compound showed significant increased food intake following peripheral administration, which highlights the potent orexigenic effect of this novel GHS-R1a receptor ligand.

Note from the Goods Reception services

CERN Multimedia

FI Department

2008-01-01

Members of the personnel are invited to take note that only parcels corresponding to official orders or contracts will be handled at CERN. Individuals are not authorised to have private merchandise delivered to them at CERN and private deliveries will not be accepted by the Goods Reception services. Goods Reception Services

Rehabilitering og 'motion på recept'

DEFF Research Database (Denmark)

Larsen, Niels Sandholm; Larsen, Kristian

2008-01-01

af disse forskningsarbejder er etablering af fænomenet 'motion på recept'. Konceptet om 'motion på recept' stammer oprindelig fra Sverige, hvor praktiserende læger i en periode har haft mulighed for at henvise visse typer af patienter til fysisk træning hos praktiserende fysioterapeuter. Ribe Amt...... 2007)....

A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.

Science.gov (United States)

Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A

2014-12-01

Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and

The immigrants’ reception system in Italy. Reflections emerging from an experience of reception upon landing

OpenAIRE

Concetta Chiara Cannella; Gandolfa Cascio; Francesca Molonia; Serena Vitulo

2014-01-01

After the description of the main migration routes toward Italian territory, the article provides an overview of the laws and administrative policy instruments that characterize the system of reception and detention of migrants in Italy. This type of information can help psychosocial workers supporting migrants to better cope with various psychosocial issues, such as the landing in a foreign country. Following a report on the first reception intervention carried out in Palermo, Sicily, by Psi...

Language, gay pornography, and audience reception.

Science.gov (United States)

Leap, William L

2011-01-01

Erotic imagery is an important component of gay pornographic cinema, particularly, where work of audience reception is concerned. However, to assume the audience engagement with the films is limited solely to the erotic realm is to underestimate the workings of ideological power in the context and aftermath of reception. For example, the director of the film under discussion here (Men of Israel; Lucas, 2009b) intended to present an erotic celebration of the nation-state. Yet, most viewers ignore the particulars of context in their comments about audience reception, placing the "Israeli" narrative within a broader framework, using transnational rather than film-specific criteria to guide their "reading" of the Israeli-centered narrative. This article uses as its entry point the language that viewers employ when describing their reactions to Men of Israel on a gay video club's Web site; this article shows how the work of audience reception may draw attention to a film's erotic details while invoking social and political messages that completely reframe the film's erotic narrative.

Mental distress and personality in women undergoing GnRH agonist versus GnRH antagonist protocols for assisted reproductive technology

DEFF Research Database (Denmark)

Stenbæk, D. S.; Toftager, M.; Hjordt, L. V.

2015-01-01

STUDY QUESTION: Do mental distress and mood fluctuations in women undergoing GnRH agonist and GnRH antagonist protocols for assisted reproductive technology (ART) differ depending on protocol and the personality trait, neuroticism? SUMMARY ANSWER: ART treatment did not induce elevated levels...... of mental distress in either GnRH antagonist or agonist protocols but neuroticism was positively associated with increased mental distress, independent of protocols. WHAT IS KNOWN ALREADY: ART treatment may increase mental distress by mechanisms linked to sex hormone fluctuations. General psychological...... characteristics, such as personality traits indexing negative emotionality, e.g. neuroticism, are likely to affect mental distress during ART treatment. STUDY DESIGN, SIZE, DURATION: A total of 83 women undergoing their first ART cycle were consecutively randomized 1:1 to GnRH antagonist (n = 42) or GnRH agonist...

ADRENAL HORMONES IN RATS BEFORE AND AFTER STRESS-EXPERIENCE - EFFECTS OF IPSAPIRONE

NARCIS (Netherlands)

KORTE, SM; BOUWS, GAH; BOHUS, B

The present study was designed to investigate the effects of the anxiolytic 5-HT1A receptor agonist ipsapirone on the hormonal responses in rats under nonstress and stress conditions by means of repeated blood sampling through an intracardiac catheter. Ipsapirone was given in doses of 2.5, 5, 10.

Resurgence of Minimal Stimulation In Vitro Fertilization with A Protocol Consisting of Gonadotropin Releasing Hormone-Agonist Trigger and Vitrified-Thawed Embryo Transfer

Directory of Open Access Journals (Sweden)

Zhang John

2016-07-01

Full Text Available Minimal stimulation in vitro fertilization (mini-IVF consists of a gentle controlled ovarian stimulation that aims to produce a maximum of five to six oocytes. There is a misbelief that mini-IVF severely compromises pregnancy and live birth rates. An appraisal of the literature pertaining to studies on mini-IVF protocols was performed. The advantages of minimal stimulation protocols are reported here with a focus on the use of clomiphene citrate (CC, gonadotropin releasing hormone (GnRH ago- nist trigger for oocyte maturation, and freeze-all embryo strategy. Literature review and the author’s own center data suggest that minimal ovarian stimulation protocols with GnRH agonist trigger and freeze-all embryo strategy along with single embryo transfer produce a reasonable clinical pregnancy and live birth rates in both good and poor responders. Additionally, mini-IVF offers numerous advantages such as: i. Reduction in cost and stress with fewer office visits, needle sticks, and ultrasounds, and ii. Reduction in the incidence of ovarian hyperstimulation syndrome (OHSS. Mini-IVF is re-emerging as a solution for some of the problems associated with conventional IVF, such as OHSS, cost, and patient discomfort.

Unaccompanied adolescents seeking asylum - Poorer mental health under a restrictive reception : poorer mental health under a restrictive reception

NARCIS (Netherlands)

Reijneveld, S.A.; de Boer, J.B.; Bean, T.; Korfker, D.G.

2005-01-01

We assessed the effects of a stringent reception policy on the mental health of unaccompanied adolescent asylum seekers by comparing the mental health of adolescents in a restricted campus reception setting and in a setting offering more autonomy (numbers [response rates]: 69 [93%] and 53 [69%],

Increase of antitumor activity of cisplatin using agonist of gonadotropin-realising hormone and inhibitor of aromatase on the model of ascites ovarian tumor.

Science.gov (United States)

Tkalia, I G; Vorobyova, L I; Grabovoy, A N; Svintsitsky, V S; Tarasova, T O; Lukyanova, N Y; Todor, I N; Chekhun, V F

2014-09-01

To study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in monotherapy and in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant ascites transplantable ovarian tumor (TOT), to assess therapeutic pathomorphosis and level of VEGF expression in tumor cells using diffe-rent combinations of cytostatics and hormonal drugs. 72 female Wistar rats, which underwent intraperitoneal transplantation of ascitic TOT, by 5·10(6) cells per animal, have been involved in the study. Rats were divided into 8 groups, 9 rats in each group. Histological study with assessment of therapeutic pathomorphosis in TOT and immunohistochemical study has been carried out. Survival of animals in the studied groups has been evaluated. Among animals treated in regimen of monotherapy, the most pronounced antiangiogenic activity in TOT has been observed on application of hormonal drugs (triptorelin - 39.4 ± 1.9 and exemestane - 33.9 ± 1.4%; р = 0.003), the highest grade of treatment pathomorphosis in TOT has been observed at treatment with cisplatin (11.7%; р = 0.001). Combination of triptorelin and exemestane has amplified antiangiogenic activity in TOT (12.2 ± 0.9%; р = 0.001), but has not significantly changed rates of pathomorphosis (22.1 ± 0.4%; р=0.005) and survival of animals (32.2%; р = 0.007) as compared with the same rates in rats treated with hormonal drugs in monotherapy. Significant correlation between VEGF expression and pathomorphosis has been established (relative part of viable tumor tissue (RPVTT)) in TOT (r = 0.712; р = 0.001), as well as between RPVTT and life-span of animals (r = -0.320; р = 0.007). However, lack of correlation between VEGF expression in cells of TOT and survival of rats has been determined (r = -0.194; р = 0.11). Combination of cytostatic agent with triptorelin or exemestane has demonstrated significantly high rates of therapeutic

Hormone abuse in sports: the antidoping perspective.

Science.gov (United States)

Barroso, Osquel; Mazzoni, Irene; Rabin, Olivier

2008-05-01

Since ancient times, unethical athletes have attempted to gain an unfair competitive advantage through the use of doping substances. A list of doping substances and methods banned in sports is published yearly by the World Anti-Doping Agency (WADA). A substance or method might be included in the List if it fulfills at least two of the following criteria: enhances sports performance; represents a risk to the athlete's health; or violates the spirit of sports. This list, constantly updated to reflect new developments in the pharmaceutical industry as well as doping trends, enumerates the drug types and methods prohibited in and out of competition. Among the substances included are steroidal and peptide hormones and their modulators, stimulants, glucocorticosteroids, beta2-agonists, diuretics and masking agents, narcotics, and cannabinoids. Blood doping, tampering, infusions, and gene doping are examples of prohibited methods indicated on the List. From all these, hormones constitute by far the highest number of adverse analytical findings reported by antidoping laboratories. Although to date most are due to anabolic steroids, the advent of molecular biology techniques has made recombinant peptide hormones readily available. These substances are gradually changing the landscape of doping trends. Peptide hormones like erythropoietin (EPO), human growth hormone (hGH), insulin, and insulin-like growth factor I (IGF-I) are presumed to be widely abused for performance enhancement. Furthermore, as there is a paucity of techniques suitable for their detection, peptide hormones are all the more attractive to dishonest athletes. This article will overview the use of hormones as doping substances in sports, focusing mainly on peptide hormones as they represent a pressing challenge to the current fight against doping. Hormones and hormones modulators being developed by the pharmaceutical industry, which could emerge as new doping substances, are also discussed. 2008, Asian

Final height after gonadotrophin releasing hormone agonist treatment for central precocious puberty : The Dutch experience

NARCIS (Netherlands)

Mul, D; Oostdijk, W; Otten, BJ; Rouwe, C; Jansen, M; Delemarre-van de Waal, HA; Waelkens, JJJ; Drop, SLS

Final height (FH) data of 96 children (87 girls) treated with GnRH agonist for central precocious puberty were studied. In girls mean FH exceeded initial height prediction by 7.4 (5.7) cm (p <0.001); FH was significantly lower than target height, but still in the genetic target range. When treatment

Diversity Networking Reception

Science.gov (United States)

2014-03-01

Join us at the APS Diversity Reception to relax, network with colleagues, and learn about programs and initiatives for women, underrepresented minorities, and LGBT physicists. You'll have a great time meeting friends in a supportive environment and making connections.

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation

DEFF Research Database (Denmark)

Frokjaer, Vibe Gedsoe; Pinborg, Anja; Holst, Klaus Kähler

2015-01-01

.6 ± 2.2) and at follow-up (16.2 ± 2.6 days after intervention start). RESULTS: Sex hormone manipulation with GnRHa significantly triggered subclinical depressive symptoms within-group (p = .003) and relative to placebo (p = .02), which were positively associated with net decreases in estradiol levels (p......BACKGROUND: An adverse response to acute and pronounced changes in sex-hormone levels during, for example, the perimenopausal or postpartum period appears to heighten risk for major depression in women. The underlying risk mechanisms remain elusive but may include transiently compromised...... serotonergic brain signaling. Here, we modeled a biphasic ovarian sex hormone fluctuation using a gonadotropin-releasing hormone agonist (GnRHa) and evaluated if emergence of depressive symptoms was associated with change in cerebral serotonin transporter (SERT) binding following intervention. METHODS...

Highly potent metallopeptide analogues of luteinizing hormone-releasing hormone.

Science.gov (United States)

Bajusz, S; Janaky, T; Csernus, V J; Bokser, L; Fekete, M; Srkalovic, G; Redding, T W; Schally, A V

1989-08-01

Metal complexes related to the cytotoxic complexes cisplatin [cis-diamminedichloroplatinum(II)] and transbis(salicylaldoximato)copper(II) were incorporated into suitably modified luteinizing hormone-releasing hormone (LH-RH) analogues containing D-lysine at position 6. Some of the metallopeptides thus obtained proved to be highly active LH-RH agonists or antagonists. For instance, SB-40, a PtCl2-containing metallopeptide in which platinum is coordinated to an N epsilon-(DL-2,3-diaminopropionyl)-D-lysine residue [D-Lys(DL-A2pr] at position 6, showed 50 times higher LH-releasing potency than the native hormone. SB-95, [Ac-D-Nal(2)1,D-Phe(pCl)2, D-Pal(3)2, Arg5,D-Lys[DL-A2pr(Sal2Cu)]6,D-Ala10]LH-RH, where Nal(2) is 3-(2-naphthyl)alanine, Pal(3) is 3-(3-pyridyl)alanine, and copper(II) is coordinated to the salicylideneimino moieties resulting from condensation of salicylaldehyde with D-Lys(DL-A2pr)6, caused 100% inhibition of ovulation at a dose of 3 micrograms in rats. Most metallopeptide analogues of LH-RH showed high affinities for the membrane receptors of rat pituitary and human breast cancer cells. Some of these metallopeptides had cytotoxic activity against human breast cancer and prostate cancer cell lines in vitro (this will be the subject of a separate paper on cytotoxicity evaluation). Such cytostatic metallopeptides could be envisioned as targeted chemotherapeutic agents in cancers that contain receptors for LH-RH-like peptides.

Triazolophostins: a library of novel and potent agonists of IP3 receptors

OpenAIRE

Vibhute, Amol M; Konieczny, Vera; Taylor, Colin William; Sureshan, Kana M

2015-01-01

IP3 receptors are channels that mediate the release of Ca2+ from the intracellular stores of cells stimulated by hormones or neurotransmitters. Adenophostin A (AdA) is the most potent agonist of IP3 receptors, with the β-anomeric adenine contributing to the increased potency. The potency of AdA and its stability towards the enzymes that degrade IP3 have aroused interest in AdA analogs for biological studies. The complex structure of AdA poses problems that have necessitated optimization of sy...

Neonatal DHT but not E2 speeds induction of sexual receptivity in the musk shrew.

Science.gov (United States)

Ewton, Tiffany A; Siboni, Ruth B; Jackson, Andrea; Freeman, Louise M

2010-06-01

Neural aromatization of testosterone (T) to estrogen during development is thought to be important for sexual differentiation of many altricial mammals. We evaluated the effects of neonatal injections of the non-aromatizable androgen dihydrotestosterone propionate (DHTP) and estradiol (E2) on the copulatory behavior of the female musk shrew, an altricial insectivore. Following adult ovariectomy and replacement T, animals were paired with a stimulus female for two 60-minute copulatory behavior tests. The latency to induce sexual receptivity (in the form of tail-wagging by the female), mount latency and total number of mounts were recorded in experimental females and in a group of untreated control males. While neither hormone treatment significantly affected mounting behavior, DHTP-treated animals induced receptivity faster and with latencies not significantly different from intact males, suggesting that early non-aromatizable androgens can have masculinizing actions by either increasing sexual motivation or making the treated animal more attractive to the stimulus female. Reliance on androgenic rather than estrogenic metabolites for the differentiation of courtship behaviors conforms to the pattern seen more typically in primates than rodents. Copyright 2009 Elsevier Inc. All rights reserved.

Receptivity to Tobacco Advertising and Susceptibility to Tobacco Products.

Science.gov (United States)

Pierce, John P; Sargent, James D; White, Martha M; Borek, Nicolette; Portnoy, David B; Green, Victoria R; Kaufman, Annette R; Stanton, Cassandra A; Bansal-Travers, Maansi; Strong, David R; Pearson, Jennifer L; Coleman, Blair N; Leas, Eric; Noble, Madison L; Trinidad, Dennis R; Moran, Meghan B; Carusi, Charles; Hyland, Andrew; Messer, Karen

2017-06-01

Non-cigarette tobacco marketing is less regulated and may promote cigarette smoking among adolescents. We quantified receptivity to advertising for multiple tobacco products and hypothesized associations with susceptibility to cigarette smoking. Wave 1 of the nationally representative PATH (Population Assessment of Tobacco and Health) study interviewed 10 751 adolescents who had never used tobacco. A stratified random selection of 5 advertisements for each of cigarettes, e-cigarettes, smokeless products, and cigars were shown from 959 recent tobacco advertisements. Aided recall was classified as low receptivity, and image-liking or favorite ad as higher receptivity. The main dependent variable was susceptibility to cigarette smoking. Among US youth, 41% of 12 to 13 year olds and half of older adolescents were receptive to at least 1 tobacco advertisement. Across each age group, receptivity to advertising was highest for e-cigarettes (28%-33%) followed by cigarettes (22%-25%), smokeless tobacco (15%-21%), and cigars (8%-13%). E-cigarette ads shown on television had the highest recall. Among cigarette-susceptible adolescents, receptivity to e-cigarette advertising (39.7%; 95% confidence interval [CI]: 37.9%-41.6%) was higher than for cigarette advertising (31.7%; 95% CI: 29.9%-33.6%). Receptivity to advertising for each tobacco product was associated with increased susceptibility to cigarette smoking, with no significant difference across products (similar odds for both cigarette and e-cigarette advertising; adjusted odds ratio = 1.22; 95% CI: 1.09-1.37). A large proportion of US adolescent never tobacco users are receptive to tobacco advertising, with television advertising for e-cigarettes having the highest recall. Receptivity to advertising for each non-cigarette tobacco product was associated with susceptibility to smoke cigarettes. Copyright © 2017 by the American Academy of Pediatrics.

GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism.

Directory of Open Access Journals (Sweden)

Hua V Lin

Full Text Available GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a GPR142-dependent manner. In contrast, Phenylalanine improves in vivo glucose disposal independently of GPR142. Noteworthy, refeeding-induced elevations in insulin and glucose-dependent insulinotropic polypeptide are blunted in Gpr142 null mice. In conclusion, these findings demonstrate GPR142 is a Tryptophan receptor critically required for insulin and incretin hormone regulation and suggest GPR142 agonists may be effective therapies that leverage amino acid sensing pathways for the treatment of type 2 diabetes.

Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist.

Science.gov (United States)

Devjak, Rok; Fon Tacer, Klementina; Juvan, Peter; Virant Klun, Irma; Rozman, Damjana; Vrtačnik Bokal, Eda

2012-01-01

In in vitro fertilization (IVF) cycles controlled ovarian hyperstimulation (COH) is established by gonadotropins in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists, to prevent premature luteinizing hormone (LH) surge. The aim of our study was to improve the understanding of gene expression profile of cumulus cells (CC) in terms of ovarian stimulation protocol and oocyte maturity. We applied Affymetrix gene expression profiling in CC of oocytes at different maturation stages using either GnRH agonists or GnRH antagonists. Two analyses were performed: the first involved CC of immature metaphase I (MI) and mature metaphase II (MII) oocytes where 359 genes were differentially expressed, and the second involved the two GnRH analogues where no differentially expressed genes were observed at the entire transcriptome level. A further analysis of 359 differentially genes was performed, focusing on anti-Müllerian hormone receptor 2 (AMHR2), follicle stimulating hormone receptor (FSHR), vascular endothelial growth factor C (VEGFC) and serine protease inhibitor E2 (SERPINE2). Among other differentially expressed genes we observed a marked number of new genes connected to cell adhesion and neurotransmitters such as dopamine, glycine and γ-Aminobutyric acid (GABA). No differential expression in CC between the two GnRH analogues supports the findings of clinical studies where no significant difference in live birth rates between both GnRH analogues has been proven.

Model of the complex of Parathyroid hormone-2 receptor and Tuberoinfundibular peptide of 39 residues

Directory of Open Access Journals (Sweden)

Persson Bengt

2010-10-01

Full Text Available Abstract Background We aim to propose interactions between the parathyroid hormone-2 receptor (PTH2R and its ligand the tuberoinfundibular peptide of 39 residues (TIP39 by constructing a homology model of their complex. The two related peptides parathyroid hormone (PTH and parathyroid hormone related protein (PTHrP are compared with the complex to examine their interactions. Findings In the model, the hydrophobic N-terminus of TIP39 is buried in a hydrophobic part of the central cavity between helices 3 and 7. Comparison of the peptide sequences indicates that the main discriminator between the agonistic peptides TIP39 and PTH and the inactive PTHrP is a tryptophan-phenylalanine replacement. The model indicates that the smaller phenylalanine in PTHrP does not completely occupy the binding site of the larger tryptophan residue in the other peptides. As only TIP39 causes internalisation of the receptor and the primary difference being an aspartic acid in position 7 of TIP39 that interacts with histidine 396 in the receptor, versus isoleucine/histidine residues in the related hormones, this might be a trigger interaction for the events that cause internalisation. Conclusions A model is constructed for the complex and a trigger interaction for full agonistic activation between aspartic acid 7 of TIP39 and histidine 396 in the receptor is proposed.

Supplementation with a recombinant human chorionic gonadotropin microdose leads to similar outcomes in ovarian stimulation with recombinant follicle-stimulating hormone using either a gonadotropin-releasing hormone agonist or antagonist for pituitary suppression.

Science.gov (United States)

Cavagna, Mario; Maldonado, Luiz Guilherme Louzada; de Souza Bonetti, Tatiana Carvalho; de Almeida Ferreira Braga, Daniela Paes; Iaconelli, Assumpto; Borges, Edson

2010-06-01

To compare the outcomes of protocols for ovarian stimulation with recombinant hCG microdose, with GnRH agonists and antagonists for pituitary suppression. Prospective nonrandomized clinical trial. A private assisted reproduction center. We studied 182 patients undergoing intracytoplasmic sperm injection (ICSI) cycles, allocated into two groups: GnRH agonist group, in which patients received a GnRH agonist (n = 73), and a GnRH antagonist group, in which patients were administered a GnRH antagonist for pituitary suppression (n = 109). Pituitary suppression with GnRH agonist or GnRH antagonist. Ovarian stimulation carried out with recombinant FSH and supplemented with recombinant hCG microdose. Total dose of recombinant FSH and recombinant hCG administered; E(2) concentrations and endometrial width on the day of hCG trigger; number of follicles aspirated, oocytes and mature oocytes retrieved; fertilization, pregnancy (PR), implantation, and miscarriage rates. The total dose of recombinant FSH and recombinant hCG administered were similar between groups, as were the E(2) concentrations and endometrial width. The number of follicles aspirated, oocytes, and metaphase II oocytes collected were also comparable. There were no statistically significant differences in fertilization, PR, implantation, and miscarriage rates in the GnRH agonist and GnRH antagonist groups. When using recombinant hCG microdose supplementation for controlled ovarian stimulation (COS), there are no differences in laboratory or clinical outcomes with the use of either GnRH antagonist or agonist for pituitary suppression. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes

DEFF Research Database (Denmark)

Lund, Asger; Knop, Filip K; Vilsbøll, Tina

2014-01-01

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, secreted in response to ingestion of nutrients, and has important effects on several of the pathophysiological features of type 2 diabetes (T2D). The effects include potentiation of insulin secretion, suppression of glucagon secretion...... effects. This review gives an overview of the clinical data on GLP-1R agonists that have been compared in head-to-head studies and focuses on relevant differences between the compounds. Highlighting these similarities and differences could be beneficial for physicians in choosing the best treatment......, slowing of gastric emptying and suppression of appetite. In circulation, GLP-1 has a half-life of approximately 2min due to rapid degradation by the enzyme dipeptidyl peptidase 4 (DPP-4). Because of this short half-life GLP-1 receptor (GLP-1R) agonists, resistant to degradation by DPP-4 have been...

High constitutive signaling of the ghrelin receptor--identification of a potent inverse agonist

DEFF Research Database (Denmark)

Holst, Birgitte; Cygankiewicz, Adam; Jensen, Tine Halkjaer

2003-01-01

Ghrelin is a GH-releasing peptide that also has an important role as an orexigenic hormone-stimulating food intake. By measuring inositol phosphate turnover or by using a reporter assay for transcriptional activity controlled by cAMP-responsive elements, the ghrelin receptor showed strong, ligand......-independent signaling in transfected COS-7 or human embryonic kidney 293 cells. Ghrelin and a number of the known nonpeptide GH secretagogues acted as agonists stimulating inositol phosphate turnover further. In contrast, the low potency ghrelin antagonist, [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-substance P was surprisingly...... found to be a high potency (EC50 = 5.2 nm) full inverse agonist as it decreased the constitutive signaling of the ghrelin receptor down to that observed in untransfected cells. The homologous motilin receptor functioned as a negative control as it did not display any sign of constitutive activity...

Receptivity to alcohol marketing predicts initiation of alcohol use.

Science.gov (United States)

Henriksen, Lisa; Feighery, Ellen C; Schleicher, Nina C; Fortmann, Stephen P

2008-01-01

This longitudinal study examined the influence of alcohol advertising and promotions on the initiation of alcohol use. A measure of receptivity to alcohol marketing was developed from research about tobacco marketing. Recall and recognition of alcohol brand names were also examined. Data were obtained from in-class surveys of sixth, seventh, and eighth graders at baseline and 12-month follow-up. Participants who were classified as never drinkers at baseline (n = 1,080) comprised the analysis sample. Logistic regression models examined the association of advertising receptivity at baseline with any alcohol use and current drinking at follow-up, adjusting for multiple risk factors, including peer alcohol use, school performance, risk taking, and demographics. At baseline, 29% of never drinkers either owned or wanted to use an alcohol branded promotional item (high receptivity), 12% students named the brand of their favorite alcohol ad (moderate receptivity), and 59% were not receptive to alcohol marketing. Approximately 29% of adolescents reported any alcohol use at follow-up; 13% reported drinking at least 1 or 2 days in the past month. Never drinkers who reported high receptivity to alcohol marketing at baseline were 77% more likely to initiate drinking by follow-up than those were not receptive. Smaller increases in the odds of alcohol use at follow-up were associated with better recall and recognition of alcohol brand names at baseline. Alcohol advertising and promotions are associated with the uptake of drinking. Prevention programs may reduce adolescents' receptivity to alcohol marketing by limiting their exposure to alcohol ads and promotions and by increasing their skepticism about the sponsors' marketing tactics.

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty

Directory of Open Access Journals (Sweden)

Jina Park

2017-03-01

Full Text Available PurposeGonadotropin-releasing hormone agonist (GnRHa is used as a therapeutic agent for central precocious puberty (CPP; however, increased obesity may subsequently occur. This study compared body mass index (BMI and insulin resistance during the first year of GnRHa treatment for CPP.MethodsPatient group included 83 girls (aged 7.0–8.9 years with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI] were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment.ResultsNo statistical difference in BMI z-score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P<0.001. In normal-weight subjects in the patient group, BMI z-score was significantly increased during GnRHa treatment (−0.1±0.7 vs. 0.1±0.8, P<0.001, whereas HOMA-IR and QUICKI exhibited no differences. In overweight subjects in the patient group; BMI z-score and HOMA-IR were not significantly different, whereas QUICKI was significantly decreased during GnRHa treatment (0.35±0.03 vs. 0.33±0.02, P=0.044.ConclusionGirls with CPP exhibited increased insulin resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z-scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z-scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

Microdose gonadotropin-releasing hormone agonist in the absence of exogenous gonadotropins is not sufficient to induce multiple follicle development.

Science.gov (United States)

Chung, Karine; Fogle, Robin; Bendikson, Kristin; Christenson, Kamilee; Paulson, Richard

2011-01-01

Because the effectiveness of the "microdose flare" stimulation protocol often is attributed to the dramatic endogenous gonadotropin release induced by the GnRH agonist, the aim of this study was to determine whether use of microdose GnRH agonist alone could induce multiple ovarian follicle development in normal responders. Based on these data, the duration of gonadotropin rise is approximately 24 to 48 hours and is too brief to sustain continued multiple follicle growth. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies

Directory of Open Access Journals (Sweden)

Lacroix A.

2000-01-01

Full Text Available Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ß-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

A review of recommendations for sequencing receptive and expressive language instruction.

Science.gov (United States)

Petursdottir, Anna Ingeborg; Carr, James E

2011-01-01

We review recommendations for sequencing instruction in receptive and expressive language objectives in early and intensive behavioral intervention (EIBI) programs. Several books recommend completing receptive protocols before introducing corresponding expressive protocols. However, this recommendation has little empirical support, and some evidence exists that the reverse sequence may be more efficient. Alternative recommendations include teaching receptive and expressive skills simultaneously (M. L. Sundberg & Partington, 1998) and building learning histories that lead to acquisition of receptive and expressive skills without direct instruction (Greer & Ross, 2008). Empirical support for these recommendations also is limited. Future research should assess the relative efficiency of receptive-before-expressive, expressive-before-receptive, and simultaneous training with children who have diagnoses of autism spectrum disorders. In addition, further evaluation is needed of the potential benefits of multiple-exemplar training and other variables that may influence the efficiency of receptive and expressive instruction.

Stigma development and receptivity in almond (Prunus dulcis).

Science.gov (United States)

Yi, Weiguang; Law, S Edward; McCoy, Dennis; Wetzstein, Hazel Y

2006-01-01

Fertilization is essential in almond production, and pollination can be limiting in production areas. This study investigated stigma receptivity under defined developmental stages to clarify the relationship between stigma morphology, pollen germination, tube growth and fruit set. Light and scanning electron microscopy were employed to examine stigma development at seven stages of flower development ranging from buds that were swollen to flowers in which petals were abscising. Flowers at different stages were hand pollinated and pollen germination and tube growth assessed. Artificial pollinations in the field were conducted to determine the effect of flower age on fruit set. Later stages of flower development exhibited greater stigma receptivity, i.e. higher percentages of pollen germination and more extensive tube growth occurred in older (those opened to the flat petal stage or exhibiting petal fall) than younger flowers. Enhanced stigma receptivity was associated with elongation of stigmatic papillae and increased amounts of stigmatic exudate that inundated papillae at later developmental stages. Field pollinations indicated that the stigma was still receptive and nut set was maintained in older flowers. Stigma receptivity in almond does not become optimal until flowers are past the fully open stage. The stigma is still receptive and fruit set is maintained in flowers even at the stage when petals are abscising. Strategies to enhance pollination and crop yield, including the timing and placement of honey bees, should consider the effectiveness of developmentally advanced flowers.

Integrated parallel reception, excitation, and shimming (iPRES).

Science.gov (United States)

Han, Hui; Song, Allen W; Truong, Trong-Kha

2013-07-01

To develop a new concept for a hardware platform that enables integrated parallel reception, excitation, and shimming. This concept uses a single coil array rather than separate arrays for parallel excitation/reception and B0 shimming. It relies on a novel design that allows a radiofrequency current (for excitation/reception) and a direct current (for B0 shimming) to coexist independently in the same coil. Proof-of-concept B0 shimming experiments were performed with a two-coil array in a phantom, whereas B0 shimming simulations were performed with a 48-coil array in the human brain. Our experiments show that individually optimized direct currents applied in each coil can reduce the B0 root-mean-square error by 62-81% and minimize distortions in echo-planar images. The simulations show that dynamic shimming with the 48-coil integrated parallel reception, excitation, and shimming array can reduce the B0 root-mean-square error in the prefrontal and temporal regions by 66-79% as compared with static second-order spherical harmonic shimming and by 12-23% as compared with dynamic shimming with a 48-coil conventional shim array. Our results demonstrate the feasibility of the integrated parallel reception, excitation, and shimming concept to perform parallel excitation/reception and B0 shimming with a unified coil system as well as its promise for in vivo applications. Copyright © 2013 Wiley Periodicals, Inc.

33 CFR 158.310 - Reception facilities: General.

Science.gov (United States)

2010-07-01

... order to pass the inspection under § 158.160, must— (1) Be a reception facility as defined under § 158... residue; (5) Be capable of receiving NLS residue from an oceangoing ship within 24 hours after notice by that ship of the need for reception facilities; and (6) Be capable of completing the transfer of NLS...

Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep--a magnetic resonance imaging study.

Science.gov (United States)

Nuruddin, Syed; Bruchhage, Muriel; Ropstad, Erik; Krogenæs, Anette; Evans, Neil P; Robinson, Jane E; Endestad, Tor; Westlye, Lars T; Madison, Cindee; Haraldsen, Ira Ronit Hebold

2013-10-01

In many species sexual dimorphisms in brain structures and functions have been documented. In ovine model, we have previously demonstrated that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) action increased sex-differences of executive emotional behavior. The structural substrate of this behavioral alteration however is unknown. In this magnetic resonance image (MRI) study on the same animals, we investigated the effects of GnRH agonist (GnRHa) treatment on the volume of total brain, hippocampus and amygdala. In total 41 brains (17 treated; 10 females and 7 males, and 24 controls; 11 females and 13 males) were included in the MRI study. Image acquisition was performed with 3-T MRI scanner. Segmentation of the amygdala and the hippocampus was done by manual tracing and total gray and white matter volumes were estimated by means of automated brain volume segmentation of the individual T2-weighted MRI volumes. Statistical comparisons were performed with general linear models. Highly significant GnRHa treatment effects were found on the volume of left and right amygdala, indicating larger amygdalae in treated animals. Significant sex differences were found for total gray matter and right amygdala, indicating larger volumes in male compared to female animals. Additionally, we observed a significant interaction between sex and treatment on left amygdala volume, indicating stronger effects of treatment in female compared to male animals. The effects of GnRHa treatment on amygdala volumes indicate that increasing GnRH concentration during puberty may have an important impact on normal brain development in mammals. These novel findings substantiate the need for further studies investigating potential neurobiological side effects of GnRHa treatment on the brains of young animals and humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hormonal regulation of phosphatidylcholine synthesis by reversible modulation of cytidylyltransferase.

OpenAIRE

Kelly, K L; Gutierrez, G; Martin, A

1988-01-01

The effect of both lipolytic and antilipolytic hormones on the turnover of phosphatidylcholine in freshly isolated rat adipocytes was investigated. Treatment of adipocytes with agonists such as glucagon or isoprenaline that stimulate lipolysis through a cyclic AMP-dependent mechanism caused an increase in the incorporation of [Me-3H]choline into phosphatidylcholine. Pulse-chase studies indicated that the stimulation was due to an increase in the conversion of choline into phosphatidylcholine,...

Changes in heart rate associated with contest outcome in agonistic encounters in lobsters.

Science.gov (United States)

Hernáindez-Falcón, Jesús; Basu, Alo C; Govindasamy, Siddhartan; Kravitz, Edward A

2005-03-01

Agonistic contests between lobsters housed together in a confined space progress through encounters of increasing intensity until a dominance relationship is established. Once this relationship is established, losing animals continually retreat from the advances of winners. These encounters are likely to consume much energy in both winning and losing animals. Therefore, one might expect involvement of many physiological systems before, during and after fights. Here, we report effects of agonistic encounters on cardiac frequency in winning and losing adult lobsters involved in dyadic interactions. The results show that: (i) small but significant increases in heart rate are observed upon chemical detection of a conspecific; (ii) during agonistic interactions, further increases in heart rate are seen; and (iii) ultimate winners exhibit greater increases in heart rate lasting longer periods of time compared to ultimate losers. Heart rate in winners remains elevated for at least 15 min after the contests have ended and animals have been returned to their home tanks. Reduced effects are seen in second and third pairings between familiar opponents. The sustained changes in heart rate that we observe in winning lobsters may result from hormonal modulation of cardiac function related to the change in social status brought about by contest outcome.

Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?

Science.gov (United States)

Irwin, Nigel; Gault, Victor; Flatt, Peter R

2010-09-01

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone. The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered. Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date. GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.

Adaptability and selectivity of human peroxisome proliferator-activated receptor (PPAR) pan agonists revealed from crystal structures

International Nuclear Information System (INIS)

Oyama, Takuji; Toyota, Kenji; Waku, Tsuyoshi; Hirakawa, Yuko; Nagasawa, Naoko; Kasuga, Jun-ichi; Hashimoto, Yuichi; Miyachi, Hiroyuki; Morikawa, Kosuke

2009-01-01

The structures of the ligand-binding domains (LBDs) of human peroxisome proliferator-activated receptors (PPARα, PPARγ and PPARδ) in complexes with a pan agonist, an α/δ dual agonist and a PPARδ-specific agonist were determined. The results explain how each ligand is recognized by the PPAR LBDs at an atomic level. Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family, which is defined as transcriptional factors that are activated by the binding of ligands to their ligand-binding domains (LBDs). Although the three PPAR subtypes display different tissue distribution patterns and distinct pharmacological profiles, they all are essentially related to fatty-acid and glucose metabolism. Since the PPARs share similar three-dimensional structures within the LBDs, synthetic ligands which simultaneously activate two or all of the PPARs could be potent candidates in terms of drugs for the treatment of abnormal metabolic homeostasis. The structures of several PPAR LBDs were determined in complex with synthetic ligands, derivatives of 3-(4-alkoxyphenyl)propanoic acid, which exhibit unique agonistic activities. The PPARα and PPARγ LBDs were complexed with the same pan agonist, TIPP-703, which activates all three PPARs and their crystal structures were determined. The two LBD–ligand complex structures revealed how the pan agonist is adapted to the similar, but significantly different, ligand-binding pockets of the PPARs. The structures of the PPARδ LBD in complex with an α/δ-selective ligand, TIPP-401, and with a related δ-specific ligand, TIPP-204, were also determined. The comparison between the two PPARδ complexes revealed how each ligand exhibits either a ‘dual selective’ or ‘single specific’ binding mode

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

Directory of Open Access Journals (Sweden)

Xin-Yuan Cao

2018-01-01

Full Text Available Triclosan (TCS, a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH, follicle-stimulating hormone (FSH and progesterone, and gonadotrophin-releasing hormone (GnRH mRNA with the lack of LH surge and elevation of prolactin (PRL. TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV and arcuate nucleus (ARC. Moreover, the estrogen (E2-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3 and thyroxine (T4 in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH and thyroid releasing hormone (TRH. In TCS mice, the treatment with Levothyroxine (L-T4 corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.

New Year’s reception

CERN Multimedia

2009-01-01

At a reception on 28 January, the CERN management presented their best wishes for 2009 to politicians and representatives of the administrations in the local area, and diplomats representing CERN’s Member States, Observer States and other countries.

The reception of Bollywood in Malaysia (1991-2012): a contextual study

OpenAIRE

Sreekumar, Rohini

2017-01-01

Bollywood films are increasingly drawing scholarly attention for their global appeal and reception. Transnational studies have examined the reception of Bollywood in Australia, Britain, Scotland, South Africa, Russia, the United States of America, Bangladesh and Nepal. However, academic work on the Southeast Asian reception of these films is scarcer. This research seeks to fill this gap by looking at the reception of Bollywood in Malaysia from 1991-2012. The thesis adopts a...

The effects of a slow release GnRH agonist implant on male rabbits

DEFF Research Database (Denmark)

Goericke-Pesch, Sandra Kathrin; Groeger, Gesa; Wehrend, Axel

2015-01-01

Surgical castration is done in male pet rabbits for reproduction control, to reduce inter-male aggression and to control hyper-sexuality, territory marking and aggression against humans. Alternatives to surgical castration are requested because of a relatively great anaesthetic risk in rabbits....... Long-term application of a GnRH agonist implant results in a fully reversible "hormonal" castration in male dogs, cats, boars and many other species. Therefore, the present study using New Zealand White hybrid and German Giant rabbits aimed to investigate the effects of a 4.7mg deslorelin implant...

Current Writing: Text and Reception in Southern Africa: Advanced ...

African Journals Online (AJOL)

Current Writing: Text and Reception in Southern Africa: Advanced Search. Journal Home > Current Writing: Text and Reception in Southern Africa: Advanced Search. Log in or Register to get access to full text downloads.

Negative cooperativity in binding of muscarinic receptor agonists and GDP as a measure of agonist efficacy.

Science.gov (United States)

Jakubík, J; Janíčková, H; El-Fakahany, E E; Doležal, V

2011-03-01

Conventional determination of agonist efficacy at G-protein coupled receptors is measured by stimulation of guanosine-5'-γ-thiotriphosphate (GTPγS) binding. We analysed the role of guanosine diphosphate (GDP) in the process of activation of the M₂ muscarinic acetylcholine receptor and provide evidence that negative cooperativity between agonist and GDP binding is an alternative measure of agonist efficacy. Filtration and scintillation proximity assays measured equilibrium binding as well as binding kinetics of [³⁵S]GTPγS and [³H]GDP to a mixture of G-proteins as well as individual classes of G-proteins upon binding of structurally different agonists to the M₂ muscarinic acetylcholine receptor. Agonists displayed biphasic competition curves with the antagonist [³H]-N-methylscopolamine. GTPγS (1 µM) changed the competition curves to monophasic with low affinity and 50 µM GDP produced a similar effect. Depletion of membrane-bound GDP increased the proportion of agonist high-affinity sites. Carbachol accelerated the dissociation of [³H]GDP from membranes. The inverse agonist N-methylscopolamine slowed GDP dissociation and GTPγS binding without changing affinity for GDP. Carbachol affected both GDP association with and dissociation from G(i/o) G-proteins but only its dissociation from G(s/olf) G-proteins. These findings suggest the existence of a low-affinity agonist-receptor conformation complexed with GDP-liganded G-protein. Also the negative cooperativity between GDP and agonist binding at the receptor/G-protein complex determines agonist efficacy. GDP binding reveals differences in action of agonists versus inverse agonists as well as differences in activation of G(i/o) versus G(s/olf) G-proteins that are not identified by conventional GTPγS binding. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Short-chain analogs of luteinizing hormone-releasing hormone containing cytotoxic moieties.

Science.gov (United States)

Janáky, T; Juhász, A; Rékási, Z; Serfözö, P; Pinski, J; Bokser, L; Srkalovic, G; Milovanovic, S; Redding, T W; Halmos, G

1992-11-01

Five hexapeptide and heptapeptide analogs of luteinizing hormone-releasing hormone (LH-RH) were synthesized for use as carriers for cytotoxic compounds. These short analogs were expected to enhance target selectivity of the antineoplastic agents linked to them. Native LH-RH-(3-9) and LH-RH-(4-9) containing D-lysine and D-ornithine at position 6 were amidated with ethylamine and acylated on the N terminus. The receptor-binding affinity of one hexapeptide carrier AJ-41 (Ac-Ser-Tyr-D-Lys-Leu-Arg-Pro-NH-Et) to human breast cancer cell membranes was similar to that of [D-Trp6]LH-RH. Alkylating nitrogen mustards (melphalan, Ac-melphalan), anthraquinone derivatives including anticancer antibiotic doxorubicin, antimetabolite (methotrexate), and cisplatin-like platinum complex were linked to these peptides through their omega-amino group at position 6. The hybrid molecules showed no LH-RH agonistic activity in vitro and in vivo but had nontypical antagonistic effects on pituitary cells in vitro at the doses tested. These analogs showed a wide range of receptor-binding affinities to rat pituitaries and cell membranes of human breast cancer and rat Dunning prostate cancer. Several of these conjugates exerted some cytotoxic effects on MCF-7 breast cancer cell line.

Amiodarone: Effects on thyroid function and the peripheral metabolism of the thyroid hormones

International Nuclear Information System (INIS)

Braverman, L.E.; Safran, M.; Bambini, G.; Pinchera, A.; Martino, E.

1985-01-01

In addition to the effects of Amiodarone on the peripheral metabolism of the thyroid hormones and on pituitary TSH secretion, a major complication of therapy is the relatively high frequency of iodide-induced thyroid dysfunction. The mean T 4 and T 3 concentration following Amiodarone application was measured in euthyroid, hypothyroid and hyperthyroid patients and in control patients with and without cardiac disorders. Furthermore, the serum TSH was determined in euthyroid Amiodarone-treated euthyroid patients. 131 I uptake was studied in patients with Amiodarone-associated thyrotoxicosis. The difficulties of the therapy of Amiodarone-induced hyper-thyroidism are outlined. Preliminary studied of the effect of Amiodarone and its analogues on the metabolism of thyroid hormones in the rat indicate that Amiodarone may act as a thyroid hormone agonist in the pituitary. (MG)

Morning Receptions in a Danish ECE Context

DEFF Research Database (Denmark)

Kornerup, Ida; Gravgaard, Mette Lykke

This paper focus on a special pedagogical context; morning receptions as a learning environment. The studies of mornings are part of a 3 year long research project in which different types of learning environments were investigated. Few studies have researched morning receptions in this perspecti...... even though pedagogues often emphasize that this particular pedagogical context have implications on the children’s wellbeing and learning possibilities throughout the day....

Comparison of Measures of E-cigarette Advertising Exposure and Receptivity.

Science.gov (United States)

Pokhrel, Pallav; Fagan, Pebbles; Herzog, Thaddeus A; Schmid, Simone; Kawamoto, Crissy T; Unger, Jennifer B

2017-10-01

We tested how various measures of e-cigarette advertising exposure and receptivity are related to each other and compare to each other in their associations with e-cigarette use susceptibility and behavior. Cross-sectional data were collected from young adult college students (N = 470; M age = 20.9, SD = 2.1; 65% women). Measures of e-cigarette advertising exposure/receptivity compared included a cued recall measure, measures of marketing receptivity, perceived ad exposure, liking of e-cigarette ads, and frequency of convenience store visit, which is considered a measure of point-of-sale ad exposure. The cued-recall measure was associated with e-cigarette use experimentation but not current e-cigarette use. Marketing receptivity was associated with current e-cigarette use but not e-cigarette use experimentation. Liking of e-cigarette ads was the only measure associated with e-cigarette use susceptibility. Frequency of convenience store visit was associated with current e-cigarette use but not e-cigarette use experimentation or susceptibility. Inclusion of multiple measures of marketing exposure and receptivity is recommended for regulatory research concerning e-cigarette marketing. Marketing receptivity and cued recall measures are strong correlates of current and ever e-cigarette use, respectively.

Comparative Functional Alanine Positional Scanning of the α-Melanocyte Stimulating Hormone and NDP-Melanocyte Stimulating Hormone Demonstrates Differential Structure-Activity Relationships at the Mouse Melanocortin Receptors.

Science.gov (United States)

Todorovic, Aleksandar; Ericson, Mark D; Palusak, Ryan D; Sorensen, Nicholas B; Wood, Michael S; Xiang, Zhimin; Haskell-Luevano, Carrie

2016-07-20

The melanocortin system has been implicated in the regulation of various physiological functions including melanogenesis, steroidogenesis, energy homeostasis, and feeding behavior. Five melanocortin receptors have been identified to date and belong to the family of G protein-coupled receptors (GPCR). Post-translational modification of the proopiomelanocortin (POMC) prohormone leads to the biosynthesis of the endogenous melanocortin agonists, including α-melanocyte stimulating hormone (α-MSH), β-MSH, γ-MSH, and adrenocorticotropic hormone (ACTH). All the melanocortin agonists derived from the POMC prohormone contain a His-Phe-Arg-Trp tetrapeptide sequence that has been implicated in eliciting the pharmacological responses at the melanocortin receptors. Herein, an alanine (Ala) positional scan is reported for the endogenous α-MSH ligand and the synthetic, more potent, NDP-MSH peptide (Ac-Ser(1)-Tyr(2)-Ser(3)-Nle(4)-Glu(5)-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-Lys(11)-Pro(12)-Val(13)-NH2) at the cloned mouse melanocortin receptors to test the assumption that the structure-activity relationships of one ligand would apply to the other. Several residues outside of the postulated pharmacophore altered potency at the melanocortin receptors, most notably the 1560-, 37-, and 15-fold potency loss when the Glu(5) position of α-MSH was substituted with Ala at the mMC1R, mMC3R, and mMC4R, respectively. Importantly, the altered potencies due to Ala substitutions in α-MSH did not necessarily correlate with equivalent Ala substitutions in NDP-MSH, indicating that structural modifications and corresponding biological activities in one of these melanocortin ligands may not be predictive for the other agonist.

Effects of melanocortin-4 receptor agonists and antagonists on expression of genes related to reproduction in spotted scat, Scatophagus argus.

