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Sample records for systemic glucocorticoid side

  1. Systems Biology of Glucocorticoids in Muscle Disease

    Science.gov (United States)

    2010-10-01

    Introduction Duchenne muscular dystrophy (DMD) is the most common and incurable muscular dystrophy of childhood. Muscle regeneration fails with...SUBJECT TERMS Duchenne Muscular dystrophy , Glucocorticoids, Systems biology, Drug mechanism 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION...better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant proposal is led by Dr. Eric Hoffman, and it

  2. Glucocorticoid receptor modulators.

    Science.gov (United States)

    Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

    2018-06-01

    The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  3. CINRG: Systems Biology of Glucocorticoids in Muscle Disease

    Science.gov (United States)

    2013-10-01

    Contract W81XWH-09-1-0726 SYSTEMS BIOLOGY OF GLUCOCORTICOIDS IN MUSCLE DISEASE Introduction Duchenne muscular dystrophy (DMD) is the most... muscle and enable the development of better targeted and more effective therapies for Duchenne muscular dystrophy dynamically. This MDA grant...common and incurable muscular dystrophy of childhood. Muscle regeneration fails with advancing age, leading to considerable fibrosis. Corticosteroid

  4. Hypersensitivity Reactions from Excipients in Systemic Glucocorticoid Formulations

    DEFF Research Database (Denmark)

    Calogiuri, Gianfranco; Garvey, Lene H; Romita, Paolo

    2016-01-01

    Glucocorticoids are the most widely used drugs for the treatment of hypersensitivity, however these drugs themselves and the excipients contained in commercial corticosteroid formulations are able to induce severe immediate-type hypersensitivity reactions. Reactions involving excipients have been...

  5. Regulation of hippocampal neurogenesis by systemic factors including stress, glucocorticoids, sleep, and inflammation

    NARCIS (Netherlands)

    Lucassen, P.J.; Oomen, C.; van Dam, A.-M.; Czéh, B.; Gage, F.H.; Kempermann, G.; Song, H.

    2008-01-01

    This review summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

  6. Glucocorticoid-induced effects on the growth plate and the IGF system

    NARCIS (Netherlands)

    Smink, Jeske Johanna

    2003-01-01

    Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive drugs. The use of these potent drugs, however, often results in side-effects, such as growth retardation in children. For already many years, this GC-induced growth retardation is suggested to involve impaired action of

  7. Glucocorticoid receptor effects on the immune system and infl ammation

    NARCIS (Netherlands)

    E.L.T. van den Akker (Erica)

    2008-01-01

    textabstractThomas Addison’s discovery in the mid-1800s that the adrenal cortex was essential for survival preceded by nearly a century the demonstration that this gland produced at least two distinct hormones, each essential for normal life. How glucocorticoids sustained life remained a mystery for

  8. Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System

    Directory of Open Access Journals (Sweden)

    Natalie G. Burford

    2017-10-01

    Full Text Available The collective of endocrine organs acting in homeostatic regulation—known as the hypothalamic-pituitary-adrenal (HPA axis—comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart.

  9. Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System.

    Science.gov (United States)

    Burford, Natalie G; Webster, Natalia A; Cruz-Topete, Diana

    2017-10-16

    The collective of endocrine organs acting in homeostatic regulation-known as the hypothalamic-pituitary-adrenal (HPA) axis-comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart.

  10. Glucocorticoids interact with the hippocampal endocannabinoid system in impairing retrieval of contextual fear memory

    Science.gov (United States)

    Atsak, Piray; Hauer, Daniela; Campolongo, Patrizia; Schelling, Gustav; McGaugh, James L.; Roozendaal, Benno

    2012-01-01

    There is extensive evidence that glucocorticoid hormones impair the retrieval of memory of emotionally arousing experiences. Although it is known that glucocorticoid effects on memory retrieval impairment depend on rapid interactions with arousal-induced noradrenergic activity, the exact mechanism underlying this presumably nongenomically mediated glucocorticoid action remains to be elucidated. Here, we show that the hippocampal endocannabinoid system, a rapidly activated retrograde messenger system, is involved in mediating glucocorticoid effects on retrieval of contextual fear memory. Systemic administration of corticosterone (0.3–3 mg/kg) to male Sprague–Dawley rats 1 h before retention testing impaired the retrieval of contextual fear memory without impairing the retrieval of auditory fear memory or directly affecting the expression of freezing behavior. Importantly, a blockade of hippocampal CB1 receptors with AM251 prevented the impairing effect of corticosterone on retrieval of contextual fear memory, whereas the same impairing dose of corticosterone increased hippocampal levels of the endocannabinoid 2-arachidonoylglycerol. We also found that antagonism of hippocampal β-adrenoceptor activity with local infusions of propranolol blocked the memory retrieval impairment induced by the CB receptor agonist WIN55,212–2. Thus, these findings strongly suggest that the endocannabinoid system plays an intermediary role in regulating rapid glucocorticoid effects on noradrenergic activity in impairing memory retrieval of emotionally arousing experiences. PMID:22331883

  11. DMPD: Glucocorticoids and the innate immune system: crosstalk with the toll-likereceptor signaling network. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17576036 Glucocorticoids and the innate immune system: crosstalk with the toll-like...07 May 13. (.png) (.svg) (.html) (.csml) Show Glucocorticoids and the innate immune system: crosstalk with t...nd the innate immune system: crosstalk with the toll-likereceptor signaling network. Authors Chinenov Y, Rog

  12. Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment

    Directory of Open Access Journals (Sweden)

    Saswati ePaul

    2015-04-01

    Full Text Available A substantial number of studies on basal forebrain cholinergic neurons (BFCN have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer’s disease (AD, and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine, glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, which could help decipher disease states and propose leads for pharmacological intervention.

  13. Efficacy of Vitamin K2 for Glucocorticoid-induced Osteoporosis in Patients with Systemic Autoimmune Diseases.

    Science.gov (United States)

    Shikano, Kotaro; Kaneko, Kaichi; Kawazoe, Mai; Kaburaki, Makoto; Hasunuma, Tomoko; Kawai, Shinichi

    2016-01-01

    Objective Vitamin K2 (menatetrenone) is an effective treatment for patients with postmenopausal osteoporosis. We herein performed a subanalysis of patients with systemic autoimmune diseases undergoing glucocorticoid therapy in our previous prospective study. Methods Sixty patients were categorized into a group with vitamin K2 treatment (n=20, Group A) and a group without vitamin K2 treatment (n=40, Group B). All patients were treated with bisphosphonates. Results Serum levels of osteocalcin and undercarboxylated osteocalcin decreased significantly after the start of glucocorticoid therapy in both groups, while the serum osteocalcin level was significantly higher in Group A than Group B during the third (p=0.0250) and fourth weeks (p=0.0155). The serum level of the N-terminal peptide of type I procollagen, a bone formation marker, decreased during glucocorticoid therapy, but was significantly higher in Group A than Group B during the fourth week (p=0.0400). The bone mineral density and fracture rate showed no significant differences between the two groups. Conclusion Although vitamin K2 improves bone turnover markers in patients with osteoporosis on glucocorticoid therapy, it has no significant effect on the bone mineral density and fracture rate after 1.5 years of treatment.

  14. [Efficacy of systemic glucocorticoids combined with inhaled steroid on children with acute laryngitis].

    Science.gov (United States)

    Chen, Q P; Zhou, R F; Zhang, Y M; Yang, L

    2018-01-07

    Objective: To evaluate the efficacy of systemic glucocorticoid (steroid) combined with high dose inhaled steroid in the treatment of children with acute laryngitis. Methods: A total of 78 children with acute laryngitis were randomly divided into study group( n =40) and control group( n =38) between November 2016 and April 2017. In addition to routine treatment of anti infection and symptomatic treatment, Dexamethasone injection(0.3-0.5 mg/kg, 1-3 d, according to the patient's condition) was provided to each group. In addition to the treatment mentioned above, the study group were assigned to receive 1.0 mg Budesonide suspension for inhalation, oxygen-driven atomizing inhalation, every/30 minutes, 2 times in a row, after that every 12 hours. The improvement of inspiratory dyspnea, hoarseness, barking cough and wheezing of both groups was evaluated at 30 min, 1 h, 2 h, 6 h, 12 h, 24 h and 72 h after treatment.Sigmaplot 11.5 software was used to analyze the data. Results: No significant difference was detected in terms of inspiratory dyspnea, hoarseness, barking cough or stridor score before treatment between the two groups( P >0.05). Compared with those before treatment, symptoms of inspiratory dyspnea, hoarseness, barking cough and stridor score of both groups improved markedly at 12 h and 24 h after treatment( P dyspnea, hoarseness, barking cough or stridor score at each time point after treatment between the two groups( P >0.05). The effective rate was 92.50% and 92.11% in study group and control group, respectively, and no significant difference was noted ( P >0.05). Conclusion: Compared with single systemic glucocorticoid, systemic glucocorticoids combined with inhaled steroid possessed similar efficacy in treating acute laryngitis and relieving laryngeal obstruction of children.

  15. Time trends for alendronate prescription practices in women with chronic obstructive pulmonary disease and women exposed to systemic glucocorticoids

    DEFF Research Database (Denmark)

    Brask-Lindemann, Dorthe; Eiken, P; Eskildsen, P

    2013-01-01

    Summary Chronic obstructive pulmonary disease (COPD) and systemic glucocorticoid exposure are well-known risk factors of osteoporosis. We evaluated alendronate prescription practices related to COPD and exposure to systemic corticosteroids from 1996 to 2008 and showed an increasing targeting...... of alendronate treatment in patients with COPD and patients with systemic corticosteroid exposure. Introduction COPD and systemic glucocorticoid exposure are well-known risk factors of osteoporosis and fragility fracture, but osteoporosis is often underdiagnosed and undertreated in these patients. This study...... aims to evaluate alendronate prescription practices related to COPD and/or to exposure to systemic glucocorticoids among Danish women. Methods A total of 388,314 female subjects >50 years old, 64,719 of whom initiated treatment with alendronate, and 323,595 age- and gender-matched controls were...

  16. The development of the glucocorticoid receptor system in the rat limbic brain. 2

    International Nuclear Information System (INIS)

    Meaney, M.J.; Sapolsky, R.M.; McEwen, B.S.

    1985-01-01

    The authors report the results of an autoradiographic analysis of the postnatal development of the hippocampal glucocorticoid receptor system in the rat brain. Quantitative analysis of the autoradiograms revealed a varied pattern of gradual development towards adult receptor concentrations during the second week of life. Receptor concentrations in the dentate gyrus increased dramatically between Days 9 and 15, while the changes during this period in the pyramidal layers of Ammon's horn seemed to reflect both structural changes in these regions as well as increases in receptor concentrations. (orig.)

  17. Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting

    Science.gov (United States)

    Wing, S. S.; Goldberg, A. L.; Goldberger, A. L. (Principal Investigator)

    1993-01-01

    Glucocorticoids are essential for the increase in protein breakdown in skeletal muscle normally seen during fasting. To determine which proteolytic pathway(s) are activated upon fasting, leg muscles from fed and fasted normal rats were incubated under conditions that block or activate different proteolytic systems. After food deprivation (1 day), the nonlysosomal ATP-dependent process increased by 250%, as shown in experiments involving depletion of muscle ATP. Also, the maximal capacity of the lysosomal process increased 60-100%, but no changes occurred in the Ca(2+)-dependent or the residual energy-independent proteolytic processes. In muscles from fasted normal and adrenalectomized (ADX) rats, the protein breakdown sensitive to inhibitors of the lysosomal or Ca(2+)-dependent pathways did not differ. However, the ATP-dependent process was 30% slower in muscles from fasted ADX rats. Administering dexamethasone to these animals or incubating their muscles with dexamethasone reversed this defect. During fasting, when the ATP-dependent process rises, muscles show a two- to threefold increase in levels of ubiquitin (Ub) mRNA. However, muscles of ADX animals failed to show this response. Injecting dexamethasone into the fasted ADX animals increased muscle Ub mRNA within 6 h. Thus glucocorticoids activate the ATP-Ub-dependent proteolytic pathway in fasting apparently by enhancing the expression of components of this system such as Ub.

  18. Glucocorticoid-induced leucine zipper expression is associated with response to treatment and immunoregulation in systemic lupus erythematosus.

    Science.gov (United States)

    Mohammadi, Saeed; Ebadpour, Mohammad Reza; Sedighi, Sima; Saeedi, Mohsen; Memarian, Ali

    2017-08-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder in which cytokine balance is disturbed. Glucocorticoids (GCs) are shown to balance immune response by transcriptional regulation of glucocorticoid receptor target genes such as Glucocorticoid-induced leucine zipper (GILZ) which has been introduced as an endogenous anti-inflammatory mediator. In the present study, we assessed the expression of GILZ in association with interferon-γ (IFN-γ), interleukine-10 (IL-10), and B lymphocyte stimulator (BLyS) plasma levels in SLE patients. A total of 40 female patients (18 under treatment and 22 newly diagnosed) were recruited in this study. Real-time RT PCR was conducted to quantify the mRNA expression of GILZ. The plasma levels of IFN-γ, IL-10, and BLyS were evaluated using ELISA method. GILZ was overexpressed among under treatment SLE patients. The mRNA expression of GILZ was significantly correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score. IFN-γ and BLyS were downregulated in response to therapies with negative correlations to GILZ. Moreover, IL-10 was upregulated among treated patients. The levels of IFN-γ and BLyS were correlated with the severity of disease, while IL-10 was negatively correlated with SLEDAI score. GILZ could be introduced as one of the acting molecules in mediating the regulatory effects of GCs on producing pro- and anti-inflammatory cytokines in SLE.

  19. Local and systemic oxidative stress and glucocorticoid receptor levels in chronic obstructive pulmonary disease patients

    Science.gov (United States)

    Zeng, Mian; Li, Yue; Jiang, Yujie; Lu, Guifang; Huang, Xiaomei; Guan, Kaipan

    2013-01-01

    BACKGROUND: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress. METHODS: Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]). RESULTS: MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]). CONCLUSIONS: Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients. PMID:23457673

  20. SIDES - Segment Interconnect Diagnostic Expert System

    International Nuclear Information System (INIS)

    Booth, A.W.; Forster, R.; Gustafsson, L.; Ho, N.

    1989-01-01

    It is well known that the FASTBUS Segment Interconnect (SI) provides a communication path between two otherwise independent, asynchronous bus segments. The SI is probably the most important module in any FASTBUS data acquisition network since it's failure to function can cause whole segments of the network to be inaccessible and sometimes inoperable. This paper describes SIDES, an intelligent program designed to diagnose SI's both in situ as they operate in a data acquisition network, and in the laboratory in an acceptance/repair environment. The paper discusses important issues such as knowledge acquisition; extracting knowledge from human experts and other knowledge sources. SIDES can benefit high energy physics experiments, where SI problems can be diagnosed and solved more quickly. Equipment pool technicians can also benefit from SIDES, first by decreasing the number of SI's erroneously turned in for repair, and secondly as SIDES acts as an intelligent assistant to the technician in the diagnosis and repair process

  1. Research on Battery Energy Storage System Based on User Side

    Science.gov (United States)

    Wang, Qian; Zhang, Yichi; Yun, Zejian; Wang, Xuguang; Zhang, Dong; Bian, Di

    2018-01-01

    This paper introduces the effect of user side energy storage on the user side and the network side, a battery energy storage system for the user side is designed. The main circuit topology of the battery energy storage system based on the user side is given, the structure is mainly composed of two parts: DC-DC two-way half bridge converter and DC-AC two-way converter, a control strategy combining battery charging and discharging characteristics is proposed to decouple the grid side and the energy storage side, and the block diagram of the charging and discharging control of the energy storage system is given. The simulation results show that the battery energy storage system of the user side can not only realize reactive power compensation of low-voltage distribution network, but also improve the power quality of the users.

  2. The glucocorticoid receptor in the limbic system of the human brain

    NARCIS (Netherlands)

    Wang, Qian

    2016-01-01

    Glucocorticoid hormones (GCs) are important mediators of the stress response in mammals including humans. GCs are released from the adrenal in response to stress and affect numerous processes in the body and brain. Their levels are controlled via negative feedback exerted by GC binding to brain

  3. Design Multi-Sides System Unmanned Surface Vehicle (USV) Rocket

    Science.gov (United States)

    Syam, Rafiudin; Sutresman, Onny; Mappaita, Abdullah; Amiruddin; Wiranata, Ardi

    2018-02-01

    This study aims to design and test USV multislide forms. This system is excellent for maneuvering on the x-y-z coordinates. The disadvantage of a single side USV is that it is very difficult to maneuver to achieve very dynamic targets. While for multi sides system easily maneuvered though x-y-z coordinates. In addition to security defense purposes, multi-side system is also good for maritime intelligence, surveillance. In this case, electric deducted fan with Multi-Side system so that the vehicle can still operate even in reverse condition. Multipleside USV experiments have done with good results. In a USV study designed to use two propulsions.

  4. Perioperative glucocorticoids in hip and knee surgery - benefit vs. harm?

    DEFF Research Database (Denmark)

    Lunn, T H; Kehlet, H

    2013-01-01

    with systemic glucocorticoid. Pain was reduced with high-dose systemic and local glucocorticoid, but not with low-dose systemic glucocorticoid. Systemic inflammatory markers were reduced with low-dose and high-dose systemic glucocorticoid, and with local glucocorticoid. Functional recovery was improved...... with local glucocorticoid. All studies were small-sized and none sufficiently powered to meaningfully evaluate uncommon adverse events. Most of the local administration studies had poor scientific quality (high risk of bias). Due to clinical heterogeneity and poor scientific quality, no meta......-analysis was performed. In conclusion, in addition to PONV reduction with low-dose systemic glucocorticoid, this review supports high-dose systemic glucocorticoid to ameliorate post-operative pain after hip and knee surgery. However, large-scale safety and dose-finding studies are warranted before final recommendations....

  5. Glucocorticoid receptor signaling in health and disease

    Science.gov (United States)

    Kadmiel, Mahita; Cidlowski, John A.

    2013-01-01

    Glucocorticoids are steroid hormones regulated in a circadian and stres-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the last few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor, a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we will provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body. PMID:23953592

  6. Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of glucocorticoid system.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Choi, Seong-Soo; Suh, Hong-Won

    2013-10-01

    The possible involvement of glucocorticoid system in interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. In the first experiment, mice were treated intrathecally (i.t.) with IL-1β (100 pg). Corticotrophin releasing hormone (CRH) mRNA (hypothalamus) and c-Fos mRNA (pituitary gland, spinal cord, and the adrenal gland) levels were measured at 30, 60 and 120 min after IL-1β administration. We found that i.t. injection with IL-1β increased CRH mRNA level in the hypothalamus. The IL-1β administered i.t. elevated c-Fos mRNA levels in the spinal cord, pituitary and adrenal glands. Furthermore, i.t. administration of IL-1β significantly increased the plasma corticosterone level up to 60 min. In addition, the adrenalectomy caused the reductions of the blood glucose level and pain behavior induced by IL-1β injected i.t. in normal and D-glucose-fed groups. Furthermore, intraperitoneal (i.p.) pretreatment with RU486 (100mg/kg) attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. in normal and D-glucose-fed groups. Our results suggest that IL-1β administered i.t. increases the blood glucose level and pain behavior via an activation of the glucocorticoid system. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Glucocorticoid programming of neuroimmune function.

    Science.gov (United States)

    Walker, David J; Spencer, Karen A

    2018-01-15

    Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  8. The invisible accounting side of ERP systems

    Directory of Open Access Journals (Sweden)

    Iliyan Dimitrov

    2017-12-01

    Full Text Available ERP (Enterprise Resource planning systems are widely used in many organizations, including companies in Bulgaria. Depending of the point of view statistical results of their implementation in recent years are contradictory (Infostat, 2017, (Eurostat, 2017. This paper reveals an overview of researchers and practitioners’ interpretations, who express opinion for an essence and advantages of adopting ERP systems. In academic and professional discussions one potential benefit stays invisible. The purpose of this publication is to provide new sight of essence and potential benefits which are given with ERP implementation. Some advantages of ERP systems are discussed. Some aspects of the links between ERP systems, management accounting and financial accounting are described.

  9. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease

    NARCIS (Netherlands)

    Smans, L.; Lentjes, E.G.W.M.; Hermus, A.R.; Zelissen, P.M.J.

    2013-01-01

    OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects.

  10. Islet-cell dysfunction induced by glucocorticoid treatment

    DEFF Research Database (Denmark)

    van Raalte, Daniël H; Kwa, Kelly A A; van Genugten, Renate E

    2013-01-01

    Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system.......Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system....

  11. Glucocorticoid-induced hyperglycaemia

    NARCIS (Netherlands)

    Gerards, M.C.

    2018-01-01

    This thesis contains studies on current practice, clinical implications and treatment of excess glucocorticoid receptor (GCR) stimulation, with a focus on glucocorticoid-induced hyperglycaemia (GCIH). Chapter 1 is a general introduction to the glucocorticoid hormone. In chapter 2 , we have

  12. Central nervous system side effects associated with zolpidem treatment.

    Science.gov (United States)

    Toner, L C; Tsambiras, B M; Catalano, G; Catalano, M C; Cooper, D S

    2000-01-01

    Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.

  13. CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

    Science.gov (United States)

    Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

    2018-06-01

    To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

  14. Effect of the systemic versus inhalatory administration of synthetic glucocorticoids on the urinary steroid profile as studied by gas chromatography-mass spectrometry

    International Nuclear Information System (INIS)

    Mazzarino, Monica; Rossi, Francesca; Giacomelli, Laura; Botre, Francesco

    2006-01-01

    This paper presents a gas chromatography-mass spectrometry (GC-MS) study carried out on human urine to verify whether the administration of glucocorticoids can affect the urinary steroid profile, and especially the levels of endogenous glucocorticoids, androgens and their main metabolites. Betamethasone and beclomethasone, administered either systemically (per os or i.m.) or locally (by inhalation) have been studied. The determination of the urinary levels of endogenous glucocorticoids and androgens was carried out by GC-MS in electron impact ionization mode. Data were evaluated taking into account the baseline individual variability, and compared with values obtained on a control group. Detectable differences were recorded in the steroids metabolites excretion profiles between men and women. The circadian variability of the steroid profile was the same for both sexes, showing a maximum during the morning hours. After systemic treatment with synthetic glucocorticoids, the relative urinary concentrations of corticosteroids, androgens and of their metabolites were significantly altered, recording a transient decrease of the concentration of cortisol and tetrahydrocortisol and a parallel, although less pronounced, increase of the concentration of testosterone, epitestosterone and related androgenic steroids; while no effects were recorded if the administration was by inhalation

  15. Effect of the systemic versus inhalatory administration of synthetic glucocorticoids on the urinary steroid profile as studied by gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Mazzarino, Monica [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Rossi, Francesca [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy); Giacomelli, Laura [Dipartimento di Scienze Chirurgiche, Universita La Sapienza, Viale Regina Elena 324, 00161 Rome (Italy); Botre, Francesco [Laboratorio Antidoping, Federazione Medico Sportiva Italiana, Largo Giulio Onesti 1, 00197 Rome (Italy) and Dipartimento CGMIA, Universita La Sapienza, Via del Castro Laurenziano 9, 00161 Rome (Italy)]. E-mail: francesco.botre@uniroma1.it

    2006-02-10

    This paper presents a gas chromatography-mass spectrometry (GC-MS) study carried out on human urine to verify whether the administration of glucocorticoids can affect the urinary steroid profile, and especially the levels of endogenous glucocorticoids, androgens and their main metabolites. Betamethasone and beclomethasone, administered either systemically (per os or i.m.) or locally (by inhalation) have been studied. The determination of the urinary levels of endogenous glucocorticoids and androgens was carried out by GC-MS in electron impact ionization mode. Data were evaluated taking into account the baseline individual variability, and compared with values obtained on a control group. Detectable differences were recorded in the steroids metabolites excretion profiles between men and women. The circadian variability of the steroid profile was the same for both sexes, showing a maximum during the morning hours. After systemic treatment with synthetic glucocorticoids, the relative urinary concentrations of corticosteroids, androgens and of their metabolites were significantly altered, recording a transient decrease of the concentration of cortisol and tetrahydrocortisol and a parallel, although less pronounced, increase of the concentration of testosterone, epitestosterone and related androgenic steroids; while no effects were recorded if the administration was by inhalation.

  16. Effects of prasterone on bone mineral density in women with active systemic lupus erythematosus receiving chronic glucocorticoid therapy.

    Science.gov (United States)

    Sánchez-Guerrero, Jorge; Fragoso-Loyo, Hilda E; Neuwelt, C Michael; Wallace, Daniel J; Ginzler, Ellen M; Sherrer, Yvonne R S; McIlwain, Harris H; Freeman, Pamela G; Aranow, Cynthia; Petri, Michelle A; Deodhar, Atul A; Blanton, Ellen; Manzi, Susan; Kavanaugh, Arthur; Lisse, Jeffrey R; Ramsey-Goldman, Rosalind; McKay, James D; Kivitz, Alan J; Mease, Philip J; Winkler, Anne E; Kahl, Leslie E; Lee, Albert H; Furie, Richard A; Strand, C Vibeke; Lou, Lillian; Ahmed, Mumtaz; Quarles, Betty; Schwartz, Kenneth E

    2008-08-01

    To assess prevention of bone mineral density (BMD) loss and durability of the response during treatment with prasterone in women with systemic lupus erythematosus (SLE) receiving chronic glucocorticoids. 155 patients with SLE received 200 mg/day prasterone or placebo for 6 months in a double-blind phase. Subsequently, 114 patients were re-randomized to receive 200 or 100 mg/day prasterone for 12 months in an open-label phase. Primary efficacy endpoints were changes in BMD at the lumbar spine (L-spine) from baseline to Month 6 and maintenance of BMD from Month 6 to 18 for patients who received prasterone during the double-blind phase. In the double-blind phase, there was a trend for a small gain in BMD at the L-spine for patients who received 200 mg/day prasterone for 6 months versus a loss in the placebo group (mean +/- SD, 0.003 +/- 0.035 vs -0.005 +/- 0.053 g/cm(2), respectively; p = 0.293 between groups). In the open-label phase, there was dose-dependent increase in BMD at the L-spine at Month 18 between patients who received 200 versus 100 mg/day prasterone (p = 0.021). For patients who received 200 mg/day prasterone for 18 months, the L-spine BMD gain was 1.083 +/- 0.512% (p = 0.042). There was no overall change in BMD at the total hip over 18 months with 200 mg/day prasterone treatment. The safety profile reflected the weak androgenic properties of prasterone. This study suggests prasterone 200 mg/day may offer mild protection against bone loss in women with SLE receiving glucocorticoids. (ClinicalTrials.gov Identifiers NCT00053560 and NCT00082511).

  17. Side-by-Side Testing of Water Heating Systems: Results from the 2013–2014 Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Colon, Carlos [Florida Solar Energy Center, Cocoa, FL (United States). Building America Partnership for Improved Residential Construction (BA-PIRC)

    2017-07-01

    The Florida Solar Energy Center (FSEC) completed a fourth year-long evaluation on residential hot water heating systems in a laboratory environment (east central Florida, hot-humid climate). The evaluation studied the performance of five hot water systems (HWS) plus a reference baseline system for each fuel, (i.e., electric and natural gas). Electric HWS consisted of two residential electric heat pump water heaters (HPWHs, 60 and 80 gallons), a solar thermal system using a polymer absorber (glazed) collector with 80-gallon storage and a duplicate 50-gallon standard electric water heater with added cap and wrap insulation. Baseline performance data were collected from a standard 50-gallon electric water heater of minimum code efficiency to compare energy savings. Similarly, a standard 40-gallon upright vented natural gas water heater served as baseline for the natural gas fuel category. The latter, having a larger jacket diameter [18 in., with an energy factor (EF) of 0.62] with increased insulation, replaced a former baseline (17 in. diameter, EF = 0.59) that served during three previous testing rotations (2009–2013). A high-efficiency, condensing natural gas hybrid water heater with 27-gallon buffered tank was also tested and compared against the gas baseline. All systems underwent testing simultaneously side-by-side under the criteria specified elsewhere in this report.

  18. Glucocorticoids as mediators of developmental programming effects.

    Science.gov (United States)

    Khulan, Batbayar; Drake, Amanda J

    2012-10-01

    Epidemiological evidence suggests that exposure to an adverse environment in early life is associated with an increased risk of cardio-metabolic and behavioral disorders in adulthood, a phenomenon termed 'early life programming'. One major hypothesis for early life programming is fetal glucocorticoid overexposure. In animal studies, prenatal glucocorticoid excess as a consequence of maternal stress or through exogenous administration to the mother or fetus is associated with programming effects on cardiovascular and metabolic systems and on the brain. These effects can be transmitted to subsequent generations. Studies in humans provide some evidence that prenatal glucocorticoid exposure may exert similar programming effects on glucose/insulin homeostasis, blood pressure and neurodevelopment. The mechanisms by which glucocorticoids mediate these effects are unclear but may include a role for epigenetic modifications. This review discusses the evidence for glucocorticoid programming in animal models and in humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Glucocorticoids interact with the noradrenergic arousal system in the nucleus accumbens shell to enhance memory consolidation of both appetitive and aversive taste learning.

    Science.gov (United States)

    Wichmann, Romy; Fornari, Raquel V; Roozendaal, Benno

    2012-09-01

    It is well established that glucocorticoid hormones strengthen the consolidation of long-term memory of emotionally arousing experiences but have little effect on memory of low-arousing experiences. Although both positive and negative emotionally arousing events tend to be well remembered, studies investigating the neural mechanism underlying glucocorticoid-induced memory enhancement focused primarily on negatively motivated training experiences. In the present study we show an involvement of glucocorticoids within the nucleus accumbens (NAc) in enhancing memory consolidation of both an appetitive and aversive form of taste learning. The specific glucocorticoid receptor (GR) agonist RU 28362 (1 or 3ng) administered bilaterally into the NAc shell, but not core, of male Sprague-Dawley rats immediately after an appetitive saccharin drinking experience dose-dependently enhanced 24-h retention of the safe taste, resulting in a facilitated attenuation of neophobia. Similarly, GR agonist infusions given into the NAc shell immediately after pairing of the saccharin taste with a malaise-inducing agent enhanced memory of this negative experience, resulting in an intensified conditioned aversion. Importantly, a suppression of noradrenergic activity within the NAc shell with the β-adrenoceptor antagonist propranolol blocked the facilitating effect of a concurrently administered GR agonist on memory consolidation in both the appetitive and aversive learning task. Thus, these findings indicate that GR activation interacts with the noradrenergic arousal system within the NAc to enhance memory consolidation of emotionally arousing training experiences regardless of valence. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. A Diffusion Model for Two-sided Service Systems

    Science.gov (United States)

    Homma, Koichi; Yano, Koujin; Funabashi, Motohisa

    A diffusion model is proposed for two-sided service systems. ‘Two-sided’ refers to the existence of an economic network effect between two different and interrelated groups, e.g., card holders and merchants in an electronic money service. The service benefit for a member of one side depends on the number and quality of the members on the other side. A mathematical model by J. H. Rohlfs explains the network (or bandwagon) effect of communications services. In Rohlfs' model, only the users' group exists and the model is one-sided. This paper extends Rohlfs' model to a two-sided model. We propose, first, a micro model that explains individual behavior in regard to service subscription of both sides and a computational method that drives the proposed model. Second, we develop macro models with two diffusion-rate variables by simplifying the micro model. As a case study, we apply the models to an electronic money service and discuss the simulation results and actual statistics.

  1. Three Sides Billboard Wind-Solar Hybrid System Design

    Directory of Open Access Journals (Sweden)

    Bai Xuefeng

    2015-01-01

    Full Text Available With the high development of world economy, the demand of energy is increasing all the time, As energy shortage and environment problem are increasing outstanding, Renewable energy has been attracting more and more attention. A kind of three sides billboard supply by wind-Solar hybrid system has been designed in this paper, the overall structure of the system, components, working principle and control strategy has been analyzed from the system perspective. The software and hardware of the system are debugged together and the result is acquired. System function is better and has achieved the expected results.

  2. Transfer of chemicals in PWR systems: secondary side

    International Nuclear Information System (INIS)

    Jonas, O.

    1978-01-01

    Transfer of chemicals in the secondary side of pressurized water reactor systems with recirculating and once-through steam generators is considered. Chemical data on water, steam and deposit chemistry of twenty-six operating units are given and major physical-chemical processes and differences between the two systems and between fossil and PWR systems are discussed. It is concluded that the limited available data show the average water and steam chemistry to be within recommended limits, but large variations of impurity concentrations and corrosion problems encountered indicate that our knowledge of the system chemistry and chemical thermodynamics, system design, sampling, analysis and operation need improvement. (author)

  3. Regulation of blood glucose level by kainic acid in mice: involvement of glucocorticoid system and non-NMDA receptors.

    Science.gov (United States)

    Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Jung, Jun-Sub; Sharma, Naveen; Suh, Hong-Won

    2017-02-28

    Kainic acid (KA) is a well-known excitatory neurotoxic substance. In the present study, effects of KA-injected intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level were investigated in ICR mice. We found that KA administered intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) increased the blood glucose and corticosterone levels, suggesting that KA-induced hyperglycemia appeared to be due to increased blood corticosterone level. In support of this finding, adrenalectomy causes a reduction of KA-induced hyperglycemia and neuronal cell death in CA3 regions of the hippocampus. In addition, pretreatment with i.c.v. or i.t. injection of CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione; a non-NMDA receptor blocker) attenuated the i.p. and i.c.v. administered KA-induced hyperglycemia. KA administered i.c.v. caused an elevation of the blood corticosterone level whereas the plasma insulin level was reduced. Moreover, i.c.v. pretreatment with CNQX inhibited the decrease of plasma insulin level induced by KA i.c.v. injection, whereas the KA-induced plasma corticosterone level was further enhanced by CNQX pretreatment. Our results suggest that KA administered systemically or centrally produces hyperglycemia. A glucocorticoid system appears to be involved in KA-induced hyperglycemia. Furthermore, central non-N-methyl-D-aspartate receptors may be responsible for KA-induced hyperglycemia.

  4. Glucocorticoid programming of intrauterine development.

    Science.gov (United States)

    Fowden, A L; Valenzuela, O A; Vaughan, O R; Jellyman, J K; Forhead, A J

    2016-07-01

    Glucocorticoids (GCs) are important environmental and maturational signals during intrauterine development. Toward term, the maturational rise in fetal glucocorticoid receptor concentrations decreases fetal growth and induces differentiation of key tissues essential for neonatal survival. When cortisol levels rise earlier in gestation as a result of suboptimal conditions for fetal growth, the switch from tissue accretion to differentiation is initiated prematurely, which alters the phenotype that develops from the genotype inherited at conception. Although this improves the chances of survival should delivery occur, it also has functional consequences for the offspring long after birth. Glucocorticoids are, therefore, also programming signals that permanently alter tissue structure and function during intrauterine development to optimize offspring fitness. However, if the postnatal environmental conditions differ from those signaled in utero, the phenotypical outcome of early-life glucocorticoid receptor overexposure may become maladaptive and lead to physiological dysfunction in the adult. This review focuses on the role of GCs in developmental programming, primarily in farm species. It examines the factors influencing GC bioavailability in utero and the effects that GCs have on the development of fetal tissues and organ systems, both at term and earlier in gestation. It also discusses the windows of susceptibility to GC overexposure in early life together with the molecular mechanisms and long-term consequences of GC programming with particular emphasis on the cardiovascular, metabolic, and endocrine phenotype of the offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. [Glucocorticoid induced osteoporosis].

    Science.gov (United States)

    Anić, Branimir; Mayer, Miroslav

    2014-01-01

    Secondary osteoporosis most often develops due to glucocorticoid therapy. Glucocorticoids affect all stages of the bone remodeling cycle, its formation and resorption. Osteoblasts are primarily affected, decreasing their activity and enhancing apoptosis. Patients treated with glucocorticoids have lower bone mineral density and increased fracture risk. Glucocorticoid-induced osteoporosis can be prevented by administering the minimal effective dose of glucocorticoids, calcium and vitamin D supplementation or, if possible, by hormone replace- ment therapy. Moreover, appropriate physical activity should be encouraged. Patients who are at higher risk for low-energy fractures (for example post-menopausal women) have to be actively treated, usually with antiresorptive drugs among which bisphosphonates are currently the first line therapy.

  6. Side effects of cancer therapies. International classification and documentation systems

    International Nuclear Information System (INIS)

    Seegenschmiedt, M.H.

    1998-01-01

    The publication presents and explains verified, international classification and documentation systems for side effects induced by cancer treatments, applicable in general and clinical practice and clinical research, and covers in a clearly arranged manner the whole range of treatments, including acute and chronic side effects of chemotherapy and radiotherapy, surgery, or combined therapies. The book fills a long-felt need in tumor documentation and is a major contribution to quality assurance in clinical oncology in German-speaking countries. As most parts of the book are bilingual, presenting German and English texts and terminology, it satisfies the principles of interdisciplinarity and internationality. The tabulated form chosen for presentation of classification systems and criteria facilitate the user's approach as well as application in daily work. (orig./CB) [de

  7. Independent association of glucocorticoids with damage accrual in SLE.

    Science.gov (United States)

    Apostolopoulos, Diane; Kandane-Rathnayake, Rangi; Raghunath, Sudha; Hoi, Alberta; Nikpour, Mandana; Morand, Eric F

    2016-01-01

    To determine factors associated with damage accrual in a prospective cohort of patients with SLE. Patients with SLE who attended the Lupus Clinic at Monash Health, Australia, between 2007 and 2013 were studied. Clinical variables included disease activity (Systemic Lupus Erythematosus Disease Activity Index-2K, SLEDAI-2K), time-adjusted mean SLEDAI, cumulative glucocorticoid dose and organ damage (Systemic Lupus International Collaborating Clinics Damage Index (SDI)). Multivariate logistic regression analyses were performed to identify factors associated with damage accrual. A total of 162 patients were observed over a median (IQR) 3.6 (2.0-4.7) years. Seventy-five per cent (n=121) of patients received glucocorticoids. Damage accrual was significantly more frequent in glucocorticoid-exposed patients (42% vs 15%, p<0.01). Higher glucocorticoid exposure was independently associated with overall damage accrual after controlling for factors including ethnicity and disease activity and was significant at time-adjusted mean doses above 4.42 mg prednisolone/day; the OR of damage accrual in patients in the highest quartile of cumulative glucocorticoid exposure was over 10. Glucocorticoid exposure was independently associated with damage accrual in glucocorticoid-related and non-glucocorticoid related domains of the SDI. Glucocorticoid use is independently associated with the accrual of damage in SLE, including in non-glucocorticoid related domains.

  8. A dual-sided coded-aperture radiation detection system

    International Nuclear Information System (INIS)

    Penny, R.D.; Hood, W.E.; Polichar, R.M.; Cardone, F.H.; Chavez, L.G.; Grubbs, S.G.; Huntley, B.P.; Kuharski, R.A.; Shyffer, R.T.; Fabris, L.; Ziock, K.P.; Labov, S.E.; Nelson, K.

    2011-01-01

    We report the development of a large-area, mobile, coded-aperture radiation imaging system for localizing compact radioactive sources in three dimensions while rejecting distributed background. The 3D Stand-Off Radiation Detection System (SORDS-3D) has been tested at speeds up to 95 km/h and has detected and located sources in the millicurie range at distances of over 100 m. Radiation data are imaged to a geospatially mapped world grid with a nominal 1.25- to 2.5-m pixel pitch at distances out to 120 m on either side of the platform. Source elevation is also extracted. Imaged radiation alarms are superimposed on a side-facing video log that can be played back for direct localization of sources in buildings in urban environments. The system utilizes a 37-element array of 5x5x50 cm 3 cesium-iodide (sodium) detectors. Scintillation light is collected by a pair of photomultiplier tubes placed at either end of each detector, with the detectors achieving an energy resolution of 6.15% FWHM (662 keV) and a position resolution along their length of 5 cm FWHM. The imaging system generates a dual-sided two-dimensional image allowing users to efficiently survey a large area. Imaged radiation data and raw spectra are forwarded to the RadioNuclide Analysis Kit (RNAK), developed by our collaborators, for isotope ID. An intuitive real-time display aids users in performing searches. Detector calibration is dynamically maintained by monitoring the potassium-40 peak and digitally adjusting individual detector gains. We have recently realized improvements, both in isotope identification and in distinguishing compact sources from background, through the installation of optimal-filter reconstruction kernels.

  9. Visualizing and Quantifying the Suppressive Effects of Glucocorticoids on the Tadpole Immune System in Vivo

    Science.gov (United States)

    Schreiber, Alexander M.

    2011-01-01

    A challenging topic in undergraduate physiology courses is the complex interaction between the vertebrate endocrine system and the immune system. There are relatively few established and accessible laboratory exercises available to instructors to help their students gain a working understanding of these interactions. The present laboratory module…

  10. Glucocorticoids and hemopoietic stem cells

    International Nuclear Information System (INIS)

    Romashko, O.O.; Berin, G.I.

    1978-01-01

    Analyzing the data of home and foreign investigators the problems of the glucocorticoid effect on blood and bone marrow of experimental (including irradiated ones) animals are discussed. Considered are a character and mechanism of the adrenal cortex hormones effect on blood formation, as well as the effect of pharmacological doses of corticosteroids on CFU, their erythropoietic effect in physiological doses on a morphological picture of bone marrow after irradiation and subsequent introduction of hormones and the hormone effect on intensity of erythropoiesis recovery in irradiated mice. Presented are the experimental data on studying the effect of endogenic hypercorticoidism and a reduced level of endogenic corticosteroids on blood-forming stem cells in the irradiated mice and the data on the ACTH injection effect on CFU migration after irradiation. Evaluated are already available data and further investigations to ground advisability and conditions of using corticosteroids as well as determining rational therapeutic effects on secretion of endogenic glucocorticoids when treating blood system diseases

  11. Fatal and non-fatal adverse events of glucocorticoid therapy for Graves' orbitopathy

    DEFF Research Database (Denmark)

    Marcocci, Claudio; Watt, Torquil; Altea, Maria Antonietta

    2012-01-01

    The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO).......The objective of this study was to investigate the side effects of glucocorticoid (GC) therapy observed by European thyroidologists during the treatment of Graves' orbitopathy (GO)....

  12. Glucocorticoids and fetal programming part 2: Mechanisms.

    Science.gov (United States)

    Moisiadis, Vasilis G; Matthews, Stephen G

    2014-07-01

    The lifelong health of an individual is shaped during critical periods of development. The fetus is particularly susceptible to internal and external stimuli, many of which can alter developmental trajectories and subsequent susceptibility to disease. Glucocorticoids are critical in normal development of the fetus, as they are involved in the growth and maturation of many organ systems. The surge in fetal glucocorticoid levels that occurs in most mammalian species over the last few days of pregnancy is an important developmental switch leading to fundamental changes in gene regulation in many organs, including the brain. These changes are important for the transition to postnatal life. Exposure of the fetus to increased levels of glucocorticoids, resulting from maternal stress or treatment with synthetic glucocorticoids, can lead to long-term 'programming' of hypothalamic-pituitary-adrenal function and behaviours. Glucocorticoids act at multiple levels within the fetal brain. Growing evidence indicates that they can exert powerful effects on the epigenome, including on DNA methylation, histone acetylation and microRNA, to influence gene expression. Such influences probably represent a critical component of the 'programming' process, and might be partly responsible for the transgenerational effects of antenatal glucocorticoid exposure on neurologic, cardiovascular and metabolic function.