Science.gov (United States)

Jiang, Dong-Neng; Li, Jian-Tao; Tao, Ya-Xiong; Chen, Hua-Pu; Deng, Si-Ping; Zhu, Chun-Hua; Li, Guang-Li

2017-05-01

Melanocortin-4 receptor (Mc4r) function related to reproduction in fish has not been extensively investigated. Here, we report on gene expression changes by real-time PCR following treatment with Mc4r agonists and antagonists in the spotted scat (Scatophagus argus). Using in vitro incubated hypothalamus, the Mc4r nonselective agonist NDP-MSH ([Nle 4 , D-Phe 7 ]-α-melanocyte stimulating hormone; 10 -6 M) and selective agonist THIQ (N-[(3R)-1, 2, 3, 4-Tetrahydroisoquinolinium-3-ylcarbonyl]- (1R)-1-(4-chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl) piperidin-1-yl]-2-oxoethylamine; 10 -7 M) significantly increased the expression of gnrh (Gonadotropin releasing hormone), while the Mc4r nonselective antagonist SHU9119 (Ac-Nle-[Asp-His-DPhe/DNal(2')-Arg-Trp-Lys]-NH2; 10 -6 M) and selective antagonist Ipsen 5i (compound 5i synthesized in Ipsen Research Laboratories; 10 -6 M) significantly inhibited gnrh expression after 3 h of incubation. In incubated pituitary tissue, NDP-MSH and THIQ significantly increased the expression of fshb (Follicle-stimulating hormone beta subunit) and lhb (Luteinizing hormone beta subunit), while SHU9119 and Ipsen 5i significantly decreased fshb and lhb expression after 3 h of incubation. During the in vivo experiment, THIQ (1 mg/kg bw) significantly increased gnrh expression in hypothalamic tissue, as well as the fshb and lhb expression in pituitary tissue 12 h after abdominal injection. Furthermore, Ipsen 5i (1 mg/kg bw) significantly inhibited gnrh expression in hypothalamic tissue, as well as fshb and lhb gene expression in pituitary tissue 12 h after abdominal injection. In summary, Mc4r singling appears to stimulate gnrh expression in the hypothalamus, thereby modulating the synthesis of Fsh and Lh in the pituitary. In addition, Mc4r also appears to directly regulate fshb and lhb levels in the pituitary in spotted scat. Our study suggests that Mc4r, through the hypothalamus and pituitary, participates in reproductive

Learning receptive fields using predictive feedback.

Science.gov (United States)

Jehee, Janneke F M; Rothkopf, Constantin; Beck, Jeffrey M; Ballard, Dana H

2006-01-01

Previously, it was suggested that feedback connections from higher- to lower-level areas carry predictions of lower-level neural activities, whereas feedforward connections carry the residual error between the predictions and the actual lower-level activities [Rao, R.P.N., Ballard, D.H., 1999. Nature Neuroscience 2, 79-87.]. A computational model implementing the hypothesis learned simple cell receptive fields when exposed to natural images. Here, we use predictive feedback to explain tuning properties in medial superior temporal area (MST). We implement the hypothesis using a new, biologically plausible, algorithm based on matching pursuit, which retains all the features of the previous implementation, including its ability to efficiently encode input. When presented with natural images, the model developed receptive field properties as found in primary visual cortex. In addition, when exposed to visual motion input resulting from movements through space, the model learned receptive field properties resembling those in MST. These results corroborate the idea that predictive feedback is a general principle used by the visual system to efficiently encode natural input.

Receptivity of Hypersonic Boundary Layers to Distributed Roughness and Acoustic Disturbances

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Balakumar, P.

2013-01-01

Boundary-layer receptivity and stability of Mach 6 flows over smooth and rough seven-degree half-angle sharp-tipped cones are numerically investigated. The receptivity of the boundary layer to slow acoustic disturbances, fast acoustic disturbances, and vortical disturbances is considered. The effects of three-dimensional isolated roughness on the receptivity and stability are also simulated. The results for the smooth cone show that the instability waves are generated in the leading edge region and that the boundary layer is much more receptive to slow acoustic waves than to the fast acoustic waves. Vortical disturbances also generate unstable second modes, however the receptivity coefficients are smaller than that of the slow acoustic wave. Distributed roughness elements located near the nose region decreased the receptivity of the second mode generated by the slow acoustic wave by a small amount. Roughness elements distributed across the continuous spectrum increased the receptivity of the second mode generated by the slow and fast acoustic waves and the vorticity wave. The largest increase occurred for the vorticity wave. Roughness elements distributed across the synchronization point did not change the receptivity of the second modes generated by the acoustic waves. The receptivity of the second mode generated by the vorticity wave increased in this case, but the increase is lower than that occurred with the roughness elements located across the continuous spectrum. The simulations with an isolated roughness element showed that the second mode waves generated by the acoustic disturbances are not influenced by the small roughness element. Due to the interaction, a three-dimensional wave is generated. However, the amplitude is orders of magnitude smaller than the two-dimensional wave.

Structural basis for constitutive activity and agonist-induced activation of the enteroendocrine fat sensor GPR119

DEFF Research Database (Denmark)

Engelstoft, Maja Storm; Norn, C; Pedersen, Maria Hauge

2014-01-01

BACKGROUND AND PURPOSE: GPR119 is a Gαs-coupled 7TM receptor activated by endogenous lipids such as oleoylethanolamide (OEA) and by the dietary triglyceride metabolite 2-monoacylglycerol. GPR119 stimulates enteroendocrine hormone and insulin secretion. But despite massive drug discovery efforts...... activation (AR231453 and OEA). Novel Rosetta-based receptor modelling was applied, using a composite template approach with segments from different X-ray structures and fully flexible ligand docking. KEY RESULTS: The increased signalling induced by increasing the cell surface expression of GPR119...... in the absence of agonist and the inhibitory effect of two synthetic inverse agonists demonstrated that GRP119 signals with a high degree of constitutive activity through the Gαs pathway. The mutational maps for AR231453 and OEA were very similar and, surprisingly, also similar to the mutational map for residues...

Role of emotional processing in depressive responses to sex-hormone manipulation: a pharmacological fMRI study

DEFF Research Database (Denmark)

Henningsson, S.; Madsen, Kristoffer Hougaard; Pinborg, A.

2015-01-01

resonance imaging (fMRI) to investigate if sex-steroid hormone manipulation with a gonadotropin-releasing hormone agonist (GnRHa) influences emotional processing. Fifty-six healthy women were investigated twice: at baseline (follicular phase of menstrual cycle) and 16 +/- 3 days post intervention. At both...... sessions, fMRI-scans during exposure to faces expressing fear, anger, happiness or no emotion, depressive symptom scores and estradiol levels were acquired. The fMRI analyses focused on regions of interest for emotional processing. As expected, GnRHa initially increased and subsequently reduced estradiol...

Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice

Science.gov (United States)

Silva, L.A.S.; Felix, F.B.; Araujo, J.M.D.; Souza, E.V.; Camargo, E.A.; Grespan, R.

2017-01-01

Arthritis is positively associated with the decline of sex hormones, especially estrogen. Tamoxifen (TMX) is a selective estrogen receptor modulator, possessing agonist or antagonistic activity in different tissues. Thus, the objective of this study was to investigate the effect of TMX on the zymosan-induced arthritis model. Female Swiss normal and ovariectomized (OVX) mice were divided into groups and treated for five days with TMX (0.3, 0.9 or 2.7 mg/kg) or 17-β-estradiol (E2, 50 µg/kg). On the fifth day, arthritis was induced and 4 h later, leukocyte migration into joint cavities was evaluated. The neutrophil migration in OVX animals, but not in normal mice, treated with TMX (all tested doses) was significantly decreased compared with mice that received the vehicle (P≤0.05). Similarly, this effect was also demonstrated in the E2-treated group. Therefore, the present study demonstrates that TMX presented agonist effects in inhibiting neutrophil migration and preventing arthritis progression in OVX mice. PMID:29160416

Broodstock management and hormonal manipulations of fish reproduction.

Science.gov (United States)

Mylonas, Constantinos C; Fostier, Alexis; Zanuy, Silvia

2010-02-01

Control of reproductive function in captivity is essential for the sustainability of commercial aquaculture production, and in many fishes it can be achieved by manipulating photoperiod, water temperature or spawning substrate. The fish reproductive cycle is separated in the growth (gametogenesis) and maturation phase (oocyte maturation and spermiation), both controlled by the reproductive hormones of the brain, pituitary and gonad. Although the growth phase of reproductive development is concluded in captivity in most fishes-the major exemption being the freshwater eel (Anguilla spp.), oocyte maturation (OM) and ovulation in females, and spermiation in males may require exogenous hormonal therapies. In some fishes, these hormonal manipulations are used only as a management tool to enhance the efficiency of egg production and facilitate hatchery operations, but in others exogenous hormones are the only way to produce fertilized eggs reliably. Hormonal manipulations of reproductive function in cultured fishes have focused on the use of either exogenous luteinizing hormone (LH) preparations that act directly at the level of the gonad, or synthetic agonists of gonadotropin-releasing hormone (GnRHa) that act at the level of the pituitary to induce release of the endogenous LH stores, which, in turn act at the level of the gonad to induce steroidogenesis and the process of OM and spermiation. After hormonal induction of maturation, broodstock should spawn spontaneously in their rearing enclosures, however, the natural breeding behavior followed by spontaneous spawning may be lost in aquaculture conditions. Therefore, for many species it is also necessary to employ artificial gamete collection and fertilization. Finally, a common question in regards to hormonal therapies is their effect on gamete quality, compared to naturally maturing or spawning broodfish. The main factors that may have significant consequences on gamete quality-mainly on eggs-and should be considered

Molecular determinants of juvenile hormone action as revealed by 3D QSAR analysis in Drosophila.

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Denisa Liszeková

Full Text Available BACKGROUND: Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH. While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. METHODOLOGY/PRINCIPAL FINDINGS: To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 A or longer than 13.5 A, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. CONCLUSIONS/SIGNIFICANCE: The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions.

The Comparative Reception of Darwinism: A Brief History

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Glick, Thomas F.

2010-01-01

The subfield of Darwin studies devoted to comparative reception coalesced around 1971 with the planning of a conference on the subject, at the University of Texas at Austin held in April 1972. The original focus was western Europe, Russia and the United States. Subsequently a spate of studies on the Italian reception added to the Eurocentric…

Discovery and cardioprotective effects of the first non-Peptide agonists of the G protein-coupled prokineticin receptor-1.

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Adeline Gasser

Full Text Available Prokineticins are angiogenic hormones that activate two G protein-coupled receptors: PKR1 and PKR2. PKR1 has emerged as a critical mediator of cardiovascular homeostasis and cardioprotection. Identification of non-peptide PKR1 agonists that contribute to myocardial repair and collateral vessel growth hold promises for treatment of heart diseases. Through a combination of in silico studies, medicinal chemistry, and pharmacological profiling approaches, we designed, synthesized, and characterized the first PKR1 agonists, demonstrating their cardioprotective activity against myocardial infarction (MI in mice. Based on high throughput docking protocol, 250,000 compounds were computationally screened for putative PKR1 agonistic activity, using a homology model, and 10 virtual hits were pharmacologically evaluated. One hit internalizes PKR1, increases calcium release and activates ERK and Akt kinases. Among the 30 derivatives of the hit compound, the most potent derivative, IS20, was confirmed for its selectivity and specificity through genetic gain- and loss-of-function of PKR1. Importantly, IS20 prevented cardiac lesion formation and improved cardiac function after MI in mice, promoting proliferation of cardiac progenitor cells and neovasculogenesis. The preclinical investigation of the first PKR1 agonists provides a novel approach to promote cardiac neovasculogenesis after MI.

Protein phosphorylation in isolated human adipocytes - Adrenergic control of the phosphorylation of hormone-sensitive lipase

International Nuclear Information System (INIS)

Smiley, R.M.; Paul, S.; Browning, M.D.; Leibel, R.L.; Hirsch, J.

1990-01-01

The effect of adrenergic agents on protein phosphorylation in human adipocytes was examined. Freshly isolated human fat cells were incubated with 32 PO 4 in order to label intracellular ATP, then treated with a variety of adrenergic and other pharmacologic agents. Treatment with the β-adrenergic agonist isoproterenol led to a significant increase in phosphate content of at least five protein bands (M r 52, 53, 63, 67, 84 kDa). The increase in phosphorylation was partially inhibited by the α-2 agonist clonidine. Epinephrine, a combined α and β agonist, was less effective at increasing phosphate content of the proteins than was isoproterenol. Neither insulin nor the α-1 agonist phenylephrine had any discernible effect on the pattern of protein phosphorylation. The 84 kDa phosphorylated peptide band appears to contain hormone-sensitive lipase, a key enzyme in the lipolytic pathway which is activated by phosphorylation. These results are somewhat different than previously reported results for rat adipocytes, and represent the first report of overall pattern and adrenergic modulation of protein phosphorylation in human adipocytes

Functional and molecular neuroimaging of menopause and hormone replacement therapy

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Erika eComasco

2014-12-01

Full Text Available The level of gonadal hormones to which the female brain is exposed considerably changes across the menopausal transition, which in turn, is likely to be of great relevance for neurodegenerative diseases and psychiatric disorders. However, the neurobiological consequences of these hormone fluctuations and of hormone replacement therapy in the menopause have only begun to be understood. This review summarizes the findings of thirty-four studies of human brain function, including functional magnetic resonance imaging, positron and single-photon computed emission tomography studies, in peri- and postmenopausal women treated with estrogen, or estrogen-progestagen replacement therapy. Seven studies using gonadotropin-releasing hormone agonist intervention as a model of hormonal withdrawal are also included. Cognitive paradigms are employed by the majority of studies evaluating the effect of unopposed estrogen or estrogen-progestagen treatment on peri- and postmenopausal women’s brain. In randomized-controlled trials, estrogen treatment enhances activation of fronto-cingulate regions during cognitive functioning, though in many cases no difference in cognitive performance was present. Progestagens seems to counteract the effects of estrogens. Findings on cognitive functioning during acute ovarian hormone withdrawal suggest a decrease in activation of the inferior frontal gyrus, thus essentially corroborating the findings in postmenopausal women. Studies of the cholinergic and serotonergic systems indicate these systems as biological mediators of hormonal influences on the brain. More, hormonal replacement appears to increase cerebral blood flow in cortical regions. On the other hand, studies on emotion processing in postmenopausal women are lacking. These results call for well-powered randomized-controlled multi-modal prospective neuroimaging studies as well as investigation on the related molecular mechanisms of effects of menopausal hormonal

No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.

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Demeestere, Isabelle; Brice, Pauline; Peccatori, Fedro A; Kentos, Alain; Dupuis, Jehan; Zachee, Pierre; Casasnovas, Olivier; Van Den Neste, Eric; Dechene, Julie; De Maertelaer, Viviane; Bron, Dominique; Englert, Yvon

2016-08-01

We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drug's benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma. © 2016 by American Society of Clinical Oncology.

Diagnosis of polycystic ovary disease in obese women with a 24-hour hormone profile after buserelin stimulation.

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Hagag, P; Ben-Shlomo, A; Herzianu, I; Weiss, M

2000-03-01

To evaluate the 24-hour hormone response to GnRH agonist stimulation in the diagnosis of polycystic ovary disease (PCOD) in obese women. Forty-three obese PCOD patients and 23 controls were randomized to 1 mg buserelin (BSRL) stimulation (PCOD group P-1, n = 31; control group C-1, n = 12) or 0.1 mg (PCOD group P-0.1, n = 12; control group C-0.1, n = 11). Whereas following 1 mg BSRL administration, serum levels of 17 hydroxyprogesterone (17OHP), delta 4 androstenedione, estradiol (E2) and luteinizing hormone increment (delta LH) as well as the delta LH/delta follicle stimulating hormone ratio were all higher in group P-1 than in group C-1 (P PCOD. The hormone response to BSRL administration is related to obesity, not to insulin resistance.

Pharmacologically Induced Sex Hormone Fluctuation Effects on Resting-State Functional Connectivity in a Risk Model for Depression

DEFF Research Database (Denmark)

Fisher, Patrick MacDonald; Larsen, Camilla Borgsted; Beliveau, Vincent

2017-01-01

Women are at relatively greater lifetime risk for depression than men. This elevated risk in women is partly due to heightened risk during time periods characterized by marked fluctuations in sex hormones, including postpartum and perimenopausal periods. How sex hormone fluctuations contribute...... to heightened risk is not fully understood but may involve intrinsic functional connectivity. We induced a biphasic ovarian sex hormone fluctuation using the gonadotropin-releasing hormone agonist (GnRHa) goserelin to determine, with a randomized placebo-controlled design, intervention effects on or Gn....... Considering the GnRHa group only, the emergence of depressive symptoms following intervention was positively associated with amygdala-right temporal cortex and negatively associated with hippocampus-cingulate rs-FC. A test for mediation suggested that rs-FC changes in these networks marginally mediated...

Development of a new comprehensive and reliable endometrial receptivity map (ER Map/ER Grade) based on RT-qPCR gene expression analysis.

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Enciso, M; Carrascosa, J P; Sarasa, J; Martínez-Ortiz, P A; Munné, S; Horcajadas, J A; Aizpurua, J

2018-02-01

Is it possible to determine the receptivity status of an endometrium by combined quantitative reverse transcription PCR (RT-qPCR) expression analysis of genes involved in endometrial proliferation and immunity? The new ER Map®/ER Grade® test can predict endometrial receptivity status by RT-qPCR using a new panel of genes involved in endometrial proliferation and the maternal immune response associated to embryonic implantation. The human endometrium reaches a receptive status adequate for embryonic implantation around Days 19-21 of the menstrual cycle. During this period, known as the window of implantation (WOI), the endometrium shows a specific gene expression profile suitable for endometrial function evaluation. The number of molecular diagnostic tools currently available to characterize this process is very limited. In this study, a new system for human endometrial receptivity evaluation was optimized and presented for the first time. ER Map®/ER Grade® validation was achieved on 312 endometrial samples including fertile women and patients undergoing fertility treatment between July 2014 and March 2016. Expression analyses of 184 genes involved in endometrial receptivity and immune response were performed. Samples were additionally tested with an independent endometrial receptivity test. A total of 96 fertile women and 120 assisted reproduction treatment (ART) patients participated in the study. Endometrial biopsy samples were obtained at LH + 2 and LH + 7 days in fertile subjects in a natural cycle and at the window of implantation (WOI) in patients in a hormone-replacement therapy (HRT) cycle. Total RNA was purified, quality-checked and reverse-transcribed. Gene expression was quantified by high-throughput RT-qPCR and statistically analyzed. Informative genes were selected and used to classify samples into four different groups of endometrial receptivity status. Significantly different gene expression levels were found in 85 out of 184 selected genes when

Measuring receptive collocational competence across proficiency levels

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Déogratias Nizonkiza

2015-12-01

Full Text Available The present study investigates, (i English as Foreign Language (EFL learners’ receptive collocational knowledge growth in relation to their linguistic proficiency level; (ii how much receptive collocational knowledge is acquired as proficiency develops; and (iii the extent to which receptive knowledge of collocations of EFL learners varies across word frequency bands. A proficiency measure and a collocation test were administered to English majors at the University of Burundi. Results of the study suggest that receptive collocational competence develops alongside EFL learners’ linguistic proficiency; which lends empirical support to Gyllstad (2007, 2009 and Author (2011 among others, who reported similar findings. Furthermore, EFL learners’ collocations growth seems to be quantifiable wherein both linguistic proficiency level and word frequency occupy a crucial role. While more gains in terms of collocations that EFL learners could potentially add as a result of change in proficiency are found at lower levels of proficiency; collocations of words from more frequent word bands seem to be mastered first, and more gains are found at more frequent word bands. These results confirm earlier findings on the non-linearity nature of vocabulary growth (cf. Meara 1996 and the fundamental role played by frequency in word knowledge for vocabulary in general (Nation 1983, 1990, Nation and Beglar 2007, which are extended here to collocations knowledge.

Evaluation of Computational Docking to Identify Pregnane X Receptor Agonists in the ToxCast Database

OpenAIRE

Kortagere, Sandhya; Krasowski, Matthew D.; Reschly, Erica J.; Venkatesh, Madhukumar; Mani, Sridhar; Ekins, Sean

2010-01-01

Background The pregnane X receptor (PXR) is a key transcriptional regulator of many genes [e.g., cytochrome P450s (CYP2C9, CYP3A4, CYP2B6), MDR1] involved in xenobiotic metabolism and excretion. Objectives As part of an evaluation of different approaches to predict compound affinity for nuclear hormone receptors, we used the molecular docking program GOLD and a hybrid scoring scheme based on similarity weighted GoldScores to predict potential PXR agonists in the ToxCast database of pesticides...

Developing Reception Competence in Children with a Mild Intellectual Disability

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Ana Koritnik

2015-06-01

Full Text Available The paper presents research paradigms which study factors that allow influencing the language development of children with mild intellectual disabilities to the greatest extent possible. Special attention is dedicated to the development of the reception competence with the use of reception didactics methods based on a relatively frequent use of less demanding non-language semiotic functions. The core of the paper presents results of an experimental case study (on a sample of five children with a mild intellectual disability over a one school year period, through which the reception competence in these children was developed with a systematic use of an adapted communication model of literary education as an experimental factor. The results have confirmed the initially set hypothesis about reception progress.

The Early Literary Reception of Ernest Hemingway in Iran

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Atefeh Ghasemnejad

2018-01-01

Full Text Available This essay investigates the dynamics that led to the literary reception of Ernest Hemingway before the Islamic Revolution in Iran. This article deploys reception studies as a branch of Comparative Literature with a focus upon conceptions of Siegbert Salomon Prawer and the practical method of George Asselineau to unearth the ideological, political, and historical milieu that embraced Hemingway’s literary fortune in Iran. This investigation, unprecedented in the study of Iranian literature, discusses how and why Hemingway was initially received in Iran. As such, the inception of literary fortune of Ernest Hemingway in Iran is examined by the contextual features, Persian literary taste, and the translator’s incentives that paved the way for this reception. This article also uncovers the reasons for the delay in the literary reception of Hemingway in Iran and discussed why some of Hemingway’s oeuvres enjoyed recognition while others were neglected by the Iranian readership.

Expressive and receptive language skills in preschool children from a socially disadvantaged area.

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Ryan, Ashling; Gibbon, Fiona E; O'shea, Aoife

2016-02-01

Evidence suggests that children present with receptive language skills that are equivalent to or more advanced than expressive language skills. This profile holds true for typical and delayed language development. This study aimed to determine if such a profile existed for preschool children from an area of social deprivation and to investigate if particular language skills influence any differences found between expressive and receptive skills. Data from 187 CELF P2 UK assessments conducted on preschool children from two socially disadvantaged areas in a city in southern Ireland. A significant difference was found between Receptive Language Index (RLI) and Expressive Language Index (ELI) scores with Receptive scores found to be lower than Expressive scores. The majority (78.6%) of participants had a lower Receptive Language than Expressive score (RLI ELI), with very few (3.2%) having the same Receptive and Expressive scores (RLI = ELI). Scores for the Concepts and Following Directions (receptive) sub-test were significantly lower than for the other receptive sub tests, while scores for the Expressive Vocabulary sub-test were significantly higher than for the other expressive sub tests. The finding of more advanced expressive than receptive language skills in socially deprived preschool children is previously unreported and clinically relevant for speech-language pathologists in identifying the needs of this population.

Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist or human chorionic gonadotropin. Live birth after frozen-thawed embryo replacement cycles

DEFF Research Database (Denmark)

Griesinger, Georg; Kolibianakis, E M; Papanikolaou, E G

2007-01-01

OBJECTIVE: To report the outcome of frozen-thawed embryo replacement cycles after GnRH-agonist triggering of final oocyte maturation in the collecting cycle with GnRH-antagonist. DESIGN: Prospective, observational, multicentric clinical study. SETTING: Tertiary university-affiliated IVF centers...... a total of 228 participants. Surplus embryos or oocytes at the pronuclear stage were cryopreserved in 53 patients after hCG administration and 32 patients after GnRH-agonist administration on the basis of patient choice, pronuclear/embryo availability, and local laws. INTERVENTION(S): Transfer of frozen......-thawed embryos. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): Thirty-one and 23 patients after administration of hCG and GnRH-agonist, respectively, started a frozen-embryo replacement cycle by September 2005, with 25 and 16 patients eventually undergoing at least one frozen-thawed ET. Live birth rate per...

Transcriptome analysis of endometrial tissues following GnRH agonist treatment in a mouse adenomyosis model

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Guo S

2017-03-01

Full Text Available Song Guo,1,* Xiaowei Lu,1,* Ruihuan Gu,2 Di Zhang,3 Yijuan Sun,2 Yun Feng1 1Department of Obstetrics and Gynecology, Reproductive Medicine Center, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Gynecology, Shanghai Ji Ai Genetics & In Vitro Fertilization Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Gynecology and Obstetrics, Jinan Military General Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Adenomyosis is a common, benign gynecological condition of the female reproductive tract characterized by heavy menstrual bleeding and dysmenorrhea. Gonadotropin-releasing hormone (GnRH agonists are one of the medications used in adenomyosis treatment; however, their underlying mechanisms are poorly understood. Moreover, it is difficult to obtain endometrial samples from women undergoing such treatment. To overcome this, we generated an adenomyosis mouse model, which we treated with an GnRH agonist to determine its effect on pregnancy outcomes. We also analyzed endometrial gene expression following GnRH agonist treatment to determine the mechanisms that may affect pregnancy outcome in individuals with adenomyosis.Methods: Neonatal female mice were divided into a control group, an untreated adenomyosis group, and an adenomyosis group treated with a GnRH agonist (n=6 each. The pregnancy outcome was observed and compared among the groups. Then, three randomly chosen transcriptomes from endometrial tissues from day 4 of pregnancy were analyzed between the adenomyosis group and the GnRH agonist treatment group by RNA sequencing and quantitative reverse transcription polymerase chain reaction (PCR.Results: The litter size was significantly smaller in the adenomyosis group than in the control group (7±0.28 vs 11±0.26; P<0.05. However, the average live litter

Hormonotherapy and chemotherapy in hormone refractory prostate cancer

International Nuclear Information System (INIS)

Droz, J.

2004-01-01

The median survival of patients with metastatic prostate cancer is 3 years, though it is only one year when the tumor is hormone refractory (HRPC). The number of possible problems is great, but the major one is pain. The number of therapeutics is also great. They have only palliative and symptomatic impact. Early hormone suppression in patients with advanced disease may have slight survival impact. Thus, a general scheme of management can be proposed, based on several principles: 1- Early hormone suppression is proposed is metastatic prostate cancer. Hormone suppression is castration or LH-RH agonist. 2- Powerful tools must be used to measure palliative impact: pain and analgesic scales, quality of life evaluation. PSA decrease may only be a surrogate of clinical response evaluation. 3- After first line hormone suppression, indication of further hormone therapy, chemotherapy and radio pharmaceutics is based only on symptomatic progression. It is not based on tumor progression as measured by PSA increase or metastasis evolution, because it is well established that, till now, treatment has only palliative effect. 4- Management of local problems (urinary obstruction, fracture, nerve compression) must be done depending on the situation. 4- Patients must be clearly informed of the palliative end-points, of the therapeutic tools, of the current side effects and goals of treatments. The strategy must be prospectively explained at the early beginning of treatment. Chemotherapy has become a standard treatment in HRPC because it has shown palliative improvement (Mitoxantrone studies), and more recently survival improvement (Docetaxel studies). However new drugs are under development. It will be focussed on drugs acting on EGF-receptor, endothelin-A, proteasome and V EGF. Practical management of HRPC will be discussed

Microdose GnRH Agonist Flare-Up versus Ultrashort GnRH Agonist Combined with Fixed GnRH Antagonist in Poor Responders of Assisted Reproductive Techniques Cycles.

Science.gov (United States)

Eftekhar, Maryam; Mohammadian, Farnaz; Yousefnejad, Fariba; Khani, Parisa

2013-01-01

This study compares the microdose flare-up protocol to the ultrashort gonadotropinreleasing hormone (GnRH) agonist flare combined with the fixed multidose GnRH antagonist protocol in poor responders undergoing ovarian stimulation. In this randomized clinical trial, 120 women who were candidates for assisted reproductive techniques (ART) and had histories of one or more failed in vitro fertilization (IVF) cycles with three or fewer retrieved oocytes were prospectively randomized into two groups. Group I (60 patients) received the microdose flare-up regimen and group II (60 patients) received the ultrashort GnRH agonist combined with fixed GnRH antagonist. There were no significant differences between the groups in the number of used gonadotropin ampoules (p=0.591), duration of stimulation (p=0.610), number of retrieved oocytes (p=0.802), fertilization rate (p=0.456), and the number of transferred embryos (p=0.954). The clinical pregnancy rates were statistically similar in group I (10%) compared with group II (13.3%, p=0.389). According to our results, there is no significant difference between these protocols for improving the ART outcome in poor responders. Additional prospective, randomized studies with more patients is necessary to determine the best protocol (Registration Number: IRCT201105096420N1).

An examination of the concept of driving point receptance

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Sheng, X.; He, Y.; Zhong, T.

2018-04-01

In the field of vibration, driving point receptance is a well-established and widely applied concept. However, as demonstrated in this paper, when a driving point receptance is calculated using the finite element (FE) method with solid elements, it does not converge as the FE mesh becomes finer, suggesting that there is a singularity. Hence, the concept of driving point receptance deserves a rigorous examination. In this paper, it is firstly shown that, for a point harmonic force applied on the surface of an elastic half-space, the Boussinesq formula can be applied to calculate the displacement amplitude of the surface if the response point is sufficiently close to the load. Secondly, by applying the Betti reciprocal theorem, it is shown that the displacement of an elastic body near a point harmonic force can be decomposed into two parts, with the first one being the displacement of an elastic half-space. This decomposition is useful, since it provides a solid basis for the introduction of a contact spring between a wheel and a rail in interaction. However, according to the Boussinesq formula, this decomposition also leads to the conclusion that a driving point receptance is infinite (singular), and would be undefinable. Nevertheless, driving point receptances have been calculated using different methods. Since the singularity identified in this paper was not appreciated, no account was given to the singularity in these calculations. Thus, the validity of these calculation methods must be examined. This constructs the third part of the paper. As the final development of the paper, the above decomposition is utilised to define and determine driving point receptances required for dealing with wheel/rail interactions.

Music, Brain Plasticity and the Resilience: the Pillars of New Receptive Therapy.

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Dukić, Helena

2018-04-01

This paper describes a new type of receptive music therapy which aims to build the patients' psychological resilience by increasing the levels of dopamine, serotonin and oxytocin in order to increase standard psychopharmacological treatment efficiency. Previous research concerning the musically induced production of the two neurotransmitters and a hormone is discussed and reviewed. Based upon the existent studies concerning the influence of music on dopamine, serotonin and oxytocin induction, a new design of specific music features for this purpose is proposed and elaborated upon. The music features are numerically described using Music Information Retrieval software in order to objectivise the otherwise intuitively chosen music elements such as event density (number of notes started in one second of time), tempo, harmonic rhythm (number of harmonies changes in one second), dynamics, key changes and roughness coefficient (level of sensory dissonance). Finally, the new concept of resilience enhancing therapy is proposed and defined using the music features described above.

Modulation of horizontal cell receptive fields in the light adapted goldfish retina

NARCIS (Netherlands)

Verweij, J.; Kamermans, M.; van den Aker, E. C.; Spekreijse, H.

1996-01-01

In the isolated goldfish retina, 700 nm background illumination increases the horizontal cell receptive field size, as measured with 565 nm slits of light, but decreases the receptive field size, when measured with 660 nm slits. These background-induced changes in receptive field size are absent

Hormonal predictors of women's extra-pair vs. in-pair sexual attraction in natural cycles: Implications for extended sexuality.

Science.gov (United States)

Grebe, Nicholas M; Emery Thompson, Melissa; Gangestad, Steven W

2016-02-01

In naturally cycling women, Roney and Simmons (2013) examined hormonal correlates of their desire for sexual contact. Estradiol was positively associated, and progesterone negatively associated, with self-reported desire. The current study extended these findings by examining, within a sample of 33 naturally cycling women involved in romantic relationships, hormonal correlates of sexual attraction to or interests in specific targets: women's own primary partner or men other than women's primary partner. Women's sexual interests and hormone (estradiol, progesterone, and testosterone) levels were assessed at two different time points. Whereas estradiol levels were associated with relatively greater extra-pair sexual interests than in-pair sexual interests, progesterone levels were associated with relatively greater in-pair sexual interests. Both hormones specifically predicted in-pair sexual desire, estradiol negatively and progesterone positively. These findings have implications for understanding the function of women's extended sexuality - their sexual proceptivity and receptivity outside the fertile phase, especially during the luteal phase. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward

DEFF Research Database (Denmark)

Macoveanu, Julian; Henningsson, Susanne; Pinborg, Anja

2016-01-01

's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo...... or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map...

Hormonal stimulation of the recovery of spermatogenesis following chemo- or radiotherapy

International Nuclear Information System (INIS)

Meistrich, M.L.

1998-01-01

Radiation and chemotherapeutic drugs produce prolonged depression of sperm counts in rodents and humans. Previously, three approaches have been developed in experimental animals that have had some success in preventing or reversing this toxicity. These approaches included pretreatment with hormones that suppress spermatogenesis, stimulation of stem cell number, and supplementation with testosterone. A different rationale for the ability of particular hormonal treatments to reverse prolonged azoospermia is presented in this review. In many cases prolonged azoospermia occurs even though the stem spermatogonia survive the toxic insult, but the differentiation of these spermatogonia to produce sperm fails. In the rat, the block appears to be at the differentiation of the A spermatogonia. Hormone treatments with testosterone or with GnRH agonists, which suppress intratesticular testosterone levels, relieve this block and result in the production of differentiating cells. When the hormone treatment is stopped the production of differentiating cells continues, mature sperm are produced, and fertility is restored. If a similar mechanism can be demonstrated to hold in humans, the fertility of men who have been rendered infertile by treatments for testicular and other cancers could be improved. (au)

The epileptogenic spectrum of opiate agonists.

Science.gov (United States)

Snead, O C; Bearden, L J

1982-11-01

The present authors gave mu, delta, kappa, epsilon and sigma opiate receptor agonists intracerebroventricularly to rats both singly and in combination while monitoring the electroencephalogram from cortical and depth electrodes. Dose-response curves were plotted with naloxone against the changes produced by each agonist, and the effect of a number of anticonvulsant drugs on agonist-induced seizures was ascertained. Each opiate agonist produced a different seizure pattern with a different naloxone dose-response curve and anticonvulsant profile. The order of convulsive potency was epsilon greater than delta greater than mu greater than sigma much greater than kappa. Petit mal-like seizure activity was unique to the delta agonist, leucine-enkephalin, while only the mu agonist, morphine produced generalized convulsive seizures. These experiments raise the possibility that opiate systems in the brain may be involved in the pathogenesis of a wide spectrum of seizure disorders.

Receptivity of Hypersonic Boundary Layers to Acoustic and Vortical Disturbances (Invited)

Science.gov (United States)

Balakumar, P.

2015-01-01

Boundary-layer receptivity to two-dimensional acoustic and vortical disturbances for hypersonic flows over two-dimensional and axi-symmetric geometries were numerically investigated. The role of bluntness, wall cooling, and pressure gradients on the receptivity and stability were analyzed and compared with the sharp nose cases. It was found that for flows over sharp nose geometries in adiabatic wall conditions the instability waves are generated in the leading-edge region and that the boundary layer is much more receptive to slow acoustic waves as compared to the fast waves. The computations confirmed the stabilizing effect of nose bluntness and the role of the entropy layer in the delay of boundary layer transition. The receptivity coefficients in flows over blunt bodies are orders of magnitude smaller than that for the sharp cone cases. Wall cooling stabilizes the first mode strongly and destabilizes the second mode. However, the receptivity coefficients are also much smaller compared to the adiabatic case. The adverse pressure gradients increased the unstable second mode regions.

Health Challenges in Refugee Reception: Dateline Europe 2016.

Science.gov (United States)

Blitz, Brad K; d'Angelo, Alessio; Kofman, Eleonore; Montagna, Nicola

2017-11-30

The arrival of more than one million migrants, many of them refugees, has proved a major test for the European Union. Although international relief and monitoring agencies have been critical of makeshift camps in Calais and Eidomeni where infectious disease and overcrowding present major health risks, few have examined the nature of the official reception system and its impact on health delivery. Drawing upon research findings from an Economic and Social Research Council (ESRC) funded project, this article considers the physical and mental health of asylum-seekers in transit and analyses how the closure of borders has engendered health risks for populations in recognised reception centres in Sicily and in Greece. Data gathered by means of a survey administered in Greece (300) and in Sicily (400), and complemented by in-depth interviews with migrants (45) and key informants (50) including representatives of government offices, humanitarian and relief agencies, NGOs and activist organisations, are presented to offer an analysis of the reception systems in the two frontline states. We note that medical provision varies significantly from one centre to another and that centre managers play a critical role in the transmission of vital information. A key finding is that, given such disparity, the criteria used by the UNHCR to grade health services reception do not address the substantive issue that prevent refugees from accessing health services, even when provided on site. Health provision is not as recorded in UNHCR reporting but rather there are critical gaps between provision, awareness, and access for refugees in reception systems in Sicily and in Greece. This article concludes that there is a great need for more information campaigns to direct refugees to essential services.

Predicting Receptive-Expressive Vocabulary Discrepancies in Preschool Children With Autism Spectrum Disorder.

Science.gov (United States)

McDaniel, Jena; Yoder, Paul; Woynaroski, Tiffany; Watson, Linda R

2018-05-15

Correlates of receptive-expressive vocabulary size discrepancies may provide insights into why language development in children with autism spectrum disorder (ASD) deviates from typical language development and ultimately improve intervention outcomes. We indexed receptive-expressive vocabulary size discrepancies of 65 initially preverbal children with ASD (20-48 months) to a comparison sample from the MacArthur-Bates Communicative Development Inventories Wordbank (Frank, Braginsky, Yurovsky, & Marchman, 2017) to quantify typicality. We then tested whether attention toward a speaker and oral motor performance predict typicality of the discrepancy 8 months later. Attention toward a speaker correlated positively with receptive-expressive vocabulary size discrepancy typicality. Imitative and nonimitative oral motor performance were not significant predictors of vocabulary size discrepancy typicality. Secondary analyses indicated that midpoint receptive vocabulary size mediated the association between initial attention toward a speaker and end point receptive-expressive vocabulary size discrepancy typicality. Findings support the hypothesis that variation in attention toward a speaker might partially explain receptive-expressive vocabulary size discrepancy magnitude in children with ASD. Results are consistent with an input-processing deficit explanation of language impairment in this clinical population. Future studies should test whether attention toward a speaker is malleable and causally related to receptive-expressive discrepancies in children with ASD.

Growth hormone response to guanfacine in boys with attention deficit hyperactivity disorder: a preliminary study.

Science.gov (United States)

Halperin, Jeffrey M; Newcorn, Jeffrey H; McKay, Kathleen E; Siever, Larry J; Sharma, Vanshdeep

2003-01-01

This preliminary study evaluated a method for assessing central noradrenergic function in children via the growth hormone response to a single dose of the alpha-2 adrenergic receptor agonist guanfacine and examined whether this measure distinguishes between attention deficit hyperactivity disorder (ADHD) boys with and without reading disabilities (RD). Plasma growth hormone was assessed before and after the oral administration of guanfacine and placebo in boys with ADHD who were divided into subgroups based on the presence (n = 3) or absence (n = 5) of RD. Guanfacine and placebo conditions did not differ at baseline, but peak growth hormone was significantly higher following guanfacine. The increase in growth hormone following guanfacine was significantly greater in boys without RD as compared to those with RD, with no overlap between the groups. Consistent with findings using peripheral measures of noradrenergic function, these preliminary data suggest that ADHD boys with and without RD may differ in central noradrenergic function.

Dietary modification of metabolic pathways via nuclear hormone receptors.

Science.gov (United States)

Caiozzi, Gianella; Wong, Brian S; Ricketts, Marie-Louise

2012-10-01

Nuclear hormone receptors (NHRs), as ligand-dependent transcription factors, have emerged as important mediators in the control of whole body metabolism. Because of the promiscuous nature of several members of this superfamily that have been found to bind ligand with lower affinity than the classical steroid NHRs, they consequently display a broader ligand selectivity. This promiscuous nature has facilitated various bioactive dietary components being able to act as agonist ligands for certain members of the NHR superfamily. By binding to these NHRs, bioactive dietary components are able to mediate changes in various metabolic pathways, including, glucose, cholesterol and triglyceride homeostasis among others. This review will provide a general overview of the nuclear hormone receptors that have been shown to be activated by dietary components. The physiological consequences of such receptor activation by these dietary components will then be discussed in more detail. Copyright © 2012 John Wiley & Sons, Ltd.

First-year university students’ receptive and productive use of academic vocabulary

Directory of Open Access Journals (Sweden)

Déogratias Nizonkiza

2016-05-01

Full Text Available The present study explores academic vocabulary knowledge, operationalised through the Academic Word List, among first-year higher education students. Both receptive and productive knowledge and the proportion between the two are examined. Results show that while receptive knowledge is readily acquired by first-year students, productive knowledge lags behind and remains problematic. This entails that receptive knowledge is much larger than productive knowledge, which confirms earlier indications that receptive vocabulary knowledge is larger than productive knowledge for both academic vocabulary (Zhou 2010 and general vocabulary (cf. Laufer 1998, Webb 2008, among others. Furthermore, results reveal that the ratio between receptive and productive knowledge is slightly above 50%, which lends empirical support to previous findings that the ratio between the two aspects of vocabulary knowledge can be anywhere between 50% and 80% (Milton 2009. This finding is extended here to academic vocabulary; complementing Zhou’s (2010 study that investigated the relationship between the two aspects of vocabulary knowledge without examining the ratio between them. On the basis of these results, approaches that could potentially contribute to fostering productive knowledge growth are discussed. Avenues worth exploring to gain further insight into the relationship between receptive and productive knowledge are also suggested.

The Past in the Future: Problems and Potentials of Historical Reception Studies.

Science.gov (United States)

Jensen, Klaus Bruhn

1993-01-01

Gives examples of how qualitative methodologies have been employed to study media reception in the present. Identifies some forms of evidence that can creatively fill the gaps in knowledge about media reception in the past. Argues that the field must develop databases documenting media reception, which may broaden the scope of audience research in…

Evaluation of partial beta-adrenoceptor agonist activity.

Science.gov (United States)

Lipworth, B J; Grove, A

1997-01-01

A partial beta-adrenoceptor (beta-AR) agonist will exhibit opposite agonist and antagonist activity depending on the prevailing degree of adrenergic tone or the presence of a beta-AR agonist with higher intrinsic activity. In vivo partial beta-AR agonist activity will be evident at rest with low endogenous adrenergic tone, as for example with chronotropicity (beta 1/beta 2), inotropicity (beta 1) or peripheral vasodilatation and finger tremor (beta 2). beta-AR blocking drugs which have partial agonist activity may exhibit a better therapeutic profile when used for hypertension because of maintained cardiac output without increased systemic vascular resistance, along with an improved lipid profile. In the presence of raised endogenous adrenergic tone such as exercise or an exogenous full agonist, beta-AR subtype antagonist activity will become evident in terms of effects on exercise induced heart rate (beta 1) and potassium (beta 2) responses. Reduction of exercise heart rate will occur to a lesser degree in the case of a beta-adrenoceptor blocker with partial beta 1-AR agonist activity compared with a beta-adrenoceptor blocker devoid of partial agonist activity. This may result in reduced therapeutic efficacy in the treatment of angina on effort when using beta-AR blocking drugs with partial beta 1-AR agonist activity. Effects on exercise hyperkalaemia are determined by the balance between beta 2-AR partial agonist activity and endogenous adrenergic activity. For predominantly beta 2-AR agonist such as salmeterol and salbutamol, potentiation of exercise hyperkalaemia occurs. For predominantly beta 2-AR antagonists such as carteolol, either potentiation or attenuation of exercise hyperkalaemia occurs at low and high doses respectively. beta 2-AR partial agonist activity may also be expressed as antagonism in the presence of an exogenous full agonist, as for example attenuation of fenoterol induced responses by salmeterol. Studies are required to investigate whether

Cost-efficacy analysis of hormonal treatments for advanced prostate cancer

Directory of Open Access Journals (Sweden)

Sergio Iannazzo

2008-09-01

Full Text Available Introduction: prostatic cancer is the second more frequent cancer in Italy (after lung cancer and is the third cancer-related death cause. Age is the principal risk factor and, given the ageing process undergoing in the Italian population, it seems clear that the public sanitary expenditure to treat the disease is bound to increase, arising the need to perform pharmacoeconomic evaluations of the therapeutic strategies available. Methods: we performed a cost/utility analysis, through a Markov model, of several hormonal therapies in patients with advanced prostate cancer who underwent radical prostatectomy, from the biochemical recurrence to death. Nine androgen suppression therapies were considered: orchiectomy, two nonsteroidal antiandrogens (NSAA, four luteinizing hormone-releasing hormone (LHRH agonists, cyproterone acetate and the association of a NSAA and a LHRH (BAT. In the simulation the androgen suppression therapies were started at the PSA recurrence and never stopped until death. The model used the Italian NHS prospective and a time horizon corresponding to patient’s lifetime. Drug costs were calculated for each therapy, considering the less costly brand. Results: all the considered therapies produced a life expectancy (LE of about 12 life years (LYs with a small variability ranging from 12.3 LYs for BAT (the most effective to 11.37 LYs for NSAA-flutamide (the least effective. Quality adjusted life expectancy ranged from 9.98 QALYs for BAT to 9.28 QALYs for NSAA-flutamide. The average cost per patient presented a more enhanced variability, from 12,538 Euro for orchiectomy to 59,496 Euro for NSAA-bicalutamide. Among all the alternatives orchiectomy resulted the most cost/effective alternative with a cost/utility ratio of about 1,300 Euro/QALY. In the LHRH-agonists class leuprorelin was the most cost/effective with about 2,200 Euro/QALY. A one-way sensitivity analysis showed a substantial stability of the results. Conclusions: BAT

What is so ‘classical’ about Classical Reception? Theories, Methodologies and Future Prospects

OpenAIRE

Anastasia Bakogianni

2016-01-01

This paper delivered at the University of Rio on 3rd June 2015 seeks to explore different approaches to the most fundamental questions in classical reception studies. What is classical reception? And more particularly what is so ‘classical’ about classical reception? It discusses current trends in theory and methodology via an analysis of two cinematic receptions of the ancient story of Electra; one that proclaims its debt to a classical text while the other masks its classical connections.

Empty sella syndrome associated with hormone deficiency in adults; Silla turca vacia asociada a disfuncion hormonal en adultos

Energy Technology Data Exchange (ETDEWEB)

Oleaga, L.; Paja, M.; Goni, F.; Grande, J.; Grande, D. [Hospital de Basurto. Bilbao (Spain); Merino, M. [Hospital General Yague (Spain); Delgado, A. [Hospital Marques de Valdecilla. Santander (Spain)

1999-07-01

The objective of this study was to correlate the magnetic resonance (MR) images in patients with hormone deficiencies with the clinical data and the hormonal status. We studied 11 cases ef empty sella with different peripheral pituitary deficiencies. Hormone levels were determined according to standard laboratory methods. All the patients underwent MR imaging. The studies were carried out with a 1 Tesla superconducting magnet, using the cranial cavity for transmission and reception. Segittal and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms), axial T2-weighted spin-echo sequences (TR/TE: 3,500/19/93 ms) and gadolinium-enhanced (=.2 cc/kg body weight) sagital and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms) were employed. Six of the patients presented partial or total hypopituitarism associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH); there was one case of panhypopituitarism without SIADH and four cases of primary hypothyroidism, there of which were associated with pituitary deficiency, MR imaging revealed five cases of partially empty sella with residual pituitary gland on the sella floor and six cases in which the sella was completely empty. This study also identified six cases of normally situated neurohypophysis, another four in which the neurohypophysis could not be identified and one case of ectopic neurohypophysis. MR imaging is the technique of choice in the study of abnormal hypothalamic-pituitary activity. Empty and partially empty sella should be included among the frequent causes of hypopituitarism, although there is no clear relationship between the degree of adenohypophyseal insufficiency and the degree of atrophy of this system as viewed in MR images. In some cases, this entity may be the radiological sign of a phase in the development of an autoimmune inflammatory process involving the pituitary gland. (Author) 16 refs.

Health Challenges in Refugee Reception: Dateline Europe 2016

Science.gov (United States)

Blitz, Brad K.; d’Angelo, Alessio; Kofman, Eleonore; Montagna, Nicola

2017-01-01

The arrival of more than one million migrants, many of them refugees, has proved a major test for the European Union. Although international relief and monitoring agencies have been critical of makeshift camps in Calais and Eidomeni where infectious disease and overcrowding present major health risks, few have examined the nature of the official reception system and its impact on health delivery. Drawing upon research findings from an Economic and Social Research Council (ESRC) funded project, this article considers the physical and mental health of asylum–seekers in transit and analyses how the closure of borders has engendered health risks for populations in recognised reception centres in Sicily and in Greece. Data gathered by means of a survey administered in Greece (300) and in Sicily (400), and complemented by in-depth interviews with migrants (45) and key informants (50) including representatives of government offices, humanitarian and relief agencies, NGOs and activist organisations, are presented to offer an analysis of the reception systems in the two frontline states. We note that medical provision varies significantly from one centre to another and that centre managers play a critical role in the transmission of vital information. A key finding is that, given such disparity, the criteria used by the UNHCR to grade health services reception do not address the substantive issue that prevent refugees from accessing health services, even when provided on site. Health provision is not as recorded in UNHCR reporting but rather there are critical gaps between provision, awareness, and access for refugees in reception systems in Sicily and in Greece. This article concludes that there is a great need for more information campaigns to direct refugees to essential services. PMID:29189766

Health Challenges in Refugee Reception: Dateline Europe 2016

Directory of Open Access Journals (Sweden)

Brad K. Blitz

2017-11-01

Full Text Available The arrival of more than one million migrants, many of them refugees, has proved a major test for the European Union. Although international relief and monitoring agencies have been critical of makeshift camps in Calais and Eidomeni where infectious disease and overcrowding present major health risks, few have examined the nature of the official reception system and its impact on health delivery. Drawing upon research findings from an Economic and Social Research Council (ESRC funded project, this article considers the physical and mental health of asylum–seekers in transit and analyses how the closure of borders has engendered health risks for populations in recognised reception centres in Sicily and in Greece. Data gathered by means of a survey administered in Greece (300 and in Sicily (400, and complemented by in-depth interviews with migrants (45 and key informants (50 including representatives of government offices, humanitarian and relief agencies, NGOs and activist organisations, are presented to offer an analysis of the reception systems in the two frontline states. We note that medical provision varies significantly from one centre to another and that centre managers play a critical role in the transmission of vital information. A key finding is that, given such disparity, the criteria used by the UNHCR to grade health services reception do not address the substantive issue that prevent refugees from accessing health services, even when provided on site. Health provision is not as recorded in UNHCR reporting but rather there are critical gaps between provision, awareness, and access for refugees in reception systems in Sicily and in Greece. This article concludes that there is a great need for more information campaigns to direct refugees to essential services.

Attention operates uniformly throughout the classical receptive field and the surround

Science.gov (United States)

Verhoef, Bram-Ernst; Maunsell, John HR

2016-01-01

Shifting attention among visual stimuli at different locations modulates neuronal responses in heterogeneous ways, depending on where those stimuli lie within the receptive fields of neurons. Yet how attention interacts with the receptive-field structure of cortical neurons remains unclear. We measured neuronal responses in area V4 while monkeys shifted their attention among stimuli placed in different locations within and around neuronal receptive fields. We found that attention interacts uniformly with the spatially-varying excitation and suppression associated with the receptive field. This interaction explained the large variability in attention modulation across neurons, and a non-additive relationship among stimulus selectivity, stimulus-induced suppression and attention modulation that has not been previously described. A spatially-tuned normalization model precisely accounted for all observed attention modulations and for the spatial summation properties of neurons. These results provide a unified account of spatial summation and attention-related modulation across both the classical receptive field and the surround. DOI: http://dx.doi.org/10.7554/eLife.17256.001 PMID:27547989

Nonlinear Hebbian Learning as a Unifying Principle in Receptive Field Formation.

Science.gov (United States)

Brito, Carlos S N; Gerstner, Wulfram

2016-09-01

The development of sensory receptive fields has been modeled in the past by a variety of models including normative models such as sparse coding or independent component analysis and bottom-up models such as spike-timing dependent plasticity or the Bienenstock-Cooper-Munro model of synaptic plasticity. Here we show that the above variety of approaches can all be unified into a single common principle, namely nonlinear Hebbian learning. When nonlinear Hebbian learning is applied to natural images, receptive field shapes were strongly constrained by the input statistics and preprocessing, but exhibited only modest variation across different choices of nonlinearities in neuron models or synaptic plasticity rules. Neither overcompleteness nor sparse network activity are necessary for the development of localized receptive fields. The analysis of alternative sensory modalities such as auditory models or V2 development lead to the same conclusions. In all examples, receptive fields can be predicted a priori by reformulating an abstract model as nonlinear Hebbian learning. Thus nonlinear Hebbian learning and natural statistics can account for many aspects of receptive field formation across models and sensory modalities.

Efficacy and Safety of GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus Treatment: Systematic Review

Directory of Open Access Journals (Sweden)

Ana Paula Martins

2016-04-01

Full Text Available Introduction: Glucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes mellitus that mimic the endogenous hormone glucagon-like peptide 1. Glucagon-like peptide 1 regulates glucose levels by stimulating glucose-dependent insulin secretion, suppressing glucagon secretion, delayed gastric emptying and promoting satiety. The individualized treatment of type 2 diabetes mellitus, using various glucagon--like peptide receptor agonists, has recently been described and the interest related to these drugs continues to grow. Objectives: To review the efficacy and safety of glucagon-like peptide 1 agonists in patients with inadequately controlled type 2 diabetes mellitus on metformin alone, highlighting their added value in therapeutic use comparatively to second line oral therapies used in type 2 diabetes mellitus. Methods: Studies were obtained from electronic searches of The Cochrane Library and PubMed. Randomized controlled trials were selected if they were at least 8 weeks in duration; compared a glucagon-like peptide 1 analogue with an oral anti-diabetic agent in patients experiencing inadequate glycemic control with metformin monotherapy; and reported hemoglobin A1c data in non-pregnant adults with type 2 diabetes mellitus. Results: Of 72 potentially relevant articles identified, 23 were retrieved for detailed evaluation and 10 met the inclusion criteria. The majority of glucagon-like peptide 1 agonists showed equivalent or superior efficacy than most active comparators for reducing hemoglobin A1c, with a greater proportion of patients achieving hemoglobin A1c <7%. Glucagon-like peptide 1 agonists also showed extra-glycemic effects such as weight loss and the reduction of important cardiovascular parameters. Side effects included gastrointestinal complications, mainly nausea, vomiting and diarrhea. The incidence of hypoglycemia was less common for this class of agents. Conclusion: Glucagon-like peptide 1

What is so ‘classical’ about Classical Reception? Theories, Methodologies and Future Prospects

Directory of Open Access Journals (Sweden)

Anastasia Bakogianni

2016-06-01

Full Text Available This paper delivered at the University of Rio on 3rd June 2015 seeks to explore different approaches to the most fundamental questions in classical reception studies. What is classical reception? And more particularly what is so ‘classical’ about classical reception? It discusses current trends in theory and methodology via an analysis of two cinematic receptions of the ancient story of Electra; one that proclaims its debt to a classical text while the other masks its classical connections.

Advertising Receptivity and Youth Initiation of Smokeless Tobacco.

Science.gov (United States)

Timberlake, David S

2016-07-28

Cross-sectional data suggests that adolescents' receptivity to the advertising of smokeless tobacco is correlated with use of chewing tobacco or snuff. Lack of longitudinal data has precluded determination of whether advertising receptivity precedes or follows initiation of smokeless tobacco. The objective of this study was to test for the association between advertising receptivity and subsequent initiation of smokeless tobacco among adolescent males. Adolescent males from the 1993-1999 Teen Longitudinal California Tobacco Survey were selected at the baseline survey for never having used smokeless tobacco. Separate longitudinal analyses corresponded to two dependent variables, ever use of smokeless tobacco (1993-1996; N = 1,388) and use on 20 or more occasions (1993-1999; N = 1,014). Models were adjusted for demographic variables, risk factors for smokeless tobacco use, and exposure to users of smokeless tobacco. Advertising receptivity at baseline was predictive of ever use by late adolescence (RR(95% CI) = 2.0 (1.5, 2.8)) and regular use by young adulthood (RR(95% CI) = 3.7 (2.1, 6.7)) in models that were adjusted for covariates. Conclusions/ Importance: The findings challenge the tobacco industry's assertion that tobacco marketing does not impact youth initiation. This is particularly relevant to tobacco control in the United States because the 2009 Tobacco Control Act places fewer restrictions on smokeless tobacco products compared to cigarettes.

Longitudinal analysis of receptive vocabulary growth in young Spanish English-speaking children from migrant families.

Science.gov (United States)

Jackson, Carla Wood; Schatschneider, Christopher; Leacox, Lindsey

2014-01-01

The authors of this study described developmental trajectories and predicted kindergarten performance of Spanish and English receptive vocabulary acquisition of young Latino/a English language learners (ELLs) from socioeconomically disadvantaged migrant families. In addition, the authors examined the extent to which gender and individual initial performance in Spanish predict receptive vocabulary performance and growth rate. The authors used hierarchical linear modeling of 64 children's receptive vocabulary performance to generate growth trajectories, predict performance at school entry, and examine potential predictors of rate of growth. The timing of testing varied across children. The ELLs (prekindergarten to 2nd grade) participated in 2-5 testing sessions, each 6-12 months apart. The ELLs' average predicted standard score on an English receptive vocabulary at kindergarten was nearly 2 SDs below the mean for monolingual peers. Significant growth in the ELLs' receptive vocabulary was observed between preschool and 2nd grade, indicating that the ELLs were slowly closing the receptive vocabulary gap, although their average score remained below the standard score mean for age-matched monolingual peers. The ELLs demonstrated a significant decrease in Spanish receptive vocabulary standard scores over time. Initial Spanish receptive vocabulary was a significant predictor of growth in English receptive vocabulary. High initial Spanish receptive vocabulary was associated with greater growth in English receptive vocabulary and decelerated growth in Spanish receptive vocabulary. Gender was not a significant predictor of growth in either English or Spanish receptive vocabulary. ELLs from low socioeconomic backgrounds may be expected to perform lower in English compared with their monolingual English peers in kindergarten. Performance in Spanish at school entry may be useful in identifying children who require more intensive instructional support for English vocabulary

Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

Science.gov (United States)

Johnson, Megan; Vitacco, Michael J; Shirtcliff, Elizabeth A

2018-03-01

The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

Incretin hormones as immunomodulators of atherosclerosis

Directory of Open Access Journals (Sweden)

Nuria eAlonso

2012-09-01

Full Text Available Atherosclerosis results from endothelial cell dysfunction and inflammatory processes affecting both macro-and microvasculature which are involved in vascular diabetic complications. Glucagon-like peptide 1 (GLP-1 is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally as opposed to intravenously and it retains its insulinotropic activity in patients with type 2 diabetes mellitus (T2D. GLP-1 based therapies, such as GLP-1 receptor (R agonists and inhibitors of dipeptidyl peptidase 4 (DPP-4, an enzyme that degrades endogenous GLP-1 are routinely used to treat patients with T2D. Recent experimental model studies have established that GLP-1R mRNA is widely expressed in several immune cells. Moreover, its activation contributes to the regulation of both thymocyte and peripheral T cells proliferation and is involved in the maintenance of peripheral regulatory T cells. GLP-1 R is also expressed in endothelial and smooth muscle cells. The effect of incretin hormones on atherosclerogenesis have recently been studied in animal models of apolipoprotein E-deficient mice (apo E-/-. These studies have demonstrated that treatment with incretin hormones or related compounds suppresses the progression of atherosclerosis and macrophage infiltration in the arterial wall as well as a marked anti-oxidative and anti-inflammatory effect on endothelial cells. This effect may have a major impact on the attenuation of atherosclerosis and may help in the design of new therapies for cardiovascular disease in patients with type 2 diabetes.

Pharmacological characterization of 30 human melanocortin-4 receptor polymorphisms with the endogenous proopiomelanocortin-derived agonists, synthetic agonists, and the endogenous agouti-related protein antagonist.

Science.gov (United States)

Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L; Litherland, Sally A; Haskell-Luevano, Carrie

2010-06-08

The melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic biomarker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and nonobese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [alpha-, beta-, and gamma(2)-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-dPhe-Arg-Trp-NH(2) (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219 V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F, and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface

Sparse coding can predict primary visual cortex receptive field changes induced by abnormal visual input.

Science.gov (United States)

Hunt, Jonathan J; Dayan, Peter; Goodhill, Geoffrey J

2013-01-01

Receptive fields acquired through unsupervised learning of sparse representations of natural scenes have similar properties to primary visual cortex (V1) simple cell receptive fields. However, what drives in vivo development of receptive fields remains controversial. The strongest evidence for the importance of sensory experience in visual development comes from receptive field changes in animals reared with abnormal visual input. However, most sparse coding accounts have considered only normal visual input and the development of monocular receptive fields. Here, we applied three sparse coding models to binocular receptive field development across six abnormal rearing conditions. In every condition, the changes in receptive field properties previously observed experimentally were matched to a similar and highly faithful degree by all the models, suggesting that early sensory development can indeed be understood in terms of an impetus towards sparsity. As previously predicted in the literature, we found that asymmetries in inter-ocular correlation across orientations lead to orientation-specific binocular receptive fields. Finally we used our models to design a novel stimulus that, if present during rearing, is predicted by the sparsity principle to lead robustly to radically abnormal receptive fields.

Absorption and metabolization of sex hormones and their transformation into contraceptive technologies: the paths taken by medical thought in Brazil.

Science.gov (United States)

Bonan, Claudia; Teixeira, Luiz Antonio; Nakano, Andreza Rodrigues

2017-01-01

The article analyses knowledge assimilation and the development of clinical and research practices relating to sex hormones among Brazilian gynaecologists. It discusses the paths taken by medical thought from the reception of the hormones to their transformation into contraceptives. Our objective is to comprehend styles of introducing and disseminating medical technologies in the area of reproductive health in Brazil. It uses methods of historical analysis and takes as its source the Anais Brasileiros de Ginecologia, a journal published between 1936 and 1970. From the outset, the accompaniment of scientific breakthroughs in relation to sex hormones and their use to treat diverse female illnesses played a key role in the rapid medical acceptance of hormonal contraception. Scientific and technical questions (side effects, dosages) and the demographic issue formed part of the majority of the debates. Objections from the Catholic Church were considered but did not set the agenda of medical thought on contraceptives. The quest to consolidate gynaecology as a scientific, modern and cosmopolitan area of expertise, along with sanitary and demographic motives that allowed contraceptives to be classed as ethical drugs, are identified as processes underlying the assimilation and metabolization of sex hormones as hormonal contraceptives.

Receptive fields selection for binary feature description.

Science.gov (United States)

Fan, Bin; Kong, Qingqun; Trzcinski, Tomasz; Wang, Zhiheng; Pan, Chunhong; Fua, Pascal

2014-06-01

Feature description for local image patch is widely used in computer vision. While the conventional way to design local descriptor is based on expert experience and knowledge, learning-based methods for designing local descriptor become more and more popular because of their good performance and data-driven property. This paper proposes a novel data-driven method for designing binary feature descriptor, which we call receptive fields descriptor (RFD). Technically, RFD is constructed by thresholding responses of a set of receptive fields, which are selected from a large number of candidates according to their distinctiveness and correlations in a greedy way. Using two different kinds of receptive fields (namely rectangular pooling area and Gaussian pooling area) for selection, we obtain two binary descriptors RFDR and RFDG .accordingly. Image matching experiments on the well-known patch data set and Oxford data set demonstrate that RFD significantly outperforms the state-of-the-art binary descriptors, and is comparable with the best float-valued descriptors at a fraction of processing time. Finally, experiments on object recognition tasks confirm that both RFDR and RFDG successfully bridge the performance gap between binary descriptors and their floating-point competitors.

Problems of generation and reception of gravitational waves

International Nuclear Information System (INIS)

Pisarev, A.F.

1975-01-01

The present day status of the problems of gravitation, wave radiation and reception is surveyed. The physical presentation and mathematical description of the processes of radiation, propagation and interaction of gravitation waves with matter and the electromagnetic field are given. The experiments on the search for gravitation waves of astophysical nature are analysed. The laboratory and cosmic sources of these waves and the methods of their reception are described. Special attention is drawn to the analysis of the proposals to perform a complete laboratory gravitation wave experiment

Nonlinear Hebbian Learning as a Unifying Principle in Receptive Field Formation.

Directory of Open Access Journals (Sweden)

Carlos S N Brito

2016-09-01

Full Text Available The development of sensory receptive fields has been modeled in the past by a variety of models including normative models such as sparse coding or independent component analysis and bottom-up models such as spike-timing dependent plasticity or the Bienenstock-Cooper-Munro model of synaptic plasticity. Here we show that the above variety of approaches can all be unified into a single common principle, namely nonlinear Hebbian learning. When nonlinear Hebbian learning is applied to natural images, receptive field shapes were strongly constrained by the input statistics and preprocessing, but exhibited only modest variation across different choices of nonlinearities in neuron models or synaptic plasticity rules. Neither overcompleteness nor sparse network activity are necessary for the development of localized receptive fields. The analysis of alternative sensory modalities such as auditory models or V2 development lead to the same conclusions. In all examples, receptive fields can be predicted a priori by reformulating an abstract model as nonlinear Hebbian learning. Thus nonlinear Hebbian learning and natural statistics can account for many aspects of receptive field formation across models and sensory modalities.

The Foucault-Habermas Debate: the Reflexive and Receptive Aspects of Critique

DEFF Research Database (Denmark)

Hansen, Ejvind

2005-01-01

In this paper I discuss the relationship between two different approaches to critical theory – the reflective and the receptive approaches. I show how it can be fruitful to discuss the relationship between Habermas and Foucault through this distinction. My point is that whereas Habermas focusses...... on critique as a reflexive activity, Foucault mainly focusses on the receptive conditions for critique to be possible. I argue further that Foucault focusses on the receptive aspects of critique, the quest for universality is not as pressing as it is in Habermas’ approach, because problematizing critique can...

Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

Directory of Open Access Journals (Sweden)

Ji Woo Lee

2014-09-01

Full Text Available PurposeLong-acting gonadotropin-releasing hormone agonists (GnRHa are commonly used to treat central precocious puberty (CPP in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects.MethodsThis retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate.ResultsSix serious side effects (0.9% were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621. Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy.ConclusionSterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

Deaf Students' Receptive and Expressive American Sign Language Skills: Comparisons and Relations

Science.gov (United States)

Beal-Alvarez, Jennifer S.

2014-01-01

This article presents receptive and expressive American Sign Language skills of 85 students, 6 through 22 years of age at a residential school for the deaf using the American Sign Language Receptive Skills Test and the Ozcaliskan Motion Stimuli. Results are presented by ages and indicate that students' receptive skills increased with age and…

[Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation].

Science.gov (United States)

Schally, Andrew V; Gual, Carlos

2002-01-01

Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

The Receptive Side of Teaching

Science.gov (United States)

Hruska, Barbara

2008-01-01

When observing teachers in action, one is likely to witness explaining, modeling, managing, guiding, and encouraging. These expressive behaviors constitute a directive force moving outward from teacher to students. Though less visible to an outside observer, teaching also requires receptive skills, the ability to take in information by being fully…

Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure.

Science.gov (United States)

Chen, Rui; Wan, Jing; Song, Jing; Qian, Yan; Liu, Yong; Gu, Shuiming

2017-12-01

Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy. This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay. A large library of structurally diverse, drug-like natural products was compiled, from which those with unsatisfactory pharmacokinetic profile and/or structurally redundant compounds were excluded. The binding mode of remaining candidates to PPARγ ligand-binding domain (LBD) was computationally modelled using molecular docking and their relative binding potency was ranked by an empirical scoring scheme. Consequently, eight commercially available hits with top scores were selected and their biological activity was determined using a cell-based reporter-gene assay. Four natural product compounds, namely ZINC13408172, ZINC4292805, ZINC44179 and ZINC901461, were identified to have high or moderate agonistic potency against human PPARγ with EC 50 values of 0.084, 2.1, 0.35 and 5.6 μM, respectively, which are comparable to or even better than that of the approved PPARγ full agonists pioglitazone (EC 50  =   0.16 μM) and rosiglitazone (EC 50  =   0.034 μM). Hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PPARγ LBD domain with these agonist ligands, while few hydrogen bonds, salt bridges and/or π-π stacking at the complex interfaces confer selectivity and specificity for the domain-agonist recognition. The integrated in vitro-in silico screening strategy can be successfully applied to rational discovery of

Pharmacological Characterization of 30 Human Melanocortin-4 Receptor Polymorphisms with the Endogenous Proopiomelanocortin Derived Agonists, Synthetic Agonists, and the Endogenous Agouti-Related Protein (AGRP) Antagonist

Science.gov (United States)

Xiang, Zhimin; Proneth, Bettina; Dirain, Marvin L.; Litherland, Sally A.; Haskell-Luevano, Carrie

2010-01-01

The melanocortin-4 receptor (MC4R) is a G-protein coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic bio marker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and non-obese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [α-, β, γ2-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface expression by flow

The gonadotropin-releasing hormone antagonist protocol--the protocol of choice for the polycystic ovary syndrome patient undergoing controlled ovarian stimulation

DEFF Research Database (Denmark)

Kol, Shahar; Homburg, Roy; Alsbjerg, Birgit

2012-01-01

Polycystic ovary syndrome (PCOS) patients are prone to develop ovarian hyperstimulation syndrome (OHSS), a condition which can be minimized or completely eliminated by the use of a gonadotropin-releasing hormone agonist (GnRHa) trigger. In this commentary paper, we maintain that the gonadotropin-...... ongoing pregnancy rates in the subsequent frozen-thawed transfer cycles....

Developmental Stages in Receptive Grammar Acquisition: A Processability Theory Account

Science.gov (United States)

Buyl, Aafke; Housen, Alex

2015-01-01

This study takes a new look at the topic of developmental stages in the second language (L2) acquisition of morphosyntax by analysing receptive learner data, a language mode that has hitherto received very little attention within this strand of research (for a recent and rare study, see Spinner, 2013). Looking at both the receptive and productive…

Effect of ghrelin receptor agonist and antagonist on the activity of arcuate nucleus tyrosine hydroxylase containing neurons in C57BL/6 male mice exposed to normal or high fat diet

Czech Academy of Sciences Publication Activity Database

Pirník, Z.; Majerčíková, Z.; Holubová, Martina; Pirník, R.; Železná, Blanka; Maletínská, Lenka; Kiss, A.

2014-01-01

Roč. 65, č. 4 (2014), s. 477-486 ISSN 0867-5910 Institutional support: RVO:61388963 Keywords : growth hormone secretagogue receptor * ghrelin receptor agonist * ghrelin receptor antagonist * high fat diet * tyrosine hydroxylase * arcuate nucleus * food intake Subject RIV: CE - Biochemistry Impact factor: 2.386, year: 2014

Regulation regarding the reception of the construction works and the corresponding installations in Romania

Directory of Open Access Journals (Sweden)

Simona Chirică

2017-12-01

Full Text Available The new Regulation regarding the reception of construction works and corresponding installations, approved by Government's Decision no. 347/2017 (“Regulation 2017” has general applicability for all construction works for which there is an obligation to obtain a building permit. Regulation 2017 brings significant changes and clarifications expected by the real estate sector regarding: (i the composition of the commissions involved in the reception procedure, (ii the role of the site supervisor who thus gains significant participation in the reception procedure, and (iii the participation of the public authorities' representatives at the reception, having the veto right on the decision of the reception commission upon the completion of the construction works. Another element of novelty brought by Regulation 2017 is the possibility to do the reception upon the completion of the construction works, respectively the final reception for parts / objectives / sectors of or from the building, if they are distinct/ independent from a physical and functional point of view. Thus, the new regulation facilitates the procedure of authorizing investment objectives and the costs of the process. The partial reception is another innovation brought by the Regulation 2017 in support of the investor, who can thus take over a part of the construction, at a certain stage, and obtain its registration with the Land Book.

Communication from Goods Reception services

CERN Multimedia

2007-01-01

Members of the personnel are invited to take note that only parcels corresponding to official orders or contracts will be handled at CERN. Individuals are not authorised to have private merchandise delivered to them at CERN and private deliveries will not be accepted by the Goods Reception services. Thank you for your understanding.

Chimeric NDP-MSH and MTII melanocortin peptides with agouti-related protein (AGRP) Arg-Phe-Phe amino acids possess agonist melanocortin receptor activity.

Science.gov (United States)

Joseph, Christine G; Wilczynski, Andrzej; Holder, Jerry R; Xiang, Zhimin; Bauzo, Rayna M; Scott, Joseph W; Haskell-Luevano, Carrie

2003-12-01

Agouti-related protein (AGRP) is one of only two known endogenous antagonists of G-protein coupled receptors (GPCRs). Specifically, AGRP antagonizes the brain melanocortin-3 and -4 receptors involved in energy homeostasis, regulation of feeding behavior, and obesity. Alpha-melanocyte stimulating hormone (alpha-MSH) is one of the known endogenous agonists for these receptors. It has been hypothesized that the Arg-Phe-Phe (111-113) human AGRP amino acids may be mimicking the melanocortin agonist Phe-Arg-Trp (7-9) residue interactions with the melanocortin receptors that are important for both receptor molecular recognition and stimulation. To test this hypothesis, we generated thirteen chimeric peptide ligands based upon the melanocortin agonist peptides NDP-MSH (Ac-Ser-Tyr-Ser-Nle4-Glu-His-DPhe-Arg-Trp-Gly-Lys-Pro-Val-NH2) and MTII (Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2). In these chimeric ligands, the agonist DPhe-Arg-Trp amino acids were replaced by the AGRP Arg-Phe-Phe residues, and resulted in agonist activity at the mouse melanocortin receptors (mMC1R and mMC3-5Rs), supporting the hypothesis that the AGRP antagonist ligand Arg-Phe-Phe residues mimic the agonist Phe-Arg-Trp amino acids. Interestingly, the Ac-Ser-Tyr-Ser-Nle4-Glu-His-Arg-DPhe-Phe-Gly-Lys-Pro-Val-NH2 peptide possessed 7 nM mMC1R agonist potency, and is 850-fold selective for the mMC1R versus the mMC3R, 2300-fold selective for the mMC1R versus the mMC4R, and 60-fold selective for the MC1R versus the mMC5R, resulting in the discovery of a new peptide template for the design of melanocortin receptor selective ligands.

The receptive-expressive gap in the vocabulary of young second-language learners: Robustness and possible mechanisms

OpenAIRE

Gibson, Todd A.; Oller, D. Kimbrough; Jarmulowicz, Linda; Ethington, Corinna A.

2012-01-01

Adults and children learning a second language show difficulty accessing expressive vocabulary that appears accessible receptively in their first language (L1). We call this discrepancy the receptive-expressive gap. Kindergarten Spanish (L1) - English (L2) sequential bilinguals were given standardized tests of receptive and expressive vocabulary in both Spanish and English. We found a small receptive-expressive gap in English but a large receptive-expressive gap in Spanish. We categorized chi...

Unaccompanied adolescents seeking asylum: Poorer mental health under a restrictive reception

NARCIS (Netherlands)

Reijneveld, S.A.; Boer, J.B.de; Bean, T.; Korfker, D.G.

2005-01-01

We assessed the effects of a stringent reception policy on the mental health of unaccompanied adolescent asylum seekers by comparing the mental health of adolescents in a restricted campus reception setting and in a setting offering more autonomy (numbers [response rates]: 69 [93%] and 53 [69%],

Dopaminergic agonists for hepatic encephalopathy

DEFF Research Database (Denmark)

Als-Nielsen, B; Gluud, L L; Gluud, C

2004-01-01

Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy.......Hepatic encephalopathy may be associated with an impairment of the dopaminergic neurotransmission. Dopaminergic agonists may therefore have a beneficial effect on patients with hepatic encephalopathy....

In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

Science.gov (United States)

Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

2013-04-01

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

Activation of PPAR by Rosiglitazone Does Not Negatively Impact Male Sex Steroid Hormones in Diabetic Rats

Directory of Open Access Journals (Sweden)

Mahmoud Mansour

2009-01-01

Full Text Available Peroxisome proliferator-activated receptor gamma (PPAR activation decreased serum testosterone (T in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2 in female rats. This implies modulation of female sex steroid hormones by PPAR. It is not clear if PPAR modulates sex steroid hormones in diabetic males. Because PPAR activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPAR activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPAR activation on serum and intratesticular T, luteinizing hormone (LH, follicle stimulating hormone (FSH and E2 concentrations in male Zucker diabetic fatty (ZDF rats treated with the PPAR agonist rosiglitazone (a thiazolidinedione. Treatment for eight weeks increased PPAR mRNA and protein in the testis and elevated serum adiponectin, an adipokine marker for PPAR activation. PPAR activation did not alter serum or intratesticular T concentrations. In contrast, serum T level but not intratesticular T was reduced by diabetes. Neither diabetes nor PPAR activation altered serum E2 or gonadotropins FSH and LH concentrations. The results suggest that activation of PPAR by rosiglitazone has no negative impact on sex hormones in male ZDF rats.

Beta-agonists and animal welfare

Science.gov (United States)

The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

Are They Listening? Parental Social Coaching and Parenting Emotional Climate Predict Adolescent Receptivity.

Science.gov (United States)

Gregson, Kim D; Erath, Stephen A; Pettit, Gregory S; Tu, Kelly M

2016-12-01

Associations linking parenting emotional climate and quality of parental social coaching with young adolescents' receptivity to parental social coaching were examined (N = 80). Parenting emotional climate was assessed with adolescent-reported parental warmth and hostility. Quality of parental social coaching (i.e., prosocial advice, benign framing) was assessed via parent-report and behavioral observations during a parent-adolescent discussion about negative peer evaluation. An adolescent receptivity latent variable score was derived from observations of adolescents' behavior during the discussion, change in adolescents' peer response plan following the discussion, and adolescent-reported tendency to seek social advice from the parent. Parenting climate moderated associations between coaching and receptivity: Higher quality coaching was associated with greater receptivity in the context of a more positive climate. Analyses suggested a stronger association between coaching and receptivity among younger compared to older adolescents. © 2015 The Authors. Journal of Research on Adolescence © 2015 Society for Research on Adolescence.

Teaching receptive naming of Chinese characters to children with autism by incorporating echolalia.

OpenAIRE

Leung, J P; Wu, K I

1997-01-01

The facilitative effect of incorporating echolalia on teaching receptive naming of Chinese characters to children with autism was assessed. In Experiment 1, echoing the requested character name prior to the receptive naming task facilitated matching a character to its name. In addition, task performance was consistently maintained only when echolalia preceded the receptive manual response. Positive results from generalization tests suggested that learned responses occurred across various nove...

Receptivity to television fast-food restaurant marketing and obesity among U.S. youth.

Science.gov (United States)

McClure, Auden C; Tanski, Susanne E; Gilbert-Diamond, Diane; Adachi-Mejia, Anna M; Li, Zhigang; Li, Zhongze; Sargent, James D

2013-11-01

Advertisement of fast food on TV may contribute to youth obesity. The goal of the study was to use cued recall to determine whether TV fast-food advertising is associated with youth obesity. A national sample of 2541 U.S. youth, aged 15-23 years, were surveyed in 2010-2011; data were analyzed in 2012. Respondents viewed a random subset of 20 advertisement frames (with brand names removed) selected from national TV fast-food restaurant advertisements (n=535) aired in the previous year. Respondents were asked if they had seen the advertisement, if they liked it, and if they could name the brand. A TV fast-food advertising receptivity score (a measure of exposure and response) was assigned; a 1-point increase was equivalent to affirmative responses to all three queries for two separate advertisements. Adjusted odds of obesity (based on self-reported height and weight), given higher TV fast-food advertising receptivity, are reported. The prevalence of overweight and obesity, weighted to the U.S. population, was 20% and 16%, respectively. Obesity, sugar-sweetened beverage consumption, fast-food restaurant visit frequency, weekday TV time, and TV alcohol advertising receptivity were associated with higher TV fast-food advertising receptivity (median=3.3 [interquartile range: 2.2-4.2]). Only household income, TV time, and TV fast-food advertising receptivity retained multivariate associations with obesity. For every 1-point increase in TV fast-food advertising receptivity score, the odds of obesity increased by 19% (OR=1.19, 95% CI=1.01, 1.40). There was no association between receptivity to televised alcohol advertisements or fast-food restaurant visit frequency and obesity. Using a cued-recall assessment, TV fast-food advertising receptivity was found to be associated with youth obesity. © 2013 American Journal of Preventive Medicine.

Receptivity to Television Fast-Food Restaurant Marketing and Obesity Among U.S. Youth

Science.gov (United States)

McClure, Auden C.; Tanski, Susanne E.; Gilbert-Diamond, Diane; Adachi-Mejia, Anna M.; Li, Zhigang; Li, Zhongze; Sargent, James D.

2013-01-01

Background Advertisement of fast food on TV may contribute to youth obesity. Purpose The goal of the study was to use cued recall to determine whether TV fast-food advertising is associated with youth obesity. Methods A national sample of 2541 U.S. youth, aged 15–23 years, were surveyed in 2010–2011; data were analyzed in 2012. Respondents viewed a random subset of 20 advertisement frames (with brand names removed) selected from national TV fast-food restaurant advertisements (n=535) aired in the previous year. Respondents were asked if they had seen the advertisement, if they liked it, and if they could name the brand. A TV fast-food advertising receptivity score (a measure of exposure and response) was assigned; a 1-point increase was equivalent to affirmative responses to all three queries for two separate advertisements. Adjusted odds of obesity (based on self-reported height and weight), given higher TV fast-food advertising receptivity, are reported. Results The prevalence of overweight and obesity, weighted to the U.S. population, was 20% and 16%, respectively. Obesity, sugar-sweetened beverage consumption, fast-food restaurant visit frequency, weekday TV time, and TV alcohol advertising receptivity were associated with higher TV fast-food advertising receptivity (median=3.3 [interquartile range: 2.2–4.2]). Only household income, TV time, and TV fast-food advertising receptivity retained multivariate associations with obesity. For every 1-point increase in TV fast-food advertising receptivity score, the odds of obesity increased by 19% (OR=1.19, 95% CI=1.01, 1.40). There was no association between receptivity to televised alcohol advertisements or fast-food restaurant visit frequency and obesity. Conclusions Using a cued-recall assessment, TV fast-food advertising receptivity was found to be associated with youth obesity. PMID:24139768

Effect of leading-edge geometry on boundary-layer receptivity to freestream sound

Science.gov (United States)

Lin, Nay; Reed, Helen L.; Saric, W. S.

1991-01-01

The receptivity to freestream sound of the laminar boundary layer over a semi-infinite flat plate with an elliptic leading edge is simulated numerically. The incompressible flow past the flat plate is computed by solving the full Navier-Stokes equations in general curvilinear coordinates. A finite-difference method which is second-order accurate in space and time is used. Spatial and temporal developments of the Tollmien-Schlichting wave in the boundary layer, due to small-amplitude time-harmonic oscillations of the freestream velocity that closely simulate a sound wave travelling parallel to the plate, are observed. The effect of leading-edge curvature is studied by varying the aspect ratio of the ellipse. The boundary layer over the flat plate with a sharper leading edge is found to be less receptive. The relative contribution of the discontinuity in curvature at the ellipse-flat-plate juncture to receptivity is investigated by smoothing the juncture with a polynomial. Continuous curvature leads to less receptivity. A new geometry of the leading edge, a modified super ellipse, which provides continuous curvature at the juncture with the flat plate, is used to study the effect of continuous curvature and inherent pressure gradient on receptivity.

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

Problems of generation and reception of gravitational waves. [Review

Energy Technology Data Exchange (ETDEWEB)

Pisarev, A F [Joint Inst. for Nuclear Research, Dubna (USSR)

1975-01-01

The present day status of the problems of gravitation, wave radiation and reception is surveyed. The physical presentation and mathematical description of the processes of radiation, propagation and interaction of gravitation waves with matter and the electromagnetic field are given. The experiments on the search for gravitation waves of astophysical nature are analysed. The laboratory and cosmic sources of these waves and the methods of their reception are described. Special attention is drawn to the analysis of the proposals to perform a complete laboratory gravitation wave experiment.

Role and development of GLP-1 receptor agonists in the management of diabetes

Directory of Open Access Journals (Sweden)

Chee W Chia

2009-05-01

Full Text Available Chee W Chia, Josephine M EganNational Institutes of Health, National Institute on Aging, Intramural Research Program, Baltimore, Maryland, USAAbstract: Glucagon-like peptide-1 (GLP-1 is a hormone secreted from enteroendocrine L cells of the intestine in response to food. Exogenous GLP-1 administration at pharmacological doses results in many effects that are beneficial for treating type 2 diabetes, these include: (1 an increase in insulin secretion from β cells; (2 a suppression of glucagon secretion from α cells in the presence of hyperglycemia but not hypoglycemia; (3 a delay in gastric emptying and gut motility which in turns delays absorption of ingested nutrients and dampens post-prandial glucose excursion; and (4 an increase in the duration of postprandial satiety therefore suppressing appetite and decreasing food intake which eventually leads to weight loss. However, GLP-1 is subject to rapid enzymatic degradation, and therefore, not suitable for long-term treatment. A synthetic enzyme-resistant GLP-1 receptor agonist that reproduces the biological effects of GLP-1 is in use and more are under development. This review aims at providing a summary of the properties of GLP-1 and the development of GLP-1-based therapies for treatment of diabetes.Keywords: incretin, GLP-1, GLP-1R agonist, diabetes

Profound and Rapid Reduction in Body Temperature Induced by the Melanocortin Receptor Agonists

Science.gov (United States)

Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

2014-01-01

The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5′AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII’s effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. PMID:25065745

Agonistic reciprocity is associated with reduced male reproductive success within haremic social networks

Science.gov (United States)

Solomon-Lane, Tessa K.; Pradhan, Devaleena S.; Willis, Madelyne C.; Grober, Matthew S.

2015-01-01

While individual variation in social behaviour is ubiquitous and causes social groups to differ in structure, how these structural differences affect fitness remains largely unknown. We used social network analysis of replicate bluebanded goby (Lythrypnus dalli) harems to identify the reproductive correlates of social network structure. In stable groups, we quantified agonistic behaviour, reproduction and steroid hormones, which can both affect and respond to social/reproductive cues. We identified distinct, optimal social structures associated with different reproductive measures. Male hatching success (HS) was negatively associated with agonistic reciprocity, a network structure that describes whether subordinates ‘reciprocated’ agonism received from dominants. Egg laying was associated with the individual network positions of the male and dominant female. Thus, males face a trade-off between promoting structures that facilitate egg laying versus HS. Whether this reproductive conflict is avoidable remains to be determined. We also identified different social and/or reproductive roles for 11-ketotestosterone, 17β-oestradiol and cortisol, suggesting that specific neuroendocrine mechanisms may underlie connections between network structure and fitness. This is one of the first investigations of the reproductive and neuroendocrine correlates of social behaviour and network structure in replicate, naturalistic social groups and supports network structure as an important target for natural selection. PMID:26156769

Profound and rapid reduction in body temperature induced by the melanocortin receptor agonists.

Science.gov (United States)

Xu, Yuanzhong; Kim, Eun Ran; Fan, Shengjie; Xia, Yan; Xu, Yong; Huang, Cheng; Tong, Qingchun

2014-08-22

The melanocortin receptor 4 (MC4R) plays a major role in body weight regulation and its agonist MTII has been widely used to study the role of MC4Rs in energy expenditure promotion and feeding reduction. Unexpectedly, we observed that intraperitoneal (i.p.) administration of MTII induced a rapid reduction in both body temperature and energy expenditure, which was independent of its effect on feeding and followed by a prolonged increase in energy expenditure. The rapid reduction was at least partly mediated by brain neurons since intracerebroventricular (icv) administration of alpha melanocyte-stimulating hormone, an endogenous melanocortin receptor agonist, produced a similar response. In addition, the body temperature-lowering effect of MTII was independent of the presence of MC4Rs, but in a similar fashion to the previously shown effect on body temperature by 5'AMP. Moreover, β-adrenergic receptors (β-ARs) were required for the recovery from low body temperature induced by MTII and further pharmacological studies showed that the MTII's effect on body temperature may be partially mediated by the vasopressin V1a receptors. Collectively, our results reveal a previously unappreciated role for the melanocortin pathway in rapidly lowering body temperature. Copyright © 2014 Elsevier Inc. All rights reserved.

From conciliar ecumenism to transformative receptive ecumenism

Directory of Open Access Journals (Sweden)

Mary-Anne Plaatjies van Huffel

2017-09-01

Full Text Available This article attends to ecumenicity as the second reformation. The ecumenical organisations and agencies hugely influenced the theological praxis and reflection of the church during the past century. The First World Council of Churches (WCC Assembly in Amsterdam, the Netherlands, has been described as the most significant event in church history since the Reformation during the past decade. We saw the emergence of two initiatives that are going to influence ecumenical theology and practice in future, namely the Receptive Ecumenism and Catholic Learning research project, based in Durham, United Kingdom, and the International Theological Colloquium for Transformative Ecumenism of the WCC. Both initiatives constitute a fresh approach in methodology to ecumenical theology and practice. Attention will be given in this article to conciliar ecumenism, receptive ecumenism, transformative ecumenism and its implications for the development of an African transformative receptive ecumenism. In doing so, we should take cognisance of what Küng says about a confessionalist ghetto mentality: ‘We must avoid a confessionalistic ghetto mentality. Instead we should espouse an ecumenical vision that takes into consideration the world religions as well as contemporary ideologies: as much tolerance as possible toward those things outside the Church, toward the religious in general, and the human in general, and the development of that which is specifically Christian belong together!’

47 CFR 73.825 - Protection to reception of TV channel 6.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Protection to reception of TV channel 6. 73.825... RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.825 Protection to reception of TV... separation distances in the following table are met with respect to all full power TV Channel 6 stations. FM...

Efficiency of an automated reception and turnaround time management system for the phlebotomy room.

Science.gov (United States)

Yun, Soon Gyu; Shin, Jeong Won; Park, Eun Su; Bang, Hae In; Kang, Jung Gu

2016-01-01

Recent advances in laboratory information systems have largely been focused on automation. However, the phlebotomy services have not been completely automated. To address this issue, we introduced an automated reception and turnaround time (TAT) management system, for the first time in Korea, whereby the patient's information is transmitted directly to the actual phlebotomy site and the TAT for each phlebotomy step can be monitored at a glance. The GNT5 system (Energium Co., Ltd., Korea) was installed in June 2013. The automated reception and TAT management system has been in operation since February 2014. Integration of the automated reception machine with the GNT5 allowed for direct transmission of laboratory order information to the GNT5 without involving any manual reception step. We used the mean TAT from reception to actual phlebotomy as the parameter for evaluating the efficiency of our system. Mean TAT decreased from 5:45 min to 2:42 min after operationalization of the system. The mean number of patients in queue decreased from 2.9 to 1.0. Further, the number of cases taking more than five minutes from reception to phlebotomy, defined as the defect rate, decreased from 20.1% to 9.7%. The use of automated reception and TAT management system was associated with a decrease of overall TAT and an improved workflow at the phlebotomy room.

Housing Service: Receptions of the CERN and St.-Genis-Pouilly Hostels

CERN Multimedia

2005-01-01

Opening times Please note the new and definitive opening times of the Receptions of the hostels on the Swiss site of CERN and in St. Genis : CERN hostels St.-Genis hostel from Monday to Friday 7:30 - 19:30 8:00 - 12:00 16:00 - 19:00 Saturday 9:00 - 13:00 closed Sunday 9:00 - 13:00 closed Outside these times keys to rooms reserved in advance can be obtained from the guards on duty at the main entrance to the Meyrin, Switzerland, CERN site (Gate B), where they are deposited some fifteen minutes after the closure of the Reception. As for the St. Genis hostel, for arrivals on Saturdays and Sundays, the keys are deposited with the guards in advance on the preceding Friday evening. Reminder : reservations, whether for the CERN hostels or the St. Genis hostel, are available through the Reception of the CERN hostels. Once the reservation has been confirmed, in the case of St. Genis, all other business, including payment, is dealt with by the St. Genis hostel reception. As far as possible, all r...

The Critical Reception of Lewis Nordan

DEFF Research Database (Denmark)

Bjerre, Thomas Ærvold

2010-01-01

The essay covers the critical reception of Mississippi-writer Lewis Nordan from his debut in 1983 to the boost in scholarly attention in the new millennium. The essay covers newspaper reviews but pays particular attention to the many academic essays that have placed Nordan as a writer...

Modification of kindled amygdaloid seizures by opiate agonists and antagonists.

Science.gov (United States)

Albertson, T E; Joy, R M; Stark, L G

1984-03-01

The effects of 19 opiate agonists and antagonists on kindled amygdaloid seizures in the rat were studied. The mu agonists tended to reduce the length of elicited afterdischarges and behavioral ranks, while markedly increasing postictal electroencephalogram spikes and behavioral arrest time. These effects were reversed by naloxone. The kappa agonists reduced behavioral rank and variably reduced afterdischarge length with a concomitant lengthening of postictal behavioral arrest time and number of electroencephalogram spikes. The putative sigma agonist, SKF 10,047, reduced afterdischarge durations only at the higher doses tested. The decreases found after the sigma agonists in postictal electroencephalogram spiking and time of behavioral arrest were not reversed by naloxone. Only the lower doses of normeperidine were found to decrease seizure thresholds. The mixed agonist/antagonists (MAA) cyclazocine and cyclorphan markedly increased seizure threshold and reduced afterdischarge duration and behavioral rank. Only the MAA pentazocine tended to increase threshold but not suprathreshold afterdischarge durations. The order of ability to modify the ictal events was MAA (selected) greater than kappa agonists greater than mu agonists greater than sigma agonists. The increase in postictal events (behavior arrest and spikes) was caused most effectively by pretreatment with mu agonist greater than kappa agonist greater than selected MAA greater than sigma agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Spectrotemporal dynamics of auditory cortical synaptic receptive field plasticity.

Science.gov (United States)

Froemke, Robert C; Martins, Ana Raquel O

2011-09-01

The nervous system must dynamically represent sensory information in order for animals to perceive and operate within a complex, changing environment. Receptive field plasticity in the auditory cortex allows cortical networks to organize around salient features of the sensory environment during postnatal development, and then subsequently refine these representations depending on behavioral context later in life. Here we review the major features of auditory cortical receptive field plasticity in young and adult animals, focusing on modifications to frequency tuning of synaptic inputs. Alteration in the patterns of acoustic input, including sensory deprivation and tonal exposure, leads to rapid adjustments of excitatory and inhibitory strengths that collectively determine the suprathreshold tuning curves of cortical neurons. Long-term cortical plasticity also requires co-activation of subcortical neuromodulatory control nuclei such as the cholinergic nucleus basalis, particularly in adults. Regardless of developmental stage, regulation of inhibition seems to be a general mechanism by which changes in sensory experience and neuromodulatory state can remodel cortical receptive fields. We discuss recent findings suggesting that the microdynamics of synaptic receptive field plasticity unfold as a multi-phase set of distinct phenomena, initiated by disrupting the balance between excitation and inhibition, and eventually leading to wide-scale changes to many synapses throughout the cortex. These changes are coordinated to enhance the representations of newly-significant stimuli, possibly for improved signal processing and language learning in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

Time- and dose-related effects of a gonadotropin-releasing hormone agonist and dopamine antagonist on reproduction in the Northern leopard frog (Lithobates pipiens).