  13. Modeling Supermarket Refrigeration Systems for Demand-Side Management

    Directory of Open Access Journals (Sweden)

    Jakob Stoustrup

    2013-02-01

    Full Text Available Modeling of supermarket refrigeration systems for supervisory control in the smart grid is presented in this paper. A modular modeling approach is proposed in which each module is modeled and identified separately. The focus of the work is on estimating the power consumption of the system while estimating the cold reservoir temperatures as well. The models developed for each module as well as for the overall integrated system are validated by real data collected from a supermarket in Denmark. The results show that the model is able to estimate the actual electrical power consumption with a high fidelity. Moreover a simulation benchmark is introduced based on the produced model for demand-side management in smart grid. Finally, a potential application of the proposed benchmark in direct control of the power/energy consumption is presented by a simple simulation example.

  14. Measurement system analysis for one-sided tolerance

    Directory of Open Access Journals (Sweden)

    Szemik Kamil

    2017-01-01

    Full Text Available Measurement system analysis is carried out in order to determine if a capability to perform measurements in terms of product and process control is sufficient, indicating that the type I and the type II appraisal errors probability are acceptable. Statistical analyses for measurement system evaluation presented in the literature and the industrial manuals are not applicable for all complex and unusual applications. Therefore, the purpose of this study was to develop a robust statistical analysis method for measurement system variability analysis, in terms of product control scenario applied to one-sided tolerance. In the hereby presented study, the authors presented the theoretical principles of statistical techniques for measurement variations evaluation. Subsequently, the formula of gauge repeatability and reproducibility in terms of lower specification limit was proposed. The research hypothesis was tested using the statistical analysis.

  15. Bone metabolism in patients with systemic lupus erythematosus. Effect of disease activity and glucocorticoid treatment

    DEFF Research Database (Denmark)

    Hansen, M; Halberg, P; Kollerup, G

    1998-01-01

    The bone metabolism in patients with systemic lupus erythematosus (SLE) has previously been examined, but the results are conflicting. In the present study the bone mineral density (BMD) of the axial and the appendicular skeleton was examined by means of dual energy x-ray absorptiometry. The bone...

  16. The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort.

    Science.gov (United States)

    Conti, F; Ceccarelli, F; Perricone, C; Leccese, I; Massaro, L; Pacucci, V A; Truglia, S; Miranda, F; Spinelli, F R; Alessandri, C; Valesini, G

    2016-06-01

    Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings. We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K ≥ 4 compared with the previous visit. We evaluated 349 SLE patients (M/F 25/324, mean age ± SD 42.7 ± 12.4 years, mean disease duration ± SD 164.9 ± 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI ≥ 1 (mean SDI ± SD 1.7 ± 0.9, range 0-5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-β2GPI antibodies (P = 0.01, OR 6.2). In the present study chronic damage was identified in about one third of SLE patients. The

  17. Intelligent demand side management of residential building energy systems

    Science.gov (United States)

    Sinha, Maruti N.

    Advent of modern sensing technologies, data processing capabilities and rising cost of energy are driving the implementation of intelligent systems in buildings and houses which constitute 41% of total energy consumption. The primary motivation has been to provide a framework for demand-side management and to improve overall reliability. The entire formulation is to be implemented on NILM (Non-Intrusive Load Monitoring System), a smart meter. This is going to play a vital role in the future of demand side management. Utilities have started deploying smart meters throughout the world which will essentially help to establish communication between utility and consumers. This research is focused on investigation of a suitable thermal model of residential house, building up control system and developing diagnostic and energy usage forecast tool. The present work has considered measurement based approach to pursue. Identification of building thermal parameters is the very first step towards developing performance measurement and controls. The proposed identification technique is PEM (Prediction Error Method) based, discrete state-space model. The two different models have been devised. First model is focused toward energy usage forecast and diagnostics. Here one of the novel idea has been investigated which takes integral of thermal capacity to identify thermal model of house. The purpose of second identification is to build up a model for control strategy. The controller should be able to take into account the weather forecast information, deal with the operating point constraints and at the same time minimize the energy consumption. To design an optimal controller, MPC (Model Predictive Control) scheme has been implemented instead of present thermostatic/hysteretic control. This is a receding horizon approach. Capability of the proposed schemes has also been investigated.

  18. Inlfuence of Different-Frequency Glucocorticoid Induction on Morphological Structures of Humeri, Soft Tissues and Immune System in Rats

    Institute of Scientific and Technical Information of China (English)

    LI Jian-min; LI Heng

    2016-01-01

    Objective: To explore the influence of different-frequency glucocorticoid (GC) induction on morphological structures of humeri and soft tissues as well as immune system in rats. Methods: A total of 32 speciifc pathogen-free (SPF) SD rats at the age of 3 months were selected and randomly divided into 4 groups, 8 cases in each group. The rats in control group were not given any treatment, while those in low-, moderate- and high-frequency groups were treated with intramuscular injection of dexamethasone 1 mg/kg per time for twice, 4 times and 6 times per week, respectively. All the rats were sacriifced on d30 to measure their body mass and qualities of soft tissues and immune organs, and bone histomorphometry was applied to analyze humeral bone mass and bone structural changes. Results: Compared with control group, there was no change in cancellous bone mass and bone structures of upper humeri in low-frequency group, but serious loss of bone mass, signiifcantly degenerated bone structure, markedly reduced trabecular thickness and number as well as notably increased trabecular separation was all observed in moderate- and high-frequency groups. The size of cortical bones, total size of bone structure, thickness of cortical bones and size percentage of cortical bones in middle humeri reduced apparently, while the size percentage of medullary cavity increased dramatically in high-frequency group. Growth plate thickness of upper humeri decreased in low-, moderate- and high-frequency groups, and the diameters of mastocytes diminished in moderate- and high-frequency groups. Compared with control group, body mass decreased obviously, qualities and indexes of spleen and thymus showed decreasing tendency along with the increase of drug administration frequency in low-, moderate- and high-frequency groups. Conclusion: Low-frequency GC cannot change humeral morphology. The higher the frequency of drug administration is, the more the loss of cancellous bone mass is. When the

  19. Solving modified systems with multiple right-hand sides

    Energy Technology Data Exchange (ETDEWEB)

    Simoncini, V.; Gallopoulos, E. [Univ. of Patras (Greece)

    1996-12-31

    In this talk we discuss the iterative solution of large linear systems of the form (A + USV{sup H})X = B, where A is an n x n non-Hermitian matrix, USV{sup H} is a rank-r modification of A and B is of rank s with s, r {much_lt} n. We analyze several approaches that exploit the structure of the coefficient matrix so as to solve the systems more efficiently than if one were to apply a non-hermitian solver to the original systems. In the development of procedures, we take into account the presence of both the low-rank modification and the several right-hand sides. Interesting issues connected to this problem originate from the quest for techniques that accelerate the underlying iterative solvers: preconditioning (e.g. inner-outer iteration strategies), domain decomposition, and continuation methods. Experiments are provided to analyze the behavior of the methods depending on the structure of the rectangular matrices. Preconditioning strategies are explored for an efficient implementation on the transformed systems.

  20. The Regulation of Muscle Mass by Endogenous Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Daniel L Marks

    2015-02-01

    Full Text Available Glucocorticoids are highly conserved fundamental regulators of energy homeostasis. In response to stress in the form of perceived danger or acute inflammation, glucocorticoids are released from the adrenal gland, rapidly mobilizing energy from carbohydrate, fat and protein stores. In the case of inflammation, mobilized protein is critical for the rapid synthesis of acute phase reactants and an efficient immune response to infection. While adaptive in response to infection, chronic mobilization can lead to a p rofound depletion of energy stores. Skeletal muscle represents the major body store of protein, and can become substantially atrophied under conditions of chronic inflammation. Glucocorticoids elicit the atrophy of muscle by increasing the rate of protein degradation by the ubiquitin-proteasome system and autophagy lysosome system. Protein synthesis is also suppressed at the level of translational initiation, preventing the production of new myofibrillar protein. Glucocorticoids also antagonize the action of anabolic regulators such as insulin further exacerbating the loss of protein and muscle mass. The loss of muscle mass in the context of chronic disease is a key feature of cachexia and contributes substantially to morbidity and mortality. A growing body of evidence demonstrates that glucocorticoid signaling is a common mediator of wasting, irrespective of the underlying initiator or disease state. This review will highlight fundamental mechanisms of glucocorticoid signaling and detail the mechanisms of glucocorticoid-induced muscle atrophy. Additionally, the evidence for glucocorticoids as a driver of muscle wasting in numerous disease states will be discussed. Given the burden of wasting diseases and the nodal nature of glucocorticoid signaling, effective anti-glucocorticoid therapy would be a valuable clinical tool. Therefore, the progress and potential pitfalls in the development of glucocorticoid antagonists for muscle wasting will

  1. Glucocorticoid-Induced Osteoporosis

    Science.gov (United States)

    ... nervosa Cigarette smoking Alcohol abuse Low calcium and vitamin D, by low dietary intake or poor absorption in your gut Sedentary (inactive) lifestyle or immobility Certain medications besides glucocorticoids, including the following: excess thyroid hormone replacement the blood thinner heparin some ...

  2. Side-by-Side Testing of Water Heating Systems: Results from the 2013-2014 Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Colon, Carlos [Florida Solar Energy Center, Cocoa, FL (United States). Bulding America Partnership for Improved Residential Construction

    2017-07-12

    The Florida Solar Energy Center (FSEC) has completed a fourth year-long evaluation on residential hot water heating systems in a laboratory environment (east central Florida, hot-humid climate). This report contains a summary of research activities regarding the evaluation of two residential electric heat pump water heaters (HPWHs), a solar thermal system utilizing a polymer glazed absorber and a high efficiency natural gas system.

  3. Glucocorticoid-related bone changes from endogenous or exogenous glucocorticoids.

    Science.gov (United States)

    Warriner, Amy H; Saag, Kenneth G

    2013-12-01

    Glucocorticoids have a negative impact on bone through direct effects on bone cells and indirect effects on calcium absorption. Here, recent findings regarding glucocorticoid-induced osteoporosis, bone changes in patients with endogenous glucocorticoid derangements, and treatment of steroid-induced bone disease are reviewed. Although the majority of our understanding arises from the outcomes of patients treated with exogenous steroids, endogenous overproduction appears to be similarly destructive to bone, but these effects are reversible with cure of the underlying disease process. Additionally, there are bone changes that occur in diseases that interrupt adrenal glucocorticoid production, both in response to our inability to perfectly match glucocorticoid replacement and also related to the underlying disease process. More investigation is required to understand which patients with endogenous overproduction or underproduction of glucocorticoid would benefit from osteoporosis treatment. Better understood is the benefit that can be achieved with currently approved treatments for glucocorticoid-induced osteoporosis from exogenous steroids. With growing concern of long-term use of bisphosphonates, however, further investigation into the duration of use and use in certain populations, such as children and premenopausal women, is essential. Glucocorticoid-induced osteoporosis is a complex disease that is becoming better understood through advances in the study of exogenous and endogenous glucocorticoid exposure. Further advancement of proper treatment and prevention is on the horizon.

  4. Pathophysiology of Glucocorticoid Signaling.

    Science.gov (United States)

    Vitellius, Géraldine; Trabado, Séverine; Bouligand, Jérôme; Delemer, Brigitte; Lombès, Marc

    2018-06-01

    Glucocorticoids (GC), such as cortisol or dexamethasone, control various physiological functions, notably those involved in development, metabolism, inflammatory processes and stress, and exert most of their effects upon binding to the glucocorticoid receptor (GR, encoded by NR3C1 gene). GC signaling follows several consecutive steps leading to target gene transactivation, including ligand binding, nuclear translocation of ligand-activated GR complexes, DNA binding, coactivator interaction and recruitment of functional transcriptional machinery. Any step may be impaired and may account for altered GC signaling. Partial or generalized glucocorticoid resistance syndrome may result in a reduced level of functional GR, a decreased hormone affinity and binding, a defect in nuclear GR translocation, a decrease or lack of DNA binding and/or post-transcriptional GR modifications. To date, 26 loss-of-function NR3C1 mutations have been reported in the context of hypertension, hirsutism, adrenal hyperplasia or metabolic disorders. These clinical signs are generally associated with biological features including hypercortisolism without negative regulatory feedback loop on the hypothalamic-pituitary-adrenal axis. Patients had often low plasma aldosterone and renin levels despite hypertension. Only one GR gain-of-function mutation has been described associating Cushing's syndrome phenotype with normal urinary-free cortisol. Some GR polymorphisms (ER22/23EK, GR-9β) have been linked to glucocorticoid resistance and a healthier metabolic profile whereas some others seemed to be associated with GC hypersensitivity (N363S, BclI), increasing cardiovascular risk (diabetes type 2, visceral obesity). This review focuses on the earlier findings on the pathophysiology of GR signaling and presents criteria facilitating identification of novel NR3C1 mutations in selected patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. Glucocorticoid Signaling and Bone Biology.

    Science.gov (United States)

    Komori, T

    2016-11-01

    Since glucocorticoids remain an effective therapeutic option for the treatment of many inflammatory and autoimmune diseases, glucocorticoid-induced osteoporosis is the most common form of secondary osteoporosis. Fractures may occur in as many as 30-50% of patients receiving chronic glucocorticoid therapy. Under physiological conditions, glucocorticoids are required for normal bone development due to their regulation of osteoblast differentiation, possibly via the Wnt/β-catenin pathway and TSC22D3. However, serum levels of endogenous corticosterone are elevated in aged mice and glucocorticoids exert negative effects on the survival of osteoblasts and osteocytes as well as angiogenesis. Glucocorticoid treatments impair bone formation and enhance bone resorption. Excess glucocorticoids induce osteoblast and osteocyte apoptosis by increasing pro-apoptotic molecules, reactive oxygen species, and endoplasmic reticulum stress and suppressing the Wnt/β-catenin pathway. Autophagy protects osteocytes from glucocorticoid-induced apoptosis, but passed some threshold, the process of autophagy leads the cells to apoptosis. Excess glucocorticoids impair osteoblastogenesis by inducing Wnt antagonists, including Dkk1, Sost, and sFRP-1. However, the findings are controversial and the involvement of Wnt antagonists requires further study. Excess glucocorticoids reduce the phosphorylation of Akt and GSK3β, which enhances the degradation of β-catenin. Excess glucocorticoids have been shown to modulate the expression of miRNAs, including miR-29a, miR-34a-5p, and miR-199a-5p, which regulate the proliferation and differentiation of osteoblast lineage cells. Excess glucocorticoids also enhance bone resorption by reducing OPG expression, increasing Rankl expression and reactive oxygen species, and prolonging the life span of osteoclasts; however, they also suppress the bone-degrading capacity of osteoclasts by disturbing the organization of the cytoskeleton. © Georg Thieme Verlag KG

  6. Long-term safety, efficacy, and patient acceptability of teriparatide in the management of glucocorticoid-induced osteoporosis

    Directory of Open Access Journals (Sweden)

    Dore RK

    2013-05-01

    Full Text Available Robin K DoreDavid Geffen School of Medicine, University of California, Los Angeles, CA, USAAbstract: Glucocorticoids are commonly prescribed medications to treat multiple diseases across many medical specialties. One of the most common yet largely unappreciated side effect of glucocorticoid use is increased risk of fracture. Many different therapies are indicated to prevent and treat this condition; many guidelines exist that suggest appropriate use of both glucocorticoids and the medications approved to prevent this common side effect of glucocorticoid therapy. Nevertheless, 30%–50% of patients on long-term glucocorticoid therapy sustain a fracture. Teriparatide, recombinant human parathyroid hormone (1–34, is a daily self-injectable therapy for 24 months approved for use in patients taking long-term glucocorticoids. Teriparatide has been shown to increase bone mineral density and reduce vertebral fracture risk in glucocorticoid-treated patients. Glucocorticoids have many adverse effects on bone that teriparatide has been shown to prevent or negate. Given the fact that preventive therapy for glucocorticoid-induced osteoporosis is often not prescribed, one wonders whether a daily self-injectable therapy for this condition would be prescribed by physicians and accepted by patients. This article reviews the epidemiology, pathophysiology, treatment, guidelines, and persistence data (when available for patients with glucocorticoid-induced osteoporosis treated with teriparatide.Keywords: glucocorticoid-induced osteoporosis, teriparatide, anabolic, PTH, parathyroid hormone

  7. A Smart Grid Framework for Optimally Integrating Supply-Side, Demand-Side and Transmission Line Management Systems

    Directory of Open Access Journals (Sweden)

    Chukwuka Monyei

    2018-04-01

    Full Text Available A coordinated centralized energy management system (ConCEMS is presented in this paper that seeks to integrate for optimal grid operation—the supply side energy management system (SSEMS, home energy management system (HEMS and transmission line management system (TLMS. ConCEMS in ensuring the optimal operation of an IEEE 30-bus electricity network harmonizes the individual objective function of SSEMS, HEMS and TLMS to evolve an optimal dispatch of participating demand response (DR loads that does not violate transmission line ampacity limits (TLMS constraint while minimizing consumer cost (HEMS constraint and supply side operations cost (SSEMS constraint. An externally constrained genetic algorithm (ExC-GA that is influenced by feedback from TLMS is also presented that intelligently varies the dispatch time of participating DR loads to meet the individual objective functions. Hypothetical day ahead dynamic pricing schemes (Price1, Price2 and Price3 have also been adopted alongside an existing time of use (Price0 pricing scheme for comparison and discussion while a dynamic thermal line rating (DTLR algorithm has also been incorporated to dynamically compute power limits based on real time associated data.

  8. Systemic hypertension and the right-sided cardiovascular system: a review of the available evidence.

    Science.gov (United States)

    Pedrinelli, Roberto; Dell'Omo, Giulia; Talini, Enrica; Canale, Maria Laura; Di Bello, Vitantonio

    2009-02-01

    Abnormal vasoconstriction of the lesser circulation characterizes a subset of patients with essential hypertension, a possible effect of mechanisms, such as enhanced sympathetic tone, increased delivery of blood-borne vasoconstrictor substances or abnormal local release of vasoactive factors, acting on both sides of the circulation or to backward transmission of increased pressure due to stiffer left ventricles with more advanced diastolic dysfunction. Elevated systemic pressure also associates with thickening of the right ventricle, a central element of the low-pressure system. Right ventricular remodelling develops in parallel with a similar process occurring at the left side, likely as a result of ventricular interdependence under the influence of trophic factors targeting both ventricles, though other mechanisms, including increased pulmonary afterload, may also be operative. By and large independent of the extent of structural remodelling of both ventricles, systemic hypertension also conditions an impaired filling rate of the right ventricle that accompanies a similar phenomenon at the left side. Thus, quite in contrast with the common and simplistic assumption of a separate behaviour of the two ventricles, the right-sided cardiovascular system is not immune to the effect of systemic hypertension, a concept whose clinical and pathophysiological implications require further studies.

  9. On the retinal toxicity of intraocular glucocorticoids.

    Science.gov (United States)

    Torriglia, Alicia; Valamanesh, Fatemeh; Behar-Cohen, Francine

    2010-12-15

    Corticosteroids are hormones involved in many physiological responses such as stress, immune modulation, protein catabolism and water homeostasis. The subfamily of glucocorticoids is used systemically in the treatment of inflammatory diseases or allergic reactions. In the eye, glucocorticoides are used to treat macular edema, inflammation and neovascularization. The most commonly used glucocorticoid is triamcinolone acetonide (TA). The pharmaceutical formulation of TA is not adapted for intravitreal administration but has been selected by ophthalmologists because its very low intraocular solubility provides sustained effect. Visual benefits of intraocular TA do not clearly correlate with morpho-anatomical improvements, suggesting potential toxicity. We therefore studied, non-common, but deleterious effects of glucocorticoids on the retina. We found that the intravitreal administration of TA is beneficial in the treatment of neovascularization because it triggers cell death of endothelial cells of neovessels by a caspase-independent mechanism. However, this treatment is toxic for the retina because it induces a non-apoptotic, caspase-independent cell death related to paraptosis, mostly in the retinal pigmented epithelium cells and the Müller cells. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. From receptor balance to rational glucocorticoid therapy.

    Science.gov (United States)

    de Kloet, E Ron

    2014-08-01

    Corticosteroids secreted as end product of the hypothalamic-pituitary-adrenal axis act like a double-edged sword in the brain. The hormones coordinate appraisal processes and decision making during the initial phase of a stressful experience and promote subsequently cognitive performance underlying the management of stress adaptation. This action exerted by the steroids on the initiation and termination of the stress response is mediated by 2 related receptor systems: mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). The receptor types are unevenly distributed but colocalized in abundance in neurons of the limbic brain to enable these complementary hormone actions. This contribution starts from a historical perspective with the observation that phasic occupancy of GR during ultradian rhythmicity is needed to maintain responsiveness to corticosteroids. Then, during stress, initially MR activation enhances excitability of limbic networks that are engaged in appraisal and emotion regulation. Next, the rising hormone concentration occupies GR, resulting in reallocation of energy to limbic-cortical circuits with a role in behavioral adaptation and memory storage. Upon MR:GR imbalance, dysregulation of the hypothalamic-pituitary-adrenal axis occurs, which can enhance an individual's vulnerability. Imbalance is characteristic for chronic stress experience and depression but also occurs during exposure to synthetic glucocorticoids. Hence, glucocorticoid psychopathology may develop in susceptible individuals because of suppression of ultradian/circadian rhythmicity and depletion of endogenous corticosterone from brain MR. This knowledge generated from testing the balance hypothesis can be translated to a rational glucocorticoid therapy.