Science.gov (United States)

Vu, Maria; Weiler, Bradley; Trudeau, Vance L

2017-12-01

Gonadotropin-releasing hormone (GnRH) stimulates luteinizing hormone release to control ovulation and spermiation in vertebrates. Dopamine (DA) has a clear inhibitory role in the control of reproduction in numerous teleosts, and emerging evidence suggests that similar mechanisms may exist in amphibians. The interactions between GnRH and DA on spawning success and pituitary gene expression in the Northern leopard frog (Lithobates pipiens) were therefore investigated. Frogs were injected during the natural breeding season with a GnRH agonist [GnRH-A; (Des-Gly 10 , D-Ala 6 , Pro-NHEt 9 )-LHRH; 0.1μg/g and 0.4μg/g] alone and in combination with the dopamine receptor D2 antagonist metoclopramide (MET; 5μg/g and 10μg/g). Injected animals were allowed to breed in outdoor mesocosms. Time to amplexus and oviposition were assessed, and egg mass release, incidences of amplexus, egg mass weight, total egg numbers and fertilization rates were measured. To examine gene expression, female pituitaries were sampled at 12, 24 and 36h following injection of GnRH-A (0.4μg/g) alone and in combination with MET (10μg/g). The mRNA levels of the genes lhb, fshb, gpha, drd2 and gnrhr1 were measured using quantitative real-time PCR. Data were analyzed by a two-way ANOVA. Both GnRH-A doses increased amplexus, oviposition and fertilization alone. Co-injection of MET with GnRH-A did not further enhance spawning success. Injection of GnRH-A alone time-dependently increased expression of lhb, fshb, gpha and gnrhr1. The major effect of MET alone was to decrease expression of drd2. Importantly, the stimulatory effects of GnRH-A on lhb, gpha and gnrhr1 were potentiated by the co-injection of MET at 36h. At this time, expression of fshb was increased only in animals injected with both GnRH-A and MET. Spawning success was primarily driven by the actions of GnRH-A. The hypothesized inhibitory action of DA was supported by pituitary gene expression analysis. The results from this study provide a

GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism

OpenAIRE

Lin, Hua V.; Efanov, Alexander M.; Fang, Xiankang; Beavers, Lisa S.; Wang, Xuesong; Wang, Jingru; Gonzalez Valcarcel, Isabel C.; Ma, Tianwei

2016-01-01

GPR142, a putative amino acid receptor, is expressed in pancreatic islets and the gastrointestinal tract, but the ligand affinity and physiological role of this receptor remain obscure. In this study, we show that in addition to L-Tryptophan, GPR142 signaling is also activated by L-Phenylalanine but not by other naturally occurring amino acids. Furthermore, we show that Tryptophan and a synthetic GPR142 agonist increase insulin and incretin hormones and improve glucose disposal in mice in a G...

Design of signal reception and processing system of embedded ultrasonic endoscope

Science.gov (United States)

Li, Ming; Yu, Feng; Zhang, Ruiqiang; Li, Yan; Chen, Xiaodong; Yu, Daoyin

2009-11-01

Embedded Ultrasonic Endoscope, based on embedded microprocessor and embedded real-time operating system, sends a micro ultrasonic probe into coelom through the biopsy channel of the Electronic Endoscope to get the fault histology features of digestive organs by rotary scanning, and acquires the pictures of the alimentary canal mucosal surface. At the same time, ultrasonic signals are processed by signal reception and processing system, forming images of the full histology of the digestive organs. Signal Reception and Processing System is an important component of Embedded Ultrasonic Endoscope. However, the traditional design, using multi-level amplifiers and special digital processing circuits to implement signal reception and processing, is no longer satisfying the standards of high-performance, miniaturization and low power requirements that embedded system requires, and as a result of the high noise that multi-level amplifier brought, the extraction of small signal becomes hard. Therefore, this paper presents a method of signal reception and processing based on double variable gain amplifier and FPGA, increasing the flexibility and dynamic range of the Signal Reception and Processing System, improving system noise level, and reducing power consumption. Finally, we set up the embedded experiment system, using a transducer with the center frequency of 8MHz to scan membrane samples, and display the image of ultrasonic echo reflected by each layer of membrane, with a frame rate of 5Hz, verifying the correctness of the system.

A Rationally Designed Agonist Defines Subfamily IIIA Abscisic Acid Receptors As Critical Targets for Manipulating Transpiration.

Science.gov (United States)

Vaidya, Aditya S; Peterson, Francis C; Yarmolinsky, Dmitry; Merilo, Ebe; Verstraeten, Inge; Park, Sang-Youl; Elzinga, Dezi; Kaundal, Amita; Helander, Jonathan; Lozano-Juste, Jorge; Otani, Masato; Wu, Kevin; Jensen, Davin R; Kollist, Hannes; Volkman, Brian F; Cutler, Sean R

2017-11-17

Increasing drought and diminishing freshwater supplies have stimulated interest in developing small molecules that can be used to control transpiration. Receptors for the plant hormone abscisic acid (ABA) have emerged as key targets for this application, because ABA controls the apertures of stomata, which in turn regulate transpiration. Here, we describe the rational design of cyanabactin, an ABA receptor agonist that preferentially activates Pyrabactin Resistance 1 (PYR1) with low nanomolar potency. A 1.63 Å X-ray crystallographic structure of cyanabactin in complex with PYR1 illustrates that cyanabactin's arylnitrile mimics ABA's cyclohexenone oxygen and engages the tryptophan lock, a key component required to stabilize activated receptors. Further, its sulfonamide and 4-methylbenzyl substructures mimic ABA's carboxylate and C6 methyl groups, respectively. Isothermal titration calorimetry measurements show that cyanabactin's compact structure provides ready access to high ligand efficiency on a relatively simple scaffold. Cyanabactin treatments reduce Arabidopsis whole-plant stomatal conductance and activate multiple ABA responses, demonstrating that its in vitro potency translates to ABA-like activity in vivo. Genetic analyses show that the effects of cyanabactin, and the previously identified agonist quinabactin, can be abolished by the genetic removal of PYR1 and PYL1, which form subclade A within the dimeric subfamily III receptors. Thus, cyanabactin is a potent and selective agonist with a wide spectrum of ABA-like activities that defines subfamily IIIA receptors as key target sites for manipulating transpiration.

Difficulties Using Standardized Tests to Identify the Receptive Expressive Gap in Bilingual Children's Vocabularies.

Science.gov (United States)

Gibson, Todd A; Oller, D Kimbrough; Jarmulowicz, Linda

2018-03-01

Receptive standardized vocabulary scores have been found to be much higher than expressive standardized vocabulary scores in children with Spanish as L1, learning L2 (English) in school (Gibson et al., 2012). Here we present evidence suggesting the receptive-expressive gap may be harder to evaluate than previously thought because widely-used standardized tests may not offer comparable normed scores. Furthermore monolingual Spanish-speaking children tested in Mexico and monolingual English-speaking children in the US showed other, yet different statistically significant discrepancies between receptive and expressive scores. Results suggest comparisons across widely used standardized tests in attempts to assess a receptive-expressive gap are precarious.

Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

Science.gov (United States)

Elkind-Hirsch, K E; Anania, C; Malinak, R

1996-09-01

To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

Extended and structurally supported insights into extracellular hormone binding, signal transduction and organization of the thyrotropin receptor.

Directory of Open Access Journals (Sweden)

Gerd Krause

Full Text Available The hormone thyrotropin (TSH and its receptor (TSHR are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR and lutropin/choriogonadotropin (LHR and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One major reason for these open questions is the lack of any structural information about the extracellular segment of TSHR that connects the N-terminal leucine-rich repeat domain (LRRD with the transmembrane helix (TMH 1, the hinge region. It has been shown experimentally that this segment is important for fine tuning of signaling and ligand interactions. A new crystal structure containing most of the extracellular hFSHR region in complex with hFSH has recently been published. Now, we have applied these new structural insights to the homologous TSHR and have generated a structural model of the TSHR LRRD/hinge-region/TSH complex. This structural model is combined and evaluated with experimental data including hormone binding (bTSH, hTSH, thyrostimulin, super-agonistic effects, antibody interactions and signaling regulation. These studies and consideration of significant and non-significant amino acids have led to a new description of mechanisms at the TSHR, including ligand-induced displacements of specific hinge region fragments. This event triggers conformational changes at a convergent center of the LRRD and the hinge region, activating an "intramolecular agonistic unit" close to the transmembrane domain.

Extended and structurally supported insights into extracellular hormone binding, signal transduction and organization of the thyrotropin receptor.

Science.gov (United States)

Krause, Gerd; Kreuchwig, Annika; Kleinau, Gunnar

2012-01-01

The hormone thyrotropin (TSH) and its receptor (TSHR) are crucial for the growth and function of the thyroid gland. The TSHR is evolutionary linked with the receptors of follitropin (FSHR) and lutropin/choriogonadotropin (LHR) and their sequences and structures are similar. The extracellular region of TSHR contains more than 350 amino acids and binds hormone and antibodies. Several important questions related to functions and mechanisms of TSHR are still not comprehensively understood. One major reason for these open questions is the lack of any structural information about the extracellular segment of TSHR that connects the N-terminal leucine-rich repeat domain (LRRD) with the transmembrane helix (TMH) 1, the hinge region. It has been shown experimentally that this segment is important for fine tuning of signaling and ligand interactions. A new crystal structure containing most of the extracellular hFSHR region in complex with hFSH has recently been published. Now, we have applied these new structural insights to the homologous TSHR and have generated a structural model of the TSHR LRRD/hinge-region/TSH complex. This structural model is combined and evaluated with experimental data including hormone binding (bTSH, hTSH, thyrostimulin), super-agonistic effects, antibody interactions and signaling regulation. These studies and consideration of significant and non-significant amino acids have led to a new description of mechanisms at the TSHR, including ligand-induced displacements of specific hinge region fragments. This event triggers conformational changes at a convergent center of the LRRD and the hinge region, activating an "intramolecular agonistic unit" close to the transmembrane domain.

Intermittent hormonal therapy in the treatment of post-irradiation residual/recurrent prostate cancer

International Nuclear Information System (INIS)

Williams, Aaron O; Kocherill, Paul G; Wallace, Michelle; Forman, Jeffrey D

1996-01-01

Purpose: To evaluate the efficacy and toxicity of intermittent hormonal therapy in the treatment of residual/recurrent prostate cancer. Materials and Methods: Seventeen patients with biochemical evidence of residual/recurrent prostate cancer were initially treated with radiation therapy (RT)(13), neo-adjuvant hormonal therapy and RT (3), or RT following prostatectomy (1). The mean follow-up time was 19.4 months from the initiation of hormonal therapy. Hormonal therapy consisted of an LH-RH agonist alone (7), an anti-androgen alone (1) or a combination of both (9). Hormonal therapy was continued until the prostatic specific antigen (PSA) level became undetectable. IHT was reinstituted when the PSA reached a pre-determined level, usually greater than or equal to 10ng/ml. Results: The mean time from completion of primary treatment to the initiation of hormonal therapy was 32.5 months. The mean PSA at the start of the first cycle of hormonal therapy was 43.9ng/ml, the second cycle, 11.9ng/ml and the third cycle, 24ng/ml. The mean PSA levels at the end of the first and second cycle of hormonal therapy were .48 and .42ng/ml, respectively. No patient has yet completed the third cycle of hormonal therapy. The average duration of hormonal therapy was 10 months for the first cycle and 4 months for the second cycle. The mean intermittent time off hormones were 9.3 months between cycles 1 and 2, and 10 months between cycles 2 and 3. No patient has yet become refractory to hormonal therapy. Currently all patients are alive. All patients experienced hot flashes and decreased libido at varying degrees during treatment. Thirty-five percent experienced gynecomastia. During the intervals between hormonal therapy, most patients reported a decrease in hot flashes. Conclusion: This analysis supplies preliminary evidence that intermittent hormonal therapy is a viable option in patients with biochemical evidence of disease following initial therapy. It is associated with less treatment

Effects of Humor Production, Humor Receptivity, and Physical Attractiveness on Partner Desirability

Directory of Open Access Journals (Sweden)

Michelle Tornquist

2015-10-01

Full Text Available This study examined women’s and men’s preferences for humor production and humor receptivity in long-term and short-term relationships, and how these factors interact with physical attractiveness to influence desirability. Undergraduates viewed photographs of the opposite sex individuals who were high or low in physical attractiveness, along with vignettes varying in humor production and receptivity. Participants rated physical attractiveness and desirability for long-term and short-term relationships. The main findings were that individuals desired partners who were high in humor production and receptivity, though the effects were particularly pronounced for women judging long-term relationships. Moreover, humor production was more important than receptivity for women’s ratings of male desirability. Notably, we also found that ratings of physical attractiveness were influenced by the humor conditions. These results are discussed in terms of the fitness indicator, interest indicator, and encryption hypotheses of the evolutionary functions of humor.

Dopamine agonist withdrawal syndrome: implications for patient care.

Science.gov (United States)

Nirenberg, Melissa J

2013-08-01

Dopamine agonists are effective treatments for a variety of indications, including Parkinson's disease and restless legs syndrome, but may have serious side effects, such as orthostatic hypotension, hallucinations, and impulse control disorders (including pathological gambling, compulsive eating, compulsive shopping/buying, and hypersexuality). The most effective way to alleviate these side effects is to taper or discontinue dopamine agonist therapy. A subset of patients who taper a dopamine agonist, however, develop dopamine agonist withdrawal syndrome (DAWS), which has been defined as a severe, stereotyped cluster of physical and psychological symptoms that correlate with dopamine agonist withdrawal in a dose-dependent manner, cause clinically significant distress or social/occupational dysfunction, are refractory to levodopa and other dopaminergic medications, and cannot be accounted for by other clinical factors. The symptoms of DAWS include anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. The severity and prognosis of DAWS is highly variable. While some patients have transient symptoms and make a full recovery, others have a protracted withdrawal syndrome lasting for months to years, and therefore may be unwilling or unable to discontinue DA therapy. Impulse control disorders appear to be a major risk factor for DAWS, and are present in virtually all affected patients. Thus, patients who are unable to discontinue dopamine agonist therapy may experience chronic impulse control disorders. At the current time, there are no known effective treatments for DAWS. For this reason, providers are urged to use dopamine agonists judiciously, warn patients about the risks of DAWS prior to the initiation of dopamine agonist therapy, and follow patients closely for withdrawal symptoms during dopamine agonist taper.

Empty sella syndrome associated with hormone deficiency in adults

International Nuclear Information System (INIS)

Oleaga, L.; Paja, M.; Goni, F.; Grande, J.; Grande, D.; Merino, M.; Delgado, A.

1999-01-01

The objective of this study was to correlate the magnetic resonance (MR) images in patients with hormone deficiencies with the clinical data and the hormonal status. We studied 11 cases ef empty sella with different peripheral pituitary deficiencies. Hormone levels were determined according to standard laboratory methods. All the patients underwent MR imaging. The studies were carried out with a 1 Tesla superconducting magnet, using the cranial cavity for transmission and reception. Segittal and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms), axial T2-weighted spin-echo sequences (TR/TE: 3,500/19/93 ms) and gadolinium-enhanced (=.2 cc/kg body weight) sagital and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms) were employed. Six of the patients presented partial or total hypopituitarism associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH); there was one case of panhypopituitarism without SIADH and four cases of primary hypothyroidism, there of which were associated with pituitary deficiency, MR imaging revealed five cases of partially empty sella with residual pituitary gland on the sella floor and six cases in which the sella was completely empty. This study also identified six cases of normally situated neurohypophysis, another four in which the neurohypophysis could not be identified and one case of ectopic neurohypophysis. MR imaging is the technique of choice in the study of abnormal hypothalamic-pituitary activity. Empty and partially empty sella should be included among the frequent causes of hypopituitarism, although there is no clear relationship between the degree of adenohypophyseal insufficiency and the degree of atrophy of this system as viewed in MR images. In some cases, this entity may be the radiological sign of a phase in the development of an autoimmune inflammatory process involving the pituitary gland. (Author) 16 refs

More than Decadence - Johannes Jørgensen's early reception of Arthur Schopenhauer

DEFF Research Database (Denmark)

Nord, Johan Christian

Fremmedsproglig forskningsformidling af hovedpunkterne i artiklen "En Poet og en Religionsstifter, med hvem jeg er enig i næsten alle Ting" Indledende betragtninger over Johannes Jørgensens Schopenhauer-reception.......Fremmedsproglig forskningsformidling af hovedpunkterne i artiklen "En Poet og en Religionsstifter, med hvem jeg er enig i næsten alle Ting" Indledende betragtninger over Johannes Jørgensens Schopenhauer-reception....

Endocrine processes underlying victory and defeat in the male rat

NARCIS (Netherlands)

Schuurman, Teunis

1981-01-01

The central questions of the present study were:1. does base line hormonal state determine agonistic behavior in male-male encounters? 2. does agonistic behavior affect hormonal state? Such an interrelationship between agonistic behavior and hormonal processes might serve as a regulatory system for

Genome-Wide Association Study of Receptive Language Ability of 12-Year-Olds

Science.gov (United States)

Harlaar, Nicole; Meaburn, Emma L.; Hayiou-Thomas, Marianna E.; Davis, Oliver S. P.; Docherty, Sophia; Hanscombe, Ken B.; Haworth, Claire M. A.; Price, Thomas S.; Trzaskowski, Maciej; Dale, Philip S.; Plomin, Robert

2014-01-01

Purpose: Researchers have previously shown that individual differences in measures of receptive language ability at age 12 are highly heritable. In the current study, the authors attempted to identify some of the genes responsible for the heritability of receptive language ability using a "genome-wide association" approach. Method: The…

Prediction of turning stability using receptance coupling

Science.gov (United States)

Jasiewicz, Marcin; Powałka, Bartosz

2018-01-01

This paper presents an issue of machining stability prediction of dynamic "lathe - workpiece" system evaluated using receptance coupling method. Dynamic properties of the lathe components (the spindle and the tailstock) are assumed to be constant and can be determined experimentally based on the results of the impact test. Hence, the variable of the system "machine tool - holder - workpiece" is the machined part, which can be easily modelled analytically. The method of receptance coupling enables a synthesis of experimental (spindle, tailstock) and analytical (machined part) models, so impact testing of the entire system becomes unnecessary. The paper presents methodology of analytical and experimental models synthesis, evaluation of the stability lobes and experimental validation procedure involving both the determination of the dynamic properties of the system and cutting tests. In the summary the experimental verification results would be presented and discussed.

Mapping the receptivity of malaria risk to plan the future of control in Somalia.

Science.gov (United States)

Noor, Abdisalan Mohamed; Alegana, Victor Adagi; Patil, Anand Prabhakar; Moloney, Grainne; Borle, Mohammed; Yusuf, Fahmi; Amran, Jamal; Snow, Robert William

2012-01-01

To measure the receptive risks of malaria in Somalia and compare decisions on intervention scale-up based on this map and the more widely used contemporary risk maps. Cross-sectional community Plasmodium falciparum parasite rate (PfPR) data for the period 2007-2010 corrected to a standard age range of 2 to contemporary (2010) mean PfPR(2-10) and the maximum annual mean PfPR(2-10) (receptive) from the highest predicted PfPR(2-10) value over the study period as an estimate of receptivity. Randomly sampled communities in Somalia. Randomly sampled individuals of all ages. Cartographic descriptions of malaria receptivity and contemporary risks in Somalia at the district level. The contemporary annual PfPR(2-10) map estimated that all districts (n=74) and population (n=8.4 million) in Somalia were under hypoendemic transmission (≤10% PfPR(2-10)). Of these, 23% of the districts, home to 13% of the population, were under transmission of 10%-50% PfPR(2-10)) and the rest as hypoendemic. Compared with maps of receptive risks, contemporary maps of transmission mask disparities of malaria risk necessary to prioritise and sustain future control. As malaria risk declines across Africa, efforts must be invested in measuring receptivity for efficient control planning.

Multi-reception strategy with improved SNR for multichannel MR imaging.

Directory of Open Access Journals (Sweden)

Bing Wu

Full Text Available A multi-reception strategy with extended GRAPPA is proposed in this work to improve MR imaging performance at ultra-high field MR systems with limited receiver channels. In this method, coil elements are separated to two or more groups under appropriate grouping criteria. Those groups are enabled in sequence for imaging first, and then parallel acquisition is performed to compensate for the redundant scan time caused by the multiple receptions. To efficiently reconstruct the data acquired from elements of each group, a specific extended GRAPPA was developed. This approach was evaluated by using a 16-element head array on a 7 Tesla whole-body MRI scanner with 8 receive channels. The in-vivo experiments demonstrate that with the same scan time, the 16-element array with twice receptions and acceleration rate of 2 can achieve significant SNR gain in the periphery area of the brain and keep nearly the same SNR in the center area over an eight-element array, which indicates the proposed multi-reception strategy and extended GRAPPA are feasible to improve image quality for MRI systems with limited receive channels. This study also suggests that it is advantageous for a MR system with N receiver channels to utilize a coil array with more than N elements if an appropriate acquisition strategy is applied.

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

Science.gov (United States)

Weitzman, Vanessa N; Engmann, Lawrence; DiLuigi, Andrea; Maier, Donald; Nulsen, John; Benadiva, Claudio

2009-07-01

To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. Retrospective analysis. University-based IVF center. Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

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

Science.gov (United States)

Galbraith, Hugh

2002-12-01

proliferation in cells maintaining receptivity. Mathematical models describing quantitative relationships between consumption of small amounts of oestrogens in meat in addition to greater concentrations from endogenous production, chemical stoichiometry at cellular level and human pathology have not been developed. Such an approach will be necessary to establish 'molecular materiality' of the additional hormone intake as a component of relative risk assessment. The other hormones, although generally less well researched, are similarly subject to a range of tests to determine potentially adverse effects. The resulting limited international consensus relates to the application of the 'precautionary principle' and non-acceptance by the European Commission of the recommendations of the Codex Alimentarius Commission, which determined that meat from cattle, hormone-treated according to good practice, was safe for human consumers. The present review considers the hormone issue in the context of current international social methodology and regulation, recent advances in knowledge of biological activity of hormones and current status of science-based evaluation of food safety and risk for human consumers.

Natural image sequences constrain dynamic receptive fields and imply a sparse code.

Science.gov (United States)

Häusler, Chris; Susemihl, Alex; Nawrot, Martin P

2013-11-06

In their natural environment, animals experience a complex and dynamic visual scenery. Under such natural stimulus conditions, neurons in the visual cortex employ a spatially and temporally sparse code. For the input scenario of natural still images, previous work demonstrated that unsupervised feature learning combined with the constraint of sparse coding can predict physiologically measured receptive fields of simple cells in the primary visual cortex. This convincingly indicated that the mammalian visual system is adapted to the natural spatial input statistics. Here, we extend this approach to the time domain in order to predict dynamic receptive fields that can account for both spatial and temporal sparse activation in biological neurons. We rely on temporal restricted Boltzmann machines and suggest a novel temporal autoencoding training procedure. When tested on a dynamic multi-variate benchmark dataset this method outperformed existing models of this class. Learning features on a large dataset of natural movies allowed us to model spatio-temporal receptive fields for single neurons. They resemble temporally smooth transformations of previously obtained static receptive fields and are thus consistent with existing theories. A neuronal spike response model demonstrates how the dynamic receptive field facilitates temporal and population sparseness. We discuss the potential mechanisms and benefits of a spatially and temporally sparse representation of natural visual input. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

The Social Nature of Argumentative Practices: The Philosophy of Argument and Audience Reception

OpenAIRE

Paula Olmos

2018-01-01

Abstract: This article reviews Christopher W. Tindale’s The Philosophy of Argument and Audience Reception (Cambridge, 2015). Résumé: Cet article est une critique de The Philosophy of Argument and Audience Reception (Cambridge, 2015) de Christopher W. Tindale.

The receptiveness toward remotely supported myofeedback treatment

NARCIS (Netherlands)

Huis in 't Veld, M.H.A.; Voerman, Gerlienke; Hermens, Hermanus J.; Vollenbroek-Hutten, Miriam Marie Rosé

Remotely supported myofeedback treatment (RSMT) is considered to be a potentially valuable alternative to the conventional myofeedback treatment, as it might increase efficiency of care. This study was aimed at examining the receptiveness of potential end users (patients and professionals) with

Adrenal hormones in rats before and after stress-experience: effects of ipsapirone.

Science.gov (United States)

Korte, S M; Bouws, G A; Bohus, B

1992-06-01

The present study was designed to investigate the effects of the anxiolytic 5-HT1A receptor agonist ipsapirone on the hormonal responses in rats under nonstress and stress conditions by means of repeated blood sampling through an intracardiac catheter. Ipsapirone was given in doses of 2.5, 5, 10, and 20 mg/kg (IP) under nonstress conditions in the home cages of the rats. Plasma corticosterone levels increased in a dose-dependent way in the dose range of 5 to 20 mg/kg, whereas the plasma catecholamines were only significantly increased with the highest dose of the drug. The effect of ipsapirone in control and in stressed rats was studied with the selected dose of 5 mg/kg. Conditioned fear of inescapable electric footshock (0.6 mA, AC for 3 s) given one day earlier was used as stressor. Surprisingly, ipsapirone potentiated the magnitude of the neuroendocrine responses. Rats receiving an inescapable footshock 1 day earlier showed a further elevated corticosterone response to the 5-HT1A receptor agonist ipsapirone even before exposing them to the conditioned stress situation. The present findings suggest that if an animal has no possibilities to escape or avoid a noxious event, functional hypersensitivity will develop in the serotonergic neuronal system, which is reflected in the increased responsiveness of the HPA axis to a 5-HT1A agonist challenge.

Knockout mutations of insulin-like peptide genes enhance sexual receptivity in Drosophila virgin females.

Science.gov (United States)

Watanabe, Kazuki; Sakai, Takaomi

2016-01-01

In the fruitfly Drosophila melanogaster, females take the initiative to mate successfully because they decide whether to mate or not. However, little is known about the molecular and neuronal mechanisms regulating sexual receptivity in virgin females. Genetic tools available in Drosophila are useful for identifying molecules and neural circuits involved in the regulation of sexual receptivity. We previously demonstrated that insulin-producing cells (IPCs) in the female brain are critical to the regulation of female sexual receptivity. Ablation and inactivation of IPCs enhance female sexual receptivity, suggesting that neurosecretion from IPCs inhibits female sexual receptivity. IPCs produce and release insulin-like peptides (Ilps) that modulate various biological processes such as metabolism, growth, lifespan and behaviors. Here, we report a novel role of the Ilps in sexual behavior in Drosophila virgin females. Compared with wild-type females, females with knockout mutations of Ilps showed a high mating success rate toward wild-type males, whereas wild-type males courted wild-type and Ilp-knockout females to the same extent. Wild-type receptive females retard their movement during male courtship and this reduced female mobility allows males to copulate. Thus, it was anticipated that knockout mutations of Ilps would reduce general locomotion. However, the locomotor activity in Ilp-knockout females was significantly higher than that in wild-type females. Thus, our findings indicate that the high mating success rate in Ilp-knockout females is caused by their enhanced sexual receptivity, but not by improvement of their sex appeal or by general sluggishness.

Receptivity of a high-speed boundary layer to temperature spottiness

OpenAIRE

Fedorov, A. V.; Ryzhov, A. A.; Soudakov, V. G.; Utyuzhnikov, S. V.

2013-01-01

Two-dimensional direct numerical simulation (DNS) of the receptivity of a flat-plate boundary layer to temperature spottiness in the Mach 6 free stream is carried out. The influence of spottiness parameters on the receptivity process is studied. It is shown that the temperature spots propagating near the upper boundary-layer edge generate mode F inside the boundary layer. Further downstream mode F is synchronized with unstable mode S (Mack second mode) and excites the latter via the inter-mod...

Effective Strategies for Turning Receptive Vocabulary into Productive Vocabulary in EFL Context

Science.gov (United States)

Faraj, Avan Kamal Aziz

2015-01-01

Vocabulary acquisition has been a main concern of EFL English teachers and learners. There have been tons of research to examine the student's level of receptive vocabulary and productive vocabulary, but no research has conducted on how turning receptive vocabulary into productive vocabulary. This study has reported the impact of the teaching…

Effect of an obesogenic diet on circadian activity and serum hormones in old monkeys

Directory of Open Access Journals (Sweden)

Henryk F Urbanski

2017-07-01

Full Text Available Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD. Old female rhesus macaques were ovo-hysterectomized (OvH to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E, beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS. These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.

New benzylureas as a novel series of potent, nonpeptidic vasopressin V2 receptor agonists.

Science.gov (United States)

Yea, Christopher M; Allan, Christine E; Ashworth, Doreen M; Barnett, James; Baxter, Andy J; Broadbridge, Janice D; Franklin, Richard J; Hampton, Sally L; Hudson, Peter; Horton, John A; Jenkins, Paul D; Penson, Andy M; Pitt, Gary R W; Rivière, Pierre; Robson, Peter A; Rooker, David P; Semple, Graeme; Sheppard, Andy; Haigh, Robert M; Roe, Michael B

2008-12-25

Vasopressin (AVP) is a hormone that stimulates an increase in water permeability through activation of V2 receptors in the kidney. The analogue of AVP, desmopressin, has proven an effective drug for diseases where a reduction of urine output is desired. However, its peptidic nature limits its bioavailability. We report herein the discovery of potent, nonpeptidic, benzylurea derived agonists of the vasopressin V2 receptor. We describe substitutions on the benzyl group to give improvements in potency and subsequent modifications to the urea end group to provide improvements in solubility and increased oral efficacy in a rat model of diuresis. The lead compound 20e (VA106483) is reported for the first time and has been selected for clinical development.

Repeat dose of gonadotropin-releasing hormone agonist trigger in polycystic ovarian syndrome undergoing In Vitro fertilization cycles provides a better cycle outcome - a proof-of-concept study

Directory of Open Access Journals (Sweden)

Krishna Deepika

2017-01-01

Full Text Available Objective: Is a single dose of gonadotropin-releasing hormone agonist (GnRHa trigger to induce final oocyte maturation in polycystic ovarian syndrome (PCOS undergoing in vitro fertilization (IVF cycles with GnRH antagonist protocol sufficient to provide optimal oocyte maturity? Design: This is a prospective, randomized, double-blind, proof-of-concept study. Setting: This study was carried out at a tertiary care center. Material and Methods: A total of 125 patients diagnosed with PCOS defined as per the ESHRE/ASRM Rotterdam criteria (2003 undergoing IVF in antagonist protocol were randomized into two groups. Group A: single dose of GnRHa 0.2 mg, 35 h prior to oocyte retrieval, and Group B: 0.2 mg GnRHa 35 h prior to oocyte retrieval + repeat dose of 0.1 mg 12 h following the 1st dose. 12 h post-trigger, luteinizing hormone (LH, progesterone (P4, and follicle-stimulating hormone (FSH values were estimated. Statistical Analysis: Continuous variables were expressed as mean ± standard deviation and categorical variables as proportions where applicable. Independent sample t-test was used for continuous variables which were normally distributed and Mann–Whitney U-test for data not normally distributed. Chi-square test or Fisher's exact test was used for categorical variables where appropriate. Odds ratio (OR with 95% confidence intervals (CIs was calculated. In addition, receiver operating characteristic curve was used to evaluate the post-trigger LH, P4, and FSH values at 12 h as predictors of oocyte maturity. Main Outcome Measures: Primary outcome: maturity rate of the oocytes. Secondary outcomes: oocyte yield, fertilization rate, availability of good quality embryos on day 3, blastocyst conversion, OHSS rates, post-trigger serum LH (IU/L, FSH (IU/L, and P4 (ng/mL levels implantation rate and clinical pregnancy rate. Results: A higher number of mature (metaphase II oocytes were obtained in Group B compared to Group A (OR of 0.47; CI: 0.38–0

Sports doping: emerging designer and therapeutic β2-agonists.

Science.gov (United States)

Fragkaki, A G; Georgakopoulos, C; Sterk, S; Nielen, M W F

2013-10-21

Beta2-adrenergic agonists, or β2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of β2-agonists is prohibited in sports by the World Anti-Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as growth promoters in cattle fattening in the European Union. This paper reviews the last seven-year (2006-2012) literature concerning the development of novel β2-agonists molecules either by modifying the molecule of known β2-agonists or by introducing moieties producing indole-, adamantyl- or phenyl urea derivatives. New emerging β2-agonists molecules for future therapeutic use are also presented, intending to emphasize their potential use for doping purposes or as growth promoters in the near future. © 2013.

Technological Development and Its Impact on Student Reception of a Campus Radio

Science.gov (United States)

Mohamed, Shafizan; Wok, Saodah; Lahabou, Mahaman

2018-01-01

In 2011, a study was conducted to look at students' reception of IIUM.FM, a newly launched online campus radio. Using the Technological Acceptance Model (TAM), the study found that factors such as perceived ease of use, perceived usefulness, and attitude highly influenced audience reception of the online radio. In 2016, a corresponding study,…

The Receptive-Expressive Gap in the Vocabulary of Young Second-Language Learners: Robustness and Possible Mechanisms

Science.gov (United States)

Gibson, Todd A.; Oller, D. Kimbrough; Jarmulowicz, Linda; Ethington, Corinna A.

2012-01-01

Adults and children learning a second language show difficulty accessing expressive vocabulary that appears accessible receptively in their first language (L1). We call this discrepancy the receptive-expressive gap. Kindergarten Spanish (L1)-English (L2) sequential bilinguals were given standardized tests of receptive and expressive vocabulary in…

Review of foreign reception of Jovan Babić’s works

Directory of Open Access Journals (Sweden)

Dobrijević Aleksandar

2015-01-01

Full Text Available In this paper, the author discusses foreign reception of Jovan Babić’s works, which turns out to be very much alive and diverse. More precisely, the author limits himself to a short and very partial review of reception of only two Babić’s texts that, so far, attracted the most attention. [Projekat Ministarstva nauke Republike Srbije, br. 43007 i br. 179041

Exploring the binding energy profiles of full agonists, partial agonists, and antagonists of the α7 nicotinic acetylcholine receptor.

Science.gov (United States)

Tabassum, Nargis; Ma, Qianyun; Wu, Guanzhao; Jiang, Tao; Yu, Rilei

2017-09-01

Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop receptor family and are important drug targets for the treatment of neurological diseases. However, the precise determinants of the binding efficacies of ligands for these receptors are unclear. Therefore, in this study, the binding energy profiles of various ligands (full agonists, partial agonists, and antagonists) were quantified by docking those ligands with structural ensembles of the α7 nAChR exhibiting different degrees of C-loop closure. This approximate treatment of interactions suggested that full agonists, partial agonists, and antagonists of the α7 nAChR possess distinctive binding energy profiles. Results from docking revealed that ligand binding efficacy may be related to the capacity of the ligand to stabilize conformational states with a closed C loop.

Tobacco marketing receptivity and other tobacco product use among young adult bar patrons

Science.gov (United States)

Thrul, Johannes; Lisha, Nadra E.; Ling, Pamela M.

2016-01-01

Purpose Use of other tobacco products (smokeless tobacco, hookah, cigarillo, e-cigarettes) is increasing, particularly among young adults, and there are few regulations on marketing for these products. We examined the associations between tobacco marketing receptivity and other tobacco product (OTP) use among young adult bar patrons (aged 18-26 years). Methods Time-location sampling was used to collect cross-sectional surveys from 7,540 young adult bar patrons from January 2012 through March of 2014. Multivariable logistic regression analyses in 2015 examined if tobacco marketing receptivity was associated (1) with current (past 30 day) OTP use controlling for demographic factors, and (2) with dual/poly use among current cigarette smokers (n=3,045), controlling for demographics and nicotine dependence. Results Among the entire sample of young adult bar patrons (Mage=23.7, SD=1.8; 48.1% female), marketing receptivity was consistently associated with current use of all OTP including smokeless tobacco (adjusted odds ratio [AOR]= 2.49, 95% confidence interval [CI] 1.90-3.27, pmarketing receptivity was significantly associated with use of smokeless tobacco (AOR=1.44, 95% CI 1.05-1.98, pmarketing receptivity. Efforts to limit tobacco marketing should address OTP in addition to cigarettes. PMID:27707516

Speech recognition employing biologically plausible receptive fields

DEFF Research Database (Denmark)

Fereczkowski, Michal; Bothe, Hans-Heinrich

2011-01-01

spectro-temporal receptive fields to auditory spectrogram input, motivated by the auditory pathway of humans, and ii) the adaptation or learning algorithms involved are biologically inspired. This is in contrast to state-of-the-art combinations of Mel-frequency cepstral coefficients and Hidden Markov...

Ableism and the Reception of Improvised Soundsinging

NARCIS (Netherlands)

Tonelli, Christopher

2016-01-01

Soundsinging is one name for the practice of making music using an idiosyncratic palette of vocal and non-vocal oral techniques. This paper is concerned with the reception of soundsinging and, more specifically, with listeners whose reactions to soundsinging involve attempts to contain the practice.

The reception of relativity in the Netherlands

NARCIS (Netherlands)

van Besouw, J.; van Dongen, J.A.E.F.

2013-01-01

This article reviews the early academic and public reception of Albert Einstein's theory of relativity in the Netherlands, particularly after Arthur Eddington's eclipse experiments of 1919. Initially, not much attention was given to relativity, as it did not seem an improvement over Hendrik A.

Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration

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Delphine Haouzi

2014-01-01

Full Text Available The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

Aesthetic-Receptive and Critical-Creative in Appreciative Reading

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Titin Setiartin

2017-10-01

Full Text Available Reading is a process of aesthetically appreciative receptive to emphasize critical-creative reading activities. Metacognitively students understand, address any and explore the idea of the author in the text. Students responded, criticize, and evaluate the author's ideas in the text. At this stage, students can construct their post read text into other forms (new text. The aim of this strategy equips students to understand the meaning of the story, explore ideas, responding critically, and creatively pouring backstory idea. Reading strategies aesthetically-critical-creative receptive grabbed cognitive, effective, and psychomotor toward literacy critical reading and creative writing. Read appreciative included into the activities of reading comprehension. This activity involves the sensitivity and ability to process aesthetically-receptive reading and critical-creative. Readers imagination roam the author to obtain meaningful understanding and experience of reading. Some models of reading comprehension proposed experts covering the steps before reading, when reading, and after reading. At that stage to enable students after reading thinking abilities. Activities that can be done at this stage, for example, examine the back story, retell, make drawings, diagrams, or maps the concept of reading, as well as making a road map that describes the event. Other activities that can be done is to transform our student's text stories through reinforcement form illustrated stories into comic book form, for example (transliteration.

Role of dopamine D4 receptors in copulatory behavior: Studies with selective D4 agonists and antagonists in male rats.

Science.gov (United States)

Sanna, Fabrizio; Contini, Andrea; Melis, Maria Rosaria; Argiolas, Antonio

2015-10-01

Dopamine influences the anticipatory and consummatory phases of sexual behavior, by acting on receptors of the D2 family (D2, D3 and D4) and in particular of the D2 subtype, although evidence for a role of D4 receptors in erectile function and copulatory behavior is also available. In order to clarify such a role of D4 receptors, the effect of selective D4 receptor agonists and antagonists on copulatory behavior of sexually potent male rats in classic copulation tests with a receptive female, was compared with that of apomorphine and haloperidol, a classic dopamine receptor agonist and antagonist, respectively. PD-168,077 (0.05-0.2mg/kg) and ABT-724 (0.01-0.04mg/kg), two selective D4 receptor agonists, given subcutaneously, improved dose-dependently copulatory behavior as shown by the decrease of mount frequency and post ejaculatory interval induced by PD-168,077, and of mount frequency, ejaculation latency, post ejaculatory and inter intromission intervals induced by ABT-724, and by the increase of ejaculation frequency and copulatory efficacy induced by both drugs. Conversely, L-745,870 (1-5mg/kg), a selective D4 receptor antagonist, given intraperitoneally, impaired dose-dependently copulatory behavior, as shown by the increase in intromission and ejaculation latencies, mount frequency, post ejaculatory interval and the decrease in ejaculation frequency and copulatory efficacy induced by this drug. L-745,870 (5mg/kg) administered before PD-168,077 (0.2mg/kg) or ABT-724 (0.04mg/kg), also abolished completely the facilitatory effects of both PD-168,077 and ABT-724 on sexual behavior. These results confirm the involvement of D4 receptors in specific aspects of male rat copulatory behavior that overlap only partially with those influenced by apomorphine and haloperidol. Copyright © 2015 Elsevier Inc. All rights reserved.

Sports doping: Emerging designer and therapeutic B2-agonists

NARCIS (Netherlands)

Fragkaki, A.G.; Georgakopoulos, C.; Sterk, S.S.; Nielen, M.W.F.

2013-01-01

Beta2-adrenergic agonists, or ß2-agonists, are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptom-relievers and, in combination with inhaled corticosteroids, as disease-controllers. The use of ß2-agonists is prohibited in sports by the World Anti-Doping

Thyrotropin-secreting pituitary tumor presenting with congestive heart failure and good response to dopaminergic agonist cabergoline

Directory of Open Access Journals (Sweden)

Yu-Hsi Kao

2013-11-01

Full Text Available Hyperthyroidism is an important inducing factor in patients with atrial fibrillation, and may trigger heart failure. Thyrotropin (thyroid stimulating hormone, TSH-secreting pituitary tumors are rare causes of hyperthyroidism. Here, we report a 66-year-old man with a pituitary TSH-secreting tumor who presented with hyperthyroidism and congestive heart failure. Endonasal trans-sphenoidal pituitary adenomectomy was performed. After the operation, the symptoms of hyperthyroidism and congestive heart failure were relieved, associated with normalization of thyroid function tests. Unfortunately, hand tremor and progressively elevated free T4 and TSH concentrations recurred 5 months after surgery. A dopaminergic agonist, cabergoline was administered and euthyroidism was restored for at least 11 months.

A Methodology for Conus APOE Reception Planning.

Science.gov (United States)

1982-09-01

mentioned, the reception process is a service-type system, which produces services to be rendered to the personnel and cargo flowing through it. The... Heizer , Ramon N. Chief, Supply Systems Branch, Dir- ectorate of Distribution, DCS/Logistics Operations, HQ AFLC, Wright-Patterson AFB OH. Personal inter

Chamber of Commerce reception for Dr. Lucas

Science.gov (United States)

1986-01-01

Dr. William R. Lucas, Marshall's fourth Center Director (1974-1986), delivers a speech in front of a picture of the lunar landscape with Earth looming in the background while attending a Huntsville Chamber of Commerce reception honoring his achievements as Director of Marshall Space Flight Center (MSFC).

Reception Shop Special Stand

CERN Multimedia

Education and Technology Transfer Unit/ETT-EC

2004-01-01

Friday 15.10.2004 CERN 50th Anniversary articles will be sold in the Main Building, ground floor on Friday 15th October from 10h00 to 16h00. T-shirt, (S, M, L, XL) 20.- K-way (M, L, XL) 20.- Silk tie (2 models) 30.- Einstein tie 45.- Umbrella 20.- Caran d'Ache pen 5.- 50th Anniversary Pen 5.- Kit of Cartoon Album & Crayons 10.- All the articles are also available at the Reception Shop in Building 33 from Monday to Saturday between 08.30 and 17.00 hrs. Education and Technology Transfer Unit/ETT-EC

Teaching Receptive Naming of Chinese Characters to Children with Autism by Incorporating Echolalia.

Science.gov (United States)

Leung, Jin-Pang; Wu, Kit-I

1997-01-01

The facilitative effect of incorporating echolalia on teaching receptive naming of Chinese characters to four Hong Kong children (ages 8-10) with autism was assessed. Results from two experiments indicated echolalia was the active component contributing to the successful acquisition and maintenance of receptive naming of Chinese characters.…

An Examination of College Students' Receptiveness to Alcohol-Related Information and Advice

Science.gov (United States)

Leahy, Matthew M.; Jouriles, Ernest N.; Walters, Scott T.

2013-01-01

This project examined the reliability and validity of a newly developed measure of college students' receptiveness to alcohol related information and advice. Participants were 116 college students who reported having consumed alcohol at some point in their lifetime. Participants completed a measure of receptiveness to alcohol-related…

Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling

DEFF Research Database (Denmark)

Holst, Birgitte; Brandt, Erik; Bach, Anders

2005-01-01

Two nonpeptide (L692,429 and MK-677) and two peptide [GH-releasing peptide (GHRP)-6 and ghrelin] agonists were compared in binding and in signal transduction assays: calcium mobilization, inositol phosphate turnover, cAMP-responsive element (CRE), and serum-responsive element (SRE) controlled tra...

The Effects of Receptive and Productive Learning of Word Pairs on Vocabulary Knowledge

Science.gov (United States)

Webb, Stuart

2009-01-01

English as a foreign language students in Japan learned target words in word pairs receptively and productively. Five aspects of vocabulary knowledge--orthography, association, syntax, grammatical functions, and meaning and form--were each measured by receptive and productive tests. The study uses an innovative methodology in that each target word…

Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats.

Science.gov (United States)

Bokser, L; Szende, B; Schally, A V

1990-06-01

The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs.

Triggering ovulation with gonadotropin-releasing hormone agonist versus human chorionic gonadotropin in polycystic ovarian syndrome. A randomized trial

Directory of Open Access Journals (Sweden)

Amr Hassaan Farag

2015-12-01

Full Text Available Objectives: To compare GnRH agonist to hCG for triggering ovulation in polycystic ovarian syndrome treated with clomiphene citrate. Study design: Prospective randomized study. Materials & methods: Eighty five infertile women with PCOS participated in a randomized allocation concealed prospective trial and had induction of ovulation with clomiphene citrate. GnRH agonist 0.2 mg subcutaneously (group 1 or hCG 10,000 IU intramuscularly (group 2 was given to trigger ovulation. Primary outcome was mid-luteal serum progesterone, while secondary outcomes were ovulation rates and clinical pregnancy rates along 3 cycles. Results: No difference was found between group 1 and group 2 regarding mean serum progesterone and clinical pregnancy rates in each cycle. Cumulative pregnancy rates were similar (17.14% versus 20% respectively; P = 0.332. Ovulation rates were 80% versus 68.6% (P = 0.413; 94.3% versus 90.9% (P = 0.669; 97.1% versus 93.7% (P = 0.603 in the two groups respectively. However, a significant rise in number of patients with mid-luteal serum progesterone >10 ng/mL was noted in the 3rd cycle between both groups, (P < 0.0001 for group 1 while P = 0.007 for group 2. Conclusion: Triggering ovulation with GnRH-a after treatment with clomiphene citrate in PCOS, in view of its known protective effect against OHSS, may be an effective physiological alternative to conventional hCG without compromising luteal function and pregnancy rates after repeated cycles of treatment.

Could dopamine agonists aid in drug development for anorexia nervosa?

Science.gov (United States)

Frank, Guido K W

2014-01-01

Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

Directory of Open Access Journals (Sweden)

Guido eFrank

2014-11-01

Full Text Available Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways.

Could Dopamine Agonists Aid in Drug Development for Anorexia Nervosa?

Science.gov (United States)

Frank, Guido K. W.

2014-01-01

Anorexia nervosa is a severe psychiatric disorder most commonly starting during the teenage-years and associated with food refusal and low body weight. Typically there is a loss of menses, intense fear of gaining weight, and an often delusional quality of altered body perception. Anorexia nervosa is also associated with a pattern of high cognitive rigidity, which may contribute to treatment resistance and relapse. The complex interplay of state and trait biological, psychological, and social factors has complicated identifying neurobiological mechanisms that contribute to the illness. The dopamine D1 and D2 neurotransmitter receptors are involved in motivational aspects of food approach, fear extinction, and cognitive flexibility. They could therefore be important targets to improve core and associated behaviors in anorexia nervosa. Treatment with dopamine antagonists has shown little benefit, and it is possible that antagonists over time increase an already hypersensitive dopamine pathway activity in anorexia nervosa. On the contrary, application of dopamine receptor agonists could reduce circuit responsiveness, facilitate fear extinction, and improve cognitive flexibility in anorexia nervosa, as they may be particularly effective during underweight and low gonadal hormone states. This article provides evidence that the dopamine receptor system could be a key factor in the pathophysiology of anorexia nervosa and dopamine agonists could be helpful in reducing core symptoms of the disorder. This review is a theoretical approach that primarily focuses on dopamine receptor function as this system has been mechanistically better described than other neurotransmitters that are altered in anorexia nervosa. However, those proposed dopamine mechanisms in anorexia nervosa also warrant further study with respect to their interaction with other neurotransmitter systems, such as serotonin pathways. PMID:25988121

Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation.