  11. Glucocorticoids, chronic stress, and obesity

    NARCIS (Netherlands)

    Dallman, Mary F.; Pecoraro, Norman C.; la Fleur, Susanne E.; Warne, James P.; Ginsberg, Abigail B.; Akana, Susan F.; Laugero, Kevin C.; Houshyar, Hani; Strack, Alison M.; Bhatnagar, Seema; Bell, Mary E.

    2006-01-01

    Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a

  12. NPP Temelin automatic monitoring and diagnostic system of secondary side of the unit 1

    International Nuclear Information System (INIS)

    Heidenreich, S.; Pisl, M.; Drab, F.

    1997-01-01

    Two measuring and evaluating systems by SKODA PRAHA are described, designed for the Temelin nuclear power plant: a permanent secondary side diagnostic system for technology monitoring in the period of startup and operation; and the system of physical and power starting-up for monitoring during the first and repeated startup. The purposes of both systems are outlined. The scope of diagnostics covered and the functioning of the secondary side system is dealt with in some detail. (A.K.)

  13. Dibutyltin disrupts glucocorticoid receptor function and impairs glucocorticoid-induced suppression of cytokine production.

    Directory of Open Access Journals (Sweden)

    Christel Gumy

    Full Text Available BACKGROUND: Organotins are highly toxic and widely distributed environmental chemicals. Dibutyltin (DBT is used as stabilizer in the production of polyvinyl chloride plastics, and it is also the major metabolite formed from tributyltin (TBT in vivo. DBT is immunotoxic, however, the responsible targets remain to be defined. Due to the importance of glucocorticoids in immune-modulation, we investigated whether DBT could interfere with glucocorticoid receptor (GR function. METHODOLOGY: We used HEK-293 cells transiently transfected with human GR as well as rat H4IIE hepatoma cells and native human macrophages and human THP-1 macrophages expressing endogenous receptor to study organotin effects on GR function. Docking of organotins was used to investigate the binding mechanism. PRINCIPAL FINDINGS: We found that nanomolar concentrations of DBT, but not other organotins tested, inhibit ligand binding to GR and its transcriptional activity. Docking analysis indicated that DBT inhibits GR activation allosterically by inserting into a site close to the steroid-binding pocket, which disrupts a key interaction between the A-ring of the glucocorticoid and the GR. DBT inhibited glucocorticoid-induced expression of phosphoenolpyruvate carboxykinase (PEPCK and tyrosine-aminotransferase (TAT and abolished the glucocorticoid-mediated transrepression of TNF-alpha-induced NF-kappaB activity. Moreover, DBT abrogated the glucocorticoid-mediated suppression of interleukin-6 (IL-6 and TNF-alpha production in lipopolysaccharide (LPS-stimulated native human macrophages and human THP-1 macrophages. CONCLUSIONS: DBT inhibits ligand binding to GR and subsequent activation of the receptor. By blocking GR activation, DBT may disturb metabolic functions and modulation of the immune system, providing an explanation for some of the toxic effects of this organotin.

  14. Modeling Supermarket Refrigeration Systems for Demand-Side Management

    DEFF Research Database (Denmark)

    Shafiei, Seyed Ehsan; Rasmussen, Henrik; Stoustrup, Jakob

    2013-01-01

    Modeling of supermarket refrigeration systems for supervisory control in the smart grid is presented in this paper. A modular modeling approach is proposed in which each module is modeled and identified separately. The focus of the work is on estimating the power consumption of the system while...

  15. Xenobiotics and the Glucocorticoid Receptor

    International Nuclear Information System (INIS)

    Gulliver, Linda S M

    2017-01-01

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  16. Xenobiotics and the Glucocorticoid Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Gulliver, Linda S M, E-mail: linda.gulliver@otago.ac.nz

    2017-03-15

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  17. Assessing the potential of residential HVAC systems for demand-side management

    NARCIS (Netherlands)

    van der Klauw, Thijs; Hoogsteen, Gerwin; Gerards, Marco Egbertus Theodorus; Hurink, Johann L.; Feng, Xianyong; Hebner, Robert E.

    This paper investigates the potential of residential heating, ventilation and air conditioning systems to contribute to dynamic demand-side management. Thermal models for seven houses in Austin, Texas are developed with the goal of using them in a planning based demand-side management methodology.

  18. System for notational analysis in small-sided soccer games

    NARCIS (Netherlands)

    Van Maarseveen, Mariette J.J.; Oudejans, Raoul R.D.; Savelsbergh, Geert J.P.

    2017-01-01

    The objective of this study was to compose an objective and detailed notational analysis system for 3 vs. 2GK smallsided soccer games, in which three roles are examined: attacker with ball, attacker without ball and defender. The actions and the outcome of the actions were registered for each player

  19. Demand side resource operation on the Irish power system with high wind power penetration

    International Nuclear Information System (INIS)

    Keane, A.; Tuohy, A.; Meibom, P.; Denny, E.; Flynn, D.; Mullane, A.; O'Malley, M.

    2011-01-01

    The utilisation of demand side resources is set to increase over the coming years with the advent of advanced metering infrastructure, home area networks and the promotion of increased energy efficiency. Demand side resources are proposed as an energy resource that, through aggregation, can form part of the power system plant mix and contribute to the flexible operation of a power system. A model for demand side resources is proposed here that captures its key characteristics for commitment and dispatch calculations. The model is tested on the all island Irish power system, and the operation of the model is simulated over one year in both a stochastic and deterministic mode, to illustrate the impact of wind and load uncertainty. The results illustrate that demand side resources can contribute to the efficient, flexible operation of systems with high penetrations of wind by replacing some of the functions of conventional peaking plant. Demand side resources are also shown to be capable of improving the reliability of the system, with reserve capability identified as a key requirement in this respect. - Highlights: → Demand side resource model presented for use in unit commitment and dispatch calculations. → Benefits of demand side aggregation demonstrated specifically as a peaking unit and provider of reserve. → Potential to displace or defer construction of conventional peaking units.

  20. Impact of glucocorticoid on neurogenesis

    Directory of Open Access Journals (Sweden)

    Haruki Odaka

    2017-01-01

    Full Text Available Neurogenesis is currently an area of great interest in neuroscience. It is closely linked to brain diseases, including mental disorders and neurodevelopmental disease. Both embryonic and adult neurogeneses are influenced by glucocorticoids secreted from the adrenal glands in response to a variety of stressors. Moreover, proliferation/differentiation of the neural stem/progenitor cells (NSPCs is affected by glucocorticoids through intracellular signaling pathways such as phosphoinositide 3-kinase (PI3K/Akt, hedgehog, and Wnt. Our review presents recent evidence of the impact of glucocorticoids on NSPC behaviors and the underlying molecular mechanisms; this provides important information for understanding the pathological role of glucocorticoids on neurogenesis-associated brain diseases.

  1. The Pro-inflammatory Effects of Glucocorticoids in the Brain

    Science.gov (United States)

    Duque, Erica de Almeida; Munhoz, Carolina Demarchi

    2016-01-01

    Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

  2. Glucocorticoids and Preterm Hypoxic-Ischemic Brain Injury: The Good and the Bad

    Directory of Open Access Journals (Sweden)

    Laura Bennet

    2012-01-01

    Full Text Available Fetuses at risk of premature delivery are now routinely exposed to maternal treatment with synthetic glucocorticoids. In randomized clinical trials, these substantially reduce acute neonatal systemic morbidity, and mortality, after premature birth and reduce intraventricular hemorrhage. However, the overall neurodevelopmental impact is surprisingly unclear; worryingly, postnatal glucocorticoids are consistently associated with impaired brain development. We review the clinical and experimental evidence on how glucocorticoids may affect the developing brain and highlight the need for systematic research.

  3. Fermilab linac upgrade side coupled cavity temperature control system

    International Nuclear Information System (INIS)

    Crisp, J.; Satti, J.

    1991-05-01

    Each cavity section has a temperature control system which maintains the resonant frequency by exploiting the 17.8 ppm/degree C frequency sensitivity of the copper cavities. Each accelerating cell has a cooling tube brazed azimuthally to the outside surface. Alternate supply and return connection to the water manifolds reduce temperature gradients and maintain physical alignment of the cavity string. Special tubing with spiral inner fins and large flow rate are used to reduce the film coefficient. Temperature is controlled by mixing chilled water with the water circulating between the cavity and the cooling skid located outside the radiation enclosure. Chilled water flow is regulated with a valve controlled by a local microcomputer. The temperature loop set point will be obtained from a slower loop which corrects the phase error between the cavity section and the rf drive during normal beam loaded conditions. Time constants associated with thermal gradients induced in the cavity with the rf power require programming it to the nominal 7.1 MW level over a 1 minute interval to limit the reverse power. 4 refs., 4 figs

  4. Optimal glucocorticoid therapy.

    Science.gov (United States)

    Debono, Miguel; Ross, Richard J

    2011-01-01

    The rhythmic regulation of human physiology and behaviour is controlled by a central endogenous clock located in the suprachiasmatic nucleus. Most tissues have peripheral clocks that oscillate in time with this central clock. How the central time keeper controls peripheral clocks is not established, however there is evidence to suggest that the cortisol rhythm is one important secondary messenger. Loss of the endogenous cortisol rhythm is associated with sleep disturbance, depression, and metabolic abnormalities. In adrenal insufficiency, current glucocorticoid replacement regimens cannot replace the normal circadian rhythm of cortisol, and patients have an increased mortality and impaired quality of life. We propose that reproducing circadian cortisol levels may improve quality of life in patients with adrenal insufficiency and we have been investigating the impact of circadian hydrocortisone replacement. Using Chronocort, a modified release preparation of hydrocortisone, we have demonstrated that it is possible to simulate the overnight rise in cortisol release and, in preliminary studies in patients with congenital adrenal hyperplasia, control morning androgen levels. Future studies are now required to determine whether Chronocort can improve quality of life in patients with adrenal insufficiency. Copyright © 2011 S. Karger AG, Basel.

  5. The Ups and Downs of Glucocorticoid Signaling | Center for Cancer Research

    Science.gov (United States)

    Glucocorticoids are steroids that react to stress by regulating inflammation and controlling metabolism. Because of their anti-inflammatory and immunosuppressive properties, corticosteroids are among the most frequently prescribed drugs. Glucocorticoids are often used to treat arthritis and autoimmune diseases and are also given in combination with other drugs to treat cancers—such as leukemias and lymphomas—or to alleviate side effects from chemotherapy and radiation. In humans, a glucocorticoid called cortisol is released from the adrenal gland approximately every hour to send signals to cells throughout the body. This pulsed release of hormone is called ultradian secretion.  

  6. Performance evaluation of a 'dual-side read' dedicated mammography computed radiography system

    International Nuclear Information System (INIS)

    Fetterly, Kenneth A.; Schueler, Beth A.

    2003-01-01

    The image quality of a dedicated mammography computed radiography (CR) system was characterized. A unique feature of this system is that it collects image signals from both sides of the storage phosphor. Measurements of the modulation transfer function (MTF), noise power spectrum (NPS), and detective quantum efficiency (DQE) were made. This work included improvements in our measurement methods to specifically account for the detrimental effects of system glare on the MTF and to accurately characterize the low-frequency NPS components. Image quality measurements were performed using a 25 kVp beam filtered with 2 mm Al and an exposure range of 1 to 100 mR (87 to 870 μGy). The DQE was found to decrease with increasing exposure due to an increased contribution of storage phosphor structure noise. The DQE of this system was compared to similar measurements made using a standard CR system. The dual-side read system demonstrated superior DQE compared to the standard system. The decrease in DQE with increasing exposure was more severe for the standard system than the dual-side read system. This finding suggests that the CR system noise was reduced for the dual-side read system compared to the standard system

  7. Glucocorticoids interact with the noradrenergic arousal system in the nucleus accumbens shell to enhance memory consolidation of both appetitive and aversive taste learning

    NARCIS (Netherlands)

    Wichmann, Romy; Fornari, Raquel V.; Roozendaal, Benno

    It is well established that glucocorticoid hormones strengthen the consolidation of long-term memory of emotionally arousing experiences but have little effect on memory of low-arousing experiences. Although both positive and negative emotionally arousing events tend to be well remembered, studies

  8. Glucocorticoids interact with the noradrenergic arousal system in the nucleus accumbens shell to enhance memory consolidation of both appetitive and aversive taste learning

    NARCIS (Netherlands)

    Wichmann, R.; Fornari, R.V.; Roozendaal, B.

    2012-01-01

    It is well established that glucocorticoid hormones strengthen the consolidation of long-term memory of emotionally arousing experiences but have little effect on memory of low-arousing experiences. Although both positive and negative emotionally arousing events tend to be well remembered, studies

  9. Demand side resource operation on the Irish power system with high wind power penetration

    DEFF Research Database (Denmark)

    Keane, A.; Tuohy, A.; Meibom, Peter

    2011-01-01

    part of the power system plant mix and contribute to the flexible operation of a power system. A model for demand side resources is proposed here that captures its key characteristics for commitment and dispatch calculations. The model is tested on the all island Irish power system, and the operation...... of the functions of conventional peaking plant. Demand side resources are also shown to be capable of improving the reliability of the system, with reserve capability identified as a key requirement in this respect....... of the model is simulated over one year in both a stochastic and deterministic mode, to illustrate the impact of wind and load uncertainty. The results illustrate that demand side resources can contribute to the efficient, flexible operation of systems with high penetrations of wind by replacing some...

  10. 2-D Reflectometer Modeling for Optimizing the ITER Low-field Side Reflectometer System

    International Nuclear Information System (INIS)

    Kramer, G.J.; Nazikian, R.; Valeo, E.J.; Budny, R.V.; Kessel, C.; Johnson, D.

    2005-01-01

    The response of a low-field side reflectometer system for ITER is simulated with a 2?D reflectometer code using a realistic plasma equilibrium. It is found that the reflected beam will often miss its launch point by as much as 40 cm and that a vertical array of receiving antennas is essential in order to observe a reflection on the low-field side of ITER

  11. Static and dynamic stability of the guidance force in a side-suspended HTS maglev system

    Science.gov (United States)

    Zhou, Dajin; Cui, Chenyu; Zhao, Lifeng; Zhang, Yong; Wang, Xiqing; Zhao, Yong

    2017-02-01

    The static and dynamic stability of the guidance force in a side-suspended HTS-PMG (permanent magnetic guideway) system were studied theoretically and experimentally. It is found that there are two types of guidance force that exist in the HTS-PMG system, which are sensitive to the levitation gap and the arrangement of YBCO bulks around the central axis of the PMG. An optimized YBCO array was used to stabilize the system, which enabled a side-suspended HTS-PMG maglev vehicle to run stably at 102 km h-1 on a circular test track with 6.5 m in diameter.

  12. Software design of control system of CCD side-scatter lidar

    Science.gov (United States)

    Kuang, Zhiqiang; Liu, Dong; Deng, Qian; Zhang, Zhanye; Wang, Zhenzhu; Yu, Siqi; Tao, Zongming; Xie, Chenbo; Wang, Yingjian

    2018-03-01

    Because of the existence of blind zone and transition zone, the application of backscattering lidar in near-ground is limited. The side-scatter lidar equipped with the Charge Coupled Devices (CCD) can separate the transmitting and receiving devices to avoid the impact of the geometric factors which is exited in the backscattering lidar and, detect the more precise near-ground aerosol signals continuously. Theories of CCD side-scatter lidar and the design of control system are introduced. The visible control of laser and CCD and automatic data processing method of the side-scatter lidar are developed by using the software of Visual C #. The results which are compared with the calibration of the atmospheric aerosol lidar data show that signals from the CCD side- scatter lidar are convincible.

  13. Cell-specific expression of the glucocorticoid receptor within granular convoluted tubules of the rat submaxillary gland

    International Nuclear Information System (INIS)

    Antakly, T.; Zhang, C.X.; Sarrieau, A.; Raquidan, D.

    1991-01-01

    The submaxillary gland, a heterogeneous tissue composed essentially of two functionally distinct cell types (tubular epithelial and acinar), offers an interesting system in which to study the mechanisms of steroid-dependent growth and differentiation. One cell type, the granular convoluted tubular (GCT) cell, secretes a large number of physiologically important polypeptides, including epidermal and nerve growth factors. Two steroids, androgens and glucocorticoids, greatly influence the growth, differentiation, and secretory activity of GCT cells. Because glucocorticoids can partially mimic or potentiate androgen effects, it has been thought that glucocorticoids act via androgen receptors. Since the presence of glucocorticoid receptors is a prerequisite for glucocorticoid action, we have investigated the presence and cellular distribution of glucocorticoid receptors within the rat submaxillary gland. Binding experiments using [3H]dexamethasone revealed the presence of high affinity binding sites in rat submaxillary tissue homogenates. Most of these sites were specifically competed by dexamethasone, corticosterone, and a pure glucocorticoid agonist RU 28362. Neither testosterone nor dihydrotestosterone competed for glucocorticoid binding. The cellular distribution of glucocorticoid receptors within the submaxillary gland was investigated by immunocytochemistry, using two highly specific glucocorticoid receptor antibodies. The receptor was localized in the GCT cells, but not in the acinar cells of rat and mouse submaxillary tissue sections. In GCT cells, the glucocorticoid receptor colocalized with several secretory polypeptides, including epidermal growth factor, nerve growth factor, alpha 2u-globulin, and atrial natriuretic factor

  14. Side-by-side comparisons of evacuated compound parabolic concentrator and flat plate solar collector systems at temperatures of 90 to 100C

    Science.gov (United States)

    Allen, J. W.; Schertz, W. W.; Wantroba, A. S.

    1987-03-01

    This collector system study is an extension of a previous system study in which Argonne National Laboratory (ANL) compared the performance of three solar energy systems operated side by side for over a year. In the present system study, four solar energy systems were operated side by side for part of a year. Two of the collector systems used commercially available compound parabolic concentrator (CPC) collectors, one used a commercially available flat plate collector, and one used an experimental CPC collector built by The University of Chicago. The collectors were mounted in fixed positions; they did not track the Sun, and their tilt angles were not seasonally adjusted. All of the collector arrays faced south and were tilted at 42 deg with respect to the horizon (to match the 42 deg N latitude at ANL). All four collector systems started each day with their storage temperatures at 90 C. During the day, each system was operated by its own solar controller. At the end of the day, the tanks were mixed and the temperature changes in the tanks were measured. The change in storage energy was calculated from the temperature change, the heat capacity of the storage system, and the pump energy.

  15. Investigation of radioprotective properties of synthetic antagonist of glucocorticoids RU 38 486

    International Nuclear Information System (INIS)

    Sejliev, A.A.; Zvonareva, N.B.; Zhivotovskij, B.D.; Khanson, K.P.; Akademiya Meditsinskikh Nauk SSSR, Leningrad

    1992-01-01

    Radioprotective properties of synthetic antiglucocorticoid RU 38 486 were investigated. It was demonstrated that this antigonist of glucocorticoids possesses radioprotective effect in vitro and in vivo systems. Radioprotective properties at molecular level exhibited in inhibition of postirradiation endonuclease activation and in prevention of internucleosome chromatin degradation. Involvement of cytosol glucocorticoid receptors in initiation of radiation-induced programmed cell death is discussed

  16. Functional interaction between the glucocorticoid receptor and GANP/MCM3AP

    International Nuclear Information System (INIS)

    Osman, Waffa; Laine, Sanna; Zilliacus, Johanna

    2006-01-01

    Glucocorticoids are widely used to treat inflammatory diseases but have a number of side effects that partly are connected to inhibition of cell proliferation. Glucocorticoids mediated their action by binding to the glucocorticoid receptor. In the present study, we have identified by two-hybrid screens the germinal center-associated protein (GANP) and MCM3-associated protein (MCM3AP), a splicing variant of GANP, as glucocorticoid receptor interacting proteins. GANP and MCM3AP can bind to the MCM3 protein involved in initiation of DNA replication. Glutathione-S-transferase-pull-down and co-immunoprecipitation assays showed that the C-terminal domain of GANP, encompassing MCM3AP, interacts with the ligand-binding domain of the glucocorticoid receptor. Characterization of the intracellular localization of GANP revealed that GANP is shuttling between the nucleus and the cytoplasm. Furthermore, we show that glucocorticoids are unable to inhibit DNA replication in HeLa cells overexpressing MCM3AP suggesting a role for both glucocorticoid receptor and GANP/MCM3AP in regulating cell proliferation

  17. Flexibility analysis in adolescent idiopathic scoliosis on side-bending images using the EOS imaging system.

    Science.gov (United States)

    Hirsch, C; Ilharreborde, B; Mazda, K

    2016-06-01

    Analysis of preoperative flexibility in adolescent idiopathic scoliosis (AIS) is essential to classify the curves, determine their structurality, and select the fusion levels during preoperative planning. Side-bending x-rays are the gold standard for the analysis of preoperative flexibility. The objective of this study was to examine the feasibility and performance of side-bending images taken in the standing position using the EOS imaging system. All patients who underwent preoperative assessment between April 2012 and January 2013 for AIS were prospectively included in the study. The work-up included standing AP and lateral EOS x-rays of the spine, standard side-bending x-rays in the supine position, and standing bending x-rays in the EOS booth. The irradiation dose was measured for each of the tests. Two-dimensional reducibility of the Cobb angle was measured on both types of bending x-rays. The results were based on the 50 patients in the study. No significant difference was demonstrated for reducibility of the Cobb angle between the standing side-bending images with the EOS imaging system and those in the supine position for all types of Lenke deformation. The irradiation dose was five times lower during the EOS bending imaging. The standing side-bending images in the EOS device contributed the same results as the supine images, with five times less irradiation. They should therefore be used in clinical routine. 2. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Glucocorticoids in early rheumatoid arthritis

    NARCIS (Netherlands)

    Everdingen, Amalia A. van

    2002-01-01

    For 50 years, glucocorticoids (GC) are used for symptomatic treatment of rheumatoid arthritis (RA). In the last decade, results from clinical studies of treatment with GC as additional therapy to long-acting antirheumatic drugs in patients with early RA suggested also disease-modifying properties of

  19. The generative power of weighted one-sided and regular sticker systems

    Science.gov (United States)

    Siang, Gan Yee; Heng, Fong Wan; Sarmin, Nor Haniza; Turaev, Sherzod

    2014-06-01

    Sticker systems were introduced in 1998 as one of the DNA computing models by using the recombination behavior of DNA molecules. The Watson-Crick complementary principle of DNA molecules is abstractly used in the sticker systems to perform the computation of sticker systems. In this paper, the generative power of weighted one-sided sticker systems and weighted regular sticker systems are investigated. Moreover, the relationship of the families of languages generated by these two variants of sticker systems to the Chomsky hierarchy is also presented.