Science.gov (United States)

Matousek, P; Novotný, J; Svoboda, P

2004-01-01

Low-density membrane-domain fractions were prepared from S49 lymphoma cells and clone e2m11 of HEK293 cells expressing a large number of thyrotropin-releasing hormone receptor (TRH-R) and G(11)alpha by flotation on sucrose density gradients. The intact cell structure was broken by detergent-extraction, alkaline-treatment or drastic homogenization. Three types of low-density membranes were resolved by two-dimensional electrophoresis and analyzed for G(s)alpha (S49) or G(q)alpha/G11) (e2m11) content. Four individual immunoblot signals of Gsalpha protein were identified in S49 lymphoma cells indicating complete resolution of the long G(s)alpha L+/-ser and short G(s)alpha S+/-ser variants of G(s)alpha. All these were diminished by prolonged agonist (isoprenaline) stimulation. In e2m11-HEK cells, five different immunoblot signals were detected indicating post-translational modification of G proteins of G(q)alpha/G(11)alpha family. The two major spots corresponding to exogenously (over)expressed G(11)alpha and endogenous G(q)alpha were reduced; the minor spots diminished by hormonal stimulation. Parallel analysis by silver staining of the total protein content indicated that no major changes in protein composition occurred under these conditions. Our data thus indicate that agonist-stimulation of target cells results in down-regulation of all different members of G(s) and G(q)/G(11) families. This agonist-specific effect may be demonstrated in crude membrane as well as domain/raft preparations and it is not accompanied by changes in overall protein composition.

Active versus receptive group music therapy for major depressive disorder-A pilot study.

Science.gov (United States)

Atiwannapat, Penchaya; Thaipisuttikul, Papan; Poopityastaporn, Patchawan; Katekaew, Wanwisa

2016-06-01

To compare the effects of 1) active group music therapy and 2) receptive group music therapy to group counseling in treatment of major depressive disorder (MDD). On top of standard care, 14 MDD outpatients were randomly assigned to receive 1) active group music therapy (n=5), 2) receptive group music therapy (n=5), or 3) group counseling (n=4). There were 12 one-hour weekly group sessions in each arm. Participants were assessed at baseline, 1 month (after 4 sessions), 3 months (end of interventions), and 6 months. Primary outcomes were depressive scores measured by Montgomery-Åsberg Depression Rating Scale (MADRS) Thai version. Secondary outcomes were self-rated depression score and quality of life. At 1 month, 3 months, and 6 months, both therapy groups showed statistically non-significant reduction in MADRS Thai scores when compared with the control group (group counseling). The reduction was slightly greater in the active group than the receptive group. Although there were trend toward better outcomes on self-report depression and quality of life, the differences were not statistically significant. Group music therapy, either active or receptive, is an interesting adjunctive treatment option for outpatients with MDD. The receptive group may reach peak therapeutic effect faster, but the active group may have higher peak effect. Group music therapy deserves further comprehensive studies. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Tobacco Marketing Receptivity and Other Tobacco Product Use Among Young Adult Bar Patrons.

Science.gov (United States)

Thrul, Johannes; Lisha, Nadra E; Ling, Pamela M

2016-12-01

Use of other tobacco products (smokeless tobacco, hookah, cigarillo, and e-cigarettes) is increasing, particularly among young adults, and there are few regulations on marketing for these products. We examined the associations between tobacco marketing receptivity and other tobacco product (OTP) use among young adult bar patrons (aged 18-26 years). Time-location sampling was used to collect cross-sectional surveys from 7,540 young adult bar patrons from January 2012 through March of 2014. Multivariable logistic regression analyses in 2015 examined if tobacco marketing receptivity was associated (1) with current (past 30 day) OTP use controlling for demographic factors and (2) with dual/poly use among current cigarette smokers (n = 3,045), controlling for demographics and nicotine dependence. Among the entire sample of young adult bar patrons (Mean age  = 23.7, standard deviation = 1.8; 48.1% female), marketing receptivity was consistently associated with current use of all OTP including smokeless tobacco (adjusted odds ratio [AOR]= 2.56, 95% confidence interval [CI] 2.08-3.16, p marketing receptivity was significantly associated with use of smokeless tobacco (AOR = 1.63, 95% CI 1.22-2.18, p marketing receptivity. Efforts to limit tobacco marketing should address OTP in addition to cigarettes. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

In vitro assessment of thyroid hormone disrupting activities in drinking water sources along the Yangtze River

International Nuclear Information System (INIS)

Hu Xinxin; Shi Wei; Zhang Fengxian; Cao Fu; Hu Guanjiu; Hao Yingqun; Wei Si; Wang Xinru; Yu Hongxia

2013-01-01

The thyroid hormone disrupting activities of drinking water sources from the lower reaches of Yangtze River were examined using a reporter gene assay based on African green monkey kidney fibroblast (CV-1) cells. None of the eleven tested samples showed thyroid receptor (TR) agonist activity. Nine water samples exhibited TR antagonist activities with the equivalents referring to Di-n-butyl phthalate (DNBP) (TR antagonist activity equivalents, ATR-EQ 50 s) ranging from 6.92 × 10 1 to 2.85 × 10 2 μg DNBP/L. The ATR-EQ 50 s and TR antagonist equivalent ranges (ATR-EQ 30–80 ranges) for TR antagonist activities indicated that the water sample from site WX-8 posed the greatest health risks. The ATR-EQ 80 s of the water samples ranging from 1.56 × 10 3 to 6.14 × 10 3 μg DNBP/L were higher than the NOEC of DNBP. The results from instrumental analysis showed that DNBP might be responsible for the TR antagonist activities in these water samples. Water sources along Yangtze River had thyroid hormone disrupting potential. - Highlights: ► We examined thyroidal activities of drinking water sources at lower reaches of Yangtze River. ► Nine sites showed TR antagonist activities and no site exhibited TR agonist activity. ► ATR-EQ 50 s and ATR-EQ 30–80 ranges showed that the tested water samples had potential risks. ► The drinking water after water treatment processes may pose potential risks to residents. ► DBP, DEHP, NP and OP might contribute to TR antagonist activities in the aquatic environment. - Drinking water sources from the lower reaches of Yangtze River showed thyroid hormone disrupting potential in reporter gene assays.

Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

Directory of Open Access Journals (Sweden)

Yelena Nersesyan

2017-11-01

Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

Sex steroid hormones during the ovarian cycle of an all-female, parthenogenetic lizard and their correlation with pseudosexual behavior.

Science.gov (United States)

Moore, M C; Whittier, J M; Crews, D

1985-11-01

Cnemidophorus uniparens is a unisexual lizard that reproduces by parthenogenesis. Individuals of this species display male-like and female-like copulatory behaviors during different phases of the ovarian cycle suggesting that these pseudocopulatory behaviors are hormonally activated. To learn more about both the endocrinology of parthenogenesis and the possible hormonal activation of male-like copulatory behavior in female individuals, we (1) characterized changes in plasma levels of the sex steroid hormones progesterone, 5 alpha-dihydrotestosterone, testosterone, and 17 beta-estradiol during the ovarian cycle in both free-living and captive individuals, and (2) measured sex steroid hormones in plasma collected from captive individuals immediately after they expressed male-like or female-like copulatory behavior. In general, the pattern of secretion of ovarian hormones in C. uniparens appears to be similar to that of other oviparous vertebrates with similar reproductive cycles. Estradiol is elevated only during the preovulatory phase, whereas progesterone increases slightly during vitellogenesis and then increases dramatically following ovulation. Circulating levels of androgen are very low and are generally below the sensitivity of our radioimmunoassay at all stages of the ovarian cycle. The hormonal correlates of female-like copulatory behavior suggest that, as in other vertebrates, female receptivity is activated by a synergism of estradiol and progesterone. There is no evidence that the hormonal cycle has been altered to produce elevated levels of androgens during the phase of the cycle when male-like behavior is expressed. Rather it seems more likely that the central nervous system has evolved a novel response to a typical pattern of ovarian steroid hormone secretion. At present, the best hormonal correlate of male-like behavior is that changes in plasma levels of progesterone closely parallel changes in probability of expressing male-like behavior.

Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

Science.gov (United States)

Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

2014-06-01

The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

K-pop Reception and Participatory Fan Culture in Austria

Directory of Open Access Journals (Sweden)

Sang-Yeon Sung

2013-12-01

Full Text Available K-pop’s popularity and its participatory fan culture have expanded beyond Asia and become significant in Europe in the past few years. After South Korean pop singer Psy’s “Gangnam Style” music video topped the Austrian chart in October 2012, the number and size of K-pop events in Austria sharply increased, with fans organizing various participatory events, including K-pop auditions, dance festivals, club meetings, quiz competitions, dance workshops, and smaller fan-culture gatherings. In the private sector, longtime fans have transitioned from participants to providers, and in the public sector, from observers to sponsors. Through in-depth interviews with event organizers, sponsors, and fans, this article offers an ethnographic study of the reception of K-pop in Europe that takes into consideration local interactions between fans and Korean sponsors, perspectives on the genre, patterns of social integration, and histories. As a case study, this research stresses the local situatedness of K-pop fan culture by arguing that local private and public sponsors and fans make the reception of K-pop different in each locality. By exploring local scenes of K-pop reception and fan culture, the article demonstrates the rapidly growing consumption of K-pop among Europeans and stresses multidirectional understandings of globalization.

[New data on olfactory control of estral receptivity of female rats].

Science.gov (United States)

Satli, M A; Aron, C

1976-03-01

Olfactory bulb deprivation increased sexual receptivity in 4-day cyclic female rats on the late afternoon of prooestrus (6-7, p.m.). The proportion of receptive females was higher in bulbectomized (B) than in sham operated (SH) animals. On the contrary the same proportion of B and SH females mated in the evening of prooestrus (10. 30-11. 30 p.m.). An increased lordosis quotient was observed in the B females at either of these two stages of the cycle.

The sentence verification task: a reliable fMRI protocol for mapping receptive language in individual subjects

International Nuclear Information System (INIS)

Sanjuan, Ana; Avila, Cesar; Forn, Cristina; Ventura-Campos, Noelia; Rodriguez-Pujadas, Aina; Garcia-Porcar, Maria; Belloch, Vicente; Villanueva, Vicente

2010-01-01

To test the capacity of a sentence verification (SV) task to reliably activate receptive language areas. Presurgical evaluation of language is useful in predicting postsurgical deficits in patients who are candidates for neurosurgery. Productive language tasks have been successfully elaborated, but more conflicting results have been found in receptive language mapping. Twenty-two right-handed healthy controls made true-false semantic judgements of brief sentences presented auditorily. Group maps showed reliable functional activations in the frontal and temporoparietal language areas. At the individual level, the SV task showed activation located in receptive language areas in 100% of the participants with strong left-sided distributions (mean lateralisation index of 69.27). The SV task can be considered a useful tool in evaluating receptive language function in individual subjects. This study is a first step towards designing the fMRI task which may serve to presurgically map receptive language functions. (orig.)

The sentence verification task: a reliable fMRI protocol for mapping receptive language in individual subjects

Energy Technology Data Exchange (ETDEWEB)

Sanjuan, Ana; Avila, Cesar [Universitat Jaume I, Departamento de Psicologia Basica, Clinica y Psicobiologia, Castellon de la Plana (Spain); Hospital La Fe, Unidad de Epilepsia, Servicio de Neurologia, Valencia (Spain); Forn, Cristina; Ventura-Campos, Noelia; Rodriguez-Pujadas, Aina; Garcia-Porcar, Maria [Universitat Jaume I, Departamento de Psicologia Basica, Clinica y Psicobiologia, Castellon de la Plana (Spain); Belloch, Vicente [Hospital La Fe, Eresa, Servicio de Radiologia, Valencia (Spain); Villanueva, Vicente [Hospital La Fe, Unidad de Epilepsia, Servicio de Neurologia, Valencia (Spain)

2010-10-15

To test the capacity of a sentence verification (SV) task to reliably activate receptive language areas. Presurgical evaluation of language is useful in predicting postsurgical deficits in patients who are candidates for neurosurgery. Productive language tasks have been successfully elaborated, but more conflicting results have been found in receptive language mapping. Twenty-two right-handed healthy controls made true-false semantic judgements of brief sentences presented auditorily. Group maps showed reliable functional activations in the frontal and temporoparietal language areas. At the individual level, the SV task showed activation located in receptive language areas in 100% of the participants with strong left-sided distributions (mean lateralisation index of 69.27). The SV task can be considered a useful tool in evaluating receptive language function in individual subjects. This study is a first step towards designing the fMRI task which may serve to presurgically map receptive language functions. (orig.)

Thyroid hormone analogs for the treatment of dyslipidemia: past, present, and future.

Science.gov (United States)

Delitala, Alessandro P; Delitala, Giuseppe; Sioni, Paolo; Fanciulli, Giuseppe

2017-11-01

Treatment of dyslipidemia is a major burden for public health. Thyroid hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR), but the use of thyroid hormone to treat dyslipidemia is not indicated due to its deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been conceived to selectively activate TR in the liver, thus reducing potential side-effects. The authors searched the PubMed database to review TR and the action of thyromimetics in vitro and in animal models. Then, all double-blind, placebo controlled trials that analyzed the use of thyroid hormone analog for the treatment of dyslipidemia in humans were included. Finally, the ongoing research on the use of TR agonists was searched, searching the US National Institutes of Health Registry and the WHO International Clinical Trial Registry Platform (ICTRP). Thyromimetics were tested in humans for the treatment of dyslipidemia, as a single therapeutic agent or as an add-on therapy to the traditional lipid-lowering drugs. In most trials, thyromimetics lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides, but their use has been associated with adverse side-effects, both in pre-clinical studies and in humans. The use of thyromimetics for the treatment of dyslipidemia is not presently recommended. Future possible clinical applications might include their use to promote weight reduction. Thyromimetics might also represent an interesting alternative, both for the treatment of non-alcoholic steatohepatitis, and type 2 diabetes due to their positive effects on insulin sensitivity. Finally, additional experimental and clinical studies are needed for a better comprehension of the effect(s) of a long-term therapy.

Building Harmony through Religious Reception in Culture: Lesson Learned from Radin Jambat Folktale of Lampung

Directory of Open Access Journals (Sweden)

Agus Iswanto

2018-12-01

Full Text Available Understanding of the existence of various religious receptions in culture gives a great opportunity for the building and nurturance of harmony among religious followers and for the creating of solidarities in the society. This article uncovers receptions of religious aspects (ultimate truth aspect/god, cosmological aspect and religious ritual aspect in the cultural products of Radin Lambat, a folktale from Lampung. The article is based on the texts of Radin Lambat folktale, interviews, and other literary sources about Lampung cultures. Religious receptions as shown in Radin Lambat folktale indicate the preservation of past beliefs, coupled with the gentle addition and inclusion of Islamic teachings, to create harmonization between religion and tradition through folktale. This shows that Islam in the societies of Lampung is Islam that values cultures through the processes of gradual and varied receptions. This article is expected to add evidence to related sources about the concepts and practices of harmony among religious followers in Indonesia in local tradition, and the addition to the range of the rare religious-cultural reception studies of Lampung society

Modification of opiate agonist binding by pertussis toxin

Energy Technology Data Exchange (ETDEWEB)

Abood, M.E.; Lee, N.M.; Loh, H.H.

1986-03-05

Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

Modification of opiate agonist binding by pertussis toxin

International Nuclear Information System (INIS)

Abood, M.E.; Lee, N.M.; Loh, H.H.

1986-01-01

Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

Science.gov (United States)

Khalil, Raouf A

2013-12-15

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Humor Production, Humor Receptivity, and Physical Attractiveness on Partner Desirability

OpenAIRE

Michelle Tornquist; Dan Chiappe

2015-01-01

This study examined women’s and men’s preferences for humor production and humor receptivity in long-term and short-term relationships, and how these factors interact with physical attractiveness to influence desirability. Undergraduates viewed photographs of the opposite sex individuals who were high or low in physical attractiveness, along with vignettes varying in humor production and receptivity. Participants rated physical attractiveness and desirability for long-term and short-term rela...

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

Science.gov (United States)

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessment of hemispheric dominance for receptive language in pediatric patients under sedation using magnetoencephalography.

Science.gov (United States)

Rezaie, Roozbeh; Narayana, Shalini; Schiller, Katherine; Birg, Liliya; Wheless, James W; Boop, Frederick A; Papanicolaou, Andrew C

2014-01-01

Non-invasive assessment of hemispheric dominance for receptive language using magnetoencephalography (MEG) is now a well-established procedure used across several epilepsy centers in the context of pre-surgical evaluation of children and adults while awake, alert and attentive. However, the utility of MEG for the same purpose, in cases of sedated patients, is contested. Establishment of the efficiency of MEG is especially important in the case of children who, for a number of reasons, must be assessed under sedation. Here we explored the efficacy of MEG language mapping under sedation through retrospective review of 95 consecutive pediatric patients, who underwent our receptive language test as part of routine clinical evaluation. Localization of receptive language cortex and subsequent determination of laterality was successfully completed in 78% (n = 36) and 55% (n = 27) of non-sedated and sedated patients, respectively. Moreover, the proportion of patients deemed left hemisphere dominant for receptive language did not differ between non-sedated and sedated patients, exceeding 90% in both groups. Considering the challenges associated with assessing brain function in pediatric patients, the success of passive MEG in the context of the cases reviewed in this study support the utility of this method in pre-surgical receptive language mapping.

Assessment of hemispheric dominance for receptive language in pediatric patients under sedation using magnetoencephalography

Directory of Open Access Journals (Sweden)

Roozbeh eRezaie

2014-08-01

Full Text Available Non-invasive assessment of hemispheric dominance for receptive language using Magnetoencephalography (MEG is now a well-established procedure used across several epilepsy centers in the context of pre-surgical evaluation of children and adults while awake, alert and attentive. However, the utility of MEG for the same purpose, in cases of sedated patients, is contested. Establishment of the efficiency of MEG is especially important in the case of children who, for a number of reasons, must be assessed under sedation. Here we explored the efficacy of MEG language mapping under sedation through retrospective review of 95 consecutive pediatric patients, who underwent our receptive language test as part of routine clinical evaluation. Localization of receptive language cortex and subsequent determination of laterality was successfully completed in 78% (n=36 and 55% (n=27 of non-sedated and sedated patients, respectively. Moreover, the proportion of patients deemed left hemisphere dominant for receptive language did not differ between non-sedated and sedated patients, exceeding 90% in both groups. Considering the challenges associated with assessing brain function in pediatric patients, the success of passive MEG in the context of the cases reviewed in this study support the utility of this method in pre-surgical receptive language mapping.

Contour detection based on nonclassical receptive field inhibition

NARCIS (Netherlands)

Grigorescu, Cosmin; Petkov, Nicolai; Westenberg, Michel A.

We propose a biologically motivated computational step, called nonclassical receptive field (non-CRF) inhibition, more generally surround inhibition or suppression, to improve contour detection in machine vision. Non-CRF inhibition is exhibited by 80% of the orientation-selective neurons in the

Hormone therapy in metastatic prostate cancer

Directory of Open Access Journals (Sweden)

Jebelameli P

1997-09-01

Full Text Available Only orchiectomy is still commonly used today either as a single therapy or in combination regimens. Hypophysectomy & adrenalectomy showed such devastating effects on the endocrine equilibrium as to be inconsistent with an acceptable quality of life or even with survival. Chemical adrenalectomy was also tried with drugs (eg. aminoglutethmide, spironolactone leading to consequences superimposable to those of surgical adrenalectomy. Along with orchiectomy, three groups of substances are commonly used today for the hormonal therapy of prostate cancer: estrogens, LHRH agonists & anti androgens. Bilateral orchiectomy removes 90-95% of circulating testosterone. Clinical studies document 60-80% of positive responders to castration, on continued evaluation, relapse occurs usually within 6-24 months in responders, with a death rate of 50% within 6 months. The androgenic activity still remaining after castration may explain the partial & progressively decreasing effectiveness of this & other testosterone reducing therapies. Antiandrogens define substances that act directly at the target site, where interacting with steroid hormone receptors, they impede the binding of androgens. A trend towards the combination of testosterone-reducing & androgen-blocking treatment is developing in modern therapy of prostate cancer. This is due to the complementary characteristics of the two different pharmacological mechanisms that are involved. In this study castration+antiandrogen is compared to castration alone. The results demonstrate a significantly greater percentage of positive objective & subjective responses with antiandrogen than with placebo. In addition survival time was increased in patients treated with castration+antiandrogen than castration+placebo.

A Macrocyclic Agouti-Related Protein/[Nle4, DPhe7]α-Melanocyte Stimulating Hormone Chimeric Scaffold Produces Sub-nanomolar Melanocortin Receptor Ligands

OpenAIRE

Ericson, Mark D.; Freeman, Katie T.; Schnell, Sathya M.; Haskell-Luevano, Carrie

2017-01-01

The melanocortin system consists of five receptor subtypes, endogenous agonists, and naturally occurring antagonists. These receptors and ligands have been implicated in numerous biological pathways including processes linked to obesity and food intake. Herein, a truncation structure-activity relationship study of chimeric agouti-related protein (AGRP)/[Nle4, DPhe7]α-Melanocyte Stimulating Hormone (NDP-MSH) ligands is reported. The tetrapeptide His-DPhe-Arg-Trp or tripeptide DPhe-Arg-Trp repl...

Effects of leuprolide acetate on selected blood and fecal sex hormones in Hispaniolan Amazon parrots (Amazona ventrais).

Science.gov (United States)

Klaphake, Eric; Fecteau, Kellie; DeWit, Martine; Greenacre, Cheryl; Grizzle, Judith; Jones, Michael; Zagaya, Nancy; Abney, L Kim; Oliver, Jack

2009-12-01

The luteinizing hormone-releasing hormone agonist leuprolide acetate is used commonly to anage reproductive problems in pet birds. To determine the effect of leuprolide acetate on plas a and fecal hormone levels in a psittacine species, a single 800 microg/kg dose of the 30-day depot form of leuprolide acetate was administered IM in 11 healthy, nonbreeding adult Hispaniolan Amazon parrots (Amazona ventralis), and plasma and fecal hormone levels were measured before and after leuprolide administration. At pooled baseline to 21 days postleuprolide acetate administration, sample collection day was significantly associated with plasma 17beta-estradiol and androstenedione levels and fecal 17beta-estradiol levels (evaluated in females only). Both plasma androstenedione and plasma 17beta-estradiol levels decreased significantly from baseline to a nadir at 7 days postleuprolide acetate administration but did not differ significantly 14 days later from that nadir or from pooled baseline samples, suggesting that the effect of leuprolide on hormone levels remained about 2 weeks. Fecal 17beta-estradiol levels increased significantly from the nadir at 7 days postleuprolide to 21 days postleuprolide administration, with trends of the level at 21 days postleuprolide being higher than the pooled baseline level and of decreasing levels from pooled baseline to 7 days postleuprolide administration. Plasma luteinizing hormone and fecal testosterone levels did not change significantly from baseline levels after leuprolide administration over the 2-day period. No significant correlations were found between plasma hormone and fecal hormone levels. These results suggest that measurement of plasma androstenedione, plasma 17beta-estradiol, and fecal 17beta-estradiol levels might be useful in assessing the effects of 30-day depot leuprolide acetate in Hispaniolan Amazon parrots.

Surface-Borne Time-of-Reception Measurements (STORM), Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Invocon proposes the Surface-borne Time-Of-Reception Measurements (STORM) system as a method to locate the position of lightning strikes on aerospace vehicles....

Reciprocity of agonistic support in ravens.

Science.gov (United States)

Fraser, Orlaith N; Bugnyar, Thomas

2012-01-01

Cooperative behaviour through reciprocation or interchange of valuable services in primates has received considerable attention, especially regarding the timeframe of reciprocation and its ensuing cognitive implications. Much less, however, is known about reciprocity in other animals, particularly birds. We investigated patterns of agonistic support (defined as a third party intervening in an ongoing conflict to attack one of the conflict participants, thus supporting the other) in a group of 13 captive ravens, Corvus corax. We found support for long-term, but not short-term, reciprocation of agonistic support. Ravens were more likely to support individuals who preened them, kin and dominant group members. These results suggest that ravens do not reciprocate on a calculated tit-for-tat basis, but aid individuals from whom reciprocated support would be most useful and those with whom they share a good relationship. Additionally, dyadic levels of agonistic support and consolation (postconflict affiliation from a bystander to the victim) correlated strongly with each other, but we found no evidence to suggest that receiving agonistic support influences the victim's likelihood of receiving support (consolation) after the conflict ends. Our findings are consistent with an emotionally mediated form of reciprocity in ravens and provide additional support for convergent cognitive evolution in birds and mammals.

Improved CORF model of simple cell combined with non-classical receptive field and its application on edge detection

Science.gov (United States)

Sun, Xiao; Chai, Guobei; Liu, Wei; Bao, Wenzhuo; Zhao, Xiaoning; Ming, Delie

2018-02-01

Simple cells in primary visual cortex are believed to extract local edge information from a visual scene. In this paper, inspired by different receptive field properties and visual information flow paths of neurons, an improved Combination of Receptive Fields (CORF) model combined with non-classical receptive fields was proposed to simulate the responses of simple cell's receptive fields. Compared to the classical model, the proposed model is able to better imitate simple cell's physiologic structure with consideration of facilitation and suppression of non-classical receptive fields. And on this base, an edge detection algorithm as an application of the improved CORF model was proposed. Experimental results validate the robustness of the proposed algorithm to noise and background interference.

Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart.

Science.gov (United States)

Granata, Riccarda; Trovato, Letizia; Gallo, Maria Pia; Destefanis, Silvia; Settanni, Fabio; Scarlatti, Francesca; Brero, Alessia; Ramella, Roberta; Volante, Marco; Isgaard, Jorgen; Levi, Renzo; Papotti, Mauro; Alloatti, Giuseppe; Ghigo, Ezio

2009-07-15

The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

Consuming Carmen Miranda: Dislocations and Dissonances in the Reception of an Icon

Directory of Open Access Journals (Sweden)

Fernando de Figueiredo Balieiro

2017-02-01

Full Text Available From the perspective of cultural studies, in its dialogs with feminist and queer studies, this article analyzes the identification of various publics with Carmen Miranda based on the consumption of her filmic, musical and artistic products, accessing her professional trajectory in its imbrication with its various forms of reception. The focus will be on the negotiations of the artist with her publics, touching on how her career involved reconfigurations concerning aspects of gender, race and sexuality. It is based on a perspective that considers the dynamism of mass culture, considering possibilities for various forms of appropriation of cultural products, as well as shifts and dissonances in receptions. To analyze these aspects, the paper focuses on feminine receptions in Brazil and the United States, and those of a male homosexual public contemporary to her career.

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)

Membrane–initiated estradiol signaling regulating sexual receptivity

Directory of Open Access Journals (Sweden)

Paul E Micevych

2011-09-01

Full Text Available Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor; GPER, and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH. Using both activation of μ-opioid receptors (MOR in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX receptor participate in the required MIES. ERα and the STX receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a that augment progesterone synthesis in astrocytes and protein kinase C (PKC in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum and DRGs.

Membrane-Initiated Estradiol Signaling Regulating Sexual Receptivity

Science.gov (United States)

Micevych, Paul E.; Dewing, Phoebe

2011-01-01

Estradiol has profound actions on the structure and function of the nervous system. In addition to nuclear actions that directly modulate gene expression, the idea that estradiol can rapidly activate cell signaling by binding to membrane estrogen receptors (mERs) has emerged. Even the regulation of sexual receptivity, an action previously thought to be completely regulated by nuclear ERs, has been shown to have a membrane-initiated estradiol signaling (MIES) component. This highlighted the question of the nature of mERs. Several candidates have been proposed, ERα, ERβ, ER-X, GPR30 (G protein coupled estrogen receptor), and a receptor activated by a diphenylacrylamide compound, STX. Although each of these receptors has been shown to be active in specific assays, we present evidence for and against their participation in sexual receptivity by acting in the lordosis-regulating circuit. The initial MIES that activates the circuit is in the arcuate nucleus of the hypothalamus (ARH). Using both activation of μ-opioid receptors (MOR) in the medial preoptic nucleus and lordosis behavior, we document that both ERα and the STX-receptor participate in the required MIES. ERα and the STX-receptor activation of cell signaling are dependent on the transactivation of type 1 metabotropic glutamate receptors (mGluR1a) that augment progesterone synthesis in astrocytes and protein kinase C (PKC) in ARH neurons. While estradiol-induced sexual receptivity does not depend on neuroprogesterone, proceptive behaviors do. Moreover, the ERα and the STX-receptor activation of medial preoptic MORs and augmentation of lordosis were sensitive to mGluR1a blockade. These observations suggest a common mechanism through which mERs are coupled to intracellular signaling cascades, not just in regulating reproduction, but in actions throughout the neuraxis including the cortex, hippocampus, striatum, and dorsal root ganglias. PMID:22649369

PPAR Agonists for the Prevention and Treatment of Lung Cancer

Directory of Open Access Journals (Sweden)

Sowmya P. Lakshmi

2017-01-01

Full Text Available Lung cancer is the most common and most fatal of all malignancies worldwide. Furthermore, with more than half of all lung cancer patients presenting with distant metastases at the time of initial diagnosis, the overall prognosis for the disease is poor. There is thus a desperate need for new prevention and treatment strategies. Recently, a family of nuclear hormone receptors, the peroxisome proliferator-activated receptors (PPARs, has attracted significant attention for its role in various malignancies including lung cancer. Three PPARs, PPARα, PPARβ/δ, and PPARγ, display distinct biological activities and varied influences on lung cancer biology. PPARα activation generally inhibits tumorigenesis through its antiangiogenic and anti-inflammatory effects. Activated PPARγ is also antitumorigenic and antimetastatic, regulating several functions of cancer cells and controlling the tumor microenvironment. Unlike PPARα and PPARγ, whether PPARβ/δ activation is anti- or protumorigenic or even inconsequential currently remains an open question that requires additional investigation. This review of current literature emphasizes the multifaceted effects of PPAR agonists in lung cancer and discusses how they may be applied as novel therapeutic strategies for the disease.

Binding Mode of Insulin Receptor and Agonist Peptide

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

Insulin is a protein hormone secreted by pancreatic β cells. One of its main functions is to keep the balance of glucose inside the body by regulating the absorption and metabolism of glucose in the periphery tissue, as well as the production and storage of hepatic glycogen. The insulin receptor is a transmembrane glycoprotein in which two α subunits with a molecular weight of 135 kD and twoβ subunits with a molecular weight of 95 kD are joined by a disulfide bond to form a β-α-α-β structure. The extracellular α subunit, especially, its three domains near the N-terminal are partially responsible for signal transduction or ligand-binding, as indicated by the experiments. The extracellular α subunits are involved in binding the ligands. The experimental results indicate that the three domains of the N-terminal of the α subunits are the main determinative parts of the insulin receptor to bind the insulin or mimetic peptide.We employed the extracellular domain (PDBID: 1IGR) of the insulin-like growth factor-1 receptor (IGF-1 R ) as the template to simulate and optimize the spatial structures of the three domains in the extracellular domain of the insulin receptor, which includes 468 residues. The work was accomplished by making use of the homology program in the Insight Ⅱ package on an Origin3800 server. The docking calculations of the insulin receptor obtained by homology with hexapeptides were carried out by means of the program Affinity. The analysis indicated that there were hydrogen bonding, and electrostatic and hydrophobic effects in the docking complex of the insulin receptor with hexapeptides.Moreover, we described the spatial orientation of a mimetic peptide with agonist activity in the docking complex. We obtained a rough model of binding of DLAPSQ or STIVYS with the insulin receptor, which provides the powerful theoretical support for designing the minimal insulin mimetic peptide with agonist activity, making it possible to develop oral small

Transfer and Reception of New Institutional Economics: An Example of Two Universities in Serbia

Directory of Open Access Journals (Sweden)

Aleksandra Jovanović

2016-02-01

Full Text Available The research “Transfer and Reception of New Institutional Economics: An Example of Two Universities in Serbia” was conducted in 2005/2006. In order to achieve the goals of the Serbian team of the DIOSCURI project, the main aim of the case study is analysis of the influence of Western institutions in the light of transfer and reception of new institutional economics in two academic institutions in Serbia: The Faculty of Law (The Department of Law and Economics of the University of Belgrade, and The Faculty of Management of BK University. The title of the case study illustrates the focus of the entire research: analysis of Western influence, namely transfer and reception of new institutional economics, on the two institutions and possible obstacles caused by old-fashioned stakeholders and informal institutions. Bearing in mind that the Department of Law and Economics is the leader in the reception of the new institutional economics (NIE in Serbia, the case study will be mostly about it. The Faculty of Management was chosen because of its “greenfield” character and the fact that from its very beginning it followed the experiences of North American universities. The research investigates whether and how the transfer and reception of the Western ideas and economic theory, particularly the NIE, is affected by the difference between an institution with a two-hundred-year tradition and a newly established one. The question is how a traditionalist institution like the Faculty of Law communicated Western economic thought and whether endurance in teaching the exclusively Marxian paradigm up until the 1990s, was an obstacle to the reception of Western economic thought, particularly NIE.

Adolescent weight status and receptivity to food TV advertisements.

Science.gov (United States)

Adachi-Mejia, Anna M; Sutherland, Lisa A; Longacre, Meghan R; Beach, Michael L; Titus-Ernstoff, Linda; Gibson, Jennifer J; Dalton, Madeline A

2011-01-01

This study examined the relationship between adolescent weight status and food advertisement receptivity. Survey-based evaluation with data collected at baseline (initial and at 2 months), and at follow-up (11 months). New Hampshire and Vermont. Students (n = 2,281) aged 10-13 in 2002-2005. Overweight. Generalized estimating equations to model the relationship between identifying a food advertisement as their favorite and being overweight. Overall, 35.9% of the adolescents were overweight. Less than one fifth named a food advertisement as their favorite (16.1%). Most of the food advertisements were for less-healthful food (89.6%). After controlling for school, age, sex, sociodemographics, physical activity, number of TV sessions watched, and having a TV in the bedroom, overweight adolescents were significantly less likely to be receptive to food advertisements (relative risk = 0.83, 95% confidence interval 0.70, 0.98) compared to non-overweight adolescents. This study provides preliminary evidence that normal-weight adolescents are receptive to unhealthful food advertisements. Longitudinal studies are needed to evaluate whether consistent exposure to advertisements for unhealthful food, particularly if they are promoted with healthful behaviors such as being physically active, influence adolescents' food choices, and ultimately their body mass index, over the long term. Copyright © 2011 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Depression. Does it affect the comprehension of receptive skills?

Science.gov (United States)

Rashtchi, Mojgan; Zokaee, Zahra; Ghaffarinejad, Ali R; Sadeghi, Mohammad M

2012-07-01

To compare the comprehension of depressed and non-depressed male and female Iranian learners of English as a Foreign Language (EFL) in receptive skills, and to investigate whether inefficiency in learning English could be due to depression. We selected 126 boys and 96 girls aged between 15 and 18 by simple random sampling from 2 high schools in Kerman, Iran to examine whether there was any significant relationship between depression and comprehension of receptive skills in males and females. We undertook this descriptive, correlational study between January and May 2011 in Kerman, Iran. After administration of the Beck Depression Inventory (BDI), we found that 93 students were non-depressed, 65 had minimal depression, 48 mild depression, and 16 suffered from severe depression. The correlation between participants` scores on listening and reading test with depression level indicated a significant relationship between depression and comprehension of both listening, and reading. Males had higher scores in both reading and listening. In listening, there was no significant difference among the levels of depression and males and females. Regarding the reading skill, there was no significant difference among levels of depression; however, the reading comprehension of males and females differed significantly. Learners who show a deficiency in receptive skills should be examined for the possibility of suffering from some degree of depression.

Changes in proliferating and apoptotic markers of leiomyoma following treatment with a selective progesterone receptor modulator or gonadotropin-releasing hormone agonist.

Science.gov (United States)

Yun, Bo Seong; Seong, Seok Ju; Cha, Dong Hyun; Kim, Ji Yeon; Kim, Mi-La; Shim, Jeong Yun; Park, Ji Eun

2015-08-01

To evaluate changes in proliferating and apoptotic markers of myoma tissue from patients treated with a selective progesterone receptor modulator (SPRM) or GnRH agonist by measuring expression of PDGF-A mRNA, IGF-1 mRNA, bcl-2 mRNA, and PCNA and caspase-3 protein. Between December 2013 and July 2014, women with symptomatic leiomyoma were divided into control (no treatment before surgery), SPRM (treatment with ulipristal acetate [SPRM] for 3 months before surgery), and GnRHa (treatment with leuprolide acetate [GnRH agonist] for 3 months before surgery) groups. Tissue specimens were collected from the myoma core and normal myometrium of all patients. The expression of mRNA and protein was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction and Western blot. A total of 38 patients were enrolled (control group, n=14; SPRM group, n=13; GnRHa group, n=11). PDGF-A mRNA expression was lower in both the myoma core and normal myometrium tissues of the SPRM compared with the control group, but there was no difference between the control and GnRHa group. There were also no group differences in bcl-2 mRNA or IGF-1 mRNA expression. Both PCNA and caspase-3 protein expression were higher in the leiomyoma tissue of the SPRM compared with the control group, but there was no difference between the control and GnRHa groups in the expression of either protein. Both proliferation and apoptosis were increased in the leiomyoma of patients after SPRM treatment, but there was no change following GnRH agonist treatment, in vivo. However, PDGF-A mRNA was decreased after SPRM treatment, indicating a dual effect of progesterone on the regulation of growth factors. Furthermore, there was an increase in caspase-3 protein, but not bcl-2 mRNA, expression in the SPRM group suggesting that SPRM may exert its effects in pathways other than the bcl-2 apoptotic pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Microdose Flare-up Gonadotropin-releasing Hormone (GnRH) Agonist Versus GnRH Antagonist Protocols in Poor Ovarian Responders Undergoing Intracytoplasmic Sperm Injection.

Science.gov (United States)

Boza, Aysen; Cakar, Erbil; Boza, Barıs; Api, Murat; Kayatas, Semra; Sofuoglu, Kenan

2016-01-01

Microdose flare-up GnRH agonist and GnRH antagonist have become more popular in the management of poor ovarian responders (POR) in recent years; however, the optimal protocol for POR patients undergoing in vitro fertilization has still been a challenge. In this observational study design, two hundred forty four poor ovarian responders were retrospectively evaluated for their response to GnRH agonist protocol (group-1, n=135) or GnRH antagonist protocol (group-2, n=109). Clinical pregnancy rate was the primary end point and was compared between the groups. Student t-test, Mann Whitney U test and χ (2)-test were used to compare the groups. The pmicrodose flare-up protocol has favorable outcomes with respect to the number of oocytes retrieved and implantation rate; nevertheless, the clinical pregnancy rate was found to be similar in comparison to GnRH antagonist protocol in poor ovarian responders. GnRH antagonist protocol appears to be promising with significantly lower gonadotropin requirement and lower treatment cost in poor ovarian responders.

Radiation Emergency Preparedness Tools: Virtual Community Reception Center

Centers for Disease Control (CDC) Podcasts

This podcast is an overview of resources from the Clinician Outreach and Communication Activity (COCA) Call: Practical Tools for Radiation Emergency Preparedness. A specialist working with CDC's Radiation Studies Branch describes a web-based training tool known as a Virtual Community Reception Center (vCRC).

”Savage Spain”? On the reception of Spanish art in Britain and Ireland

Directory of Open Access Journals (Sweden)

Edward Payne

2011-12-01

Full Text Available Review of: Nigel Glendinning and Hilary Macartney, eds, Spanish Art in Britain and Ireland, 1750–1920: Studies in Reception in Memory of Enriqueta Harris Frankfort, Woodbridge: Tamesis, 2010. This review evaluates the first scholarly study exclusively dedicated to the reception history of Spanish art in Britain and Ireland, 1750–1920. Progressing systematically through the different chapters, it highlights the various responses and perspectives that are addressed in the book. Issues of taste and collecting are examined, followed by historiographical concerns such as the methods and techniques of writing, illustrating and reproducing Spanish art in the nineteenth century. Shifting attitudes towards Spain and Spanish art are also explored, as are the roles of prominent figures in disseminating knowledge and appreciation of Spanish art, notably Sir William Stirling Maxwell and Richard Ford. Finally, the review outlines the critical fortunes of Spain’s foremost artists: Murillo, Velázquez, Ribera, Zurbarán and Goya. It ends by suggesting how this study could be expanded methodologically, considering the reception history of Spanish art in the light of important literature on reception theory and aesthetics.

Case study of French and Spanish fan reception of Game of Thrones

Directory of Open Access Journals (Sweden)

Mélanie Bourdaa

2015-06-01

Full Text Available The reception of the American TV show Game of Thrones (2011– by French and Spanish fans and nonfans is addressed via a qualitative methodology, the goal of which is to understand how European viewers perceive themselves as fans and what it means for them to be fans. Analysis of characteristics of a specifically European reception helps us learn what fan studies tell us about fans and what fans really think about fandoms.

Estrogen receptor beta-selective agonists stimulate calcium oscillations in human and mouse embryonic stem cell-derived neurons.

Directory of Open Access Journals (Sweden)

Lili Zhang

2010-07-01

Full Text Available Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERalpha and ERbeta on calcium oscillations in neurons derived from human (hES and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERbeta, but not ERalpha. The non-selective ER agonist 17beta-estradiol (E(2 rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERalpha agonist 4,4',4''-(4-Propyl-[1H]-pyrazole-1,3,5-triyltrisphenol (PPT. In contrast, the selective ERbeta agonists, 2,3-bis(4-Hydroxyphenyl-propionitrile (DPN, MF101, and 2-(3-fluoro-4-hydroxyphenyl-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041 stimulated calcium oscillations similar to E(2. The ERbeta agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERbeta activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERbeta signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds.

First-year university students' receptive and productive use of ...

African Journals Online (AJOL)

Kate H

Keywords: academic vocabulary, receptive knowledge, productive knowledge, collocations, vocabulary ...... The challenge of validation: Assessing the performance of a test of ..... This is a new drug used to tr…………… depression. 56.

Effect of thyrotrophin releasing hormone on opiate receptors of the rat brain

Energy Technology Data Exchange (ETDEWEB)

Balashov, A.M.; Shchurin, M.R.

1987-01-01

It has recently been shown that the hypothalamic thyrotropin releasing hormone (TRH) has the properties of a morphine antagonist, blocking its inhibitory action on respiration and, to a lesser degree, its analgesic action. This suggests that the antagonistic effects of TRH are mediated through its interaction with opiate receptors. The aim of this paper is to study this hypothesis experimentally. Tritium-labelled enkephalins in conjunction with scintillation spectroscopy were used to assess the receptor binding behavior. The results indicate the existence of interconnections between the opiate systems and TRH. Although it is too early to reach definite conclusions on the mechanisms of this mutual influence and its physiological significance it can be tentatively suggested that TRH abolishes the pharmacological effects of morphine by modulating the functional state of opiate reception.

The Reception of German Progressive Education in Russia: On Regularities of International Educational Transfer

Science.gov (United States)

Mchitarjan, Irina

2015-01-01

This article reports a historical case study of extensive educational transfer: the reception, adaptation, and use of German progressive education and German school reform ideas and practices in Russia at the beginning of the twentieth century. The reception of German educational ideas greatly enriched the theory and practice of the Russian school…

Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

Directory of Open Access Journals (Sweden)

Jennifer G. Robinson

2008-01-01

Full Text Available Trials of peroxisome proliferator-activated receptor (PPAR agonists have shown mixed results for cardiovascular prevention. Fibrates are PPAR- agonists that act primarily to improve dyslipidemia. Based on low- and high-density lipoprotein cholesterol (LDL and HDL effects, gemfibrozil may be of greater cardiovascular benefit than expected, fenofibrate performed about as expected, and bezafibrate performed worse than expected. Increases in both cardiovascular and noncardiovascular serious adverse events have been observed with some fibrates. Thiazolidinediones (TZDs are PPAR- agonists used to improve impaired glucose metabolism but also influence lipids. Pioglitazone reduces atherosclerotic events in diabetic subjects, but has no net cardiovascular benefit due to increased congestive heart failure risk. Rosiglitazone may increase the risk of atherosclerotic events, and has a net harmful effect on the cardiovascular system when congestive heart failure is included. The primary benefit of TZDs appears to be the prevention of diabetic microvascular complications. Dual PPAR-/ agonists have had unacceptable adverse effects but more selective agents are in development. PPAR- and pan-agonists are also in development. It will be imperative to prove that future PPAR agonists not only prevent atherosclerotic events but also result in a net reduction on total cardiovascular events without significant noncardiovascular adverse effects with long-term use.

Principles of agonist recognition in Cys-loop receptors

DEFF Research Database (Denmark)

Lynagh, Timothy Peter; Pless, Stephan Alexander

2014-01-01

, functional studies, and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically...

Central Infusion of Angiotensin II Type 2 Receptor Agonist Compound 21 Attenuates DOCA/NaCl-Induced Hypertension in Female Rats

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Shu-Yan Dai

2016-01-01

Full Text Available The present study investigated whether central activation of angiotensin II type 2 receptor (AT2-R attenuates deoxycorticosterone acetate (DOCA/NaCl-induced hypertension in intact and ovariectomized (OVX female rats and whether female sex hormone status has influence on the effects of AT2-R activation. DOCA/NaCl elicited a greater increase in blood pressure in OVX females than that in intact females. Central infusion of compound 21, a specific AT2-R agonist, abolished DOCA/NaCl pressor effect in intact females, whereas same treatment in OVX females produced an inhibitory effect. Real-time RT-PCR analysis revealed that DOCA/NaCl enhanced the mRNA expression of hypertensive components including AT1-R, ACE-1, and TNF-α in the paraventricular nucleus of hypothalamus in both intact and OVX females. However, the mRNA expressions of antihypertensive components such as AT2-R, ACE-2, and IL-10 were increased only in intact females. Central AT2-R agonist reversed the changes in the hypertensive components in all females, while this agonist further upregulated the expression of ACE2 and IL-10 in intact females, but only IL-10 in OVX females. These results indicate that brain AT2-R activation plays an inhibitory role in the development of DOCA/NaCl-induced hypertension in females. This beneficial effect of AT2-R activation involves regulation of renin-angiotensin system and proinflammatory cytokines.

Learning color receptive fields and color differential structure

NARCIS (Netherlands)

ter Haar Romenij, B.M.

2016-01-01

In this paper we study the role of brain plasticity, and investigate the emergence and self-emergence of receptive fields from scalar and color natural images by principal component analysis of image patches. We describe the classical experiment on localized PCA on center-surround weighted patches

Long-acting β2-agonists in asthma

DEFF Research Database (Denmark)

Jacobson, Glenn A; Raidal, Sharanne; Hostrup, Morten

2018-01-01

Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without...... and effects on BHR, particularly that (S)-enantiomers of β2-agonists may be deleterious to asthma control. LABAs display enantioselective pharmacokinetics and pharmacodynamics. Biological plausibility of the deleterious effects of β2-agonists (S)-enantiomers is provided by in vitro and in vivo studies from...... mechanism in rapid asthma deaths. More effort should therefore be applied to investigating potential enantiospecific effects of LABAs on safety, specifically bronchoprotection. Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are long overdue....

Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment

NARCIS (Netherlands)

N.S. Macklon (Nick); M.J.C. Eijkemans (René); M. Ludwig (Michael); R.E. Felberbaum; K. Diedrich; S. Bustion; E. Loumaye; B.C.J.M. Fauser (Bart); N.G.M. Beckers (Nicole)

2003-01-01

textabstractReplacing GnRH agonist cotreatment for the prevention of a premature rise in LH during ovarian stimulation for in vitro fertilization (IVF) by the late follicular phase administration of GnRH antagonist may render supplementation of the luteal phase redundant, because

Risk factors for children's receptive vocabulary development from four to eight years in the longitudinal study of Australian children.

Directory of Open Access Journals (Sweden)

Catherine L Taylor

Full Text Available Receptive vocabulary develops rapidly in early childhood and builds the foundation for language acquisition and literacy. Variation in receptive vocabulary ability is associated with variation in children's school achievement, and low receptive vocabulary ability is a risk factor for under-achievement at school. In this study, bivariate and multivariate growth curve modelling was used to estimate trajectories of receptive vocabulary development in relation to a wide range of candidate child, maternal and family level influences on receptive vocabulary development from 4-8 years. The study sample comprised 4332 children from the first nationally representative Longitudinal Study of Australian Children (LSAC. Predictors were modeled as risk variables with the lowest level of risk as the reference category. In the multivariate model, risks for receptive vocabulary delay at 4 years, in order of magnitude, were: Maternal Non- English Speaking Background (NESB, low school readiness, child not read to at home, four or more siblings, low family income, low birthweight, low maternal education, maternal mental health distress, low maternal parenting consistency, and high child temperament reactivity. None of these risks were associated with a lower rate of growth from 4-8 years. Instead, maternal NESB, low school readiness and maternal mental health distress were associated with a higher rate of growth, although not sufficient to close the receptive vocabulary gap for children with and without these risks at 8 years. Socio-economic area disadvantage, was not a risk for low receptive vocabulary ability at 4 years but was the only risk associated with a lower rate of growth in receptive vocabulary ability. At 8 years, the gap between children with and without socio-economic area disadvantage was equivalent to eight months of receptive vocabulary growth. These results are consistent with other studies that have shown that social gradients in children

Risk factors for children's receptive vocabulary development from four to eight years in the longitudinal study of Australian children.

Science.gov (United States)

Taylor, Catherine L; Christensen, Daniel; Lawrence, David; Mitrou, Francis; Zubrick, Stephen R

2013-01-01

Receptive vocabulary develops rapidly in early childhood and builds the foundation for language acquisition and literacy. Variation in receptive vocabulary ability is associated with variation in children's school achievement, and low receptive vocabulary ability is a risk factor for under-achievement at school. In this study, bivariate and multivariate growth curve modelling was used to estimate trajectories of receptive vocabulary development in relation to a wide range of candidate child, maternal and family level influences on receptive vocabulary development from 4-8 years. The study sample comprised 4332 children from the first nationally representative Longitudinal Study of Australian Children (LSAC). Predictors were modeled as risk variables with the lowest level of risk as the reference category. In the multivariate model, risks for receptive vocabulary delay at 4 years, in order of magnitude, were: Maternal Non- English Speaking Background (NESB), low school readiness, child not read to at home, four or more siblings, low family income, low birthweight, low maternal education, maternal mental health distress, low maternal parenting consistency, and high child temperament reactivity. None of these risks were associated with a lower rate of growth from 4-8 years. Instead, maternal NESB, low school readiness and maternal mental health distress were associated with a higher rate of growth, although not sufficient to close the receptive vocabulary gap for children with and without these risks at 8 years. Socio-economic area disadvantage, was not a risk for low receptive vocabulary ability at 4 years but was the only risk associated with a lower rate of growth in receptive vocabulary ability. At 8 years, the gap between children with and without socio-economic area disadvantage was equivalent to eight months of receptive vocabulary growth. These results are consistent with other studies that have shown that social gradients in children's developmental outcomes

Evaluation of receptivity of the medical students in a lecture of a large group

Directory of Open Access Journals (Sweden)

Vidyarthi SurendraK, Nayak RoopaP, GuptaSandeep K

2014-04-01

Full Text Available Background: Lecturing is widely used teaching method in higher education. Instructors of large classes may have only option to deliver lecture to convey informations to large group students.Aims and Objectives: The present study was to evaluate the effectiveness/receptivity of interactive lecturing in a large group of MBBS second year students. Material and Methods: The present study was conducted in the well-equipped lecture theater of Dhanalakshmi Srinivasan Medical College and Hospital (DSMCH, Tamil Nadu. A fully prepared interactive lecture on the specific topic was delivered by using power point presentation for second year MBBS students. Before start to deliver the lecture, instructor distributed multiple choice 10 questionnaires to attempt within 10 minutes. After 30 minutes of delivering lecture, again instructor distributed same 10 sets of multiple choice questionnaires to attempt in 10 minutes. The topic was never disclosed to the students before to deliver the lecture. Statistics: We analyzed the pre-lecture & post-lecture questions of each student by applying the paired t-test formula by using www.openepi.com version 3.01 online/offline software and by using Microsoft Excel Sheet Windows 2010. Results: The 31 male, 80 female including 111 students of average age 18.58 years baseline (pre-lecture receptivity mean % was 30.99 ± 14.64 and post-lecture receptivity mean % was increased upto 53.51± 19.52. The only 12 students out of 111 post-lecture receptivity values was less (mean % 25.8± 10.84 than the baseline (mean % 45± 9.05 receptive value and this reduction of receptivity was more towards negative side. Conclusion: In interactive lecture session with power point presentation students/learners can learn, even in large-class environments, but it should be active-learner centered.

A Pixel-Encoder Retinal Ganglion Cell with Spatially Offset Excitatory and Inhibitory Receptive Fields

Directory of Open Access Journals (Sweden)

Keith P. Johnson

2018-02-01

Full Text Available The spike trains of retinal ganglion cells (RGCs are the only source of visual information to the brain. Here, we genetically identify an RGC type in mice that functions as a pixel encoder and increases firing to light increments (PixON-RGC. PixON-RGCs have medium-sized dendritic arbors and non-canonical center-surround receptive fields. From their receptive field center, PixON-RGCs receive only excitatory input, which encodes contrast and spatial information linearly. From their receptive field surround, PixON-RGCs receive only inhibitory input, which is temporally matched to the excitatory center input. As a result, the firing rate of PixON-RGCs linearly encodes local image contrast. Spatially offset (i.e., truly lateral inhibition of PixON-RGCs arises from spiking GABAergic amacrine cells. The receptive field organization of PixON-RGCs is independent of stimulus wavelength (i.e., achromatic. PixON-RGCs project predominantly to the dorsal lateral geniculate nucleus (dLGN of the thalamus and likely contribute to visual perception.

[Hormonal (levonorgestrel) emergency contraception--effectiveness and mechanism of action].

Science.gov (United States)

Medard, Lech M; Ostrowska, Lucyna

2010-07-01

Periodic abstinence and coitus interruptus are the most popular methods of contraception in Poland. Recent studies have provided us with evidence that the so-called "menstrual calendar" may be much less effective than it was believed. In these circumstances, promotion and use of safe and truly effective contraceptives is very important for Polish women. Emergency contraception (EC) is a method which could be used even in cases when other contraception methods have failed. Mechanism of action of levonorgestrel used for EC and possible disturbances in the process of implantation of the blastocyst in the endometrium, remain the source of heated discussion among medical professionals. The latest publications provide us with evidence that the use of levonorgestrel in EC neither alters endometrial receptivity nor impedes implantation. Hormonal EC effectiveness is another hot topic of gynecological endocrinology and statistics. There is, however, no better, safer, and more ethically accepted method of preventing unwanted pregnancy for patients in need of postcoital contraception.

Cryopreserved embryo transfer: adjacent or non-adjacent to failed fresh long GnRH-agonist protocol IVF cycle.

Science.gov (United States)

Volodarsky-Perel, Alexander; Eldar-Geva, Talia; Holzer, Hananel E G; Schonberger, Oshrat; Reichman, Orna; Gal, Michael

2017-03-01

The optimal time to perform cryopreserved embryo transfer (CET) after a failed oocyte retrieval-embryo transfer (OR-ET) cycle is unknown. Similar clinical pregnancy rates were recently reported in immediate and delayed CET, performed after failed fresh OR-ET, in cycles with the gonadotrophin-releasing hormone (GnRH) antagonist protocol. This study compared outcomes of CET performed adjacently (<50 days, n = 67) and non-adjacently (≥50 to 120 days, n = 62) to the last OR-day of cycles with the GnRH agonist down-regulation protocol. Additional inclusion criteria were patients' age 20-38 years, the transfer of only 1-2 cryopreserved embryos, one treatment cycle per patient and artificial preparation for CET. Significantly higher implantation, clinical pregnancy and live birth rates were found in the non-adjacent group than in the adjacent group: 30.5% versus 11.3% (P = 0.001), 41.9% versus 17.9% (P = 0.003) and 32.3% versus 13.4% (P = 0.01), respectively. These results support the postponement of CET after a failed OR-ET for at least one menstrual cycle, when a preceding long GnRH-agonist protocol is used. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Small-molecule AT2 receptor agonists

DEFF Research Database (Denmark)

Hallberg, Mathias; Sumners, Colin; Steckelings, U Muscha

2018-01-01

The discovery of the first selective, small-molecule ATR receptor (AT2R) agonist compound 21 (C21) (8) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8, encompassing a phenylthiofen scaffold is the drug-like agonist...... with the highest affinity for the AT2R reported to date (Ki = 0.4 nM). Structure-activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8......, are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8) or AT2R antagonists (e.g. 9), respectively, are briefly addressed. A summary of the pharmacological actions of C21 (8) is also...

Gravitational wave reception by a sphere

International Nuclear Information System (INIS)

Ashby, N.; Dreitlein, J.

1975-01-01

The reception of gravitational waves by an elastic self-gravitating spherical detector is studied in detail. The equations of motion of a detector driven by a gravitational wave are presented in the intuitively convenient coordinate system of Fermi. An exact analytic solution is given for the homogeneous isotropic sphere. Nonlinear effects of a massive self-gravitating system are computed for a body of mass equal to that of the earth, and are shown to be numerically important

Variation Theory and the Reception of Chinese Literature in the English-speaking World

OpenAIRE

Cao, Shunqing

2015-01-01

In his article "Variation Theory and Reception of Chinese Literature in the English-Speaking World" Shunqing Cao introduces "variation theory" he developed and suggests that the framework can be applied in studying the dissemination and reception of Chinese literature in the English-speaking world. Cao argues that cultural and literary differences produce variations in literary exchanges among different cultures and variation theory concentrates on these variations. With unique perspectives o...

A Reception Analysis on the Youth Audiences of TV Series in Marivan

Directory of Open Access Journals (Sweden)

Omid Karimi

2014-03-01

Full Text Available The aim of this article is to describe the role of foreign media as the agitators of popular culture. For that with reception analysis it’s pay to describe decoding of youth audiences about this series. Globalization theory and Reception in Communication theory are formed the theoretical system of current article. The methodology in this research is qualitative one, and two techniques as in-depth interview and observation are used for data collection. The results show different people based on individual features, social and cultural backgrounds have inclination toward special characters and identify with them. This inclination so far the audience fallow the series because of his/her favorite character. Also there is a great compatibility between audience backgrounds and their receptions. A number of audience have criticized the series and point out the negative consequences on its society. However, seeing the series continue; really they prefer watching series enjoying to risks of it.

Long-acting beta(2)-agonists in management of childhood asthma

DEFF Research Database (Denmark)

Bisgaard, H

2000-01-01

This review assesses the evidence regarding the use of long-acting beta(2)-agonists in the management of pediatric asthma. Thirty double-blind, randomized, controlled trials on the effects of formoterol and salmeterol on lung function in asthmatic children were identified. Single doses of inhaled......, long-acting beta(2)-agonists provide effective bronchodilatation and bronchoprotection when used as intermittent, single-dose treatment of asthma in children, but not when used as regular treatment. Future studies should examine the positioning of long-acting beta(2)-agonists as an "as needed" rescue...... medication instead of short-acting beta(2)-agonists for pediatric asthma management....

Sibship size, sibling cognitive sensitivity, and children's receptive vocabulary.

Science.gov (United States)

Prime, Heather; Pauker, Sharon; Plamondon, André; Perlman, Michal; Jenkins, Jennifer

2014-02-01

The aim of the current study was to examine the relationship between sibship size and children's vocabulary as a function of quality of sibling interactions. It was hypothesized that coming from a larger sibship (ie, 3+ children) would be related to lower receptive vocabulary in children. However, we expected this association to be moderated by the level of cognitive sensitivity shown by children's next-in-age older siblings. Data on 385 children (mean age = 3.15 years) and their next-in-age older siblings (mean age = 5.57 years) were collected and included demographic questionnaires, direct testing of children's receptive vocabulary, and videos of mother-child and sibling interactions. Sibling dyads were taped engaging in a cooperative building task and tapes were coded for the amount of cognitive sensitivity the older sibling exhibited toward the younger sibling. Hierarchical regression analyses were conducted and showed an interaction between sibship size and sibling cognitive sensitivity in the prediction of children's receptive vocabulary; children exposed to large sibships whose next-in-age older sibling exhibited higher levels of cognitive sensitivity were less likely to show low vocabulary skills when compared with those children exposed to large sibships whose siblings showed lower levels of cognitive sensitivity. Children who show sensitivity to the cognitive needs of their younger siblings provide a rich environment for language development. The negative impact of large sibships on language development is moderated by the presence of an older sibling who shows high cognitive sensitivity.

Trial Watch: Toll-like receptor agonists for cancer therapy.

Science.gov (United States)

Vacchelli, Erika; Eggermont, Alexander; Sautès-Fridman, Catherine; Galon, Jérôme; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-08-01

Toll-like receptors (TLRs) have long been known for their ability to initiate innate immune responses upon exposure to conserved microbial components such as lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of pattern recognition receptors has been attributed a critical role in the elicitation of anticancer immune responses, raising interest in the development of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In spite of such an intense wave of preclinical and clinical investigation, only three TLR agonists are currently licensed by FDA for use in cancer patients: bacillus Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis that operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative of Salmonella minnesota that functions as a potent agonist of TLR4; and imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the August and September issues of OncoImmunology , we described the main biological features of TLRs and discussed the progress of clinical studies evaluating the safety and therapeutic potential of TLR agonists in cancer patients. Here, we summarize the latest developments in this exciting area of research, focusing on preclinical studies that have been published during the last 13 mo and clinical trials launched in the same period to investigate the antineoplastic activity of TLR agonists.

Ascorbic acid enables reversible dopamine receptor 3H-agonist binding

International Nuclear Information System (INIS)

Leff, S.; Sibley, D.R.; Hamblin, M.; Creese, I.

1981-01-01

The effects of ascorbic acid on dopaminergic 3 H-agonist receptor binding were studied in membrane homogenates of bovine anterior pituitary and caudate, and rat striatum. In all tissues virtually no stereospecific binding (defined using 1uM (+)butaclamol) of the 3 H-agonists N-propylnorapomorphine (NPA), apomorphine, or dopamine could be demonstrated in the absence of ascorbic acid. Although levels of total 3 H-agonist binding were three to five times greater in the absence than in the presence of 0.1% ascorbic acid, the increased binding was entirely non-stereospecific. Greater amounts of dopamine-inhibitable 3 H-NPA binding could be demonstrated in the absence of 0.1% ascorbic acid, but this measure of ''specific binding'' was demonstrated not to represent dopamine receptor binding since several other catecholamines and catechol were equipotent with dopamine and more potent than the dopamine agonist (+/-)amino-6,7-dihydroxy-1,2,3,4-tetrahydronapthalene (ADTN) in inhibiting this binding. High levels of dopamine-displaceable 3 H-agonist binding were detected in fresh and boiled homogenates of cerebellum, an area of brain which receives no dopaminergic innervation, further demonstrating the non-specific nature of 3 H-agonist binding in the absence of ascorbic acid. These studies emphasize that under typical assay conditions ascorbic acid is required in order to demonstrate reversible and specific 3 H-agonist binding to dopamine receptors

Agonist-induced affinity alterations of a central nervous system. cap alpha. -bungarotoxin receptor

Energy Technology Data Exchange (ETDEWEB)

Lukas, R.J.; Bennett, E.L.

1979-01-01

The ability of cholinergic agonists to block the specific interaction of ..cap alpha..-bungarotoxin (..cap alpha..-Bgt) with membrane-bound sites derived from rat brain is enhanced when membranes are preincubated with agonist. Thus, pretreatment of ..cap alpha..-Bgt receptors with agonist (but not antagonist) causes transformation of sites to a high-affinity form toward agonist. This change in receptor state occurs with a half-time on the order of minutes, and is fully reversible on dilution of agonist. The results are consistent with the identity of ..cap alpha..-Bgt binding sites as true central nicotinic acetylcholine receptors. Furthermore, this agonist-induced alteration in receptor state may represent an in vitro correlate of physiological desensitization. As determined from the effects of agonist on toxin binding isotherms, and on the rate of toxin binding to specific sites, agonist inhibition of toxin binding to the high-affinity state is non-competitive. This result suggests that there may exist discrete toxin-binding and agonist-binding sites on central toxin receptors.

Alpha-2A Adrenoceptor Agonist Guanfacine Restores Diuretic Efficiency in Experimental Cirrhotic Ascites: Comparison with Clonidine.

Directory of Open Access Journals (Sweden)

Giovanni Sansoè

Full Text Available In human cirrhosis, adrenergic hyperfunction causes proximal tubular fluid retention and contributes to diuretic-resistant ascites, and clonidine, a sympatholytic drug, improves natriuresis in difficult-to-treat ascites.To compare clonidine (aspecific α2-adrenoceptor agonist to SSP-002021R (prodrug of guanfacine, specific α2A-receptor agonist, both associated with diuretics, in experimental cirrhotic ascites.Six groups of 12 rats were studied: controls (G1; controls receiving furosemide and potassium canrenoate (G2; rats with ascitic cirrhosis due to 14-week CCl4 treatment (G3; cirrhotic rats treated (over the 11th-14th CCl4 weeks with furosemide and canrenoate (G4, furosemide, canrenoate and clonidine (G5, or diuretics and SSP002021R (G6. Three rats of each group had their hormonal status and renal function assessed at the end of 11th, 12th, 13th, and 14th weeks of respective treatments.Cirrhotic rats in G3 and G4 gained weight over the 12th-14th CCl4 weeks. In G4, brief increase in sodium excretion over the 11th-12th weeks preceded worsening of inulin clearance and natriuresis (diuretic resistance. In comparison with G4, the addition of clonidine (G5 or guanfacine (G6 to diuretics improved, respectively, sodium excretion over the 11th-12th CCl4 weeks, or GFR and electrolytes excretion over the 13th-14th CCl4 weeks. Natriuretic responses in G5 and G6 were accompanied by reduced catecholamine serum levels.α2A-receptor agonists restore glomerular filtration rate and natriuresis, and delay diuretic-resistant ascites in experimental advanced cirrhosis. Clonidine ameliorates diuretic-dependent natriuresis just for a short time.

Structure of receptive fields in a computational model of area 3b of primary sensory cortex.

Science.gov (United States)

Detorakis, Georgios Is; Rougier, Nicolas P

2014-01-01

In a previous work, we introduced a computational model of area 3b which is built upon the neural field theory and receives input from a simplified model of the index distal finger pad populated by a random set of touch receptors (Merkell cells). This model has been shown to be able to self-organize following the random stimulation of the finger pad model and to cope, to some extent, with cortical or skin lesions. The main hypothesis of the model is that learning of skin representations occurs at the thalamo-cortical level while cortico-cortical connections serve a stereotyped competition mechanism that shapes the receptive fields. To further assess this hypothesis and the validity of the model, we reproduced in this article the exact experimental protocol of DiCarlo et al. that has been used to examine the structure of receptive fields in area 3b of the primary somatosensory cortex. Using the same analysis toolset, the model yields consistent results, having most of the receptive fields to contain a single region of excitation and one to several regions of inhibition. We further proceeded our study using a dynamic competition that deeply influences the formation of the receptive fields. We hypothesized this dynamic competition to correspond to some form of somatosensory attention that may help to precisely shape the receptive fields. To test this hypothesis, we designed a protocol where an arbitrary region of interest is delineated on the index distal finger pad and we either (1) instructed explicitly the model to attend to this region (simulating an attentional signal) (2) preferentially trained the model on this region or (3) combined the two aforementioned protocols simultaneously. Results tend to confirm that dynamic competition leads to shrunken receptive fields and its joint interaction with intensive training promotes a massive receptive fields migration and shrinkage.

Structure of Receptive Fields in a Computational Model of Area 3b of Primary Sensory Cortex

Directory of Open Access Journals (Sweden)

Georgios eDetorakis

2014-07-01

Full Text Available In a previous work, we introduced a computational model of area 3b which is built upon the neural field theory and receives input from a simplified model of the index distal finger pad populated by a random set of touch receptors(Merkell cells. This model has been shown to be able to self-organize following the random stimulation of the finger pad model and to cope, to some extent, with cortical or skin lesions. The main hypothesis of the model is that learning of skin representations occurs at the thalamo-cortical level while cortico-cortical connections serve a stereotyped competition mechanism that shapes the receptive fields. To further assess this hypothesis and the validity of the model, we reproduced in this article the exact experimental protocol of DiCarlo et al. that has been used to examine the structure of receptive fields in area 3b of the primary somatosensory cortex. Using the same analysis toolset, the model yields consistent results, having most of the receptive fields to contain a single region of excitation and one to severalregions of inhibition. We further proceeded our study using a dynamic competition that deeply influences the formation of the receptive fields. We hypothesized this dynamic competition to correspond to some form of somatosensory attention that may help to precisely shape the receptive fields. To test this hypothesis, we designed a protocol where an arbitrary region of interest is delineated on the index distal finger pad and we either (1 instructed explicitly the model to attend to this region (simulating an attentional signal (2 preferentially trained the model on this region or (3combined the two aforementioned protocols simultaneously. Results tend to confirm that dynamic competition leads to shrunken receptive fields and its joint interaction with intensive training promotes a massive receptive fields migration and shrinkage.

Comparison of the effects of ovarian cauterization and gonadotropin-releasing hormone agonist and oral contraceptive therapy combination on endocrine changes in women with polycystic ovary disease.

Science.gov (United States)

Taskin, O; Yalcinoglu, A I; Kafkasli, A; Burak, F; Ozekici, U

1996-06-01

To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease (PCOD). Prospective, randomized. University-based infertility clinic. Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months. Serum concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin (SHBG) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment. The mean serum concentrations and the clinical profiles were similar in both groups. Both groups showed significant changes in LH, FSH, A, T, and SHBG compared with pretreatment levels. There were no significant differences in the final concentrations of LH, FSH, and A between the two study groups after each treatment, whereas T and SHBG levels were significantly different in the goserelin and OC group. The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [-59% and + 5.9% versus - 70% and + 13.5%, respectively]. Although the SHBG concentration increased in both groups, the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group. Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD. Considering the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD.

Online Movie Trailers - A Reception Analysis

OpenAIRE

Jensen, Frida Videbæk; Rozé, Caroline

2014-01-01

This project is a reception analysis of how a target group receive online movie trailers. It utilized a focus group as means of research with participants from the dormitories Kollibrien and Korallen. We concluded that the group we investigated were not interested in online movie trailers as anything else than a preview of a movie. They preferred to experience movie trailers in the cinema. Their opinion of specific movie trailers were also determined by whether or not they identified with the...

Pre-adolescent Receptivity to Tobacco Marketing and Its Relationship to Acquiring Friends Who Smoke and Cigarette Smoking Initiation.

Science.gov (United States)

Strong, David R; Messer, Karen; Hartman, Sheri J; Nodora, Jesse; Vera, Lisa; White, Martha M; Leas, Eric; Pharris-Ciurej, Nikolas; Borek, Nicolette; Pierce, John P

2017-10-01

This study extends research on receptivity to tobacco marketing over a key developmental period for cigarette smoking experimentation. The purpose of this study was to understand the effect of receptivity to tobacco marketing and exposure to friends who smoke on smoking experimentation. Participants were 10 to 13 years old who had never tried cigarettes (n = 878), interviewed six times at 8-month intervals. At baseline, 25% percent of the 10 and 11 years old in the sample of never smokers were receptive to tobacco marketing, while less than 5% had friends who smoked. Having a friend who smoked at study baseline and acquiring such friends for the first time during the study were the strongest predictors of smoking experimentation. Initial receptivity to tobacco marketing increased the risk of smoking experimentation independently of having friends who smoke at baseline or acquiring friends who smoke throughout the study period. The high level of receptivity observed even among 10 and 11 years old and its robust relationship with cigarette smoking experimentation independent of the significant risk associated with having friends who smoke suggests that successful prevention of receptivity may require intervention at an early age.

Adapting a receptive vocabulary test for preschool-aged Greek-speaking children.

Science.gov (United States)

Okalidou, Areti; Syrika, Asimina; Beckman, Mary E; Edwards, Jan R

2011-01-01

Receptive vocabulary is an important measure for language evaluations. Therefore, norm-referenced receptive vocabulary tests are widely used in several languages. However, a receptive vocabulary test has not yet been normed for Modern Greek. To adapt an American English vocabulary test, the Receptive One-Word Picture Vocabulary Test-II (ROWPVT-II), for Modern Greek for use with Greek-speaking preschool children. The list of 170 English words on ROWPVT-II was adapted by (1) developing two lists (A and B) of Greek words that would match either the target English word or another concept corresponding to one of the pictured objects in the four-picture array; and (2) determining a developmental order for the chosen Greek words for preschool-aged children. For the first task, adult word frequency measures were used to select the words for the Greek wordlist. For the second task, 427 children, 225 boys and 202 girls, ranging in age from 2;0 years to 5;11 years, were recruited from urban and suburban areas of Greece. A pilot study of the two word lists was performed with the aim of comparing an equal number of list A and list B responses for each age group and deriving a new developmental list order. The relative difficulty of each Greek word item, that is, its accuracy score, was calculated by taking the average proportion of correct responses across ages for that word. Subsequently, the word accuracy scores in the two lists were compared via regression analysis, which yielded a highly significant relationship (R(2) = 0.97; p word item from the two lists was a better fit. Finally, new starting levels (basals) were established for preschool ages. The revised word list can serve as the basis for adapting a receptive vocabulary test for Greek preschool-aged children. Further steps need to be taken when testing larger numbers of 2;0 to 5;11-year-old children on the revised word list for determination of norms. This effort will facilitate early identification and remediation

How do psychological factors influence adolescent smoking progression? The evidence for indirect effects through tobacco advertising receptivity.

Science.gov (United States)

Audrain-McGovern, Janet; Rodriguez, Daniel; Patel, Vaishali; Faith, Myles S; Rodgers, Kelli; Cuevas, Jocelyn

2006-04-01

To determine whether novelty seeking and depressive symptoms had mediated or indirect effects on adolescent smoking progression through tobacco advertising receptivity. More than 1000 adolescents were monitored from 9th grade to 12th grade and completed annual surveys that measured demographic characteristics, smoking behavior, tobacco advertising receptivity, novelty-seeking personality, depressive symptoms, family and peer smoking, alcohol use, and marijuana use. Latent growth modeling indicated that novelty seeking had a significant indirect effect on smoking progression through baseline tobacco advertising receptivity. For each 1-SD increase in novelty seeking, the odds of being more receptive to tobacco advertising increased by 12% (ie, being in a specific category or higher), which in turn resulted in an 11% increase in the odds of smoking progression from 9th grade to 12th grade. The indirect effect from depressive symptoms to smoking progression did not reach significance. These findings may inform future research on other factors that influence tobacco advertising receptivity, as well as programs aimed at preventing adolescent smoking initiation and progression.

From Iser to Turner and beyond: reception theory meets cognitive criticism

Directory of Open Access Journals (Sweden)

Craig Hamilton

2012-01-01

Full Text Available In this essay, we review the work of Wolfgang Iser, the major proponent of reception theory, and Mark Turner, the major proponent of cognitive criticism. The two theoretical lines advocated by Iser and Turner focus on the cognitive processes involved with reading literary texts. Unfortunately, bibliographic blind spots in both lines lead to the assumption that there is little overlap between reception theory and cognitive criticism. We put this assumption to rest by comparing and contrasting works by Iser and Turner in detail, starting with Iser’s work in the mid-1970s and ending with Turner’s work in the late 1990s.

Mapping the receptivity of malaria risk to plan the future of control in Somalia

Science.gov (United States)

Alegana, Victor Adagi; Patil, Anand Prabhakar; Moloney, Grainne; Borle, Mohammed; Yusuf, Fahmi; Amran, Jamal; Snow, Robert William

2012-01-01

Objectives To measure the receptive risks of malaria in Somalia and compare decisions on intervention scale-up based on this map and the more widely used contemporary risk maps. Design Cross-sectional community Plasmodium falciparum parasite rate (PfPR) data for the period 2007–2010 corrected to a standard age range of 2 to Somalia. Participants Randomly sampled individuals of all ages. Main outcome measure Cartographic descriptions of malaria receptivity and contemporary risks in Somalia at the district level. Results The contemporary annual PfPR2–10 map estimated that all districts (n=74) and population (n=8.4 million) in Somalia were under hypoendemic transmission (≤10% PfPR2–10). Of these, 23% of the districts, home to 13% of the population, were under transmission of 10%–50% PfPR2–10) and the rest as hypoendemic. Conclusion Compared with maps of receptive risks, contemporary maps of transmission mask disparities of malaria risk necessary to prioritise and sustain future control. As malaria risk declines across Africa, efforts must be invested in measuring receptivity for efficient control planning. PMID:22855625

The effectiveness of correcting codes in reception in the whole in additive normal white noise

Science.gov (United States)

Shtarkov, Y. M.

1974-01-01

Some possible criteria for estimating the effectiveness of correcting codes are presented, and the energy effectiveness of correcting codes is studied for symbol-by-symbol reception. Expressions for the energetic effectiveness of binary correcting codes for reception in the whole are produced. Asymptotic energetic effectiveness and finite signal/noise ratio cases are considered.

Molecular sampling of the allosteric binding pocket of the TSH receptor provides discriminative pharmacophores for antagonist and agonists.

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Hoyer, Inna; Haas, Ann-Karin; Kreuchwig, Annika; Schülein, Ralf; Krause, Gerd

2013-02-01

The TSHR (thyrotropin receptor) is activated endogenously by the large hormone thyrotropin and activated pathologically by auto-antibodies. Both activate and bind at the extracellular domain. Recently, SMLs (small-molecule ligands) have been identified, which bind in an allosteric binding pocket within the transmembrane domain. Modelling driven site-directed mutagenesis of amino acids lining this pocket led to the delineation of activation and inactivation sensitive residues. Modified residues showing CAMs (constitutively activating mutations) indicate signalling-sensitive positions and mark potential trigger points for agonists. Silencing mutations lead to an impairment of basal activity and mark contact points for antagonists. Mapping these residues on to a structural model of TSHR indicates locations where an SML may switch the receptor to an inactive or active conformation. In the present article, we report the effects of SMLs on these signalling-sensitive amino acids at the TSHR. Surprisingly, the antagonistic effect of SML compound 52 was reversed to an agonistic effect, when tested at the CAM Y667A. Switching agonism to antagonism and the reverse by changing either SMLs or residues covering the binding pocket provides detailed knowledge about discriminative pharmacophores. It prepares the basis for rational optimization of new high-affinity antagonists to interfere with the pathogenic activation of the TSHR.

Vocabulary and Receptive Knowledge of English Collocations among Swedish Upper Secondary School Students

OpenAIRE

Bergström, Kerstin

2008-01-01

The aim of this study is to examine the vocabulary and receptive collocation knowledge in English among Swedish upper secondary school students. The primary material consists of two vocabulary tests, one collocation test, and a background questionnaire. The first research question concerns whether the students who receive a major part of their education in English have a higher level of vocabulary and receptive collocation knowledge in English than those who are taught primarily in Swedish. T...

Unique interaction pattern for a functionally biased ghrelin receptor agonist

DEFF Research Database (Denmark)

Sivertsen, Bjørn Behrens; Lang, Manja; Frimurer, Thomas M.

2011-01-01

Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers...... connecting the D-Trp-Phe-D-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH(2), where Isn is isonipecotic acid) ~80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained w......Fw-Isn-NH(2) was found to be a functionally biased agonist. Thus, wFw-Isn-NH(2) mediated potent and efficacious signaling through the Ga(q) and ERK1/2 signaling pathways, but in contrast to all previous ghrelin receptor agonists it did not signal through the serum response element, conceivably the Ga(12...

Beneficial effects of a N-terminally modified GIP agonist on tissue-level bone material properties.

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Mabilleau, Guillaume; Mieczkowska, Aleksandra; Irwin, Nigel; Simon, Yannick; Audran, Maurice; Flatt, Peter R; Chappard, Daniel

2014-06-01

Bone remodeling is under complex regulation from nervous, hormonal and local signals, including gut hormones. Among the gut hormones, a role for the glucose-dependent insulinotropic polypeptide (GIP) has been suggested. However, the rapid degradation of GIP in the bloodstream by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4) precludes therapeutic use. To circumvent this problem, a series of N-terminally modified GIP agonists have been developed, with N-AcGIP being the most promising. The aims of the present study were to investigate the effects of N-AcGIP on bone at the micro-level using trabecular and cortical microstructural morphology, and at the tissue-level in rats. Copenhagen rats were randomly assigned into control or N-AcGIP-treated groups and received daily injection for 4 weeks. Bone microstructural morphology was assessed by microCT and dynamic histomorphometry and tissue-level properties by nanoindentation, qBEI and infra-red microscopy. Four week treatment with N-AcGIP did not alter trabecular or cortical microstructural morphology. In addition, no significant modifications of mechanical response and properties at the tissue-level were observed in trabecular bone. However, significant augmentations in maximum load (12%), hardness (14%), indentation modulus (13%) and dissipated energy (16%) were demonstrated in cortical bone. These beneficial modifications of mechanical properties at the tissue-level were associated with increased mineralization (22%) and collagen maturity (13%) of the bone matrix. Taken together, the results support a beneficial role of GIP, and particularly stable analogs such as N-AcGIP, on tissue material properties of bone. Copyright © 2014 Elsevier Inc. All rights reserved.

The effects of echolalia on acquisition and generalization of receptive labeling in autistic children.

OpenAIRE

Charlop, M H

1983-01-01

This investigation, consisting of two experiments, was designed to assess the effects of autistic immediate echolalia on acquisition and generalization of receptive labeling tasks. Experiment 1 addressed whether autistic children could use their echolalia to facilitate acquisition. The results indicated that incorporating echolalia (echo of the requested object's label) into the task before manual response (handing the requested object to the experimenter) facilitated receptive labeling. Expe...

Clinical investigations of receptive and expressive musical functions after stroke

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Ken eRosslau

2015-06-01

Full Text Available There is a long tradition of investigating various disorders of musical abilities after stroke. These impairments, associated with acquired amusia, can be highly selective, affecting only music perception (i.e., receptive abilities/functions or expression (music production abilities, and some patients report that these may dramatically influence their emotional state. The aim of this study was to systematically test both the melodic and rhythmic domains of music perception and expression in left- and right-sided stroke patients compared to healthy subjects. Music perception was assessed using rhythmic and melodic discrimination tasks, while tests of expressive function involved the vocal or instrumental reproduction of rhythms and melodies. Our approach revealed deficits in receptive and expressive functions in stroke patients, mediated by musical expertise. Those patients who had experienced a short period of musical training in childhood and adolescence performed better in the receptive and expressive subtests compared to those without any previous musical training. While discrimination of specific musical patterns was unimpaired after a right-sided stroke, patients with a left-sided stroke had worse results for fine melodic and rhythmic analysis. In terms of expressive testing, the most consistent results were obtained from a test that required patients to reproduce sung melodies. This implies that the means of investigating production abilities can impact the identification of deficits.

Clinical investigations of receptive and expressive musical functions after stroke.

Science.gov (United States)

Rosslau, Ken; Steinwede, Daniel; Schröder, C; Herholz, Sibylle C; Lappe, Claudia; Dobel, Christian; Altenmüller, Eckart

2015-01-01

There is a long tradition of investigating various disorders of musical abilities after stroke. These impairments, associated with acquired amusia, can be highly selective, affecting only music perception (i.e., receptive abilities/functions) or expression (music production abilities), and some patients report that these may dramatically influence their emotional state. The aim of this study was to systematically test both the melodic and rhythmic domains of music perception and expression in left- and right-sided stroke patients compared to healthy subjects. Music perception was assessed using rhythmic and melodic discrimination tasks, while tests of expressive function involved the vocal or instrumental reproduction of rhythms and melodies. Our approach revealed deficits in receptive and expressive functions in stroke patients, mediated by musical expertise. Those patients who had experienced a short period of musical training in childhood and adolescence performed better in the receptive and expressive subtests compared to those without any previous musical training. While discrimination of specific musical patterns was unimpaired after a left-sided stroke, patients with a right-sided stroke had worse results for fine melodic and rhythmic analysis. In terms of expressive testing, the most consistent results were obtained from a test that required patients to reproduce sung melodies. This implies that the means of investigating production abilities can impact the identification of deficits.

Mechanisms of action of hormonal emergency contraceptives.

Science.gov (United States)

Leung, Vivian W Y; Levine, Marc; Soon, Judith A

2010-02-01

Hormonal emergency contraceptives have been used to prevent unwanted pregnancy for more than 3 decades. The mechanisms of action of the regimen containing a combination of estrogen and progestin, known as the Yuzpe regimen, and those of the levonorgestrel regimen continue to be controversial, especially over the possibility that these regimens might act by interfering with implantation of the fertilized ovum. We performed a search of the PubMed (1949-July 2009) and EMBASE (1980-July 2009) databases to identify literature on the mechanisms of action of these contraceptive regimens, and data were extracted from pertinent English-language studies. We classified studies according to the approach taken by the investigators to study the actions of emergency contraceptives on pregnancy: an indirect method that uses statistical models to determine whether emergency contraceptives would be as effective as reported if they act only by disrupting ovulation; direct observation of the effects of emergency contraceptives on surrogate outcomes, including ovulation, sperm activity, hormonal levels, and endometrial receptivity to implantation; and analysis of directly observed pregnancy outcomes against statistical data. Acceptability of emergency contraceptives by women and clinicians may depend on personal opinions about when life or pregnancy begins. The evidence strongly supports disruption of ovulation as a mechanism of action. The data suggest that emergency contraceptives are unlikely to act by interfering with implantation, although the possibility has not been completely excluded. The data also suggest that emergency contraceptives are ineffective after ovulation. Women and clinicians who consider implantation or later events to be the beginning of pregnancy should be aware that emergency contraceptives are likely nonabortive by this definition of pregnancy.

Receptivity to protobacco media and its impact on cigarette smoking among ethnic minority youth in California.

Science.gov (United States)

Chen, Xinguang; Cruz, Tess Boley; Schuster, Darleen V; Unger, Jennifer B; Johnson, Carl Anderson

2002-01-01

Adolescents from different ethnic groups show different cigarette smoking prevalence rates, suggesting potential differences in receptivity to and influences from protobacco media. Understanding these differences will be helpful in tailoring smoking prevention and cessation programs for diverse adolescent populations in the United States. Data from cross-sectional surveys of 20,332 randomly sampled California boys and girls, 12-17 years of age, were analyzed. Results indicate that receptivity to protobacco media was lower among African Americans, Asian Americans, and Hispanics than among White youth. There was a consistent dose-response relationship between receptivity to protobacco media and 30-day cigarette smoking across ethnic groups. Having a cigarette brand preference was associated with the highest risk for cigarette smoking, having a favorite tobacco ad showed the lowest risk, while having received or being willing to use tobacco promotional items was associated with a moderate risk. After controlling for 13 covariates, the odds ratio for receptivity to protobacco media and 30-day cigarette smoking was significant for Whites (RR = 1.38, p 0.05) and Asian American (RR = 1.17, p > 0.05) youth. African American, Asian American, and Hispanic adolescents have a lower level of receptivity to protobacco media than do Whites. The association between media receptivity and 30-day cigarette smoking exists for all four ethnic groups without controlling for other smoking predictor variables, but only for Hispanics and Whites when other variables are controlled. Protecting adolescents from protobacco advertising influences is an important element in tobacco control among ethnic minority youth.

Receptivity to Kinetic Fluctuations: A Multiple Scales Approach

Science.gov (United States)

Edwards, Luke; Tumin, Anatoli

2017-11-01

The receptivity of high-speed compressible boundary layers to kinetic fluctuations (KF) is considered within the framework of fluctuating hydrodynamics. The formulation is based on the idea that KF-induced dissipative fluxes may lead to the generation of unstable modes in the boundary layer. Fedorov and Tumin solved the receptivity problem using an asymptotic matching approach which utilized a resonant inner solution in the vicinity of the generation point of the second Mack mode. Here we take a slightly more general approach based on a multiple scales WKB ansatz which requires fewer assumptions about the behavior of the stability spectrum. The approach is modeled after the one taken by Luchini to study low speed incompressible boundary layers over a swept wing. The new framework is used to study examples of high-enthalpy, flat plate boundary layers whose spectra exhibit nuanced behavior near the generation point, such as first mode instabilities and near-neutral evolution over moderate length scales. The configurations considered exhibit supersonic unstable second Mack modes despite the temperature ratio Tw /Te > 1 , contrary to prior expectations. Supported by AFOSR and ONR.

Serum inhibin A and inhibin B in central precocious puberty before and during treatment with GnRH agonists

DEFF Research Database (Denmark)

Sehested, A; Andersson, A M; Müller, J

2000-01-01

both gonadotropins and estradiol levels become suppressed. We therefore investigated serum levels of inhibin A and inhibin B in girls with CPP at diagnosis and during treatment in order to test the hypothesis that inhibin secretion would increase and decrease in parallel with the activation......Serum levels of the gonadal hormones inhibin A and inhibin B are undetectable or low in prepubertal girls, and rise during puberty. In girls with central precocious puberty (CPP) the hypothalamic-pituitary-gonadal axis is prematurely activated, if the girl is thereafter treated with GnRH agonists...... and suppression of the hypothalamic-pituitary-gonadal axis. Serum levels of inhibin A and inhibin B were significantly (p 0.0005) elevated in 42 girls at diagnosis of CPP (inhibin A: 7 pg/ml (...

Cortico-Cortical Receptive Field Estimates in Human Visual Cortex

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Koen V Haak

2012-05-01

Full Text Available Human visual cortex comprises many visual areas that contain a map of the visual field (Wandell et al 2007, Neuron 56, 366–383. These visual field maps can be identified readily in individual subjects with functional magnetic resonance imaging (fMRI during experimental sessions that last less than an hour (Wandell and Winawer 2011, Vis Res 718–737. Hence, visual field mapping with fMRI has been, and still is, a heavily used technique to examine the organisation of both normal and abnormal human visual cortex (Haak et al 2011, ACNR, 11(3, 20–21. However, visual field mapping cannot reveal every aspect of human visual cortex organisation. For example, the information processed within a visual field map arrives from somewhere and is sent to somewhere, and visual field mapping does not derive these input/output relationships. Here, we describe a new, model-based analysis for estimating the dependence between signals in distinct cortical regions using functional magnetic resonance imaging (fMRI data. Just as a stimulus-referred receptive field predicts the neural response as a function of the stimulus contrast, the neural-referred receptive field predicts the neural response as a function of responses elsewhere in the nervous system. When applied to two cortical regions, this function can be called the cortico-cortical receptive field (CCRF. We model the CCRF as a Gaussian-weighted region on the cortical surface and apply the model to data from both stimulus-driven and resting-state experimental conditions in visual cortex.

Neoadjuvant hormonal therapy and external-beam radiotherapy versus external-beam irradiation alone for prostate cancer. A quality-of-life analysis

Energy Technology Data Exchange (ETDEWEB)

Pinkawa, Michael; Piroth, Marc D.; Asadpour, Branka; Gagel, Bernd; Fischedick, Karin; Siluschek, Jaroslav; Kehl, Mareike; Krenkel, Barbara; Eble, Michael J. [RWTH Aachen (Germany). Dept. of Radiotherapy

2009-02-15

To evaluate the impact of neoadjuvant hormonal therapy (NHT) on quality of life after external-beam radiotherapy (EBRT) for prostate cancer. A group of 170 patients (85 with and 85 without NHT) has been surveyed prospectively before EBRT (70.2-72 Gy), at the last day of EBRT, a median time of 2 months and 15 months after EBRT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Pairs with and without NHT (median treatment time of 3.5 months before EBRT) were matched according to the respective planning target volume and prostate volume. Before EBRT, significantly lower urinary function/bother, sexual function and hormonal function/bother scores were found for patients with NHT. More than 1 year after EBRT, only sexual function scores remained lower. In a multivariate analysis, NHT and adjuvant hormonal therapy (HT) versus NHT only (hazard ratio 14; 95% confidence interval 2.7-183; p = 0.02) and luteinizing hormone-releasing hormone (LHRH) agonists versus antiandrogens (hazard ratio 3.6; 95% confidence interval 1.1-12; p = 0.04) proved to be independent risk factors for long-term erectile dysfunction (no or very poor ability to have an erection). With the exception of sexual function (additional adjuvant HT and application of LHRH analog independently adverse), short-term NHT was not found to decrease quality of life after EBRT for prostate cancer. (orig.)

Comparative ovarian microarray analysis of juvenile hormone-responsive genes in water flea Daphnia magna: potential targets for toxicity.

Science.gov (United States)

Toyota, Kenji; Williams, Timothy D; Sato, Tomomi; Tatarazako, Norihisa; Iguchi, Taisen

2017-03-01

The freshwater zooplankton Daphnia magna has been extensively employed in chemical toxicity tests such as OECD Test Guidelines 202 and 211. Previously, it has been demonstrated that the treatment of juvenile hormones (JHs) or their analogues to female daphnids can induce male offspring production. Based on this finding, a rapid screening method for detection of chemicals with JH-activity was recently developed using adult D. magna. This screening system determines whether a chemical has JH-activity by investigating the male offspring inducibility. Although this is an efficient high-throughput short-term screening system, much remains to be discovered about JH-responsive pathways in the ovary, and whether different JH-activators act via the same mechanism. JH-responsive genes in the ovary including developing oocytes are still largely undescribed. Here, we conducted comparative microarray analyses using ovaries from Daphnia magna treated with fenoxycarb (Fx; artificial JH agonist) or methyl farnesoate (MF; a putative innate JH in daphnids) to elucidate responses to JH agonists in the ovary, including developing oocytes, at a JH-sensitive period for male sex determination. We demonstrate that induction of hemoglobin genes is a well-conserved response to JH even in the ovary, and a potential adverse effect of JH agonist is suppression of vitellogenin gene expression, that might cause reduction of offspring number. This is the first report demonstrating different transcriptomics profiles from MF and an artificial JH agonist in D. magna ovary, improving understanding the tissue-specific mode-of-action of JH. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Nonlinear absorption and receptivity of the third order in InAs infrared region

International Nuclear Information System (INIS)

Musayev, M.A.

2005-01-01

Nonlinear absorption and receptivity of the third order and coefficient nonlinear absorption in InAs n-type with different degree of alloying was measured. Obtained score considerably exceed sense, calculated on the basis of the models describing nonlinear receptivity of electrons, situated in the nonparabolic area of conductivity. It was shown that, observable deviations withdraw; if in the calculation apply energy dissipation of electrons. Growth of the efficiency under four-wave interaction in low-energy-gap semiconductors confines nonlinear absorption of interacting waves

Werner Sombart and his reception in Italy

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Simona Pisanelli

2015-03-01

Full Text Available This article intends to focus on the difficulty encountered by Werner Sombart’s works in gaining a hearing in various Italian intellectual circuits. As is well known, Sombart belonged to the German Historical School of economics, sharing with other scholars of that school the same problems in getting his work known in Italy. Our aim is to explain the reason for this hostile reception. First of all, we will analyze the factors which generally hindered the spread of the German Historical School in Italy, recognizing in economists like Francesco Ferrara, Idealists like Benedetto Croce and Marxists like Antonio Labriola some of its strongest opponents. We will dwell on the cases of Gustav Schmoller and Max Weber, in order to give two representative examples of the slow and complicated Italian reception of methodological approaches and analytical perspectives which characterized the scientific experience of the German Historical School. Secondly, we will try to show why Sombart was even less appreciated than other German social scientists, giving the reasons that attracted severe criticism from economists, economic historians and sociologists towards his interdisciplinary approach in the analysis of modern capitalism. Finally, we will show the reasons of the contemporary rediscovery of Sombart and of his works.