  20. Observations on side-swimming rainbow trout Oncorhynchus mykiss in water recirculation aquaculture systems

    Science.gov (United States)

    During a controlled 6-month study using six replicated water recirculation aquaculture systems (WRAS), it was observed that rainbow trout Oncorhynchus mykiss in all WRAS exhibited a higher-than-normal prevalence of side-swimming (i.e. controlled, forward swimming, but with misaligned orientation suc...

  1. Human factors study of driver assistance systems to reduce lane departures and side collision accidents.

    Science.gov (United States)

    2008-07-01

    This study investigated the human factors issues related to the implementation of lane departure warning systems (LDWS) to reduce side collision and run-off-road crashes for heavy trucks. Lane departures can be either intentional (e.g., to pass anoth...

  2. Study of Pneumatic Servo Loading System in Double-Sided Polishing

    International Nuclear Information System (INIS)

    Qian, N; Ruan, J; Li, W

    2006-01-01

    The precise double-sided polishing process is one of the main methods to get the ultra-smooth surface of workpiece. In double-sided polishing machine, a loading system is required to be able to precisely control the load superimposed on the workpiece, while the polishing is being carried out. A pneumatic servo loading system is proposed for this purpose. In the pneumatic servo system, the servo valve, which acts both the electrical to mechanical converter and the power amplifier, has a substantial influence on the performance of the loading system. Therefore a specially designed pneumatic digital servo valve is applied in the control system. In this paper, the construction of the pneumatic servo loading system in double-sided polishing machine and control strategy associated with the digital servo valve are first addressed. The mathematical model of the system established and the hardware of the pneumatic servo system is designed. Finally, the experiments are carried out by measuring the practical load on the workpiece and the quality of the surface finish. It is demonstrated that the error rate of load is less than 5% and a super-smooth surface of silicon wafer with roughness Ra 0.401 nm can be obtained

  3. CALIS—A CALibration Insertion System for the DarkSide-50 dark matter search experiment

    Energy Technology Data Exchange (ETDEWEB)

    Agnes, P.; Albuquerque, I. F. M.; Alexander, T.; Alton, A. K.; Asner, D. M.; Back, H. O.; Baldin, B.; Biery, K.; Bocci, V.; Bonfini, G.; Bonivento, W.; Bossa, M.; Bottino, B.; Brigatti, A.; Brodsky, J.; Budano, F.; Bussino, S.; Cadeddu, M.; Cadonati, L.; Cadoni, M.; Calaprice, F.; Canci, N.; Candela, A.; Caravati, M.; Cariello, M.; Carlini, M.; Catalanotti, S.; Cavalcante, P.; Chepurnov, A.; Cicalò, C.; Cocco, A. G.; Covone, G.; D' Angelo, D.; D' Incecco, M.; Davini, S.; Cecco, S. De; Deo, M. De; Vincenzi, M. De; Derbin, A.; Devoto, A.; Eusanio, F. Di; Pietro, G. Di; Dionisi, C.; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Giagu, S.; Giganti, C.; Giovanetti, G. K.; Goretti, A. M.; Granato, F.; Grandi, L.; Gromov, M.; Guan, M.; Guardincerri, Y.; Hackett, B. R.; Herner, K.; Hughes, D.; Humble, P.; Hungerford, E. V.; Ianni, Al.; Ianni, An.; James, I.; Johnson, T. N.; Jollet, C.; Keeter, K.; Kendziora, C. L.; Koh, G.; Korablev, D.; Korga, G.; Kubankin, A.; Li, X.; Lissia, M.; Loer, B.; Lombardi, P.; Longo, G.; Ma, Y.; Machado, A. A.; Machulin, I. N.; Mandarano, A.; Mari, S. M.; Maricic, J.; Marini, L.; Martoff, C. J.; Meregaglia, A.; Meyers, P. D.; Milincic, R.; Miller, J. D.; Montanari, D.; Monte, A.; Mount, B. J.; Muratova, V. N.; Musico, P.; Napolitano, J.; Agasson, A. Navrer; Odrowski, S.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Parmeggiano, S.; Pelczar, K.; Pelliccia, N.; Pocar, A.; Pordes, S.; Pugachev, D. A.; Qian, H.; Randle, K.; Ranucci, G.; Razeti, M.; Razeto, A.; Reinhold, B.; Renshaw, A. L.; Rescigno, M.; Riffard, Q.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Savarese, C.; Schlitzer, B.; Segreto, E.; Semenov, D. A.; Shields, E.; Singh, P. N.; Skorokhvatov, M. D.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Trinchese, P.; Unzhakov, E. V.; Verducci, M.; Vishneva, A.; Vogelaar, B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A. W.; Westerdale, S.; Wilhelmi, J.; Wojcik, M. M.; Xiang, Xi.; Xiao, X.; Xu, J.; Yang, C.; Zec, A.; Zhong, W.; Zhu, C.; Zuzel, G.

    2017-12-01

    This paper describes the design, fabrication, commissioning and use of a CALibration source Insertion System (CALIS) in the DarkSide-50 direct dark matter search experiment. CALIS deploys radioactive sources into the liquid scintillator veto to characterize the detector response and detection efficiency of the DarkSide-50 Liquid Argon Time Projection Chamber, and the surrounding 30 t organic liquid scintillator neutron veto. It was commissioned in September 2014 and has been used successfully in several gamma and neutron source campaigns since then. A description of the hardware and an excerpt of calibration analysis results are given below.

  4. Prevalent glucocorticoid and androgen activity in US water sources.

    Science.gov (United States)

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

    2012-01-01

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

  5. Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Warris, Lidewij T.; van den Akker, Erica L. T.; Aarsen, Femke K.; Bierings, Marc B.; van den Bos, Cor; Tissing, Wim J. E.; Sassen, Sebastiaan D. T.; Veening, Margreet A.; Zwaan, Christian M.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied

  6. Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

    Science.gov (United States)

    Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

    2018-03-08

    Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma

  7. Multi-sided metallization of textile fibres by using magnetron system with grounded cathode

    Directory of Open Access Journals (Sweden)

    Chodun Rafał

    2017-10-01

    Full Text Available The synthesis of coatings on textiles fibers enables functionalization of their properties e.g.: changing the reaction on IR radiation. In our experiment, a magnetron with a grounded cathode and positively biased anode was used as a source of plasma. A ring anode was positioned at 8 cm distance from the cathode. Samples of glass and cotton textile were placed at the plane of the anode. Ti and TiN coatings were deposited by sputtering of titanium target in Ar or Ar+ N2 atmosphere. SEM studies showed that, using the magnetron system described above, the textile fibers were covered by the 2 μm to 3 μm thick coatings. Unexpectedly, the coatings were deposited at both sides of the samples: the front side was exposed to glow discharge plasma and the backside was completely shaded from the plasma. IR optical investigation exhibited significant change in reflectance and transmittance of the coated textiles. The using of standard magnetron system (grounded anode and cathode at negative potential resulted in a coating deposition at the textile side exposed to the plasma action only. We believe that the multi-sided deposition of coatings observed during the process run with magnetron with grounded cathode is a result of an ambipolar diffusion mechanism in the anodic potential drop region.

  8. Bulk electric system reliability evaluation incorporating wind power and demand side management

    Science.gov (United States)

    Huang, Dange

    correlations and the interactive effects of wind power and load forecast uncertainty on system reliability are examined. The concept of the security cost associated with operating in the marginal state in the well-being framework is incorporated in the economic analyses associated with system expansion planning including wind power and load forecast uncertainty. Overall reliability cost/worth analyses including security cost concepts are applied to select an optimal wind power injection strategy in a bulk electric system. The effects of the various demand side management measures on system reliability are illustrated using the system, load point, and well-being indices, and the reliability index probability distributions. The reliability effects of demand side management procedures in a bulk electric system including wind power and load forecast uncertainty considerations are also investigated. The system reliability effects due to specific demand side management programs are quantified and examined in terms of their reliability benefits.

  9. Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.

    Science.gov (United States)

    Quarta, Carmelo; Clemmensen, Christoffer; Zhu, Zhimeng; Yang, Bin; Joseph, Sini S; Lutter, Dominik; Yi, Chun-Xia; Graf, Elisabeth; García-Cáceres, Cristina; Legutko, Beata; Fischer, Katrin; Brommage, Robert; Zizzari, Philippe; Franklin, Bernardo S; Krueger, Martin; Koch, Marco; Vettorazzi, Sabine; Li, Pengyun; Hofmann, Susanna M; Bakhti, Mostafa; Bastidas-Ponce, Aimée; Lickert, Heiko; Strom, Tim M; Gailus-Durner, Valerie; Bechmann, Ingo; Perez-Tilve, Diego; Tuckermann, Jan; Hrabě de Angelis, Martin; Sandoval, Darleen; Cota, Daniela; Latz, Eicke; Seeley, Randy J; Müller, Timo D; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H

    2017-10-03

    Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Benchmark of Client and Server-Side Catchment Delineation Approaches on Web-Based Systems

    Science.gov (United States)

    Demir, I.; Sermet, M. Y.; Sit, M. A.

    2016-12-01

    Recent advances in internet and cyberinfrastructure technologies have provided the capability to acquire large scale spatial data from various gauges and sensor networks. The collection of environmental data increased demand for applications which are capable of managing and processing large-scale and high-resolution data sets. With the amount and resolution of data sets provided, one of the challenging tasks for organizing and customizing hydrological data sets is delineation of watersheds on demand. Watershed delineation is a process for creating a boundary that represents the contributing area for a specific control point or water outlet, with intent of characterization and analysis of portions of a study area. Although many GIS tools and software for watershed analysis are available on desktop systems, there is a need for web-based and client-side techniques for creating a dynamic and interactive environment for exploring hydrological data. In this project, we demonstrated several watershed delineation techniques on the web with various techniques implemented on the client-side using JavaScript and WebGL, and on the server-side using Python and C++. We also developed a client-side GPGPU (General Purpose Graphical Processing Unit) algorithm to analyze high-resolution terrain data for watershed delineation which allows parallelization using GPU. The web-based real-time analysis of watershed segmentation can be helpful for decision-makers and interested stakeholders while eliminating the need of installing complex software packages and dealing with large-scale data sets. Utilization of the client-side hardware resources also eliminates the need of servers due its crowdsourcing nature. Our goal for future work is to improve other hydrologic analysis methods such as rain flow tracking by adapting presented approaches.

  11. Nonlinear stability research on the hydraulic system of double-side rolling shear

    Science.gov (United States)

    Wang, Jun; Huang, Qingxue; An, Gaocheng; Qi, Qisong; Sun, Binyu

    2015-10-01

    This paper researches the stability of the nonlinear system taking the hydraulic system of double-side rolling shear as an example. The hydraulic system of double-side rolling shear uses unsymmetrical electro-hydraulic proportional servo valve to control the cylinder with single piston rod, which can make best use of the space and reduce reversing shock. It is a typical nonlinear structure. The nonlinear state-space equations of the unsymmetrical valve controlling cylinder system are built first, and the second Lyapunov method is used to evaluate its stability. Second, the software AMEsim is applied to simulate the nonlinear system, and the results indicate that the system is stable. At last, the experimental results show that the system unsymmetrical valve controlling the cylinder with single piston rod is stable and conforms to what is deduced by theoretical analysis and simulation. The construction and application of Lyapunov function not only provide the theoretical basis for using of unsymmetrical valve controlling cylinder with single piston rod but also develop a new thought for nonlinear stability evaluation.

  12. Right-sided dominance of the bilateral vestibular system in the upper brainstem and thalamus.

    Science.gov (United States)

    Dieterich, Marianne; Kirsch, V; Brandt, T

    2017-10-01

    MRI diffusion tensor imaging tractography was performed on the bilateral vestibular brainstem pathways, which run from the vestibular nuclei via the paramedian and posterolateral thalamic subnuclei to the parieto-insular vestibular cortex. Twenty-one right-handed healthy subjects participated. Quantitative analysis revealed a rope-ladder-like system of vestibular pathways in the brainstem with crossings at pontine and mesencephalic levels. Three structural types of right-left fiber distributions could be delineated: (1) evenly distributed pathways at the lower pontine level from the vestibular nuclei to the pontine crossing, (2) a moderate, pontomesencephalic right-sided lateralization between the pontine and mesencephalic crossings, and (3) a further increase of the right-sided lateralization above the mesencephalic crossing leading to the thalamic vestibular subnuclei. The increasing lateralization along the brainstem was the result of an asymmetric number of pontine and mesencephalic crossing fibers which was higher for left-to-right crossings. The dominance of the right vestibular meso-diencephalic circuitry in right-handers corresponds to the right-hemispheric dominance of the vestibular cortical network. The structural asymmetry apparent in the upper brainstem might be interpreted in relation to the different functions of the vestibular system depending on their anatomical level: a symmetrical sensorimotor reflex control of eye, head, and body mediated by the lower brainstem; a lateralized right-sided upper brainstem-thalamic function as part of the dominant right-sided cortical/subcortical vestibular system that enables a global percept of body motion and orientation in space.

  13. Glucocorticoid control of gene transcription in neural tissue

    NARCIS (Netherlands)

    Morsink, Maarten Christian

    2007-01-01

    Glucocorticoid hormones exert modulatory effects on neural function in a delayed genomic fashion. The two receptor types that can bind glucocorticoids, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), are ligand-inducible transcription factors. Therefore, changes in gene

  14. μtrack profiles for investigating side effects of advanced silicon heads for helical scan tape systems

    NARCIS (Netherlands)

    Hozoi, A.; Groenland, J.P.J.; Lodder, J.C.; Albertini, J.B.

    2002-01-01

    Track and μtrack scans are common techniques in hard disk systems for investigating side writing and side reading, and for characterizing the response of MR read heads. These methods are implemented less in tape systems, where the contact recording mode and flexible medium make it difficult to

  15. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

    OpenAIRE

    Campolongo, Patrizia; Roozendaal, Benno; Trezza, Viviana; Hauer, Daniela; Schelling, Gustav; McGaugh, James L.; Cuomo, Vincenzo

    2009-01-01

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors, the present experiments investigated whether the endocannabinoid system in the BLA influences memory consolidation and whether glucocorticoids interact with this system. The CB1 receptor agonist WIN5...

  16. [Clinical skills and outcomes of chair-side computer aided design and computer aided manufacture system].

    Science.gov (United States)

    Yu, Q

    2018-04-09

    Computer aided design and computer aided manufacture (CAD/CAM) technology is a kind of oral digital system which is applied to clinical diagnosis and treatment. It overturns the traditional pattern, and provides a solution to restore defect tooth quickly and efficiently. In this paper we mainly discuss the clinical skills of chair-side CAD/CAM system, including tooth preparation, digital impression, the three-dimensional design of prosthesis, numerical control machining, clinical bonding and so on, and review the outcomes of several common kinds of materials at the same time.

  17. Power System Transient Stability Improvement Using Demand Side Management in Competitive Electricity Markets

    DEFF Research Database (Denmark)

    Hu, Weihao; Wang, Chunqi; Chen, Zhe

    2012-01-01

    Since the hourly spot market price is available one day ahead in Denmark, the price could be transferred to the consumers and they may shift some of their loads from high price periods to the low price periods in order to save their energy costs. The optimal load response to an electricity price...... for demand side management generates different load profiles and may provide an opportunity to improve the transient stability of power systems with high wind power penetrations. In this paper, the idea of the power system transient stability improvement by using optimal load response to the electricity...... price is proposed. A 102-bus power system which represents a simplified model of the western Danish power system is chosen as the study case. Simulation results show that the optimal load response to electricity prices is an effective measure to improve the power system transient stability with high...

  18. Impact of Demand Side Response on a Commercial Retail Refrigeration System

    Directory of Open Access Journals (Sweden)

    Ibrahim M. Saleh

    2018-02-01

    Full Text Available The UK National Grid has placed increased emphasis on the development of Demand Side Response (DSR tariff mechanisms to manage load at peak times. Refrigeration systems, along with HVAC, are estimated to consume 14% of the UK’s electricity and could have a significant role for DSR application. However, characterized by relatively low individual electrical loads and massive asset numbers, multiple low power refrigerators need aggregation for inclusion in these tariffs. In this paper, the impact of the Demand Side Response (DSR control mechanisms on food retailing refrigeration systems is investigated. The experiments are conducted in a test-rig built to resemble a typical small supermarket store. The paper demonstrates how the temperature and pressure profiles of the system, the active power and the drawn current of the compressors are affected following a rapid shut down and subsequent return to normal operation as a response to a DSR event. Moreover, risks and challenges associated with primary and secondary Firm Frequency Response (FFR mechanisms, where the load is rapidly shed at high speed in response to changes in grid frequency, is considered. For instance, measurements are included that show a significant increase in peak inrush currents of approx. 30% when the system returns to normal operation at the end of a DSR event. Consideration of how high inrush currents after a DSR event can produce voltage fluctuations of the supply and we assess risks to the local power supply system.

  19. NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells

    NARCIS (Netherlands)

    S.W. Paugh (Steven); E.J. Bonten (Erik J.); D. Savic (Daniel); L.B. Ramsey (Laura B.); W.E. Thierfelder (William E.); P. Gurung (Prajwal); R.K.S. Malireddi (R. K. Subbarao); M. Actis (Marcelo); A. Mayasundari (Anand); J. Min (Jaeki); D.R. Coss (David R.); L.T. Laudermilk (Lucas T.); J.C. Panetta (John); J.R. McCorkle (J. Robert); Y. Fan (Yiping); K.R. Crews (Kristine R.); G. Stocco (Gabriele); M.R. Wilkinson (Mark R.); A.M. Ferreira (Antonio M.); C. Cheng (Cheng); W. Yang (Wenjian); S.E. Karol (Seth E.); C.A. Fernandez (Christian A.); B. Diouf (Barthelemy); C. Smith (Colton); J.K. Hicks (J Kevin); A. Zanut (Alessandra); A. Giordanengo (Audrey); D.J. Crona; J.J. Bianchi (Joy J.); L. Holmfeldt (Linda); C.G. Mullighan (Charles); M.L. den Boer (Monique); R. Pieters (Rob); S. Jeha (Sima); T.L. Dunwell (Thomas L.); F. Latif (Farida); D. Bhojwani (Deepa); W.L. Carroll (William L.); C.-H. Pui (Ching-Hon); R.M. Myers (Richard M.); R.K. Guy (R Kiplin); T.-D. Kanneganti (Thirumala-Devi); M.V. Relling (Mary); W.E. Evans (William)

    2015-01-01

    textabstractGlucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and resistance to glucocorticoids in leukemia cells confers poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia

  20. Glucocorticoid treatment and impaired mood, memory and metabolism in people with diabetes: the Edinburgh Type 2 Diabetes Study

    Science.gov (United States)

    Reynolds, Rebecca M; Labad, Javier; Sears, Alison V; Williamson, Rachel M; Strachan, Mark W J; Deary, Ian J; Lowe, Gordon D O; Price, Jackie F; Walker, Brian R

    2012-01-01

    Objective Both type 2 diabetes and glucocorticoid therapy are highly prevalent. Although people with type 2 diabetes may be more susceptible to adverse effects of glucocorticoids, and it is recommended that glucocorticoid therapy is avoided for fear of worsening glycaemic control, the extent to which this advice is followed and the consequences when glucocorticoids are prescribed are poorly documented. The aim was to assess the characteristics of people with type 2 diabetes prescribed glucocorticoids in a real-world setting and to quantify resulting adverse effects. Design Cross-sectional cohort study. Methods Cardiometabolic variables, body fat distribution, cognitive function and mood were studied in the 1066 participants of the Edinburgh Type 2 Diabetes Study, of whom 162 (15%) were taking systemic, topical or inhaled glucocorticoids. Results Glucocorticoid therapy was more common in women and in smokers but was not avoided in patients with diabetic complications or cardiovascular risk factors. People taking glucocorticoids were more centrally obese with slightly higher HbA1c and total serum cholesterol but were no more likely to have hepatic steatosis or hypertension. Glucocorticoid treatment was associated with substantially lower mood and greater anxiety. Women taking glucocorticoid therapy were twice as likely to report depressive symptoms compared with those not taking treatment. Glucocorticoid therapy was also associated with poorer cognitive function among those with subclinical atherosclerosis, as indicated by low ankle–brachial pressure index. Conclusions Glucocorticoids are prescribed commonly for people with type 2 diabetes despite being associated with adverse indices of glycaemic control, cardiovascular risk factors, mood and cognitive function. PMID:22408122

  1. General effect of endotoxin on glucocorticoid receptors in mammalian tissues

    International Nuclear Information System (INIS)

    Stith, R.D.; McCallum, R.E.