Qualitative Audience Research: Toward an Integrative Approach to Reception.

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Jensen, Klaus Bruhn

1987-01-01

Analyzes research about the mass communication audience and describes a theoretical and methodological framework for further empirical studies. Discusses the (1) explanatory value of qualitative research; (2) social and cultural implications of the reception process, with special reference to television; and (3) applications and social relevance…

In vivo correlation between c-Fos expression and corticotroph stimulation by adrenocorticotrophic hormone secretagogues in rat anterior pituitary gland.

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Takigami, Shu; Fujiwara, Ken; Kikuchi, Motoshi; Yashiro, Takashi

2008-03-01

In the anterior pituitary gland, c-Fos expression is evoked by various stimuli. However, whether c-Fos expression is directly related to the stimulation of anterior pituitary cells by hypothalamic secretagogues is unclear. To confirm whether the reception of hormone-releasing stimuli evokes c-Fos expression in anterior pituitary cells, we have examined c-Fos expression of anterior pituitary glands in rats administered with synthetic corticotrophin-releasing hormone (CRH) intravenously or subjected to restraint stress. Single intravenous administration of CRH increases the number of c-Fos-expressing cells, and this number does not change even if the dose is increased. Double-immunostaining has revealed that most of the c-Fos-expressing cells contain adrenocorticotrophic hormone (ACTH); corticotrophs that do not express c-Fos in response to CRH have also been found. However, restraint stress evokes c-Fos expression in most of the corticotrophs and in a partial population of lactotrophs. These results suggest that c-Fos expression increases in corticotrophs stimulated by ACTH secretagogues, including CRH. Furthermore, we have found restricted numbers of corticotrophs expressing c-Fos in response to CRH. Although the mechanism underlying the different responses to CRH is not apparent, c-Fos is probably a useful immunohistochemical marker for corticotrophs stimulated by ACTH secretagogues.

Do Sex, Sex-Role Orientation, and Exposure to Gender-Congruent Therapy Models Influence Receptivity to Psychotherapy?

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Park, Heather L.; Hatchett, Gregory T.

2006-01-01

This study had two objectives. The first objective was to evaluate how well sex and sex-role orientation predicted receptivity to psychotherapy. The second objective was to evaluate whether exposure to gender-congruent therapy videos influenced participants' receptivity to psychotherapy. Participants were randomly assigned to three conditions: (1)…

Eugen Bleuler 150: Bleuler's reception of Freud.

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Dalzell, Thomas G

2007-12-01

On the 150th anniversary of Eugen Bleuler's birth, this article examines his reception of Sigmund Freud and his use of Freudian theory to understand the symptoms of schizophrenia. In addition, in contrast to earlier interpretations of Bleuler's relationship with Freud in terms of an eventual personal and theoretical incompatibility, the article demonstrates that, although Bleuler did distance himself from the psychoanalytic movement, he remained consistent in his views on Freud's theories.

Metabolic effects of beta2-agonists in relation to exercise performance

DEFF Research Database (Denmark)

Kalsen, Anders

2015-01-01

athletes. The present PhD thesis is based on four manuscripts in which the acute effects of beta2-agonists on exercise performance were investigated. The aims were 1) to investigate whether supratherapeutic inhalation of beta2-agonists enhances muscle strength, anaerobic performance and aerobic performance......, 2) to uncover the mechanisms behind potential beta2-adrenergic improvements in anaerobic performance, 3) to investigate whether inhalation of beta2-agonists is ergogenic in elite athletes with or without airway hyperresponsiveness (AHR). Results from the studies of the thesis show...... administration of a certain dose, but a further increase in dose does not seem to elicit a greater performance-enhancing effect. Moreover, the effects of beta2-agonists on performance are unaffected by training status and AHR, but athletes with AHR who regularly use beta2-agonists get a reduced ergogenic...

Conceptual scoring of receptive and expressive vocabulary measures in simultaneous and sequential bilingual children.

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Gross, Megan; Buac, Milijana; Kaushanskaya, Margarita

2014-11-01

The authors examined the effects of conceptual scoring on the performance of simultaneous and sequential bilinguals on standardized receptive and expressive vocabulary measures in English and Spanish. Participants included 40 English-speaking monolingual children, 39 simultaneous Spanish-English bilingual children, and 19 sequential bilingual children, ages 5-7. The children completed standardized receptive and expressive vocabulary measures in English and also in Spanish for those who were bilingual. After the standardized administration, bilingual children were given the opportunity to respond to missed items in their other language to obtain a conceptual score. Controlling for group differences in socioeconomic status (SES), both simultaneous and sequential bilingual children scored significantly below monolingual children on single-language measures of English receptive and expressive vocabulary. Conceptual scoring removed the significant difference between monolingual and simultaneous bilingual children in the receptive modality but not in the expressive modality; differences remained between monolingual and sequential bilingual children in both modalities. However, in both bilingual groups, conceptual scoring increased the proportion of children with vocabulary scores within the average range. Conceptual scoring does not fully ameliorate the bias inherent in single-language standardized vocabulary measures for bilingual children, but the procedures employed here may assist in ruling out vocabulary deficits, particularly in typically developing simultaneous bilingual children.

Attention directed by expectations enhances receptive fields in cortical area MT.

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Ghose, Geoffrey M; Bearl, David W

2010-02-22

Expectations, especially those formed on the basis of extensive training, can substantially enhance visual performance. However, it is not clear that the physiological mechanisms underlying this enhancement are identical to those examined by experiments in which attention is directed by explicit instructions rather than strong expectations. To study the changes in visual representations associated with strong expectations, we trained animals to detect a brief motion pulse that was embedded in noise. Because the nature of the pulse and the statistics of its appearance were well known to the animals, they formed strong expectations which determined their behavioral performance. We used white-noise methods to infer the receptive field structure of single neurons in area MT while they were performing this task. Incorporating non-linearities, we compared receptive fields during periods of time when the animals were expecting the motion pulse with periods of time when they were not. We found receptive field changes consistent with an increased reliability in signaling pulse occurrence. Moreover, these changes were not consistent with a simple gain modulation. The results suggest that strong expectations can create very specific changes in the visual representations at a cellular level to enhance performance. Copyright 2009 Elsevier Ltd. All rights reserved.

PPARα-Independent Arterial Smooth Muscle Relaxant Effects of PPARα Agonists

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Neerupma Silswal

2012-01-01

Full Text Available We sought to determine direct vascular effects of peroxisome proliferator-activated receptor alpha (PPARα agonists using isolated mouse aortas and middle cerebral arteries (MCAs. The PPARα agonists GW7647, WY14643, and gemfibrozil acutely relaxed aortas held under isometric tension and dilated pressurized MCAs with the following order of potency: GW7647≫WY14643>gemfibrozil. Responses were endothelium-independent, and the use of PPARα deficient mice demonstrated that responses were also PPARα-independent. Pretreating arteries with high extracellular K+ attenuated PPARα agonist-mediated relaxations in the aorta, but not in the MCA. In the aorta, the ATP sensitive potassium (KATP channel blocker glibenclamide also impaired relaxations whereas the other K+ channel inhibitors, 4-aminopyridine and Iberiotoxin, had no effect. In aortas, GW7647 and WY14643 elevated cGMP levels by stimulating soluble guanylyl cyclase (sGC, and inhibition of sGC with ODQ blunted relaxations to PPARα agonists. In the MCA, dilations were inhibited by the protein kinase C (PKC activator, phorbol 12,13-dibutyrate, and also by ODQ. Our results demonstrated acute, nonreceptor-mediated relaxant effects of PPARα agonists on smooth muscle of mouse arteries. Responses to PPARα agonists in the aorta involved KATP channels and sGC, whereas in the MCA the PKC and sGC pathways also appeared to contribute to the response.

The Judaeo-Karaite Reception of the Hebrew Bible

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Sabih, Joshua

DESCRIPTION: The Karaites emerged as a school of thought within Middle Eastern Judaism in the 8th century. The Karaites were a “reading community” whose intellectual activity and daily lives were based around the divine scriptures. Over time Karaism became one of the two main competing schools of...... between the Rabbinate and the Karaite reception and interpretation of the Hebrew Bible....

Intervention for Mixed Receptive-Expressive Language Impairment: A Review

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Boyle, James; McCartney, Elspeth; O'Hare, Anne; Law, James

2010-01-01

Studies indicate that language impairment that cannot be accounted for by factors such as below-average non-verbal ability, hearing impairment, behaviour or emotional problems, or neurological impairments affects some 6% of school-age children. Language impairment with a receptive language component is more resistant to intervention than specific…

Semi-quantitative analysis of endometrial receptivity marker mRNA ...

African Journals Online (AJOL)

In fertile women, expression of molecular marker of endometrial receptivity, HOXA11, leukemia inhibitory factor (LIF) and basic transcriptional element binding protein 1 (BTEB1), rises during the luteal phase with the peak occurring during the implantation window. We evaluated the transcript levels of HOXA-11, LIF and ...

The Possible Effect Of Tamoxifen Vs Whole Body Irradiation Treatment On Thyroid Hormones in Female Rats Bearing Mammary Tumors Chemically Induced

International Nuclear Information System (INIS)

Abdelgawad, M.R.

2012-01-01

Breast cancer is the most common malignancy among women in most developed and developing regions of the world. In women, this drug has tissuespecific effects, acting as an estrogen antagonist on the breast, and as an estrogen agonist on bone, lipid metabolism (increasing high-density lipoprotein cholesterol and decreasing low-density lipoprotein cholesterol), and the endometrium. Thyroid hormones act on almost all organs throughout the body and regulate the basal metabolism of the organism. Thyroid hormone can also stimulate the proliferation in vitro of certain tumor cell lines. The aim of the present study is to evaluate the significant value of tamoxifen and/or irradiation treatment on thyroid hormones in breast cancer bearing female rats. Forty two female Sprague-Dawely rats randomly divided into seven groups and the effect of tamoxifen and post-irradiation was studied on breast cancer chemically induced. The results shows a T 4 and estradiol levels not T 3 were altered in different experimental groups. It could be concluded that irradiation-induced changes in the composition of the mammary microenvironment promote the expression of neoplastic potential by affecting both estradiol and thyroid hormones, and tamoxifen may alter the thyroid hormones. Irradiation and tamoxifen administration may have worth effects on T 4 and estradiol levels and it is recommended to further studies towards the bystander effect of radiation and tamoxifen on the tissue culture and molecular biology scale.

Population receptive field (pRF) measurements of chromatic responses in human visual cortex using fMRI.

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Welbourne, Lauren E; Morland, Antony B; Wade, Alex R

2018-02-15

The spatial sensitivity of the human visual system depends on stimulus color: achromatic gratings can be resolved at relatively high spatial frequencies while sensitivity to isoluminant color contrast tends to be more low-pass. Models of early spatial vision often assume that the receptive field size of pattern-sensitive neurons is correlated with their spatial frequency sensitivity - larger receptive fields are typically associated with lower optimal spatial frequency. A strong prediction of this model is that neurons coding isoluminant chromatic patterns should have, on average, a larger receptive field size than neurons sensitive to achromatic patterns. Here, we test this assumption using functional magnetic resonance imaging (fMRI). We show that while spatial frequency sensitivity depends on chromaticity in the manner predicted by behavioral measurements, population receptive field (pRF) size measurements show no such dependency. At any given eccentricity, the mean pRF size for neuronal populations driven by luminance, opponent red/green and S-cone isolating contrast, are identical. Changes in pRF size (for example, an increase with eccentricity and visual area hierarchy) are also identical across the three chromatic conditions. These results suggest that fMRI measurements of receptive field size and spatial resolution can be decoupled under some circumstances - potentially reflecting a fundamental dissociation between these parameters at the level of neuronal populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Rethinking clinical language mapping approaches: discordant receptive and expressive hemispheric language dominance in epilepsy surgery candidates.

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Gage, Nicole M; Eliashiv, Dawn S; Isenberg, Anna L; Fillmore, Paul T; Kurelowech, Lacey; Quint, Patti J; Chung, Jeffrey M; Otis, Shirley M

2011-06-01

Neuroimaging studies have shed light on cortical language organization, with findings implicating the left and right temporal lobes in speech processing converging to a left-dominant pattern. Findings highlight the fact that the state of theoretical language knowledge is ahead of current clinical language mapping methods, motivating a rethinking of these approaches. The authors used magnetoencephalography and multiple tasks in seven candidates for resective epilepsy surgery to investigate language organization. The authors scanned 12 control subjects to investigate the time course of bilateral receptive speech processes. Laterality indices were calculated for left and right hemisphere late fields ∼150 to 400 milliseconds. The authors report that (1) in healthy adults, speech processes activated superior temporal regions bilaterally converging to a left-dominant pattern, (2) in four of six patients, this was reversed, with bilateral processing converging to a right-dominant pattern, and (3) in three of four of these patients, receptive and expressive language processes were laterally discordant. Results provide evidence that receptive and expressive language may have divergent hemispheric dominance. Right-sided receptive language dominance in epilepsy patients emphasizes the need to assess both receptive and expressive language. Findings indicate that it is critical to use multiple tasks tapping separable aspects of language function to provide sensitive and specific estimates of language localization in surgical patients.

Investigating Arabic Academic Vocabulary Knowledge Among Middle School Pupils: Receptive Versus Productive Knowledge.

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Makhoul, Baha

2017-08-01

The current study attempted to investigate the development of Arabic academic vocabulary knowledge among middle-school Arabic native speakers, taking into account the socioeconomic status of the Arab population in Israel. For this purpose, Arabic academic word list was developed, mapping the required academic words that are needed for adequate coping with informational texts as appearing in the different content areas text-books. Six-hundred Arabic speaking middle school pupils from the different areas in Israel, representing the different Arab subgroups: general Arab community, Druze and Bedouins, have participated in the current study. Two academic vocabulary tests, including receptive and productive academic vocabulary evaluation tests, were administrated to the students across the different age groups (7th, 8th and 9th). The results pointed to no significant difference between 7th and 9th grade in academic vocabulary knowledge. In contrast, significant difference was encountered between the different Arab sub-groups where the lowest scores were noted among the Bedouin sub-group, characterized by the lowest SES. When comparing receptive and productive academic vocabulary knowledge between 7th and 9th grade, the results pointed to improvement in receptive academic knowledge towards the end of middle school but not on the productive knowledge level. In addition, within participants' comparison indicated a gap between the pupils' receptive and productive vocabulary. The results are discussed in relation to the existing scientific literature and to its implication of both research and practice in the domain of Arabic literacy development.

Subtype selective kainic acid receptor agonists

DEFF Research Database (Denmark)

Bunch, Lennart; Krogsgaard-Larsen, Povl

2009-01-01

(S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (m......GluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists...

Nonredundant sparse feature extraction using autoencoders with receptive fields clustering.

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Ayinde, Babajide O; Zurada, Jacek M

2017-09-01

This paper proposes new techniques for data representation in the context of deep learning using agglomerative clustering. Existing autoencoder-based data representation techniques tend to produce a number of encoding and decoding receptive fields of layered autoencoders that are duplicative, thereby leading to extraction of similar features, thus resulting in filtering redundancy. We propose a way to address this problem and show that such redundancy can be eliminated. This yields smaller networks and produces unique receptive fields that extract distinct features. It is also shown that autoencoders with nonnegativity constraints on weights are capable of extracting fewer redundant features than conventional sparse autoencoders. The concept is illustrated using conventional sparse autoencoder and nonnegativity-constrained autoencoders with MNIST digits recognition, NORB normalized-uniform object data and Yale face dataset. Copyright © 2017 Elsevier Ltd. All rights reserved.

THE AUDIT OF RECEPTION PROCESS

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Dorina MOCUŢA

2013-01-01

Full Text Available The object of study case is to analyze the quality of the logistics department, focusing on the audit process. Purpose of this paper is to present the advantages resulting from the systematic audit processes and methods of analysis and improvement of nonconformities found. The case study is realised at SC Miele Tehnica SRL Brasov, twelfth production line, and the fourth from outside Germany. The specific objectives are: clarifying the concept of audit quality, emphasizing requirements ISO 19011:2003 "Guidelines for auditing quality management systems and / or environment" on audits; cchieving quality audit and performance analysis; improved process performance reception materials; compliance with legislation and auditing standards applicable in EU and Romania.

A Macrocyclic Agouti-Related Protein/[Nle4,DPhe7]α-Melanocyte Stimulating Hormone Chimeric Scaffold Produces Subnanomolar Melanocortin Receptor Ligands.

Science.gov (United States)

Ericson, Mark D; Freeman, Katie T; Schnell, Sathya M; Haskell-Luevano, Carrie

2017-01-26

The melanocortin system consists of five receptor subtypes, endogenous agonists, and naturally occurring antagonists. These receptors and ligands have been implicated in numerous biological pathways including processes linked to obesity and food intake. Herein, a truncation structure-activity relationship study of chimeric agouti-related protein (AGRP)/[Nle4,DPhe7]α-melanocyte stimulating hormone (NDP-MSH) ligands is reported. The tetrapeptide His-DPhe-Arg-Trp or tripeptide DPhe-Arg-Trp replaced the Arg-Phe-Phe sequence in the AGRP active loop derivative c[Pro-Arg-Phe-Phe-Xxx-Ala-Phe-DPro], where Xxx was the native Asn of AGRP or a diaminopropionic (Dap) acid residue previously shown to increase antagonist potency at the mMC4R. The Phe, Ala, and Dap/Asn residues were successively removed to generate a 14-member library that was assayed for agonist activity at the mouse MC1R, MC3R, MC4R, and MC5R. Two compounds possessed nanomolar agonist potency at the mMC4R, c[Pro-His-DPhe-Arg-Trp-Asn-Ala-Phe-DPro] and c[Pro-His-DPhe-Arg-Trp-Dap-Ala-DPro], and may be further developed to generate novel melanocortin probes and ligands for understanding and treating obesity.

Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism.

Science.gov (United States)

Hansen, Morten S S; Tencerova, Michaela; Frølich, Jacob; Kassem, Moustapha; Frost, Morten

2018-01-01

The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

THE RECEPTION OF GALATIANS 2:20 IN THE PATRISTIC PERIOD ...

African Journals Online (AJOL)

This article explores the reception of Galatians 2:20 in the Patristic period, and ... theological framework in which later generations placed the communities wherein ... quality of reality – and in Christ that is as perfect as eternal life can ever be.

Hypothesis: Co-transfer of genuine embryos and implantation-promoting compounds via artificial containers improve endometrium receptivity.

Science.gov (United States)

Celik, Onder; Acet, Mustafa; Celik, Sudenaz; Sahin, Levent; Koc, Onder; Celik, Nilufer

2017-06-01

As with other organs endometrial functions are altered with the advancing age. Age related decrease in reproductive functions leads to decline in the number of oocytes retrieved and the synthesis of endometrial receptivity molecules. Despite the significant improvement in assisted reproductive technologies we do not have so many options to enhance endometrial receptivity. Due to lack of drugs having endometrium receptivity enhancement properties, oocyte donation seems to be the only solution for women with implantation failure. The euploid oocytes come from young and healthy donors may overcome age associated endometrial receptivity defect. Nevertheless, many reasons restrict us from using oocyte donation in women with implantation failure. We, therefore, hypothesized that by mimicking a young blastocyst's effect on endometrium, the transfer of genuine embryos and implantation-promoting compounds together might be the new treatment option for infertile women with recurrent implantation failure. Artificial beads, MI or GV oocytes, and empty zona can be used as a container for intrauterine replacement of implantation-promoting compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reconstitution of high-affinity opioid agonist binding in brain membranes

Energy Technology Data Exchange (ETDEWEB)

Remmers, A.E.; Medzihradsky, F. (Univ. of Michigan Medical School, Ann Arbor (United States))

1991-03-15

In synaptosomal membranes from rat brain cortex, the {mu} selective agonist ({sup 3}H)dihydromorphine in the absence of sodium, and the nonselective antagonist ({sup 3}H)naltrexone in the presence of sodium, bound to two populations of opioid receptor sites with K{sub d} values of 0.69 and 8.7 nM for dihydromorphine, and 0.34 and 5.5 nM for naltrexone. The addition of 5 {mu}M guanosine 5{prime}-({gamma}-thio)triphosphate (GTP({gamma}S)) strongly reduced high-affinity agonist but not antagonist binding. Exposure of the membranes to high pH reduced the number of GTP({gamma}-{sup 35}S) binding sites by 90% and low K{sub m}, opioid-sensitive GTPase activity by 95%. In these membranes, high-affinity agonist binding was abolished and modulation of residual binding by GTP({gamma}S) was diminished. Alkali treatment of the glioma cell membranes prior to fusion inhibited most of the low K{sub m} GTPase activity and prevented the reconstitution of agonist binding. The results show that high-affinity opioid agonist binding reflects the ligand-occupied receptor - guanine nucleotide binding protein complex.

Trastornos Neurológicos Asociados a Terapéutica Hormonal.

Directory of Open Access Journals (Sweden)

Alfredo Jácome-Roca

2009-01-01

Full Text Available

Hypertrophic effect of inhaled beta -agonist with and without concurrent exercise training

DEFF Research Database (Denmark)

Jessen, Søren; Onslev, Johan; Lemminger, Anders

2018-01-01

INTRODUCTION: Due to a high prevalence of asthma and exercise-induced bronchoconstriction in elite athletes, there is a high use of beta2 -adrenoceptor agonists (beta2 -agonists) in the athletic population. While anabolic in rodents, no study has been able to detect hypertrophy in humans after...... chronic beta2 -agonist inhalation. METHODS: We investigated if inhaled beta2 -agonist, terbutaline, alters body composition and metabolic rate with and without concurrent exercise training in healthy young men. Sixty-seven participants completed a four-week intervention of daily terbutaline (8×0.5 mg...

Concern About Hunger May Increase Receptivity to GMOs.

Science.gov (United States)

Carter, B Elijah; Conn, Caitlin C; Wiles, Jason R

2016-07-01

Due to a phenomenon known as the 'backfire effect', intuition-based opinions can be inadvertently strengthened by evidence-based counterarguments. Students' views on genetically modified organisms (GMOs) may be subject to this effect. We explored the impact of an empathetically accessible topic, world hunger, on receptivity to GMO technology as an alternative to direct evidence-based approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

The utility of a model-based cost-effectiveness analysis of degarelix versus leuprolide in the therapy of hormone-dependent advanced prostate cancer

Directory of Open Access Journals (Sweden)

Massimo Perachino

2013-09-01

Full Text Available INTRODUCTION: Prostate cancer (PC is a very common tumor among men: in Italy its prevalence in 2006 was 0.9%. Androgen deprivation therapy is a way to treat hormone-responsive PC by decreasing testosterone levels. GnRH-analogues, including GnRH-agonists and GnRH-antagonists, are effective for this purpose. AIM: This article presents a cost-effectiveness analysis based on a semi-Markov model comparing the GnRH-antagonist degarelix and GnRH-agonist leuprolide in the treatment of hormone-dependent advanced prostate cancer from the perspective of the Regional Health Service in Veneto Region (Italy.MATERIALS AND METHODS: Effectiveness data were retrieved by a 12-month phase III non-inferiority clinical trial, comparing degarelix and 7,5 mg leuprolide in 610 patients treated for hormone-dependent prostate cancer. Epidemiological data came from a national database and were referred to Veneto Region. The values of the healthcare resources were calculated using regional and national prices (€ 2012. The model considers 3 exhaustive and mutually exclusive health status: first-line treatment, further-lines treatment and death. It lasts 10 years, with 28 days per cycle. The entry in the model is hypothesized at the age of 70 (the age with most PCs in Veneto Region. Effectiveness endpoints were life years saved and quality-adjusted life years, using 3% social discount rate. The incremental cost per QALY was related to the range of acceptability proposed by the Associazione Italiana di Economia Sanitaria (€ 25,000-40,000. The budget impact was calculated on a 5-year time horizon. Univariate and probabilistic sensitivity analyses were performed on every hypothesis of the model.RESULTS: Degarelix resulted in minor costs if compared to 7.5 mg leuprolide (€ 20,511.64 vs 22,256.49. The cost-driver was chemotherapic care (32.45% degarelix vs 44.30% 7.5 mg leuprolide. Life years saved were the same for both the alternatives (5.58, while QALYs obtained were

Adolescent Weight Status and Receptivity to Food TV Advertisements

Science.gov (United States)

Adachi-Mejia, Anna M.; Sutherland, Lisa A.; Longacre, Meghan R.; Beach, Michael L.; Titus-Ernstoff, Linda; Gibson, Jennifer J.; Dalton, Madeline A.

2011-01-01

Objective: This study examined the relationship between adolescent weight status and food advertisement receptivity. Design: Survey-based evaluation with data collected at baseline (initial and at 2 months), and at follow-up (11 months). Setting: New Hampshire and Vermont. Participants: Students (n = 2,281) aged 10-13 in 2002-2005. Main Outcome…

Nonsteroidal Selective Androgen Receptor Modulators and Selective Estrogen Receptor β Agonists Moderate Cognitive Deficits and Amyloid-β Levels in a Mouse Model of Alzheimer’s Disease

Science.gov (United States)

2013-01-01

Decreases of the sex steroids, testosterone and estrogen, are associated with increased risk of Alzheimer’s disease. Testosterone and estrogen supplementation improves cognitive deficits in animal models of Alzheimer’s disease. Sex hormones play a role in the regulation of amyloid-β via induction of the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme. To mimic the effect of dihydrotestosterone (DHT), we administered a selective androgen receptor agonist, ACP-105, alone and in combination with the selective estrogen receptor β (ERβ) agonist AC-186 to male gonadectomized triple transgenic mice. We assessed long-term spatial memory in the Morris water maze, spontaneous locomotion, and anxiety-like behavior in the open field and in the elevated plus maze. We found that ACP-105 given alone decreases anxiety-like behavior. Furthermore, when ACP-105 is administered in combination with AC-186, they increase the amyloid-β degrading enzymes neprilysin and insulin-degrading enzyme and decrease amyloid-β levels in the brain as well as improve cognition. Interestingly, the androgen receptor level in the brain was increased by chronic treatment with the same combination treatment, ACP-105 and AC-186, not seen with DHT or ACP-105 alone. Based on these results, the beneficial effect of the selective ERβ agonist as a potential therapeutic for Alzheimer’s disease warrants further investigation. PMID:24020966

KIRA1 and ORESARA1 terminate flower receptivity by promoting cell death in the stigma of Arabidopsis.

Science.gov (United States)

Gao, Zhen; Daneva, Anna; Salanenka, Yuliya; Van Durme, Matthias; Huysmans, Marlies; Lin, Zongcheng; De Winter, Freya; Vanneste, Steffen; Karimi, Mansour; Van de Velde, Jan; Vandepoele, Klaas; Van de Walle, Davy; Dewettinck, Koen; Lambrecht, Bart N; Nowack, Moritz K

2018-05-28

Flowers have a species-specific functional life span that determines the time window in which pollination, fertilization and seed set can occur. The stigma tissue plays a key role in flower receptivity by intercepting pollen and initiating pollen tube growth toward the ovary. In this article, we show that a developmentally controlled cell death programme terminates the functional life span of stigma cells in Arabidopsis. We identified the leaf senescence regulator ORESARA1 (also known as ANAC092) and the previously uncharacterized KIRA1 (also known as ANAC074) as partially redundant transcription factors that modulate stigma longevity by controlling the expression of programmed cell death-associated genes. KIRA1 expression is sufficient to induce cell death and terminate floral receptivity, whereas lack of both KIRA1 and ORESARA1 substantially increases stigma life span. Surprisingly, the extension of stigma longevity is accompanied by only a moderate extension of flower receptivity, suggesting that additional processes participate in the control of the flower's receptive life span.

Early language processing efficiency predicts later receptive vocabulary outcomes in children born preterm.

Science.gov (United States)

Marchman, Virginia A; Adams, Katherine A; Loi, Elizabeth C; Fernald, Anne; Feldman, Heidi M

2016-01-01

As rates of prematurity continue to rise, identifying which preterm children are at increased risk for learning disabilities is a public health imperative. Identifying continuities between early and later skills in this vulnerable population can also illuminate fundamental neuropsychological processes that support learning in all children. At 18 months adjusted age, we used socioeconomic status (SES), medical variables, parent-reported vocabulary, scores on the Bayley Scales of Infant and Toddler Development (third edition) language composite, and children's lexical processing speed in the looking-while-listening (LWL) task as predictor variables in a sample of 30 preterm children. Receptive vocabulary as measured by the Peabody Picture Vocabulary Test (fourth edition) at 36 months was the outcome. Receptive vocabulary was correlated with SES, but uncorrelated with degree of prematurity or a composite of medical risk. Importantly, lexical processing speed was the strongest predictor of receptive vocabulary (r = -.81), accounting for 30% unique variance. Individual differences in lexical processing efficiency may be able to serve as a marker for information processing skills that are critical for language learning.

Regulation of ventilation and oxygen consumption by delta- and mu-opioid receptor agonists.

Science.gov (United States)

Schaeffer, J I; Haddad, G G

1985-09-01

To study the effect of endorphins on metabolic rate and on the relationship between O2 consumption (VO2) and ventilation, we administered enkephalin analogues (relatively selective delta-receptor agonists) and a morphiceptin analogue (a highly selective mu-receptor agonist) intracisternally in nine unanesthetized chronically instrumented adult dogs. Both delta- and mu-agonists decreased VO2 by 40-60%. delta-Agonists induced a dose-dependent decrease in mean instantaneous minute ventilation (VT/TT) associated with periodic breathing. The decrease in VT/TT started and resolved prior to the decrease and returned to baseline of VO2, respectively. In contrast, the mu-agonists induced an increase in VT/TT associated with rapid shallow breathing. Arterial PCO2 increased and arterial PO2 decreased after both delta- and mu-agonists. Low doses of intracisternal naloxone (0.002-2.0 micrograms/kg) reversed the opioid effect on VT/TT but not on VO2; higher doses of naloxone (5-25 micrograms/kg) reversed both. Naloxone administered alone had no effect on VT/TT or VO2. These data suggest that 1) both delta- and mu-agonists induce alveolar hypoventilation despite a decrease in VO2, 2) this hypoventilation results from a decrease in VT/TT after delta-agonists but an increase in dead space ventilation after mu-agonists, and 3) endorphins do not modulate ventilation and metabolic rate tonically, but we speculate that they may do so in response to stressful stimulation.

FXR agonist activity of conformationally constrained analogs of GW 4064.

Science.gov (United States)

Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

2009-08-15

Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

Transition Prediction in Hypersonic Boundary Layers Using Receptivity and Freestream Spectra

Science.gov (United States)

Balakumar, P.; Chou, Amanda

2016-01-01

Boundary-layer transition in hypersonic flows over a straight cone can be predicted using measured freestream spectra, receptivity, and threshold values for the wall pressure fluctuations at the transition onset points. Simulations are performed for hypersonic boundary-layer flows over a 7-degree half-angle straight cone with varying bluntness at a freestream Mach number of 10. The steady and the unsteady flow fields are obtained by solving the two-dimensional Navier-Stokes equations in axisymmetric coordinates using a 5th-order accurate weighted essentially non-oscillatory (WENO) scheme for space discretization and using a third-order total-variation-diminishing (TVD) Runge-Kutta scheme for time integration. The calculated N-factors at the transition onset location increase gradually with increasing unit Reynolds numbers for flow over a sharp cone and remain almost the same for flow over a blunt cone. The receptivity coefficient increases slightly with increasing unit Reynolds numbers. They are on the order of 4 for a sharp cone and are on the order of 1 for a blunt cone. The location of transition onset predicted from the simulation including the freestream spectrum, receptivity, and the linear and the weakly nonlinear evolutions yields a solution close to the measured onset location for the sharp cone. The simulations over-predict transition onset by about twenty percent for the blunt cone.

New approaches in the management of insomnia: weighing the advantages of prolonged-release melatonin and synthetic melatoninergic agonists

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Rüdiger Hardeland

2009-06-01

Full Text Available Rüdiger HardelandJohann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, GermanyAbstract: Hypnotic effects of melatonin and melatoninergic drugs are mediated via MT1 and MT2 receptors, especially those in the circadian pacemaker, the suprachiasmatic nucleus, which acts on the hypothalamic sleep switch. Therefore, they differ fundamentally from GABAergic hypnotics. Melatoninergic agonists primarily favor sleep initiation and reset the circadian clock to phases allowing persistent sleep, as required in circadian rhythm sleep disorders. A major obstacle for the use of melatonin to support sleep maintenance in primary insomnia results from its short half-life in the circulation. Solutions to this problem have been sought by developing prolonged-release formulations of the natural hormone, or melatoninergic drugs of longer half-life, such as ramelteon, tasimelteon and agomelatine. With all these drugs, improvements of sleep are statistically demonstrable, but remain limited, especially in primary chronic insomnia, so that GABAergic drugs may be indicated. Melatoninergic agonists do not cause next-day hangover and withdrawal effects, or dependence. They do not induce behavioral changes, as sometimes observed with z-drugs. Despite otherwise good tolerability, the use of melatoninergic drugs in children, adolescents, and during pregnancy has been a matter of concern, and should be avoided in autoimmune diseases and Parkinsonism. Problems and limits of melatoninergic hypnotics are compared.Keywords: agomelatine, hypnotics, melatonin, prolonged-release, ramelteon, tasimelteon

Risk factors for low receptive vocabulary abilities in the preschool and early school years in the longitudinal study of Australian children.

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Daniel Christensen

Full Text Available Receptive vocabulary development is a component of the human language system that emerges in the first year of life and is characterised by onward expansion throughout life. Beginning in infancy, children's receptive vocabulary knowledge builds the foundation for oral language and reading skills. The foundations for success at school are built early, hence the public health policy focus on reducing developmental inequalities before children start formal school. The underlying assumption is that children's development is stable, and therefore predictable, over time. This study investigated this assumption in relation to children's receptive vocabulary ability. We investigated the extent to which low receptive vocabulary ability at 4 years was associated with low receptive vocabulary ability at 8 years, and the predictive utility of a multivariate model that included child, maternal and family risk factors measured at 4 years. The study sample comprised 3,847 children from the first nationally representative Longitudinal Study of Australian Children (LSAC. Multivariate logistic regression was used to investigate risks for low receptive vocabulary ability from 4-8 years and sensitivity-specificity analysis was used to examine the predictive utility of the multivariate model. In the multivariate model, substantial risk factors for receptive vocabulary delay from 4-8 years, in order of descending magnitude, were low receptive vocabulary ability at 4 years, low maternal education, and low school readiness. Moderate risk factors, in order of descending magnitude, were low maternal parenting consistency, socio-economic area disadvantage, low temperamental persistence, and NESB status. The following risk factors were not significant: One or more siblings, low family income, not reading to the child, high maternal work hours, and Aboriginal or Torres Strait Islander ethnicity. The results of the sensitivity-specificity analysis showed that a well

Receptive Learning Styles Of Introverts, Ambiverts And Extroverts In ...

African Journals Online (AJOL)

Learning to relate with people in their own style is important in helping to understand why they react the way they do. The purpose of this study therefore was to determine the differences in the receptive learning styles of introverts, ambiverts and extroverts in Senior High Schools (SHS) in the Sekondi-Takoradi Metropolis, ...

The routes to be followed into Alberto Caeiros’s poetry: a reception aesthetics approach

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Fabrício César Aguiar

2011-10-01

Full Text Available The aim of this article is to study the 8th poem Num meio dia de fim de primavera written by Alberto Caeiro. The analysis proposed will be based on some of the Reception Aesthetics concepts mainly focusing on enriching the sensory aspects of the text, especially the visual one. For that purpose, the poetic devices used in the construction of the text as well as its reception by the readers will be highlighted. The analysis will be based on the concepts theorized by Wolfgang Iser. Such concepts are: a the interaction between text and reader and the position of the latter at the time of the former reception; b the blank places; c the negation and negativity structures; and d it will also consider the approach to reading as an act in which the reader is responsible for achieving the meaning for the text and for creating an “aesthetic pleasure” through it. This last concept is grounded in Hans Robert Jauss theory.

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

Science.gov (United States)

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

2018-05-01

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

Hormones

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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, ...

Discriminative learning of receptive fields from responses to non-Gaussian stimulus ensembles.

Science.gov (United States)

Meyer, Arne F; Diepenbrock, Jan-Philipp; Happel, Max F K; Ohl, Frank W; Anemüller, Jörn

2014-01-01

Analysis of sensory neurons' processing characteristics requires simultaneous measurement of presented stimuli and concurrent spike responses. The functional transformation from high-dimensional stimulus space to the binary space of spike and non-spike responses is commonly described with linear-nonlinear models, whose linear filter component describes the neuron's receptive field. From a machine learning perspective, this corresponds to the binary classification problem of discriminating spike-eliciting from non-spike-eliciting stimulus examples. The classification-based receptive field (CbRF) estimation method proposed here adapts a linear large-margin classifier to optimally predict experimental stimulus-response data and subsequently interprets learned classifier weights as the neuron's receptive field filter. Computational learning theory provides a theoretical framework for learning from data and guarantees optimality in the sense that the risk of erroneously assigning a spike-eliciting stimulus example to the non-spike class (and vice versa) is minimized. Efficacy of the CbRF method is validated with simulations and for auditory spectro-temporal receptive field (STRF) estimation from experimental recordings in the auditory midbrain of Mongolian gerbils. Acoustic stimulation is performed with frequency-modulated tone complexes that mimic properties of natural stimuli, specifically non-Gaussian amplitude distribution and higher-order correlations. Results demonstrate that the proposed approach successfully identifies correct underlying STRFs, even in cases where second-order methods based on the spike-triggered average (STA) do not. Applied to small data samples, the method is shown to converge on smaller amounts of experimental recordings and with lower estimation variance than the generalized linear model and recent information theoretic methods. Thus, CbRF estimation may prove useful for investigation of neuronal processes in response to natural stimuli and

Discriminative learning of receptive fields from responses to non-Gaussian stimulus ensembles.

Directory of Open Access Journals (Sweden)

Arne F Meyer

Full Text Available Analysis of sensory neurons' processing characteristics requires simultaneous measurement of presented stimuli and concurrent spike responses. The functional transformation from high-dimensional stimulus space to the binary space of spike and non-spike responses is commonly described with linear-nonlinear models, whose linear filter component describes the neuron's receptive field. From a machine learning perspective, this corresponds to the binary classification problem of discriminating spike-eliciting from non-spike-eliciting stimulus examples. The classification-based receptive field (CbRF estimation method proposed here adapts a linear large-margin classifier to optimally predict experimental stimulus-response data and subsequently interprets learned classifier weights as the neuron's receptive field filter. Computational learning theory provides a theoretical framework for learning from data and guarantees optimality in the sense that the risk of erroneously assigning a spike-eliciting stimulus example to the non-spike class (and vice versa is minimized. Efficacy of the CbRF method is validated with simulations and for auditory spectro-temporal receptive field (STRF estimation from experimental recordings in the auditory midbrain of Mongolian gerbils. Acoustic stimulation is performed with frequency-modulated tone complexes that mimic properties of natural stimuli, specifically non-Gaussian amplitude distribution and higher-order correlations. Results demonstrate that the proposed approach successfully identifies correct underlying STRFs, even in cases where second-order methods based on the spike-triggered average (STA do not. Applied to small data samples, the method is shown to converge on smaller amounts of experimental recordings and with lower estimation variance than the generalized linear model and recent information theoretic methods. Thus, CbRF estimation may prove useful for investigation of neuronal processes in response to

A radioreceptor assay of luteinizing hormone-releasing hormone receptor and characterization of LHRH binding to pituitary receptors in Shao duck

International Nuclear Information System (INIS)

Yang Peixin; Wu Meiwen; Chen Ziyuan

2000-01-01

The properties of Shao duck pituitary luteinizing hormone-releasing hormone (LHRH) receptors were analyzed in pituitary membrane preparation and isolated pituitary cells prepared by enzymatic dispersion with collagenase and trypsin, by using a super-agonist analog of (D-Lys 6 ) LHRH. High binding of 125 I-(D-Lys 6 ) LHRH to 10 6 cultured cells of Shao duck was observed after a 90 minute incubation at 4 degree C, while binding was significantly reduced after a 24h incubation. Binding of the radioligand was a function of tissue concentration of Shao duck pituitary membrane preparation, with a positive correlation over the range of 1-2 pituitary per-tube. Specific binding for 125 I-(D-Lys 6 ) LHRH increased with the increase in the amount of 125 I-(D-Lys 6 ) LHRH. The Scatchard analysis of data revealed a linear relationship between the amount of specific binding and the ratio of specific binding to free 1 '2 5 I(D-Lys 6 )LHRH, indicating a single class of high affinity sites. Equilibrium dissociation constant (Kd) was 0.34 nM in pituitary membrane preparation and 0.43 nM in isolated pituitary cells. Both Kd values were near and the maximum binding capacity (B max ) was great in isolated cells, suggesting no significant loss of the LHRH receptor population caused by the enzymatic procedure employed for cell dispersion in the present study. Addition of 9D-Lys 6 ) LHRH displaced bound 125 I-(D-Lys 6 ) LHRH. These results demonstrated the presence and provided characterization of LHRH receptors in Shao duck pituitary

Receptive Language Skills in Slovak-Speaking Children With Intellectual Disability: Understanding Words, Sentences, and Stories.

Science.gov (United States)

Polišenská, Kamila; Kapalková, Svetlana; Novotková, Monika

2018-06-05

The study aims to describe receptive language skills in children with intellectual disability (ID) and to contribute to the debate on deviant versus delayed language development. This is the 1st study of receptive skills in children with ID who speak a Slavic language, providing insight into how language development is affected by disability and also language typology. Twenty-eight Slovak-speaking children participated in the study (14 children with ID and 14 typically developing [TD] children matched on nonverbal reasoning abilities). The children were assessed by receptive language tasks targeting words, sentences, and stories, and the groups were compared quantitatively and qualitatively. The groups showed similar language profiles, with a better understanding of words, followed by sentences, with the poorest comprehension for stories. Nouns were comprehended better than verbs; sentence constructions also showed a qualitatively similar picture, although some dissimilarities emerged. Verb comprehension was strongly related to sentence comprehension in both groups and related to story comprehension in the TD group only. The findings appear to support the view that receptive language skills follow the same developmental route in children with ID as seen in younger TD children, suggesting that language development is a robust process and does not seem to be differentially affected by ID even when delayed.

Effects of serial and concurrent training on receptive identification tasks: A Systematic replication.

Science.gov (United States)

Wunderlich, Kara L; Vollmer, Timothy R

2017-07-01

The current study compared the use of serial and concurrent methods to train multiple exemplars when teaching receptive language skills, providing a systematic replication of Wunderlich, Vollmer, Donaldson, and Phillips (2014). Five preschoolers diagnosed with developmental delays or autism spectrum disorders were taught to receptively identify letters or letter sounds. Subjects learned the target stimuli slightly faster in concurrent training and a high degree of generalization was obtained following both methods of training, indicating that both the serial and concurrent methods of training are efficient and effective instructional procedures. © 2017 Society for the Experimental Analysis of Behavior.

Receptivity to e-cigarette marketing, harm perceptions, and e-cigarette use.

Science.gov (United States)

Pokhrel, Pallav; Fagan, Pebbles; Kehl, Lisa; Herzog, Thaddeus A

2015-01-01

To test whether exposure and receptivity to e-cigarette marketing are associated with recent e-cigarette use among young adults through increased beliefs that e-cigarettes are less harmful than cigarettes. Data were collected from 307 multiethnic 4- and 2-year college students; approximately equal proportions of current, never, and former cigarette smokers [mean age = 23.5 (SD = 5.5); 65% female]. Higher receptivity to e-cigarette marketing was associated with perceptions that e-cigarettes are less harmful than cigarettes, which in turn, were associated with higher recent e-cigarette use. The findings provide preliminary support to the proposition that marketing of e-cigarettes as safer alternatives to cigarettes or cessation aids is associated with increased e-cigarette use among young adults. The findings have implications for development of e-cigarette regulations.

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury

Energy Technology Data Exchange (ETDEWEB)

Goto, Hiromasa [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Nomiyama, Takashi, E-mail: tnomiyama@fukuoka-u.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Mita, Tomoya; Yasunari, Eisuke; Azuma, Kosuke; Komiya, Koji; Arakawa, Masayuki; Jin, Wen Long; Kanazawa, Akio [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Kawamori, Ryuzo [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Sportology Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Center for Beta Cell Biology and Regeneration, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Fujitani, Yoshio; Hirose, Takahisa [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Watada, Hirotaka, E-mail: hwatada@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan); Sportology Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421 (Japan)

2011-02-04

Research highlights: {yields} Exendin-4 reduces neointimal formation after vascular injury in a mouse model. {yields} Exendin-4 dose not alter metabolic parameters in non-diabetic, non-obese mouse model. {yields} Exendin-4 reduces PDGF-induced cell proliferation in cultured SMCs. {yields} Exendin-4 may reduces neointimal formation after vascular injury at least in part through its direct action on SMCs. -- Abstract: Glucagon-like peptide-1 is a hormone secreted by L cells of the small intestine and stimulates glucose-dependent insulin response. Glucagon-like peptide-1 receptor agonists such as exendin-4 are currently used in type 2 diabetes, and considered to have beneficial effects on the cardiovascular system. To further elucidate the effect of glucagon-like peptide-1 receptor agonists on cardiovascular diseases, we investigated the effects of exendin-4 on intimal thickening after endothelial injury. Under continuous infusion of exendin-4 at 24 nmol/kg/day, C57BL/6 mice were subjected to endothelial denudation injury of the femoral artery. Treatment of mice with exendin-4 reduced neointimal formation at 4 weeks after arterial injury without altering body weight or various metabolic parameters. In addition, in vitro studies of isolated murine, rat and human aortic vascular smooth muscle cells showed the expression of GLP-1 receptor. The addition of 10 nM exendin-4 to cultured smooth muscle cells significantly reduced their proliferation induced by platelet-derived growth factor. Our results suggested that exendin-4 reduced intimal thickening after vascular injury at least in part by the suppression of platelet-derived growth factor-induced smooth muscle cells proliferation.

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces intimal thickening after vascular injury

International Nuclear Information System (INIS)

Goto, Hiromasa; Nomiyama, Takashi; Mita, Tomoya; Yasunari, Eisuke; Azuma, Kosuke; Komiya, Koji; Arakawa, Masayuki; Jin, Wen Long; Kanazawa, Akio; Kawamori, Ryuzo; Fujitani, Yoshio; Hirose, Takahisa; Watada, Hirotaka

2011-01-01

Research highlights: → Exendin-4 reduces neointimal formation after vascular injury in a mouse model. → Exendin-4 dose not alter metabolic parameters in non-diabetic, non-obese mouse model. → Exendin-4 reduces PDGF-induced cell proliferation in cultured SMCs. → Exendin-4 may reduces neointimal formation after vascular injury at least in part through its direct action on SMCs. -- Abstract: Glucagon-like peptide-1 is a hormone secreted by L cells of the small intestine and stimulates glucose-dependent insulin response. Glucagon-like peptide-1 receptor agonists such as exendin-4 are currently used in type 2 diabetes, and considered to have beneficial effects on the cardiovascular system. To further elucidate the effect of glucagon-like peptide-1 receptor agonists on cardiovascular diseases, we investigated the effects of exendin-4 on intimal thickening after endothelial injury. Under continuous infusion of exendin-4 at 24 nmol/kg/day, C57BL/6 mice were subjected to endothelial denudation injury of the femoral artery. Treatment of mice with exendin-4 reduced neointimal formation at 4 weeks after arterial injury without altering body weight or various metabolic parameters. In addition, in vitro studies of isolated murine, rat and human aortic vascular smooth muscle cells showed the expression of GLP-1 receptor. The addition of 10 nM exendin-4 to cultured smooth muscle cells significantly reduced their proliferation induced by platelet-derived growth factor. Our results suggested that exendin-4 reduced intimal thickening after vascular injury at least in part by the suppression of platelet-derived growth factor-induced smooth muscle cells proliferation.

Simultaneous measurement of hormone release and secretagogue binding by individual pituitary cells

International Nuclear Information System (INIS)

Smith, P.F.; Neill, J.D.