    1986-01-01

    Considering the ubiquitous nature of glucocorticoid actions and the fact that endotoxin inhibits glucocorticoid action in the liver, we proposed to examine whether endotoxin affected extrahepatic actions of glucocorticoids. Fasted C57BL/6J mice were injected intraperitoneally with endotoxin (LD50) at 0800 and were killed 6 h later. Control mice were injected with an equal volume of saline. 3 H-dexamethasone binding, measured by a new cytosol exchange assay utilizing molybdate plus dithiothreitol, in liver, kidney, skeletal muscle, spleen, lung, and heart tissue was significantly lower in treated than in control mice. The equilibrium dissociation constants were not significantly different, but the number of available binding sites in each tissue was reduced by endotoxin treatment. Phosphoenolpyruvate carboxykinase activity was significantly reduced in liver but not in kidney. Endotoxin treatment lowered glycogen content in liver but not in skeletal muscle. The reduction observed in the a form of liver glycogen synthase due to endotoxin was not seen in skeletal muscle glycogen synthase a. These data support the proposal that endotoxin or a mediator of its action inhibits systemic glucocorticoid action. The results also emphasize the central role of the liver in the metabolic disturbances of the endotoxin-treated mouse

  2. Adrenocorticotropic Hormone Secreting Pheochromocytoma Underlying Glucocorticoid Induced Pheochromocytoma Crisis

    Directory of Open Access Journals (Sweden)

    Gil A. Geva

    2018-01-01

    Full Text Available Context. Pheochromocytomas are hormone secreting tumors of the medulla of the adrenal glands found in 0.1–0.5% of patients with hypertension. The vast majority of pheochromocytomas secrete catecholamines, but they have been occasionally shown to also secrete interleukins, calcitonin, testosterone, and in rare cases adrenocorticotropic hormone. Pheochromocytoma crisis is a life threatening event in which high levels of catecholamines cause a systemic reaction leading to organ failure. Case Description. A 70-year-old man was admitted with acute myocardial ischemia following glucocorticoid administration as part of an endocrine workup for an adrenal mass. Cardiac catheterization disclosed patent coronary arteries and he was discharged. A year later he returned with similar angina-like chest pain. During hospitalization, he suffered additional events of chest pain, shortness of breath, and palpitations following administration of glucocorticoids as preparation for intravenous contrast administration. Throughout his admission, the patient demonstrated both signs of Cushing’s syndrome and high catecholamine levels. Following stabilization of vital parameters and serum electrolytes, the adrenal mass was resected surgically and was found to harbor an adrenocorticotropic hormone secreting pheochromocytoma. This is the first documented case of adrenocorticotropic hormone secreting pheochromocytoma complicated by glucocorticoid induced pheochromocytoma crisis. Conclusion. Care should be taken when administering high doses of glucocorticoids to patients with suspected pheochromocytoma, even in a patient with concomitant Cushing’s syndrome.

  3. Study of Running Stability in Side-Suspended HTS-PMG Maglev Circular Line System

    Science.gov (United States)

    Zhou, Dajin; Zhao, Lifeng; Li, Linbo; Cui, Chenyu; Hsieh, Chang-Chun; Zhang, Yong; Guo, Jianqiang; Zhao, Yong

    2017-07-01

    A research on stability of the side-suspended HTS-PMG maglev circular line system is carried out through simulation experiment. The results show that the maglev vehicle will gradually get close to the track surface during acceleration under the action of centrifugal force, leading to decay of guidance force and occurrence of vertical eccentric motion. In case of linear array of YBa2Cu3O7-x (YBCO) bulks, the guidance force will be changed with the decreasing of the levitation gap. It can be suppressed through the complex arrangement of YBCO bulks. Fortunately, triangle array of YBCO bulks can effectively keep the guidance force constant and realize stable running during accelerating process of the prototype vehicle. Based on the research on stability of side-suspended maglev vehicle, a side-suspended PMG circular test track with diameter of 6.5 m and circumference of 20.4 m is successfully designed and established, enabling the prototype vehicle to run stably at up to 82.5 km/h under open atmosphere (9.6 × 104 Pa).

  4. Integrated design and evaluation of biomass energy system taking into consideration demand side characteristics

    International Nuclear Information System (INIS)

    Ren, Hongbo; Zhou, Weisheng; Nakagami, Ken'ichi; Gao, Weijun

    2010-01-01

    In this paper, a linear programming model has been developed for the design and evaluation of biomass energy system, while taking into consideration demand side characteristics. The objective function to be minimized is the total annual cost of the energy system for a given customer equipped with a biomass combined cooling, heating and power (CCHP) plant, as well as a backup boiler fueled by city gas. The results obtained from the implementation of the model demonstrate the optimal system capacities that customers could employ given their electrical and thermal demands. As an illustrative example, an investigation addresses the optimal biomass CCHP system for a residential area located in Kitakyushu Science and Research Park, Japan. In addition, sensitivity analyses have been elaborated in order to show how the optimal solutions would vary due to changes of some key parameters including electricity and city gas tariffs, biogas price, electricity buy-back price, as well as carbon tax rate. (author)

  5. A system design of data acquisition and processing for side-scatter lidar

    Science.gov (United States)

    Zhang, ZhanYe; Xie, ChenBo; Wang, ZhenZhu; Kuang, ZhiQiang; Deng, Qian; Tao, ZongMing; Liu, Dong; Wang, Yingjian

    2018-03-01

    A system for collecting data of Side-Scatter lidar based on Charge Coupled Device (CCD),is designed and implemented. The system of data acquisition is based on Microsoft. Net structure and the language of C# is used to call dynamic link library (DLL) of CCD for realization of the real-time data acquisition and processing. The software stores data as txt file for post data acquisition and analysis. The system has ability to operate CCD device in all-day, automatic, continuous and high frequency data acquisition and processing conditions, which will catch 24-hour information of the atmospheric scatter's light intensity and retrieve the spatial and temporal properties of aerosol particles. The experimental result shows that the system is convenient to observe the aerosol optical characteristics near surface.

  6. A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary.

    Science.gov (United States)

    Whirledge, Shannon; Cidlowski, John A

    2013-12-01

    In addition to the well-characterized role of the sex steroid receptors in regulating fertility and reproduction, reproductive events are also mediated by the hypothalamic-pituitary-adrenal axis in response to an individual's environment. Glucocorticoid secretion in response to stress contributes to the well-characterized suppression of the hypothalamic-pituitary-gonadal axis through central actions in the hypothalamus and pituitary. However, both animal and in vitro studies indicate that other components of the reproductive system are also regulated by glucocorticoids. Furthermore, in the absence of stress, it appears that homeostatic glucocorticoid signaling plays a significant role in reproduction and fertility in all tissues comprising the hypothalamic-pituitary-gonadal axis. Indeed, as central regulators of the immune response, glucocorticoids are uniquely poised to integrate an individual's infectious, inflammatory, stress, nutritional, and metabolic status through glucocorticoid receptor signaling in target tissues. Endocrine signaling between tissues regulating the immune and stress response and those determining reproductive status provides an evolutionary advantage, facilitating the trade-off between reproductive investment and offspring fitness. This review focuses on the actions of glucocorticoids in tissues important for fertility and reproduction, highlighting recent studies that show glucocorticoid signaling plays a significant role throughout the hypothalamic-pituitary-gonadal axis and characterizing these effects as permissive or inhibitory in terms of facilitating reproductive success.

  7. A System Architecture for Autonomous Demand Side Load Management in Smart Buildings

    DEFF Research Database (Denmark)

    Costanzo, Giuseppe Tommaso; Zhu, Guchuan; Anjos, Miguel F.

    2012-01-01

    This paper presents a system architecture for load management in smart buildings which enables autonomous demand side load management in the smart grid. Being of a layered structure composed of three main modules for admission control, load balancing, and demand response management...... in multiple time-scales and allows seamless integration of diverse techniques for online operation control, optimal scheduling, and dynamic pricing. The design of a home energy manager based on this architecture is illustrated and the simulation results with Matlab/Simulink confirm the viability...

  8. Impact of jammer side information on the performance of anti-jam systems

    Science.gov (United States)

    Lim, Samuel

    1992-03-01

    The Chernoff bound parameter, D, provides a performance measure for all coded communication systems. D can be used to determine upper-bounds on bit error probabilities (BEPs) of Viterbi decoded convolutional codes. The impact on BEP bounds of channel measurements that provide additional side information can also be evaluated with D. This memo documents the results of a Chernoff bound parameter evaluation in optimum partial-band noise jamming (OPBNJ) for both BPSK and DPSK modulation schemes. Hard and soft quantized receivers, with and without jammer side information (JSI), were examined. The results of this analysis indicate that JSI does improve decoding performance. However, a knowledge of jammer presence alone achieves a performance level comparable to soft decision decoding with perfect JSI. Furthermore, performance degradation due to the lack of JSI can be compensated for by increasing the number of levels of quantization. Therefore, an anti-jam system without JSI can be made to perform almost as well as a system with JSI.

  9. Managing Sustainable Demand-side Infrastructure for Power System Ancillary Services

    Science.gov (United States)

    Parkinson, Simon Christopher

    Widespread access to renewable electricity is seen as a viable method to mitigate carbon emissions, although problematic are the issues associated with the integration of the generation systems within current power system configurations. Wind power plants are the primary large-scale renewable generation technology applied globally, but display considerable short-term supply variability that is difficult to predict. Power systems are currently not designed to operate under these conditions, and results in the need to increase operating reserve in order to guarantee stability. Often, operating conventional generation as reserve is both technically and economically inefficient, which can overshadow positive benefits associated with renewable energy exploitation. The purpose of this thesis is to introduce and assess an alternative method of enhancing power system operations through the control of electric loads. In particular, this thesis focuses on managing highly-distributed sustainable demand-side infrastructure, in the form of heat pumps, electric vehicles, and electrolyzers, as dispatchable short-term energy balancing resources. The main contribution of the thesis is an optimal control strategy capable of simultaneously balancing grid- and demand-side objectives. The viability of the load control strategy is assessed through model-based simulations that explicitly track end-use functionality of responsive devices within a power systems analysis typically implemented to observe the effects of integrated wind energy systems. Results indicate that there is great potential for the proposed method to displace the need for increased reserve capacity in systems considering a high penetration of wind energy, thereby allowing conventional generation to operate more efficiently and avoid the need for possible capacity expansions.

  10. Optimal glucocorticoid replacement in adrenal insufficiency.

    Science.gov (United States)

    Øksnes, Marianne; Ross, Richard; Løvås, Kristian

    2015-01-01

    Adrenal insufficiency (glucocorticoid deficiency) comprises a group of rare diseases, including primary adrenal insufficiency, secondary adrenal insufficiency and congenital adrenal hyperplasia. Lifesaving glucocorticoid therapy was introduced over 60 years ago, but since then a number of advances in treatment have taken place. Specifically, little is known about short- and long-term treatment effects, and morbidity and mortality. Over the past decade, systematic cohort and registry studies have described reduced health-related quality of life, an unfavourable metabolic profile and increased mortality in patients with adrenal insufficiency, which may relate to unphysiological glucocorticoid replacement. This has led to the development of new modes of replacement that aim to mimic normal glucocorticoid physiology. Here, evidence for the inadequacy of conventional glucocorticoid therapy and recent developments in treatment are reviewed, with an emphasis on primary adrenal insufficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Modeling and Simulation of Generator Side Converter of Doubly Fed Induction Generator-Based Wind Power Generation System

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Blaabjerg, Frede

    2010-01-01

    A real wind power generation system is given in this paper. SVM control strategy and vector control is applied for generator side converter and doubly fed induction generator respectively. First the mathematical models of the wind turbine rotor, drive train, generator side converter are described...

  12. Divergent effects of endogenous and exogenous glucocorticoid-induced leucine zipper in animal models of inflammation and arthritis

    NARCIS (Netherlands)

    Ngo, Devi; Beaulieu, Elaine; Gu, Ran; Leaney, Alexandra; Santos, Leilani; Fan, Huapeng; Yang, Yuanhang; Kao, Wenping; Xu, Jiake; Escriou, Virginie; Loiler, Scott; Vervoordeldonk, Margriet J.; Morand, Eric F.

    2013-01-01

    Glucocorticoid-induced leucine zipper (GILZ) has effects on inflammatory pathways that suggest it to be a key inhibitory regulator of the immune system, and its expression is exquisitely sensitive to induction by glucocorticoids. We undertook this study to test our hypothesis that GILZ deficiency

  13. Two sides of the same coin? The (techno)epistemic cultures of systems and synthetic biology.

    Science.gov (United States)

    Kastenhofer, Karen

    2013-06-01

    Systems and synthetic biology both emerged around the turn of this century as labels for new research approaches. Although their disciplinary status as well as their relation to each other is rarely discussed in depth, now and again the idea is invoked that both approaches represent 'two sides of the same coin'. The following paper focuses on this general notion and compares it with empirical findings concerning the epistemic cultures prevalent in the two contexts. Drawing on interviews with researchers from both fields, on participatory observation in conferences and courses and on documentary analysis, this paper delineates differences and similarities, incompatibilities and blurred boundaries. By reconstructing systems and synthetic biology's epistemic cultures, this paper argues that they represent two 'communities of vision', encompassing heterogeneous practices. Understanding the relation of the respective visions of understanding nature and engineering life is seen as indispensible for the characterisation of (techno)science in more general terms. Depending on the conceptualisation of understanding and construction (or: science and engineering), related practices such as in silico modelling for enhancing understanding or enabling engineering can either be seen as incommensurable or 'two sides of one coin'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. The Application of Stationary VOC-PR with PLL for Grid side Converter-based Wind Power Generation System

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Li, Lijuan

    2010-01-01

    Voltage oriented control PR is combined with space vector modulation and phase locked loop to control the grid side converter in wind power generation system in this paper. First the mathematical models of grid side converter and LCL filter as well as grid are given. Then the control strategy...... of grid side converter-based wind power generation system is given in detail. Finally the simulation model consisting of the grid side converter wind power generation system is set up. The simulation results have verified that the control strategy is feasible to be used for control of gird currents......, active power, reactive power and DC-link voltage in wind power generation system. It has laid a good basis for the real system development....

  15. Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes.

    Science.gov (United States)

    Vyas, Sheela; Maatouk, Layal

    2013-12-01

    Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high affinity mineralocorticoid receptor (MR) and low affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is only activated when GC levels rise as during circadian peak and in response to stress. Numerous recent studies have yielded important and new insights on the mechanisms concerning pulsatile secretory pattern of GCs as well as various processes that tightly control their synthesis via hypothalamic-pituitary-adrenal (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary, respectively. GR modulates neuronal functions and viability through both genomic and non-genomic actions, and importantly its transcriptional regulatory activity is tightly locked with GC secretory pattern. There is increasing evidence pointing to involvement of GC-GR in neurodegenerative disorders. Patients with Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol levels suggesting changes occurring in controls of HPA axis. In experimental models of these diseases, chronic stress or GC treatment was found to exacerbate both the clinical symptoms and neurodegenerative processes. However, recent evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any potential therapeutic strategies in these neurodegenerative diseases we need to understand the precise modifications both in HPA axis and in GR activity and find ways to harness their protective actions.

  16. Real-Time Load-Side Control of Electric Power Systems

    Science.gov (United States)

    Zhao, Changhong

    Two trends are emerging from modern electric power systems: the growth of renewable (e.g., solar and wind) generation, and the integration of information technologies and advanced power electronics. The former introduces large, rapid, and random fluctuations in power supply, demand, frequency, and voltage, which become a major challenge for real-time operation of power systems. The latter creates a tremendous number of controllable intelligent endpoints such as smart buildings and appliances, electric vehicles, energy storage devices, and power electronic devices that can sense, compute, communicate, and actuate. Most of these endpoints are distributed on the load side of power systems, in contrast to traditional control resources such as centralized bulk generators. This thesis focuses on controlling power systems in real time, using these load side resources. Specifically, it studies two problems. (1) Distributed load-side frequency control: We establish a mathematical framework to design distributed frequency control algorithms for flexible electric loads. In this framework, we formulate a category of optimization problems, called optimal load control (OLC), to incorporate the goals of frequency control, such as balancing power supply and demand, restoring frequency to its nominal value, restoring inter-area power flows, etc., in a way that minimizes total disutility for the loads to participate in frequency control by deviating from their nominal power usage. By exploiting distributed algorithms to solve OLC and analyzing convergence of these algorithms, we design distributed load-side controllers and prove stability of closed-loop power systems governed by these controllers. This general framework is adapted and applied to different types of power systems described by different models, or to achieve different levels of control goals under different operation scenarios. We first consider a dynamically coherent power system which can be equivalently modeled with

  17. Glucocorticoid effects on object recognition memory require training-associated emotional arousal

    OpenAIRE

    Okuda, Shoki; Roozendaal, Benno; McGaugh, James L.

    2004-01-01

    Considerable evidence implicates glucocorticoid hormones in the regulation of memory consolidation and memory retrieval. The present experiments investigated whether the influence of these hormones on memory depends on the level of emotional arousal induced by the training experience. We investigated this issue in male Sprague–Dawley rats by examining the effects of immediate posttraining systemic injections of the glucocorticoid corticosterone on object recognition memory under two condition...

  18. [Glucocorticoid therapy: what is the information sought by patients? Traffic analysis of the website cortisone-info.fr].

    Science.gov (United States)

    Poisson, J; Six, M; Morin, C; Fardet, L

    2013-05-01

    About 1% of the general population are receiving systemic glucocorticoids. The information about this treatment sought by patients is unknown. The website www.cortisone-info.fr aims to provide therapeutic information about glucocorticoids and glucocorticoid therapy. It was posted on January 16, 2012. The information available on the website is documented and based on the recent medical literature. The website is made of 43 pages divided into five main sections (generalities about glucocorticoids, adverse events, measures associated with glucocorticoid therapy, discontinuation of glucocorticoids and, situations requiring attention). The website traffic between February 1st, 2012 and January 4, 2013 was analyzed using Google Analytics. During the study period, the website was visited by 67,496 people (average number of visitors per day: 33 in February 2012, 326 in December 2012). The number of page views was 230,496 or an average of 3.5 pages per visitor. Of these 230,496 page views, 145,431 (63.1%) were related to adverse events and 37,722 (16.4%) were related to generalities about glucocorticoids (e.g., what is cortisone? For which disease? How does it work?). Information particularly sought by visitors was related to the diet to follow during glucocorticoid therapy (page accessed 11,946 times), data about what cortisone is (page accessed 11,829 times) and the effects of glucocorticoids on weight (page accessed 10,442 times). Knowledge of glucocorticoid-treated patients' expectations may help physicians to optimize information they give, thereby helping to reduce patients' concerns about glucocorticoids and to improve adherence to the treatment. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. Deposition of intranasal glucocorticoids--preliminary study.

    Science.gov (United States)

    Rapiejko, Piotr; Sosnowski, Tomasz R; Sova, Jarosław; Jurkiewicz, Dariusz

    2015-01-01

    Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this

  20. Domestic demand-side management (DSM): Role of heat pumps and thermal energy storage (TES) systems

    International Nuclear Information System (INIS)

    Arteconi, A.; Hewitt, N.J.; Polonara, F.

    2013-01-01

    Heat pumps are seen as a promising technology for load management in the built environment, in combination with the smart grid concept. They can be coupled with thermal energy storage (TES) systems to shift electrical loads from high-peak to off-peak hours, thus serving as a powerful tool in demand-side management (DSM). This paper analyzes heat pumps with radiators or underfloor heating distribution systems coupled with TES with a view to showing how a heat pump system behaves and how it influences the building occupants' thermal comfort under a DSM strategy designed to flatten the shape of the electricity load curve by switching off the heat pump during peak hours (16:00–19:00). The reference scenario for the analysis was Northern Ireland (UK). The results showed that the heat pump is a good tool for the purposes of DSM, also thanks to the use of TES systems, in particular with heating distribution systems that have a low thermal inertia, e.g. radiators. It proved possible to achieve a good control of the indoor temperature, even if the heat pump was turned off for 3 h, and to reduce the electricity bill if a “time of use” tariff structure was adopted. -- Highlights: ► Heat pump heating systems with thermal energy storage are considered. ► System behavior is investigated during a DSM strategy for reducing peak energy demand. ► Heat pump heating systems demonstrate to be able to have an active role in DSM programs. ► A TES system must be coupled with the heat pump in presence of low thermal inertia heating distribution systems. ► Central role played by incentives schemes to promote this technology

  1. Benefits of remote real-time side-effect monitoring systems for patients receiving cancer treatment.

    Science.gov (United States)

    Kofoed, Sarah; Breen, Sibilah; Gough, Karla; Aranda, Sanchia

    2012-03-05

    In Australia, the incidence of cancer diagnoses is rising along with an aging population. Cancer treatments, such as chemotherapy, are increasingly being provided in the ambulatory care setting. Cancer treatments are commonly associated with distressing and serious side-effects and patients often struggle to manage these themselves without specialized real-time support. Unlike chronic disease populations, few systems for the remote real-time monitoring of cancer patients have been reported. However, several prototype systems have been developed and have received favorable reports. This review aimed to identify and detail systems that reported statistical analyses of changes in patient clinical outcomes, health care system usage or health economic analyses. Five papers were identified that met these criteria. There was wide variation in the design of the monitoring systems in terms of data input method, clinician alerting and response, groups of patients targeted and clinical outcomes measured. The majority of studies had significant methodological weaknesses. These included no control group comparisons, small sample sizes, poor documentation of clinical interventions or measures of adherence to the monitoring systems. In spite of the limitations, promising results emerged in terms of improved clinical outcomes (e.g. pain, depression, fatigue). Health care system usage was assessed in two papers with inconsistent results. No studies included health economic analyses. The diversity in systems described, outcomes measured and methodological issues all limited between-study comparisons. Given the acceptability of remote monitoring and the promising outcomes from the few studies analyzing patient or health care system outcomes, future research is needed to rigorously trial these systems to enable greater patient support and safety in the ambulatory setting.

  2. How does stress affect human being—a molecular dynamic simulation study on cortisol and its glucocorticoid receptor

    Directory of Open Access Journals (Sweden)

    Dan Zhang

    2017-03-01

    Full Text Available Stress can be either positive or negative to human beings. Under stressful conditions, the mental and physical conditions of human can be affected. There exists certain relation between stress and illness. The cortisol and other glucocorticoids bind to the same receptor, which is called glucocorticoid receptor. Some evidences indicated that cortisol molecule binding to its glucocorticoid receptor was necessary for the stress response. Up to now, the structure–function relationships between cortisol molecule and its glucocorticoid receptor have not been deliberated from the atomic-level. In order to get a detailed understanding of the structure–function relationships between the cortisol molecule and glucocorticoids receptor, we have carried out molecular dynamic (MD simulations on glucocorticoid receptor (Apo system and cortisol with its glucocorticoid receptor complex (HCY system. On the basis of molecular dynamic simulations, a couple of key residues were identified, which were crucial for the binding of cortisol molecule. The results of binding free energy calculations are in good agreement with the experiment data. Our research gives clear insights from atomic-level into the structural–functional aspects of cortisol molecule and its glucocorticoid receptor, and also provides valuable information for the design of drug which can treat stress related illnesses.

  3. Study on Heat Transfer Characteristics of One Side Heated Vertical Channel Applied as Vessel Cooling System

    International Nuclear Information System (INIS)

    Kuriyama, Shinji; Takeda, Tetsuaki; Funatani, Shumpei

    2014-01-01

    The inherent properties of the Very-High-Temperature Reactor facilitate the design of the VHTR with high degree of passive safe performances, compared to other type of reactors. However; it is still not clear if the VHTR can maintain a passive safe function during the severe accident, or what would be a design criterion to guarantee the VHTR with the high degree of passive safe performances during the accidents. In the Very High Temperature Reactor (VHTR) which is a next generation nuclear reactor system, ceramics and graphite are used as a fuel coating material and a core structural material, respectively. Even if the depressurization accident occurs and the reactor power goes up instantly, the temperature of the core will change slowly. This is because the thermal capacity of the core is so large. Therefore, the VHTR system can passively remove the decay heat of the core by natural convection and radiation from the surface of the reactor pressure vessel (RPV). This study is to develop the passive cooling system for the VHTR using the vertical channel inserting porous materials. The objective of this study is to investigate heat transfer characteristics of natural convection of a one-side heated vertical channel inserting the porous materials with high porosity. In order to obtain the heat transfer and fluid flow characteristics of a vertical channel inserting porous material, we have also carried out a numerical analysis using the commercial CFD code. From the analytical results obtained in the natural convection cooling, an amount of removed heat enhanced inserting the copper wire. It was found that an amount of removed heat inserting the copper wire (porosity = 0.9972) was about 10% higher than that without the copper wire. This paper describes a thermal performance of the one-side heated vertical channel inserting copper wire with high porosity. (author)

  4. Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity

    Directory of Open Access Journals (Sweden)

    Burnsides C

    2012-08-01

    Full Text Available Christopher Burnsides,1,* Jacqueline Corry,1,* Jacob Alexander,1 Catherine Balint,1 David Cosmar,1 Gary Phillips,2 Jeanette I Webster Marketon1,31Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Center for Biostatistics, 3Institute for Behavioral Medicine Research, Wexner Medical Center at The Ohio State University, Columbus, OH, USA*JC and CB have equally contributed to this workPurpose: Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity.Patients and methods: Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay.Results: We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNFα are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC50 and IC50 concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day.Conclusion: In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.Keywords: glucocorticoid responsiveness, gene regulation, nuclear receptor, GILZ, FKBP51, cytokines

  5. Glucocorticoid and cytokine crosstalk: Feedback, feedforward, and co-regulatory interactions determine repression or resistance.

    Science.gov (United States)

    Newton, Robert; Shah, Suharsh; Altonsy, Mohammed O; Gerber, Antony N

    2017-04-28

    Inflammatory signals induce feedback and feedforward systems that provide temporal control. Although glucocorticoids can repress inflammatory gene expression, glucocorticoid receptor recruitment increases expression of negative feedback and feedforward regulators, including the phosphatase, DUSP1, the ubiquitin-modifying enzyme, TNFAIP3, or the mRNA-destabilizing protein, ZFP36. Moreover, glucocorticoid receptor cooperativity with factors, including nuclear factor-κB (NF-κB), may enhance regulator expression to promote repression. Conversely, MAPKs, which are inhibited by glucocorticoids, provide feedforward control to limit expression of the transcription factor IRF1, and the chemokine, CXCL10. We propose that modulation of feedback and feedforward control can determine repression or resistance of inflammatory gene expression toglucocorticoid. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Impacts of Demand-Side Management on Electrical Power Systems: A Review

    Directory of Open Access Journals (Sweden)

    Hussein Jumma Jabir

    2018-04-01

    Full Text Available Electricity demand has grown over the past few years and will continue to grow in the future. The increase in electricity demand is mainly due to industrialization and the shift from a conventional to a smart-grid paradigm. The number of microgrids, renewable energy sources, plug-in electric vehicles and energy storage systems have also risen in recent years. As a result, future electricity grids have to be revamped and adapt to increasing load levels. Thus, new complications associated with future electrical power systems and technologies must be considered. Demand-side management (DSM programs offer promising solutions to these issues and can considerably improve the reliability and financial performances of electrical power systems. This paper presents a review of various initiatives, techniques, impacts and recent developments of the DSM of electrical power systems. The potential benefits derived by implementing DSM in electrical power networks are presented. An extensive literature survey on the impacts of DSM on the reliability of electrical power systems is also provided for the first time. The research gaps within the broad field of DSM are also identified to provide directions for future work.

  7. Circumvention of glucocorticoid resistance in childhood leukemia.

    Science.gov (United States)

    Haarman, E G; Kaspers, G J L; Pieters, R; Rottier, M M A; Veerman, A J P

    2008-09-01

    In this study, we determined if in vitro resistance to prednisolone and dexamethasone could be circumvented by cortivazol or methylprednisolone, or reversed by meta-iodobenzylguanidine in pediatric lymphoblastic and myeloid leukemia. As there were strong correlations between the LC50 values (drug concentration inducing 50% leukemic cell kill, LCK) of the different glucocorticoids and median prednisolone/methylprednisolone, prednisolone/dexamethasone and prednisolone/cortivazol LC50 ratios did not differ between the leukemia subtypes, we conclude that none of the glucocorticoids had preferential anti-leukemic activity. Meta-iodobenzylguanidine however, partially reversed glucocorticoid resistance in 19% of the lymphoblastic leukemia samples.

  8. Side Effects

    Science.gov (United States)

    Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

  9. Cannabinoids and glucocorticoids modulate emotional memory after stress.

    Science.gov (United States)

    Akirav, Irit

    2013-12-01

    Bidirectional and functional relationships between glucocorticoids and the endocannabinoid system have been demonstrated. Here, I review the interaction between the endocannabinoid and glucocorticoid/stress systems. Specifically, stress is known to produce rapid changes in endocannabinoid signaling in stress-responsive brain regions. In turn, the endocannabinoid system plays an important role in the downregulation and habituation of hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to stress. Glucocorticoids also recruit the endocannabinoid system to exert rapid negative feedback control of the HPA axis during stress. It became increasingly clear, however, that cannabinoid CB1 receptors are also abundantly expressed in the basolateral amygdala (BLA) and other limbic regions where they modulate emotional arousal effects on memory. Enhancing cannabinoids signaling using exogenous CB1 receptor agonists prevent the effects of acute stress on emotional memory. I propose a model suggesting that the ameliorating effects of exogenously administered cannabinoids on emotional learning after acute stress are mediated by the decrease in the activity of the HPA axis via GABAergic mechanisms in the amygdala. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. The Electronics and Data Acquisition System of the DarkSide Dark Matter Search

    Energy Technology Data Exchange (ETDEWEB)

    Agnes, P.; et al.

    2014-12-09

    It is generally inferred from astronomical measurements that Dark Matter (DM) comprises approximately 27\\% of the energy-density of the universe. If DM is a subatomic particle, a possible candidate is a Weakly Interacting Massive Particle (WIMP), and the DarkSide-50 (DS) experiment is a direct search for evidence of WIMP-nuclear collisions. DS is located underground at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, and consists of three active, embedded components; an outer water veto (CTF), a liquid scintillator veto (LSV), and a liquid argon (LAr) time projection chamber (TPC). This paper describes the data acquisition and electronic systems of the DS detectors, designed to detect the residual ionization from such collisions.

  11. An innovative strategy for secondary side system lay-up using film-forming amines

    International Nuclear Information System (INIS)

    Ramminger, U.; Drexler, A.; Fandrich, J.

    2012-01-01

    The major safety function of steam generators (SG) in pressurized reactors is well known as acting as a barrier between the radioactive primary side and the non-radioactive secondary side. The main reason for SG tube failure is known to be the accumulation of deposits contributing to formation of local aggressive conditions. Consequently the SG has to be kept as clean as possible and the corrosion product transport into the SG has to be minimized. In order to reach this target, plant operators are making worldwide huge efforts to protect plant systems against corrosion during standstill and outages. Especially in case of large component replacements campaigns like steam generator or fuel channel replacements which are linked to prolonged outages lay-up strategies become important. The use of surface active agents like film-forming amines (FFA) has become very popular in the fossil power plant sector, showing a decrease of corrosion product generation by improving the surface conditions. The adherent non wettable film built by FFA acts as a shield that limits the access of water and hydrated species to the metal or metal oxide surface. This barrier lowers the corrosion rate by inhibiting the mass transfer between surface and solution. The hydrocarbon chain imparts a hydrophobic character while the amine group bounds to the metal. Advantages of the FFA application for lay-up: Significant reduction of lay-up efforts; Long-term stability of the protective film even in aggressive environmental conditions; No influence on existing oxide layers; No negative influence on plant operation and performance; No environmental hazards of the waste water after system lay-up. Nevertheless application of film-forming amines are applied in fossil fired power plants, the requirement of nuclear power reactors are more ambitious. This paper deals with a possible lay-up application scenario in pressurized heavy water reactors. The proposed lay-up strategy will consider AREVA

  12. Joint Planning Of Energy Storage and Transmission Considering Wind-Storage Combined System and Demand Side Response

    Science.gov (United States)

    Huang, Y.; Liu, B. Z.; Wang, K. Y.; Ai, X.

    2017-12-01

    In response to the new requirements of the operation mode of wind-storage combined system and demand side response for transmission network planning, this paper presents a joint planning of energy storage and transmission considering wind-storage combined system and demand side response. Firstly, the charge-discharge strategy of energy storage system equipped at the outlet of wind farm and demand side response strategy are analysed to achieve the best comprehensive benefits through the coordination of the two. Secondly, in the general transmission network planning model with wind power, both energy storage cost and demand side response cost are added to the objective function. Not only energy storage operation constraints and but also demand side response constraints are introduced into the constraint condition. Based on the classical formulation of TEP, a new formulation is developed considering the simultaneous addition of the charge-discharge strategy of energy storage system equipped at the outlet of the wind farm and demand side response strategy, which belongs to a typical mixed integer linear programming model that can be solved by mature optimization software. The case study based on the Garver-6 bus system shows that the validity of the proposed model is verified by comparison with general transmission network planning model. Furthermore, the results demonstrate that the joint planning model can gain more economic benefits through setting up different cases.

  13. Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing’s syndrome: cohort study

    Science.gov (United States)

    Petersen, Irene; Nazareth, Irwin

    2012-01-01

    Objective To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing’s syndrome during treatment with glucocorticoids. Design Cohort study. Setting 424 UK general practices contributing to The Health Improvement Network database. Participants People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome (n=547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing’s syndrome (n=3231) and those not prescribed systemic glucocorticoids (n=3282). Main outcome measures Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing’s syndrome or after a randomly selected date, and association between iatrogenic Cushing’s syndrome and risk of cardiovascular events. Results 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n=177, heart failure n=101, ischaemic stroke n=63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing’s syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing’s syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4

  14. Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study.

    Science.gov (United States)

    Fardet, Laurence; Petersen, Irene; Nazareth, Irwin

    2012-07-30

    To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing's syndrome during treatment with glucocorticoids. Cohort study. 424 UK general practices contributing to The Health Improvement Network database. People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome (n = 547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing's syndrome (n = 3231) and those not prescribed systemic glucocorticoids (n = 3282). Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing's syndrome or after a randomly selected date, and association between iatrogenic Cushing's syndrome and risk of cardiovascular events. 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n = 177, heart failure n = 101, ischaemic stroke n = 63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing's syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing's syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing's syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the group prescribed glucocorticoids and with

  15. Bilateral metal stents for hilar biliary obstruction using a 6Fr delivery system: outcomes following bilateral and side-by-side stent deployment.

    Science.gov (United States)

    Law, Ryan; Baron, Todd H

    2013-09-01

    Controversy exists on optimal endoscopic management for palliation of malignant hilar obstruction, with advocates for metal "side-by-side" (SBS) and "stent-in-stent" (SIS) techniques. We sought to evaluate the technical feasibility, efficacy, and outcomes of bilateral biliary self-expanding metal stents (SEMS) for treatment of malignant hilar obstruction using a stent with a 6Fr delivery system. This was a single-center, retrospective review of all patients who underwent bilateral placement of Zilver® biliary SEMS for malignant hilar obstruction from January 2010 to August 2012. Patients underwent endoscopic retrograde cholangiopancreatography with placement of stents using either the SIS or SBS stent techniques. Twenty-four patients (19 men, mean age 63 years) underwent bilateral stenting for malignant hilar obstruction during the study period. Seventeen and seven patients underwent the SBS and SIS technique, respectively. Cholangiocarcinoma (n=14) was the most common cause of hilar obstruction. Initial technical success was achieved in 24/24 (100%) of patients; however, 12 (50%) patients required re-intervention during the study period (median 98 days). Comparison of the SBS and SIS groups revealed no statistical difference with respect to need for re-intervention (P=0.31), successful re-intervention (P=0.60), or procedural length (P=0.89). Use of bilateral Zilver® SEMS in either the SBS or SIS configuration is safe, technically feasible, and effective for drainage of malignant hilar obstruction; however, duration of stent patency and procedure-free survival remain variable.

  16. Clinical Evaluation of a Dual-Side Readout Technique Computed Radiography System in Chest Radiography of Premature Neonates

    International Nuclear Information System (INIS)

    Carlander, A.; Hansson, J.; Soederberg, J.; Steneryd, K.; Baath, M.

    2008-01-01

    Background: Recently, the dual-side readout technique has been introduced in computed radiography, leading to an increase in detective quantum efficiency (DQE) compared with the single-side readout technique. Purpose: To evaluate if the increase in DQE with the dual-side readout technique results in a higher clinical image quality in chest radiography of premature neonates at no increase in radiation dose. Material and Methods: Twenty-four chest radiographs of premature neonates were collected from both a single-side readout technique system and a double-side readout technique system. The images were processed in the same image-processing station in order for the comparison to be only dependent on the difference in readout technique. Five radiologists rated the fulfillment of four image quality criteria, which were based on important anatomical landmarks. The given ratings were analyzed using visual grading characteristics (VGC) analysis. Results: The VGC analysis showed that the reproduction of the carina with the main bronchi and the thoracic vertebrae behind the heart was better with the dual-side readout technique, whereas no significant difference for the reproduction of the central vessels or the peripheral vessels could be observed. Conclusions: The results indicate that the higher DQE of the dual-side readout technique leads to higher clinical image quality in chest radiography of premature neonates at no increase in radiation dose. Keywords: Digital radiography; lung; observer performance; pediatrics; thorax

  17. Quadrupling Inhaled Glucocorticoid Dose to Abort Asthma Exacerbations.

    Science.gov (United States)

    McKeever, Tricia; Mortimer, Kevin; Wilson, Andrew; Walker, Samantha; Brightling, Christopher; Skeggs, Andrew; Pavord, Ian; Price, David; Duley, Lelia; Thomas, Mike; Bradshaw, Lucy; Higgins, Bernard; Haydock, Rebecca; Mitchell, Eleanor; Devereux, Graham; Harrison, Timothy

    2018-03-08

    Asthma exacerbations are frightening for patients and are occasionally fatal. We tested the concept that a plan for patients to manage their asthma (self-management plan), which included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate, would reduce the incidence of severe asthma exacerbations among adults and adolescents with asthma. We conducted a pragmatic, unblinded, randomized trial involving adults and adolescents with asthma who were receiving inhaled glucocorticoids, with or without add-on therapy, and who had had at least one exacerbation in the previous 12 months. We compared a self-management plan that included an increase in the dose of inhaled glucocorticoids by a factor of 4 (quadrupling group) with the same plan without such an increase (non-quadrupling group), over a period of 12 months. The primary outcome was the time to a first severe asthma exacerbation, defined as treatment with systemic glucocorticoids or an unscheduled health care consultation for asthma. A total of 1922 participants underwent randomization, of whom 1871 were included in the primary analysis. The number of participants who had a severe asthma exacerbation in the year after randomization was 420 (45%) in the quadrupling group as compared with 484 (52%) in the non-quadrupling group, with an adjusted hazard ratio for the time to a first severe exacerbation of 0.81 (95% confidence interval, 0.71 to 0.92; P=0.002). The rate of adverse effects, which were related primarily to local effects of inhaled glucocorticoids, was higher in the quadrupling group than in the non-quadrupling group. In this trial involving adults and adolescents with asthma, a personalized self-management plan that included a temporary quadrupling of the dose of inhaled glucocorticoids when asthma control started to deteriorate resulted in fewer severe asthma exacerbations than a plan in which the dose was not increased. (Funded by the Health Technology

  18. Glucocorticoids are ineffective in alcoholic hepatitis

    DEFF Research Database (Denmark)

    Christensen, E; Gluud, C

    1995-01-01

    The aim of this study was to perform a meta-analysis of controlled clinical trials of glucocorticoid treatment in clinical alcoholic hepatitis, adjusting for prognostic variables and their possible interaction with therapy, because these trials have given appreciably different results. Weighted...... logistic regression analysis was applied using the summarised descriptive data (for example, % with encephalopathy, mean bilirubin value) of the treatment and control groups of 12 controlled trials that gave this information. Despite evidence of publication bias favouring glucocorticoid treatment, its...... overall effect on mortality was not statistically significant (p = 0.20)--the relative risk (steroid/control) was 0.78 (95% confidence intervals 0.51, 1.18). There was indication of interaction between glucocorticoid therapy and gender, but not encephalopathy. Thus, the effect of glucocorticoid treatment...

  19. Molecular mechanisms of glucocorticoid receptor signaling

    Directory of Open Access Journals (Sweden)

    Marta Labeur

    2010-10-01

    Full Text Available This review highlights the most recent findings on the molecular mechanisms of the glucocorticoid receptor (GR. Most effects of glucocorticoids are mediated by the intracellular GR which is present in almost every tissue and controls transcriptional activation via direct and indirect mechanisms. Nevertheless the glucocorticoid responses are tissue -and gene- specific. GR associates selectively with corticosteroid ligands produced in the adrenal gland in response to changes of humoral homeostasis. Ligand interaction with GR promotes either GR binding to genomic glucocorticoid response elements, in turn modulating gene transcription, or interaction of GR monomers with other transcription factors activated by other signalling pathways leading to transrepression. The GR regulates a broad spectrum of physiological functions, including cell differentiation, metabolism and inflammatory responses. Thus, disruption or dysregulation of GR function will result in severe impairments in the maintenance of homeostasis and the control of adaptation to stress.

  20. Review: Marine Seismic And Side-Scan Sonar Investigations For Seabed Identification With Sonar System

    Directory of Open Access Journals (Sweden)

    Muhammad Zainuddin Lubis

    2017-06-01

    Full Text Available Marine seismic reflection data have been collected for decades and since the mid-to late- 1980s much of this data is positioned relatively accurately. Marine geophysical acquisition of data is a very expensive process with the rates regularly ship through dozens of thousands of euros per day. Acquisition of seismic profiles has the position is determined by a DGPS system and navigation is performed by Hypack and Maxview software that also gives all the offsets for the equipment employed in the survey. Examples of some projects will be described in terms of the project goals and the geophysical equipment selected for each survey and specific geophysical systems according to with the scope of work. For amplitude side scan sonar image, and in the multi-frequency system, color, becoming a significant properties of the sea floor, the effect of which is a bully needs to be fixed. The main confounding effect is due to absorption of water; geometric spread; shape beam sonar function (combined transmit-receive sonar beam intensity as a function of tilt angle obtained in this sonar reference frame; sonar vehicle roll; form and function of the seabed backscatter (proportion incident on the seabed backscattered signal to sonar as a function of the angle of incidence relative to the sea floor; and the slope of the seabed. The different angles of view are generated by the translation of the sonar, because of the discrete steps involved by the sequential pings, the angular sampling of the bottom.