1987-01-01

The quantitative relationship between receptor binding and hormone secretion at the single-cell level was investigated in the present study by combining a reverse hemolytic plaque assay for measurement of luteinizing hormone (LH) secretion from individual pituitary cells with an autoradiographic assay of 125 I-labeled gonadontropin-releasing hormone (GnRH) agonist binding to the same cells. In the plaque assay, LH secretion induces complement-mediated lysis of the LH-antibody-coated erythrocytes around the gonadotropes, resulting in areas of lysis (plaques). LH release from individual gonadotropes was quantified by comparing radioimmunoassayable LH release to hemolytic area in similarly treated cohort groups of cells; plaque area was linearly related to the amount of LH secreted. Receptor autoradiography was performed using 125 I-labeled GnRH-A (a superagonist analog of GnRH) both as the ligand and as the stimulant for LH release in the plaque assay. The grains appeared to represent specific and high-affinity receptors for GnRH because (i) no pituitary cells other than gonadotropes bound the labeled ligand and (ii) grain development was progressively inhibited by coincubation with increasing doses of unlabeled GnRH-A. The authors conclude that GnRH receptor number for any individual gonadotrope is a weak determinant of the amount of LH it can secrete; nevertheless, full occupancy of all its GnRH receptors is required for any gonadotrope to reach its full LH-secretory capacity. Apparently the levels of other factors comprising the steps along the secretory pathway determine the secretory capacity of an individual cell

The Anion Paradox in Sodium Taste Reception: Resolution by Voltage-Clamp Studies

Science.gov (United States)

Ye, Qing; Heck, Gerard L.; Desimone, John A.

1991-11-01

Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.

Click-Chemistry-Mediated Synthesis of Selective Melanocortin Receptor 4 Agonists

DEFF Research Database (Denmark)

Palmer, Daniel; Gonçalves, Juliana P.L.; Hansen, Louise V.

2017-01-01

The melanocortin receptor 4 (MC4R) subtype of the melanocortin receptor family is a target for therapeutics to ameliorate metabolic dysfunction. Endogenous MC4R agonists possess a critical pharmacophore (HFRW), and cyclization of peptide agonists often enhances potency. Thus, 17 cyclized peptides...

Instability of the socio-economic systems as a factor of their receptivity towards changes

Directory of Open Access Journals (Sweden)

O. A. Romanova

2010-09-01

Full Text Available In this article author marks out the life phases of socio-economic systems from the point of view of theirs stability / instability, determines the correlation between life phase and receptivity degree of system to changes. They offer the order parameters of socio-economic system and assessment methods through which instability is conveyed. The suggested methods have been used for solving the problem of assessing the degree of receptivity of the regional economic systems to the currents global crisis and the following modernization process.

Receptivity to free stream acoustic disturbances due to a roughness element on a flat plate

OpenAIRE

Ashour, Osama Naim

1993-01-01

The boundary-layer receptivity resulting from acoustic forcing over a flat plate with a surface irregularity is investigated. The unsteady free-stream disturbances couple with the steady perturbations resulting from the surface irregularity to form a traveling-wave mode. The resonance condition necessary for receptivity requires a forcing at a wave number equal to that of the Tollmien-Schlichting (TS) eigenmode and a frequency equal to that of the free-stream acoustic disturban...

Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

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Martin B. Oleksiewicz

2008-01-01

Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

Identification of novel selective V2 receptor non-peptide agonists.

Science.gov (United States)

Del Tredici, Andria L; Vanover, Kim E; Knapp, Anne E; Bertozzi, Sine M; Nash, Norman R; Burstein, Ethan S; Lameh, Jelveh; Currier, Erika A; Davis, Robert E; Brann, Mark R; Mohell, Nina; Olsson, Roger; Piu, Fabrice

2008-10-30

Peptides with agonist activity at the vasopressin V(2) receptor are used clinically to treat fluid homeostasis disorders such as polyuria and central diabetes insipidus. Of these peptides, the most commonly used is desmopressin, which displays poor bioavailability as well as potent activity at the V(1b) receptor, with possible stress-related adverse effects. Thus, there is a strong need for the development of small molecule chemistries with selective V(2) receptor agonist activity. Using the functional cell-based assay Receptor Selection and Amplification Technology (R-SAT((R))), a screening effort identified three small molecule chemotypes (AC-94544, AC-88324, and AC-110484) with selective agonist activity at the V(2) receptor. One of these compounds, AC-94544, displayed over 180-fold selectivity at the V(2) receptor compared to related vasopressin and oxytocin receptors and no activity at 28 other G protein-coupled receptors (GPCRs). All three compounds also showed partial agonist activity at the V(2) receptor in a cAMP accumulation assay. In addition, in a rat model of central diabetes insipidus, AC-94544 was able to significantly reduce urine output in a dose-dependent manner. Thus, AC-94544, AC-88324, and AC-110484 represent novel opportunities for the treatment of disorders associated with V(2) receptor agonist deficiency.

Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity

Directory of Open Access Journals (Sweden)

Croxatto Horacio B

2011-01-01

Full Text Available Abstract Background The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation. Methods Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL. For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features. Results We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation. Conclusions Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible

Principles of agonist recognition in Cys-loop receptors

Directory of Open Access Journals (Sweden)

Timothy eLynagh

2014-04-01

Full Text Available Cys-loop receptors are ligand-gated ion channels that are activated by a structurally diverse array of neurotransmitters, including acetylcholine, serotonin, glycine and GABA. After the term chemoreceptor emerged over 100 years ago, there was some wait until affinity labeling, molecular cloning, functional studies and X-ray crystallography experiments identified the extracellular interface of adjacent subunits as the principal site of agonist binding. The question of how subtle differences at and around agonist-binding sites of different Cys-loop receptors can accommodate transmitters as chemically diverse as glycine and serotonin has been subject to intense research over the last three decades. This review outlines the functional diversity and current structural understanding of agonist-binding sites, including those of invertebrate Cys-loop receptors. Together, this provides a framework to understand the atomic determinants involved in how these valuable therapeutic targets recognize and bind their ligands.

Metal ion-mediated agonism and agonist enhancement in melanocortin MC1 and MC4 receptors

DEFF Research Database (Denmark)

Holst, Birgitte; Elling, Christian E; Schwartz, Thue W

2002-01-01

-melanocortin stimulating hormone (alpha-MSH) in the MC1 and MC4 receptors, respectively. In the presence of peptide agonist, Zn(II) acted as an enhancer on both receptors, because it shifted the dose-response curves to the left: most pronounced was a 6-fold increase in alpha-MSH potency on the MC1 receptor. The effect......An endogenous metal-ion site in the melanocortin MC1 and MC4 receptors was characterized mainly in transiently transfected COS-7 cells. ZnCl(2) alone stimulated signaling through the Gs pathway with a potency of 11 and 13 microm and an efficacy of 50 and 20% of that of alpha...... affinities and profiles were similar for a number of the 2,2'-bipyridine and 1,10-phenanthroline analogs in complex with Zn(II) in the MC1 and MC4 receptors. However, the potencies and efficacies of the metal-ion complexes were very different in the two receptors, and close to full agonism was obtained...

Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex.

Science.gov (United States)

Piché, Marilyse; Thomas, Sébastien; Casanova, Christian

2015-10-01

The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex. Copyright © 2015 the American Physiological Society.

Compressibility effects on the non-linear receptivity of boundary layers to dielectric barrier discharges

Science.gov (United States)

Denison, Marie F. C.

The reduction of drag and aerodynamic heating caused by boundary layer transition is of central interest for the development of hypersonic vehicles. Receptivity to flow perturbation in the form of Tollmien-Schlichting (TS) wave growth often determines the first stage of the transition process, which can be delayed by depositing specific excitations into the boundary layer. Weakly ionized Dielectric Barrier Discharge (DBD) actuators are being investigated as possible sources of such excitations, but little is known today about their interaction with high-speed flows. In this framework, the first part of the thesis is dedicated to a receptivity study of laminar compressible boundary layers over a flat plate by linear stability analysis following an adjoint operator formulation, under DBD representative excitations assumed independent of flow conditions. The second part of the work concentrates on the development of a coupled plasma-Navier and Stokes solver targeted at the study of supersonic flow and compressibility effects on DBD forcing and non-parallel receptivity. The linear receptivity study of quasi-parallel compressible flows reveals several interesting features such as a significant shift of the region of maximum receptivity deeper into the flow at high Mach number and strong wave amplitude reduction compared to incompressible flows. The response to DBD relevant excitation distributions and to variations of the base flow conditions and system length scales follows these trends. Observed absolute amplitude changes and relative sensitivity modifications between source types are related to the evolution of the offset between forcing peak profile and relevant adjoint mode maximum. The analysis highlights the crucial importance of designing and placing the actuator in a way that matches its force field to the position of maximum boundary layer receptivity for the specific flow conditions of interest. In order to address the broad time and length scale spectrum

Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

Science.gov (United States)

Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

2010-11-01

Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. © 2010 American Academy of Forensic Sciences.

The media's reception of the risk associated with radioactive disasters

International Nuclear Information System (INIS)

Vettenranta, S.

1996-01-01

There is an urgent need to develop methodologies to examine the response by the media to radioactive disasters. 'Reception study' is a new research approach in the field of mass communication, studying how the viewers construct meaning from TV news. This ongoing reception study explores how fifteen respondents, all involved in the Chernobyl disaster in 1986, recall and interpret TV news coverage nine years after the accident. The main aim is to discover how the news affects the recipients' interpretations of a disaster and what kind of thoughts, reactions and associations risk messages provoke in retrospect, in the present and in the beliefs about the future. The initial findings indicate that the Chernobyl news on TV was mainly based on technical rationality, while viewers construct meaning founded on symbolic, cultural rationality. The transmission of catastrophe news is not just a matter of responding to the information needs of the public. Denotative risk messages simultaneously convey connotative, symbolic resonance of risk on a metaphysical level. (author)

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.

Early expressive and receptive language trajectories in high-risk infant siblings of children with autism spectrum disorder

Directory of Open Access Journals (Sweden)

Julie Longard

2017-11-01

Full Text Available Background & aims In response to limited research on early language development in infants at high risk for Autism Spectrum Disorder (ASD, the current prospective study examined early expressive and receptive language trajectories in familial high-risk (HR infants who were and were not later diagnosed with ASD (HR-ASD and HR-N, respectively, and low-risk (LR controls with no family history of ASD. Methods Participants were 523 children (371 HR siblings, 56% boys; 152 LR controls, 52% boys followed from age 6 or 12 months to 36 months. Based on independent, best-estimate clinical diagnoses at 36 months, HR participants were classified as HR-ASD (n = 94; 69% boys, or HR-N (n = 277; 52% boys; the sample also included 152 LR controls (52% boys. Expressive and receptive language trajectories were examined based on corresponding domain standard scores on the Mullen Scales of Early Learning ( MSEL at 6, 12, 24, and 36 months. In the combined sample of HR and LR infants, semi-parametric group-based modeling was used to identify distinct trajectories in MSEL standard scores. Results A 3-group solution provided optimal fit to variation in both expressive and receptive language, with the following patterns of scores: (1 inclining from average to above average, (2 stable-average, and (3 declining from average to well below average. For both expressive and receptive language, membership in these trajectories was related to 3-year diagnostic outcomes. Conclusions Although HR-ASD, HR-N, and LR control infants were in each trajectory group, membership in the declining trajectory (expressive and/or receptive was associated with an ASD diagnosis. Implications Evidence of declining trajectories in either expressive or receptive language may be a risk marker for ASD in a high-risk sample.

Synthesis of human pancreatic growth hormone-releasing factor and two omission analogs by segment-coupling method in aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Blake, J.; Westphal, M.; Li, C.H. (Laboratory of Molecular Endocrinology, University of California, San Francisco, USA)

1984-01-01

The human growth hormone-releasing factor (GRF) peptides (GlyS/sup 15/)-GRF-(1-15) (IV), trifluoroacetyl-GRF-(20-44) (VI), trifluoroacetyl-GRF-(18-44) (VIII), and trifluoroacetyl-GRF-(16-44) (X) were synthesized by the solidphase method. Each of the peptides was reacted with citraconic anhydride and the trifluoroacetyl group was removed by reaction with 10% hydrazine in water. The citraconylated GRF-(1-15) peptide was coupled to the (20-44), (18-44) or (16-44) peptides by reaction with silver nitrate/N-hydroxysuccinimide to give GRF-(1-15)-(20-44) (XII), GRF-(1-15)-(18-44) (XIII), or GRF-(1-44), respectively. GRF-(1-44) was shown to stimulate the release of rat growth hormone from rat pituitary cells with an ED/sub 50/=8.8 x 10/sup -11/M. Peptides XII and XIII were inactive, either as agonists or as antagonists of the action of GRF-(1-44).

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

Small-molecule agonists for the glucagon-like peptide 1 receptor

DEFF Research Database (Denmark)

Knudsen, Lotte Bjerre; Kiel, Dan; Teng, Min

2007-01-01

and independent agonists. Potency of GLP-1 was not changed by the allosteric agonists, but affinity of GLP-1 for the receptor was increased. The most potent compound identified stimulates glucose-dependent insulin release from normal mouse islets but, importantly, not from GLP-1 receptor knockout mice. Also...

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.

Effect of beta-agonists on LAM progression and treatment.

Science.gov (United States)

Le, Kang; Steagall, Wendy K; Stylianou, Mario; Pacheco-Rodriguez, Gustavo; Darling, Thomas N; Vaughan, Martha; Moss, Joel

2018-01-30

Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2 +/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.

Food in film : a study on audience reception

OpenAIRE

Civelek, Ece Simin

2012-01-01

Ankara : The Department of Communication and Design, İhsan Doğramacı Bilkent University, 2012. Thesis (Master's) -- Bilkent University, 2012. Includes bibliographical references leaves 140-149. This study intends to analyze audience reception of foodstuff and related practices in films. In the study foodstuff and related practices are taken into consideration as a powerful semiotic system and in that respect are evaluated as an important property of filmic narration. Study e...

Receptivity to E-cigarette Marketing, Harm Perceptions, and E-cigarette Use

Science.gov (United States)

Pokhrel, Pallav; Fagan, Pebbles; Kehl, Lisa; Herzog, Thaddeus A.

2016-01-01

Objective To test whether exposure and receptivity to e-cigarette marketing are associated with recent e-cigarette use among young adults through increased beliefs that e-cigarettes are less harmful than cigarettes. Methods Data were collected from 307 multiethnic 4- and 2-year college students; approximately equal proportions of current, never, and former cigarette smokers [mean age = 23.5 (SD = 5.5); 65% female]. Results Higher receptivity to e-cigarette marketing was associated with perceptions that e-cigarettes are less harmful than cigarettes, which in turn, were associated with higher recent e-cigarette use. Conclusions The findings provide preliminary support to the proposition that marketing of e-cigarettes as safer alternatives to cigarettes or cessation aids is associated with increased e-cigarette use among young adults. The findings have implications for development of e-cigarette regulations. PMID:25290604

Analysis of thyroid hormone receptor βA mRNA expression in Xenopus laevis tadpoles as a means to detect agonism and antagonism of thyroid hormone action

International Nuclear Information System (INIS)

Opitz, Robert; Lutz, Ilka; Nguyen, Ngoc-Ha; Scanlan, Thomas S.; Kloas, Werner

2006-01-01

Amphibian metamorphosis represents a unique biological model to study thyroid hormone (TH) action in vivo. In this study, we examined the utility of thyroid hormone receptors α (TRα) and βA (TRβA) mRNA expression patterns in Xenopus laevis tadpoles as molecular markers indicating modulation of TH action. During spontaneous metamorphosis, only moderate changes were evident for TRα gene expression whereas a marked up-regulation of TRβA mRNA occurred in hind limbs (prometamorphosis), head (late prometamorphosis), and tail tissue (metamorphic climax). Treatment of premetamorphic tadpoles with 1 nM 3,5,3'-triiodothyronine (T3) caused a rapid induction of TRβA mRNA in head and tail tissue within 6 to 12 h which was maintained for at least 72 h after initiation of T3 treatment. Developmental stage had a strong influence on the responsiveness of tadpole tissues to induce TRβA mRNA during 24 h treatment with thyroxine (0, 1, 5, 10 nM T4) or T3 (0, 1, 5, 10 nM). Premetamorphic tadpoles were highly sensitive in their response to T4 and T3 treatments, whereas sensitivity to TH was decreased in early prometamorphic tadpoles and strongly diminished in late prometamorphic tadpoles. To examine the utility of TRβA gene expression analysis for detection of agonistic and antagonistic effects on T3 action, mRNA expression was assessed in premetamorphic tadpoles after 48 h of treatment with the synthetic agonist GC-1 (0, 10, 50, 250 nM), the synthetic antagonist NH-3 (0, 40, 200, 1000 nM), and binary combinations of NH-3 (0, 40, 200, 1000 nM) and T3 (1 nM). All tested concentrations of GC-1 as well as the highest concentration of NH-3 caused an up-regulation of TRβA expression. Co-treatment with NH-3 and T3 revealed strong antagonistic effects by NH-3 on T3-induced TRβA mRNA up-regulation. Results of this study suggest that TRβA mRNA expression analysis could serve as a sensitive molecular testing approach to study effects of environmental compounds on the thyroid system in

Psychological Models of Art Reception must be Empirically Grounded

DEFF Research Database (Denmark)

Nadal, Marcos; Vartanian, Oshin; Skov, Martin

2017-01-01

We commend Menninghaus et al. for tackling the role of negative emotions in art reception. However, their model suffers from shortcomings that reduce its applicability to empirical studies of the arts: poor use of evidence, lack of integration with other models, and limited derivation of testable...... hypotheses. We argue that theories about art experiences should be based on empirical evidence....

Bioanalytical and instrumental analysis of thyroid hormone disrupting compounds in water sources along the Yangtze River

International Nuclear Information System (INIS)

Shi Wei; Wang Xiaoyi; Hu Guanjiu; Hao Yingqun; Zhang Xiaowei; Liu Hongling; Wei Si; Wang Xinru; Yu Hongxia

2011-01-01

Thyroid hormone (TH) agonist and antagonist activities of water sources along the Yangtze River in China were surveyed by a green monkey kidney fibroblast (CV-1) cell-based TH reporter gene assay. Instrumental analysis was conducted to identify the responsible thyroid-active compounds. Instrumentally derived L-3,5,3'-triiodothyronine (T 3 ) equivalents (T 3 -EQs) and thyroid receptor (TR) antagonist activity equivalents referring to dibutyl phthalate (DBP-EQs) were calculated from the concentrations of individual congeners. The reporter gene assay demonstrated that three out of eleven water sources contained TR agonist activity equivalents (TR-EQs), ranging from 286 to 293 ng T 3 /L. Anti-thyroid hormone activities were found in all water sources with the TR antagonist activity equivalents referring to DBP (Ant-TR-EQs), ranging from 51.5 to 555.3 μg/L. Comparisons of the equivalents from instrumental and biological assays suggested that high concentrations of DBP and di-2-ethylhexyl phthalate (DEHP) were responsible for the observed TR antagonist activities at some locations along the Yangtze River. - Research highlights: → First of all, we indicated the instrumentally derived L-3,5,3'-triiodothyronine (T 3 ) equivalents (T 3 -EQs) and thyroid receptor (TR) antagonist activity equivalents referring to DBP (DBP-EQs) for the very first time. → Secondly, high concentrations of DBP and DEHP might be responsible for the observed TR antagonist activities at some locations. → Finally, we found that thyroid receptor (TR) antagonist activities were very common in Yangtze River. More attentions should be paid to the TR antagonist activities and the responsible compounds. - In vitro bioassay responses observed in Yangtze River source water extracts showed great TR antagonist activities, and DBP and DEHP were responsible.

Bioanalytical and instrumental analysis of thyroid hormone disrupting compounds in water sources along the Yangtze River

Energy Technology Data Exchange (ETDEWEB)

Shi Wei [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Wang Xiaoyi [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Jiangsu Academy of Environmental Science, Nanjing 210036 (China); Hu Guanjiu; Hao Yingqun [State Environmental Protection Key Laboratory of Monitoring and Analysis for Organic Pollutants in Surface Water, Jiangsu Provincial Environmental Monitoring Center, Nanjing 210036 (China); Zhang Xiaowei [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Liu Hongling, E-mail: hlliu@nju.edu.c [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Wei Si [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Wang Xinru [Key Laboratory of Reproductive Medicine and Institute of Toxicology, Nanjing Medical University, Nanjing 210029 (China); Yu Hongxia, E-mail: hongxiayu@nju.edu.c [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China)

2011-02-15

Thyroid hormone (TH) agonist and antagonist activities of water sources along the Yangtze River in China were surveyed by a green monkey kidney fibroblast (CV-1) cell-based TH reporter gene assay. Instrumental analysis was conducted to identify the responsible thyroid-active compounds. Instrumentally derived L-3,5,3'-triiodothyronine (T{sub 3}) equivalents (T{sub 3}-EQs) and thyroid receptor (TR) antagonist activity equivalents referring to dibutyl phthalate (DBP-EQs) were calculated from the concentrations of individual congeners. The reporter gene assay demonstrated that three out of eleven water sources contained TR agonist activity equivalents (TR-EQs), ranging from 286 to 293 ng T{sub 3}/L. Anti-thyroid hormone activities were found in all water sources with the TR antagonist activity equivalents referring to DBP (Ant-TR-EQs), ranging from 51.5 to 555.3 {mu}g/L. Comparisons of the equivalents from instrumental and biological assays suggested that high concentrations of DBP and di-2-ethylhexyl phthalate (DEHP) were responsible for the observed TR antagonist activities at some locations along the Yangtze River. - Research highlights: First of all, we indicated the instrumentally derived L-3,5,3'-triiodothyronine (T{sub 3}) equivalents (T{sub 3}-EQs) and thyroid receptor (TR) antagonist activity equivalents referring to DBP (DBP-EQs) for the very first time. Secondly, high concentrations of DBP and DEHP might be responsible for the observed TR antagonist activities at some locations. Finally, we found that thyroid receptor (TR) antagonist activities were very common in Yangtze River. More attentions should be paid to the TR antagonist activities and the responsible compounds. - In vitro bioassay responses observed in Yangtze River source water extracts showed great TR antagonist activities, and DBP and DEHP were responsible.

The 1623 Plan for Global Governance: the obscure history of its reception

Directory of Open Access Journals (Sweden)

GERMAN A. DE LA REZA

2015-12-01

Full Text Available Abstract In the present article we analyze the characteristics and the reception of the first plan for global governance, the New Cyneas by Émeric Crucé. With this goal in mind, we examine the history of its readings and the possible influence on the Duke of Sully's project for European confederation, the case most often cited by historians of ideas. Our analysis takes into consideration the 17th century reception, the scant dissemination of the work and the possible causes of its limited impact. Our conclusions support, on the one hand, the novelty of Crucé's principal ideas, and on the other, their limited impact over the time with the exception of the period surrounding the creation of the League of Nations.

Generalized concentration addition: a method for examining mixtures containing partial agonists.

Science.gov (United States)

Howard, Gregory J; Webster, Thomas F

2009-08-07

Environmentally relevant toxic exposures often consist of simultaneous exposure to multiple agents. Methods to predict the expected outcome of such combinations are critical both to risk assessment and to an accurate judgment of whether combinations are synergistic or antagonistic. Concentration addition (CA) has commonly been used to assess the presence of synergy or antagonism in combinations of similarly acting chemicals, and to predict effects of combinations of such agents. CA has the advantage of clear graphical interpretation: Curves of constant joint effect (isoboles) must be negatively sloped straight lines if the mixture is concentration additive. However, CA cannot be directly used to assess combinations that include partial agonists, although such agents are of considerable interest. Here, we propose a natural extension of CA to a functional form that may be applied to mixtures including full agonists and partial agonists. This extended definition, for which we suggest the term "generalized concentration addition," encompasses linear isoboles with slopes of any sign. We apply this approach to the simple example of agents with dose-response relationships described by Hill functions with slope parameter n=1. The resulting isoboles are in all cases linear, with negative, zero and positive slopes. Using simple mechanistic models of ligand-receptor systems, we show that the same isobole pattern and joint effects are generated by modeled combinations of full and partial agonists. Special cases include combinations of two full agonists and a full agonist plus a competitive antagonist.

GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

Science.gov (United States)

Lambalk, C B; Banga, F R; Huirne, J A; Toftager, M; Pinborg, A; Homburg, R; van der Veen, F; van Wely, M

2017-09-01

pregnancy rate when the oral hormonal programming pill (OHP) pretreatment was combined with a flexible protocol (RR 0.74, 95% CI 0.59-0.91) while without OHP, the RR was 0.84, 95% CI 0.71-1.0. Subgroup analysis for the fixed antagonist schedule demonstrated no evidence of a significant difference with or without OHP (RR 0.94, 95% CI 0.79-1.12 and RR 0.94, 95% CI 0.83-1.05, respectively). Antagonists resulted in significantly lower OHSS rates both in the general IVF patients and in women with PCOS (RR 0.63, 95% CI 0.50-0.81 and RR 0.53, 95% CI 0.30-0.95, respectively). No data on OHSS was available from trials in poor responders. In a general IVF population, GnRH antagonists are associated with lower ongoing pregnancy rates when compared to long protocol agonists, but also with lower OHSS rates. Within this population, antagonist treatment prevents one case of OHSS in 40 patients but results in one less ongoing pregnancy out of every 28 women treated. Thus standard use of the long GnRH agonist treatment is perhaps still the approach of choice for prevention of premature luteinization. In couples with PCOS and poor responders, GnRH antagonists do not seem to compromise ongoing pregnancy rates and are associated with less OHSS and therefore could be considered as standard treatment. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The public reception of the Research Assessment Exercise 1996.

Directory of Open Access Journals (Sweden)

Julian Warner

1998-01-01

Full Text Available This paper reviews the public reception of the Research Assessment Exercise 1996 (RAE from its announcement in December 1996 to the decline of discussion at end May 1997. A model for diffusion of the RAE is established which distinguishes extra-communal (or exoteric from intra-communal (or esoteric media. The different characteristics of each medium and the changing nature of the discussion over time are considered. Different themes are distinguished in the public reception of the RAE: the spatial distribution of research; the organisation of universities; disciplinary differences in understanding; a perceived conflict between research and teaching; the development of a culture of accountability; and analogies with the organisation of professional football. In conclusion, it is suggested that the RAE and its effects can be more fully considered from the perspective of scholarly communication and understandings of the development of knowledge than it has been by previous contributions in information science, which have concentrated on the possibility of more efficient implementation of existing processes. A fundamental responsibility for funding councils is also identified: to promote the overall health of university education and research, while establishing meaningful differentiations between units.

Seeing, wanting, owning: the relationship between receptivity to tobacco marketing and smoking susceptibility in young people

Science.gov (United States)

Feighery, E.; Borzekowski, D.; Schooler, C.; Flora, J.

1998-01-01

OBJECTIVE—To assess the effect of the tobacco industry's marketing practices on adolescents by examining the relationship between their receptivity to these practices and their susceptibility to start smoking.
DESIGN—Paper-and-pencil surveys measuring association with other smokers, exposure to tobacco industry marketing strategies, experience with smoking, and resolve not to smoke in the future.
SETTING—25 randomly selected classrooms in five middle schools in San Jose, California.
SUBJECTS—571 seventh graders with an average age of 13 years and 8 months; 57% were female. Forty-five per cent of the students were Asian, 38% were Hispanic, 12% were white, and 5% were black.
MAIN OUTCOME MEASURES—Exposure to social influences, receptivity to marketing strategies, susceptibility to start smoking.
RESULTS—About 70% of the participants indicated at least moderate receptivity to tobacco marketing materials. Children who are more receptive are also more susceptible to start smoking. In addition to demographics and social influences, receptivity to tobacco marketing materials was found to be strongly associated with susceptibility.
CONCLUSIONS—Tobacco companies conduct marketing campaigns that effectively capture teenage attention and stimulate desire for their promotional items. These marketing strategies may function to move young teenagers from non-smoking status toward regular use of tobacco. Our results demonstrate that there is a clear association between tobacco marketing practices and youngsters' susceptibility to smoke. The findings, along with other research, provide compelling support for regulating the manner in which tobacco products are marketed, to protect young people from the tobacco industry's strategies to reach them.


Keywords: adolescents; advertising; smoking initiation PMID:9789929

The Good, the Bad, and the Ugly: Agonistic Behaviour in Juvenile Crocodilians

OpenAIRE

Brien, Matthew L.; Lang, Jeffrey W.; Webb, Grahame J.; Stevenson, Colin; Christian, Keith A.

2013-01-01

We examined agonistic behaviour in seven species of hatchling and juvenile crocodilians held in small groups (N = 4) under similar laboratory conditions. Agonistic interactions occurred in all seven species, typically involved two individuals, were short in duration (5-15 seconds), and occurred between 1600-2200 h in open water. The nature and extent of agonistic interactions, the behaviours displayed, and the level of conspecific tolerance varied among species. Discrete postures, non-contact...

Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.

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Min Gao

Full Text Available Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1 selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.

Cross-Language Associations in the Development of Preschoolers' Receptive and Expressive Vocabulary.

Science.gov (United States)

Maier, Michelle F; Bohlmann, Natalie L; Palacios, Natalia A

The increasing population of dual language learners (DLLs) entering preschool classrooms highlights a continued need for research on the development of dual language acquisition, and specifically vocabulary skills, in this age group. This study describes young DLL children's ( N = 177) vocabulary development in both English and Spanish simultaneously, and how vocabulary skills in each language relate to one another, during a contextual shift that places greater emphasis on the acquisition of academic English language skills. Findings demonstrated that DLL preschoolers made gains in vocabulary in both languages with more change evidenced in receptive, in comparison to expressive, vocabulary as well as in English in comparison to Spanish. When examining whether children's vocabulary scores in one language at the beginning of preschool interact with their vocabulary scores in the other language to predict vocabulary growth, no significant associations were found for receptive vocabulary. In contrast, the interaction between initial English and Spanish expressive vocabulary scores was negatively related to growth in English expressive vocabulary. This cross-language association suggests that children who have low expressive vocabulary skills in both languages tend to grow faster in their English expressive vocabulary. The study extends previous work on dual language development by examining growth in expressive and receptive vocabulary in both English and Spanish. It also provides suggestions for future work to inform a more comprehensive understanding of DLL children's development in both languages.

Comparison of effects of estradiol with those of octylmethoxycinnamate and 4-methylbenzylidene camphor on fat tissue, lipids and pituitary hormones

International Nuclear Information System (INIS)

Seidlova-Wuttke, Dana; Christoffel, Julie; Rimoldi, Guillermo; Jarry, Hubertus; Wuttke, Wolfgang

2006-01-01

Octylmethoxycinnamate (OMC) and 4-methylbenzylidene camphor (4MBC) are commercially used absorbers of ultraviolet (UV) light. In rats, they were shown to exert endocrine disrupting including uterotrophic, i.e. estrogenic effects. Estrogens have also metabolic effects, therefore the impact of oral application of the two UV absorbers at 2 doses for 3 months on lipids and hormones were compared with those of estradiol-17β (E2). E2, OMC and 4MBC reduced weight gain, the size of fat depots and serum leptin, a lipocyte-derived hormone, when compared to the ovariectomized control animals. Serum triglycerides were also reduced by the UV screens but not by E2. On the other hand, E2 and OMC reduced serum cholesterol, low density lipoproteins and high density lipoproteins; this effect was not shared by 4MBC. While E2 inhibited, OMC and 4MBC stimulated serum LH levels. In the uterus, both UV filters had mild stimulatory effects. 4MBC inhibited serum T4 resulting in increased serum TSH levels. It is concluded that OMC and 4MBC have effects on several metabolic parameters such as fat and lipid homeostasis as well as on thyroid hormone production. Many of these effects are not shared by E2. Hence, other than estrogen-receptive mechanisms may be responsible for these effects

Response to the gonadotropin releasing hormone agonist leuprolide in immature female sheep androgenized in utero

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SERGIO E RECABARREN

2005-01-01

Full Text Available Similar to women with Polycystic Ovary Syndrome (PCOS, female sheep treated prenatally with testosterone (T-females are hypergonadotropic, exhibit neuroendocrine defects, multifollicular ovarian morphology, hyperinsulinemia and cycle defects. Hypergonadotropism and multifollicular morphology may in part be due to developmentally regulated increase in pituitary responsiveness to GnRH and may culminate in increased ovarian estradiol production. In this study, we utilized a GnRH agonist, leuprolide, to determine the developmental impact of prenatal testosterone exposure on pituitary-gonadal function and to establish if prenatal exposure produces changes in the reproductive axis similar to those described for women with PCOS. Eight control and eight T-females were injected intravenously with 0.1 mg of leuprolide acetate per kilogram of body weight at 5, 10 and 20 weeks of age. Blood samples were collected by means of an indwelling jugular vein catheter at 0, 3, 6, 9, 12, 18, 24, 30, 36, 42 and 48 hours after leuprolide. Area under the curve (AUC of LH response to leuprolide increased progressively between the three ages studied (P<0.05. AUC of LH in T-females was higher than in control females of the same age at 5 and 10 weeks of age (P<0.05, but similar at 20 weeks of age. AUC of estradiol response was lower at 10 but higher at 20 weeks of age in T-females compared to controls of the same age (P<0.05. Our findings suggest that prenatal T treatment alters the pituitary and ovarian responsiveness in a manner comparable to that observed in women with PCOS.

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....

Long-acting beta 2-agonists in chronic obstructive pulmonary disease.

Science.gov (United States)

Llewellyn-Jones, Carol

2002-01-01

Until recently, the use of long-acting beta 2-agonists in chronic obstructive pulmonary disease has been understated. There is now evidence that they may offer benefits beyond bronchodilation. This article reviews the management of chronic obstructive pulmonary disease and looks at the place of long-acting beta 2-agonists as a first-line treatment option.

Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

DEFF Research Database (Denmark)

Goncalves de Azavedo, Carlos M. B. P.; Watterson, Kenneth R; Wargent, Ed T

2016-01-01

The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure......-activity relationship studies of a previously disclosed non-acidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although...... a significant fraction of these non-carboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice...

Hormonal regulation of phosphatidylcholine synthesis by reversible modulation of cytidylyltransferase.

Science.gov (United States)

Kelly, K L; Gutierrez, G; Martin, A

1988-01-01

The effect of both lipolytic and antilipolytic hormones on the turnover of phosphatidylcholine in freshly isolated rat adipocytes was investigated. Treatment of adipocytes with agonists such as glucagon or isoprenaline that stimulate lipolysis through a cyclic AMP-dependent mechanism caused an increase in the incorporation of [Me-3H]choline into phosphatidylcholine. Pulse-chase studies indicated that the stimulation was due to an increase in the conversion of choline into phosphatidylcholine, which was both time- and dose-dependent. The stimulatory effect of isoprenaline was inhibited in a dose-dependent manner by oxytocin or insulin. Oxytocin inhibited the incorporation of [Me-3H]choline into phosphatidylcholine in both the presence and the absence of isoprenaline, whereas in the absence of isoprenaline insulin increased the incorporation of [Me-3H]choline into phosphatidylcholine. The effects of isoprenaline, oxytocin and insulin on the incorporation of [3H]choline into phosphatidylcholine were paralleled by changes in the activity of CTP:phosphocholine cytidylyltransferase. PMID:2849424

Engagement with dietary fibre and receptiveness to resistant starch in Australia.

Science.gov (United States)

Mohr, Philip; Quinn, Sinéad; Morell, Matthew; Topping, David

2010-11-01

To investigate community engagement with the health benefits of dietary fibre (DF) and its potential as a framework for the promotion of increased consumption of resistant starch (RS). A nationwide postal Food and Health Survey conducted in Australia by CSIRO Human Nutrition. Adults aged 18 years and above, selected at random from the Australian Electoral Roll (n 849). A cross-sectional design was employed to analyse ratings of (i) the importance of various RS health and functional claims and (ii) receptiveness to different foods as RS delivery vehicles, according to the respondents' level of fibre engagement as classified under the Precaution Adoption Process Model (PAPM) of Health Behaviour. There was a high level of recognition (89·5 %) of DF as being important for health. Significant gender differences were found for ratings of RS attributes and RS delivery options. Women were both more fibre-engaged than men and more receptive than men to RS and its potential benefits. Ratings of the acceptability of several foods as means of delivering RS revealed a general preference for healthy staples over indulgences, with the margin between acceptability of staples and indulgences increasing markedly with increased fibre engagement. Application of the PAPM to awareness of DF reveals a ready-made target group for health messages about RS and pockets of differential potential receptiveness. The findings support the promotion of RS as providing health benefits of DF with the added reduction of risk of serious disease, its delivery through healthy staples and the targeting of messages at both fibre-engaged individuals and women in general.

Estrogen enhances expression of the complement C5a receptor and the C5a-agonist evoked calcium influx in hormone secreting neurons of the hypothalamus.

Science.gov (United States)

Farkas, Imre; Varju, Patricia; Szabo, Emese; Hrabovszky, Erik; Okada, Noriko; Okada, Hidechika; Liposits, Zsolt

2008-01-01

In the present study we examined presence of the complement C5a receptor (C5aR) in hypothalamic neurosecretory neurons of the rodent brain and effect of estrogen on C5aR expression. Whole cell patch clamp measurements revealed that magnocellular neurons in the supraoptic and paraventricular nuclei of hypothalamic slices of the rats responded to the C5aR-agonist PL37-MAP peptide with calcium ion current pulses. Gonadotropin-releasing hormone (GnRH) producing neurons in slices of the preoptic area of the mice also reacted to the peptide treatment with inward calcium current. PL37-MAP was able to evoke the inward ion current of GnRH neurons in slices from ovariectomized animals. The amplitude of the inward pulses became higher in slices obtained from 17beta-estradiol (E2) substituted mice. Calcium imaging experiments demonstrated that PL37-MAP increased the intracellular calcium content in the culture of the GnRH-producing GT1-7 cell line in a concentration-dependent manner. Calcium imaging also showed that E2 pretreatment elevated the PL37-MAP evoked increase of the intracellular calcium content in the GT1-7 cells. The estrogen receptor blocker Faslodex in the medium prevented the E2-evoked increase of the PL37-MAP-triggered elevation of the intracellular calcium content in the GT1-7 cells demonstrating that the effect of E2 might be related to the presence of estrogen receptor. Real-time PCR experiments revealed that E2 increased the expression of C5aR mRNA in GT1-7 neurons, suggesting that an increased C5aR synthesis could be involved in the estrogenic modulation of calcium response. These data indicate that hypothalamic neuroendocrine neurons can integrate immune and neuroendocrine functions. Our results may serve a better understanding of the inflammatory and neurodegeneratory diseases of the hypothalamus and the related neuroendocrine and autonomic compensatory responses.

Definition of neutron multiplication in a reception capacity of radioactive waste shop

International Nuclear Information System (INIS)

Dulin, V.A.; Dulin, V.V.; Pavlova, O.N.

2006-01-01

To determine neutrons multiplication the measurements and calculations of spatial distributions of neutron counting and absolute fission rates in a reception capacity of IPPE radioactive waste shop have been carried out and analyzed. A content of fissionable medium was unknown. The approach developed has allowed implementing a calculation analysis of the experimental data on determination of the most probable spatial distributions of basic parameters of the fissionable medium of unknown content. It has allowed determining the neutrons multiplication factor in a reception capacity of a tank No. 17. It has been found that the value of neutrons multiplication factor in a tank is 1.07 ± 0.03. The developed measurement method and calculation analysis used for experimental data also can be applied in other cases when the multiplication medium content is unknown [ru

Russian Translations of Writings of J.R.R. Tolkien as the Stage of their Cultural Reception in Russia

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Ellina V. Shustova

2017-11-01

Full Text Available This article identifies problems of translation of J.R.R. Tolkien`s works to the Russian language. Due to complexity of their reception in the Russian literature and culture, these problems continue at the present time. The purpose of this article is to consider the translational interpretations as a form of reception of J.R.R. Tolkien`s works in Russia and perform analysis of relevant stages of the receptive process. The leading approach to the study of this problem is the methodology of receptive aesthetics; this takes into account the development trends of the method. This research shows that it is the translation, in many respects, that sets trends for further understanding of writings by J.R.R. Tolkien in Russia and includes them in a Russian cultural and literary context, as well as set their level of systematic perception. Contents of this article may be used for readings in general and special courses for Western literature at universities, and may be useful to a wide range of readers interested in the work of J.R.R. Tolkien.

Effects of juvenile hormone (JH) analog insecticides on larval development and JH esterase activity in two spodopterans.

Science.gov (United States)

El-Sheikh, El-Sayed A; Kamita, Shizuo G; Hammock, Bruce D

2016-03-01

Juvenile hormone analog (JHA) insecticides are biological and structural mimics of JH, a key insect developmental hormone. Toxic and anti-developmental effects of the JHA insecticides methoprene, fenoxycarb, and pyriproxyfen were investigated on the larval and pupal stages of Spodoptera littoralis and Spodoptera frugiperda. Bioassays showed that fenoxycarb has the highest toxicity and fastest speed of kill in 2nd instar S. littoralis. All three JHAs affected the development of 6th instar (i.e., final instar) and pupal S. frugiperda. JH esterase (JHE) is a critical enzyme that helps to regulate JH levels during insect development. JHE activity in the last instar S. littoralis and S. frugiperda was 11 and 23 nmol min(-1) ml(-1) hemolymph, respectively. Methoprene and pyriproxyfen showed poor inhibition of JHE activity from these insects, whereas fenoxycarb showed stronger inhibition. The inhibitory activity of fenoxycarb, however, was more than 1000-fold lower than that of OTFP, a highly potent inhibitor of JHEs. Surprisingly, topical application of methoprene, fenoxycarb or pyriproxyfen on 6th instars of S. littoralis and S. frugiperda prevented the dramatic reduction in JHE activity that was found in control insects. Our findings suggest that JHAs may function as JH agonists that play a disruptive role or a hormonal replacement role in S. littoralis and S. frugiperda. Copyright © 2015 Elsevier B.V. All rights reserved.

Contamination with retinoic acid receptor agonists in two rivers in the Kinki region of Japan.

Science.gov (United States)

Inoue, Daisuke; Nakama, Koki; Sawada, Kazuko; Watanabe, Taro; Takagi, Mai; Sei, Kazunari; Yang, Min; Hirotsuji, Junji; Hu, Jianying; Nishikawa, Jun-ichi; Nakanishi, Tsuyoshi; Ike, Michihiko

2010-04-01

This study was conducted to investigate the agonistic activity against human retinoic acid receptor (RAR) alpha in the Lake Biwa-Yodo River and the Ina River in the Kinki region of Japan. To accomplish this, a yeast two-hybrid assay was used to elucidate the spatial and temporal variations and potential sources of RARalpha agonist contamination in the river basins. RARalpha agonistic activity was commonly detected in the surface water samples collected along two rivers at different periods, with maximum all-trans retinoic acid (atRA) equivalents of 47.6 ng-atRA/L and 23.5 ng-atRA/L being observed in Lake Biwa-Yodo River and Ina River, respectively. The results indicated that RARalpha agonists are always present and widespread in the rivers. Comparative investigation of RARalpha and estrogen receptor alpha agonistic activities at 20 stations along each river revealed that the spatial variation pattern of RARalpha agonist contamination was entirely different from that of the estrogenic compound contamination. This suggests that the effluent from municipal wastewater treatment plants, a primary source of estrogenic compounds, seemed not to be the cause of RARalpha agonist contamination in the rivers. Fractionation using high performance liquid chromatography (HPLC) directed by the bioassay found two bioactive fractions from river water samples, suggesting the presence of at least two RARalpha agonists in the rivers. Although a trial conducted to identify RARalpha agonists in the major bioactive fraction was not completed as part of this study, comparison of retention times in HPLC analysis and quantification with liquid chromatography-mass spectrometry analysis revealed that the major causative contaminants responsible for the RARalpha agonistic activity were not RAs (natural RAR ligands) and 4-oxo-RAs, while 4-oxo-RAs were identified as the major RAR agonists in sewage in Beijing, China. These findings suggest that there are unknown RARalpha agonists with high

Targeted Delivery of LXR Agonist Using a Site-Specific Antibody-Drug Conjugate.

Science.gov (United States)

Lim, Reyna K V; Yu, Shan; Cheng, Bo; Li, Sijia; Kim, Nam-Jung; Cao, Yu; Chi, Victor; Kim, Ji Young; Chatterjee, Arnab K; Schultz, Peter G; Tremblay, Matthew S; Kazane, Stephanie A

2015-11-18

Liver X receptor (LXR) agonists have been explored as potential treatments for atherosclerosis and other diseases based on their ability to induce reverse cholesterol transport and suppress inflammation. However, this therapeutic potential has been hindered by on-target adverse effects in the liver mediated by excessive lipogenesis. Herein, we report a novel site-specific antibody-drug conjugate (ADC) that selectively delivers a LXR agonist to monocytes/macrophages while sparing hepatocytes. The unnatural amino acid para-acetylphenylalanine (pAcF) was site-specifically incorporated into anti-CD11a IgG, which binds the α-chain component of the lymphocyte function-associated antigen 1 (LFA-1) expressed on nearly all monocytes and macrophages. An aminooxy-modified LXR agonist was conjugated to anti-CD11a IgG through a stable, cathepsin B cleavable oxime linkage to afford a chemically defined ADC. The anti-CD11a IgG-LXR agonist ADC induced LXR activation specifically in human THP-1 monocyte/macrophage cells in vitro (EC50-27 nM), but had no significant effect in hepatocytes, indicating that payload delivery is CD11a-mediated. Moreover, the ADC exhibited higher-fold activation compared to a conventional synthetic LXR agonist T0901317 (Tularik) (3-fold). This novel ADC represents a fundamentally different strategy that uses tissue targeting to overcome the limitations of LXR agonists for potential use in treating atherosclerosis.

Simultaneous bilingual language acquisition: The role of parental input on receptive vocabulary development.

Science.gov (United States)

Macleod, Andrea An; Fabiano-Smith, Leah; Boegner-Pagé, Sarah; Fontolliet, Salomé

2013-02-01

Parents often turn to educators and healthcare professionals for advice on how to best support their child's language development. These professionals frequently suggest implementing the 'one-parent-one-language' approach to ensure consistent exposure to both languages. The goal of this study was to understand how language exposure influences the receptive vocabulary development of simultaneous bilingual children. To this end, we targeted nine German-French children growing up in bilingual families. Their exposure to each language within and outside the home was measured, as were their receptive vocabulary abilities in German and French. The results indicate that children are receiving imbalanced exposure to each language. This imbalance is leading to a slowed development of the receptive vocabulary in the minority language, while the majority language is keeping pace with monolingual peers. The one-parent-one-language approach does not appear to support the development of both of the child's languages in the context described in the present study. Bilingual families may need to consider other options for supporting the bilingual language development of their children. As professionals, we need to provide parents with advice that is based on available data and that is flexible with regards to the current and future needs of the child and his family.

Lexical knowledge of Serbian L1 English L2 learners: Reception vs. production

Directory of Open Access Journals (Sweden)

Danilović-Jeremić Jelena

2015-01-01

Full Text Available The acquisition of lexical knowledge in a second/foreign language is often investigated by means of vocabulary size tests which assess two aspects of the learners' competence: reception and production. Estimates of these two dimensions, as well as the (potential gap between them, have important pedagogical implications in that they indicate the degree to which the learners can comprehend or use the language autonomously. Therefore, the aim of this paper is to explore the vocabulary size of three generations of B2-level L2 learners (CEFR, first-year students majoring in English at the Faculty of Philology and Arts in Kragujevac, Serbia, by means of Vocabulary Levels Tests (Laufer & Nation, 1999; Nation, 1990. The results of the statistical analyses show that the receptive vocabulary of Serbian L2 learners is much more developed than their productive vocabulary, and that the gap between lexical production and reception changes depending on the frequency of the lexemes and the proficiency level of L2 learners. The findings imply that, at the primary and secondary level of education, more attention should be paid to the development of productive lexical knowledge which is crucial not only for success in English degree courses but communication in English in general.

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 ...