  1. Chronic Stress and Glucocorticoids: From Neuronal Plasticity to Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Sheela Vyas

    2016-01-01

    Full Text Available Stress and stress hormones, glucocorticoids (GCs, exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer’s (AD and Parkinson’s (PD diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.

  2. Do the interactions between glucocorticoids and sex hormones regulate the development of the Metabolic Syndrome?

    Directory of Open Access Journals (Sweden)

    Marià eAlemany

    2012-02-01

    Full Text Available The metabolic syndrome is basically a maturity-onset disease. Typically, its manifestations begin to flourish years after the initial dietary or environmental aggression began. Since most hormonal, metabolic or defense responses are practically immediate, the procrastinated response don't seem justified. Only in childhood, the damages of the metabolic syndrome appear with minimal delay. Sex affects the incidence of the metabolic syndrome, but this is more an effect of timing than absolute gender differences, females holding better than males up to menopause, when the differences between sexes tend to disappear. The metabolic syndrome is related to an immune response, countered by a permanent increase in glucocorticoids, which keep the immune system at bay but also induce insulin resistance, alter the lipid metabolism, favor fat deposition, mobilize protein and decrease androgen synthesis. Androgens limit the operation of glucocorticoids, which is also partly blocked by estrogens, since they decrease inflammation (which enhances glucocorticoid release. These facts suggest that the appearance of the metabolic syndrome symptoms depends on the strength (i.e. levels of androgens and estrogens. The predominance of glucocorticoids and the full manifestation of the syndrome in men are favored by decreased androgen activity. Low androgens can be found in infancy, maturity, advanced age, or because of their inhibition by glucocorticoids (inflammation, stress, medical treatment. Estrogens decrease inflammation and reduce the glucocorticoid response. Low estrogen (infancy, menopause again allow the predominance of glucocorticoids and the manifestation of the metabolic syndrome. It is postulated that the equilibrium between sex hormones and glucocorticoids may be a critical element in the timing of the manifestation of metabolic syndrome-related pathologies.

  3. Dual-sided reading versus single-sided reading: comparison of image quality and radiation dose between the two computed radiography system

    International Nuclear Information System (INIS)

    Song Shaojuan; Qi Hengtao; Zhao Yongxia; Jiao Fanglian

    2007-01-01

    Objective: To assess and compare the difference in image quality and exposure dose between single-sided reading image plate (IP) and dual-sided reading IP. Methods: A contrast-detail phantom CDRAD 2.0 was exposed by single-sided and dual-sided reading IP with different mAs sets. The entrance surface doses were recorded for all images. Images were then presented to two radiologists on a high resolution monitor of diagnosis workstation. The image quality figure (IQF) was measured for each image. Statistical analysis was performed using Spearman's correlation test and Wilcoxon signed-rank test to compare the difference in image quality and exposure dose between single-sided IP and dual-sided reading IP. Results: With different tube current dosage of 5.6, 12.0, 20.0, 25.0, and 40.0 mAs, IQF values of single-sided reading IP were 47.95, 37.68, 34.31, 28.61, and 24.65, respectively, while those of dual- sided reading IP were 38.83, 29.81, 29.65, 25.16, and 21.43, respectively. The IQF difference between them showed statistical significance (P<0.05). Conclusion: Image quality of dual-sided reading IP has been proved to be far superior to that of single-sided reading IP, in particular for low contrast detail. The image quality of single-sided reading IP is similar to that of dual-sided reading IP only at high dose levels. The clinical application of dual-sided reading IP will reduce the exposure dose by about 25% compared with single-sided reading IP. (authors)

  4. How to introduce demand side resources in the design of low-carbon power systems in China

    Science.gov (United States)

    Zhou, Pengcheng; Liu, Yiqun; Zeng, Ming; Sun, Chenjun

    2018-04-01

    Nowadays, China's energy demand sustained rapid growth, and the coal-based energy structure has adverse effects on the environment. The flexibility of demand side resource (DSR) will be greatly improved, and DSR can reduce electricity consumption actively and temporarily, and realize energy saving and emission reduction. But there are still some problems to introduce DSR in China. This paper proposes three practices for introducing demand side resources to improve the flexibility of power systems through demand resources.

  5. Prediction of Central Nervous System Side Effects Through Drug Permeability to Blood-Brain Barrier and Recommendation Algorithm.

    Science.gov (United States)

    Fan, Jun; Yang, Jing; Jiang, Zhenran

    2018-04-01

    Drug side effects are one of the public health concerns. Using powerful machine-learning methods to predict potential side effects before the drugs reach the clinical stages is of great importance to reduce time consumption and protect the security of patients. Recently, researchers have proved that the central nervous system (CNS) side effects of a drug are closely related to its permeability to the blood-brain barrier (BBB). Inspired by this, we proposed an extended neighborhood-based recommendation method to predict CNS side effects using drug permeability to the BBB and other known features of drug. To the best of our knowledge, this is the first attempt to predict CNS side effects considering drug permeability to the BBB. Computational experiments demonstrated that drug permeability to the BBB is an important factor in CNS side effects prediction. Moreover, we built an ensemble recommendation model and obtained higher AUC score (area under the receiver operating characteristic curve) and AUPR score (area under the precision-recall curve) on the data set of CNS side effects by integrating various features of drug.

  6. A study on the computerization of secondary side on-line chemistry monitoring system of PWR

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kyung Lin; Lee, Eun Heui [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1994-12-01

    A computer system for on-line chemistry monitoring system located in secondary side of PWR plant is under developing. Keithley 500 A mainframe and AMM1A and AIM3A modules are used for data acquisition and scientific and engineering software package of ASYST is used for developing software program. The contents are as follows: (1) Data acquisition and real-time display. The output signals of monitoring chemical sensors are stored in PC showing real-time data display as true values and graphics. (2) Data management and trending graphs. The data stored in PC are outcoming in various graphic mode for data management such as simple trending graphs screen display, time duration plot and histogram plot. (3) Daily basis data manual input. The chemical analysis data of grab sample are stored in PC by manual input for supplement data. (4) Tabular data report preparation. Summarized daily, weekly, monthly, quarterly and yearly reports are prepared with various mode of graphic display. 6 figs, 9 tabs, 8 refs. (Author).

  7. A study on the computerization of secondary side on-line chemistry monitoring system of PWR

    International Nuclear Information System (INIS)

    Yang, Kyung Lin; Lee, Eun Heui

    1994-12-01

    A computer system for on-line chemistry monitoring system located in secondary side of PWR plant is under developing. Keithley 500 A mainframe and AMM1A and AIM3A modules are used for data acquisition and scientific and engineering software package of ASYST is used for developing software program. The contents are as follows: 1) Data acquisition and real-time display. The output signals of monitoring chemical sensors are stored in PC showing real-time data display as true values and graphics. 2) Data management and trending graphs. The data stored in PC are outcoming in various graphic mode for data management such as simple trending graphs screen display, time duration plot and histogram plot. 3) Daily basis data manual input. The chemical analysis data of grab sample are stored in PC by manual input for supplement data. 4) Tabular data report preparation. Summarized daily, weekly, monthly, quarterly and yearly reports are prepared with various mode of graphic display. 6 figs, 9 tabs, 8 refs. (Author)

  8. Energy Refurbishment of an Office Building with Hybrid Photovoltaic System and Demand-Side Management

    Directory of Open Access Journals (Sweden)

    Giovani Almeida Dávi

    2017-08-01

    Full Text Available On-site photovoltaic (PV and battery systems intend to improve buildings energy performance, however battery costs and monetary incentives are a major drawback for the introduction of these technologies into the electricity grids. This paper proposes an energy refurbishment of an office building based on multi-objective simulations. An innovative demand-side management approach is analyzed through the PV and battery control with the purpose of reducing grid power peaks and grid imported energy, as well as improving the project economy. Optimization results of load matching and grid interaction parameters, complemented with an economic analysis, are investigated in different scenarios. By means of battery use, the equivalent use of the grid connection is reduced by 12%, enhancing the grid interaction potential, and 10% of load matching rates can be increased. Project improvements indicate the grid connection capacity can be reduced by 13% and significant savings of up to 48% are achieved on yearly bills. The economy demonstrates the grid parity is only achieved for battery costs below 100 €/kWh and the payback period is large: 28 years. In the case with only PV system, the grid parity achieves better outcomes and the payback time is reduced by a half, making this a more attractive option.

  9. Metering systems and demand-side management models applied to hybrid renewable energy systems in micro-grid configuration

    International Nuclear Information System (INIS)

    Blasques, L.C.M.; Pinho, J.T.

    2012-01-01

    This paper proposes a demand-side management model integrated to a metering system for hybrid renewable energy systems in micro-grid configuration. The proposal is based on the management problems verified in most of this kind of renewable hybrid systems installed in Brazil. The main idea is the implementation of a pre-paid metering system with some control functions that directly act on the consumer demand, restricting the consumption proportionally to the monthly availability of renewable energy. The result is a better distribution of the electricity consumption by month and by consumer, preventing that only one user, with larger purchasing power, consumes all the renewable energy available at some time period. The proportionality between the consumption and the renewable energy's availability has the objective to prevent a lack of energy stored and a high use of the diesel generator-set on months of low renewable potential. This paper also aims to contribute to the Brazilian regulation of renewable energy systems supplying micro-grids. - Highlights: ► Review of the Brazilian electricity regulation for small-scale isolated systems. ► Renewable systems are the most feasible option in several isolated communities. ► One proposal is to guarantee government subsidies for renewable energy systems. ► Smart electronic meters to create electricity restrictions for the consumers.

  10. Asparaginase Potentiates Glucocorticoid-Induced Osteonecrosis in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Chengcheng Liu

    Full Text Available Osteonecrosis is a common dose-limiting toxicity of glucocorticoids. Data from clinical trials suggest that other medications can increase the risk of glucocorticoid-induced osteonecrosis. Here we utilized a mouse model to study the effect of asparaginase treatment on dexamethasone-induced osteonecrosis. Mice receiving asparaginase along with dexamethasone had a higher rate of osteonecrosis than those receiving only dexamethasone after 6 weeks of treatment (44% vs. 10%, P = 0.006. Similarly, epiphyseal arteriopathy, which we have shown to be an initiating event for osteonecrosis, was observed in 58% of mice receiving asparaginase and dexamethasone compared to 17% of mice receiving dexamethasone only (P = 0.007. As in the clinic, greater exposure to asparaginase was associated with greater plasma exposure to dexamethasone (P = 0.0001. This model also recapitulated other clinical risk factors for osteonecrosis, including age at start of treatment, and association with the systemic exposure to dexamethasone (P = 0.027 and asparaginase (P = 0.036. We conclude that asparaginase can potentiate the osteonecrotic effect of glucocorticoids.

  11. The Energy Implications of Air-Side Fouling in Constant Air Volume HVAC Systems

    Science.gov (United States)

    Wilson, Eric J. H.

    2011-12-01

    This thesis examines the effect of air-side fouling on the energy consumption of constant air volume (CAV) heating, ventilating, and air conditioning (HVAC) systems in residential and small commercial buildings. There is a particular focus on evaluating the potential energy savings that may result from the remediation of such fouling from coils, filters, and other air system components. A computer model was constructed to simulate the behavior of a building and its duct system under various levels of fouling. The model was verified through laboratory and field testing and then used to run parametric simulations to examine the range of energy impacts for various climates and duct system characteristics. A sensitivity analysis was conducted to determine the impact of parameters like duct insulation, duct leakage, duct location, and duct design on savings potential. Duct system pressures, temperatures, and energy consumption for two houses were monitored for one month. The houses' duct systems, which were both in conditioned space, were given a full cleaning, and were then monitored for another month. The flow rates at the houses improved by 10% and 6%. The improvements were primarily due to installing a new filter, as both houses had only light coil fouling. The results indicate that there was negligible change in heating energy efficiency due to the system cleaning. The parametric simulation results are in agreement with the field experiment: for systems in all eight climates, with flowrates degraded by 20% or less, if ducts are located within the thermal zone, HVAC source energy savings from cleaning are negligible or even slightly negative. However, if ducts are outside the thermal zone, savings are in the 1 to 5% range. For systems with flowrates degraded by 40%, if ducts are within the thermal zone, savings from cleaning occurs only for air conditioning energy, up to 8% in climates like Miami, FL. If ducts are outside the thermal zone, savings occurs with both

  12. A scoping study: demand side measures on the UK electrical system

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    The study is intended to eventually bring about a number of improvements in the UK electrical system, particularly in regard to Demand Side Management (DSM). Among the benefits envisaged are (a) increased security of supply when the network is under stress; (b) reduction in costs; (c) simpler outage management; (d) carbon saving and (e) increased energy efficiency. So far, these potential benefits have attracted little attention in the residential and small business sectors of the market: suggested reasons for this are listed. Taking into account the experience of other countries, three options are presented for a UK DSM programme: they are (i) customer initiated; (ii) supplier initiated and (iii) distributor initiated. At present, all the suggested options need further study and to aid the development for small customers, five possible initiatives are suggested. This final report (95 pages) includes a detailed description of the research required and a tender process for a customer-initiated programme. The report was prepared by KEMA Limited under contract to the DTI.

  13. Coupled-expanding maps and one-sided symbolic dynamical systems

    International Nuclear Information System (INIS)

    Shi Yuming; Ju, Hyonhui; Chen Guanrong

    2009-01-01

    This paper studies relationships between coupled-expanding maps and one-sided symbolic dynamical systems. The concept of coupled-expanding map is extended to a more general one: coupled-expansion for a transitive matrix. It is found that the subshift for a transitive matrix is strictly coupled-expanding for the matrix in certain disjoint compact subsets; the topological conjugacy of a continuous map in its compact invariant set of a metric space to a subshift for a transitive matrix has a close relationship with that the map is strictly coupled-expanding for the matrix in some disjoint compact subsets. A certain relationship between strictly coupled-expanding maps for a transitive matrix in disjoint bounded and closed subsets of a complete metric space and their topological conjugacy to the subshift for the matrix is also obtained. Dynamical behaviors of subshifts for irreducible matrices are then studied and several equivalent statements to chaos are obtained; especially, chaos in the sense of Li-Yorke is equivalent to chaos in the sense of Devaney for the subshift, and is also equivalent to that the domain of the subshift is infinite. Based on these results, several new criteria of chaos for maps are finally established via strict coupled-expansions for irreducible transitive matrices in compact subsets of metric spaces and in bounded and closed subsets of complete metric spaces, respectively, where their conditions are weaker than those existing in the literature.

  14. A scoping study: demand side measures on the UK electrical system

    International Nuclear Information System (INIS)

    2005-01-01

    The study is intended to eventually bring about a number of improvements in the UK electrical system, particularly in regard to Demand Side Management (DSM). Among the benefits envisaged are (a) increased security of supply when the network is under stress; (b) reduction in costs; (c) simpler outage management; (d) carbon saving and (e) increased energy efficiency. So far, these potential benefits have attracted little attention in the residential and small business sectors of the market: suggested reasons for this are listed. Taking into account the experience of other countries, three options are presented for a UK DSM programme: they are (i) customer initiated; (ii) supplier initiated and (iii) distributor initiated. At present, all the suggested options need further study and to aid the development for small customers, five possible initiatives are suggested. This final report (95 pages) includes a detailed description of the research required and a tender process for a customer-initiated programme. The report was prepared by KEMA Limited under contract to the DTI

  15. Preparation and Characterization of Styrene Bearing Diethanolamine Side Group, Styrene Copolymer Systems, and Their Metal Complexes

    Directory of Open Access Journals (Sweden)

    Aslışah Açıkses

    2018-01-01

    Full Text Available The two copolymer systems of styrene bearing diethanol amine side group and styrene were prepared by free radical polymerization method at 60°C in presence of 1,4-dioxane as solvent and AIBN as initiator. Their metal complexes were prepared by reaction of the copolymer used as ligand P(DEAMSt-co-StL′′ and Ni(II and Co(II metal ions, which was carried out in presence of ethanol and NaOH at 65°C for 48 h in pH = 7.5. The structures of the copolymers used as ligand and metal complexes were identified by FT-IR, 1H-NMR spectra, and elemental analysis. The properties of the copolymers used as ligand and metal complexes were characterized by SEM-EDX, AAS, DSC, TGA, and DTA techniques. Then, the electrical properties of the copolymers and metal complexes were examined as a function of the temperature and frequency, and the activation energies (Ea were estimated with conductivity measurements.

  16. Smart grids and power systems efficiency: regulatory tools and demand-side management impacts

    International Nuclear Information System (INIS)

    Bergaentzle, Claire

    2015-01-01

    The physical architecture of electricity grids and the organizational structure of power systems implemented after the reforms have traditionally be achieved according to the characteristics of the transmission infrastructures and power mixes. However, the new challenges related to energy transition favor a greater participation of decentralized generation and final consumers to system exploitation and competitive markets. This latter participation is made possible thanks to recent innovations in the fields of communication and remote control technologies. Significant evolutions are expected in power industries that share common characteristics. First, these evolutions suppose massive capital investments to modernize and adapt current power distribution grids. Second, it is expected the activation of distribution grids and final consumers will unleash substantial unexploited economic efficiency gains as well as impose new constraints. Taking these simple facts as a starting point, the objective of the thesis is twofold. In the first place, we provide a theoretical analysis of the regulatory instruments that monitor the system operators' expenses. Relying on the literature, we aim at characterizing what regulatory tools and incitation are suitable for investing in smart grids technologies. Since it is necessary to compare theoretical formulation to facts, we use an empirical approach that allows us to designate key benefits pursued by the development of smart grids and to compare our theoretical results with practical regulatory applications. Our findings eventually allow us to formulate recommendations. In the second place, the thesis focuses on the impacts of demand-side management during peak periods. We structure our approach around two general observations. Large benefits should be generated in lowering substantially peak demand. However, such situation also creates losses of profit for generators. We provide an estimation of efficiency gains and revenue losses

  17. MODULAR CAUSTIC SIDE SOLVENT EXTRACTION UNIT (MCU) GAMMA MONITORS SYSTEM FINAL REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Casella, V

    2005-12-15

    The Department of Energy (DOE) selected Caustic-Side Solvent Extraction (CSSX) as the preferred technology for the removal of radioactive cesium from High-Level Waste (HLW) at the Savannah River Site (SRS). Before the full-scale Salt Waste Processing Facility (SWPF) becomes operational, the Closure Business Unit (CBU) plans to process a portion of dissolved saltcake waste through a Modular CSSX Unit (MCU). This work was derived from Technical Task Request SP-TTR-2004-00013, ''Gamma Monitor for MCU''. The deliverables for this task are the hardware and software for the gamma monitors and a report summarizing the testing and acceptance of this equipment for use in the MCU. Gamma-ray monitors are required to: (1) Measure the Cs-137 concentration in the decontaminated salt solution before entering the DSS (Decontaminated Salt Solution) Hold Tank, (2) Measure the Cs-137 concentration in the strip effluent before entering the Strip Effluent Hold Tank, (3) Verify proper operation of the solvent extraction system by verifying material balance within the process (The DSS Hold Tank Cs-137 concentration will be very low and the Cs-137 concentration in the Strip Effluent Hold Tank will be fifteen times higher than the Cs-137 concentration in the Feed Tank.) Sodium iodide monitors are used to measure the Cs-137 concentration in the piping before the DSS Hold tank, while GM monitors are used for Cs-137 measurements before the Strip Effluent Hold Tank. Tungsten shields were designed using Monte Carlo calculations and fabricated to reduce the process background radiation at the detector positions. These monitors were calibrated with NIST traceable standards that were specially made to be the same as the piping being monitored. Since this gamma ray monitoring system is unique, specially designed software was written and acceptance tested by Savannah River National Laboratory personnel. The software is a LabView-based application that serves as a unified

  18. MODULAR CAUSTIC SIDE SOLVENT EXTRACTION UNIT (MCU) GAMMA MONITORS SYSTEM FINAL REPORT

    International Nuclear Information System (INIS)

    Casella, V

    2005-01-01

    The Department of Energy (DOE) selected Caustic-Side Solvent Extraction (CSSX) as the preferred technology for the removal of radioactive cesium from High-Level Waste (HLW) at the Savannah River Site (SRS). Before the full-scale Salt Waste Processing Facility (SWPF) becomes operational, the Closure Business Unit (CBU) plans to process a portion of dissolved saltcake waste through a Modular CSSX Unit (MCU). This work was derived from Technical Task Request SP-TTR-2004-00013, ''Gamma Monitor for MCU''. The deliverables for this task are the hardware and software for the gamma monitors and a report summarizing the testing and acceptance of this equipment for use in the MCU. Gamma-ray monitors are required to: (1) Measure the Cs-137 concentration in the decontaminated salt solution before entering the DSS (Decontaminated Salt Solution) Hold Tank, (2) Measure the Cs-137 concentration in the strip effluent before entering the Strip Effluent Hold Tank, (3) Verify proper operation of the solvent extraction system by verifying material balance within the process (The DSS Hold Tank Cs-137 concentration will be very low and the Cs-137 concentration in the Strip Effluent Hold Tank will be fifteen times higher than the Cs-137 concentration in the Feed Tank.) Sodium iodide monitors are used to measure the Cs-137 concentration in the piping before the DSS Hold tank, while GM monitors are used for Cs-137 measurements before the Strip Effluent Hold Tank. Tungsten shields were designed using Monte Carlo calculations and fabricated to reduce the process background radiation at the detector positions. These monitors were calibrated with NIST traceable standards that were specially made to be the same as the piping being monitored. Since this gamma ray monitoring system is unique, specially designed software was written and acceptance tested by Savannah River National Laboratory personnel. The software is a LabView-based application that serves as a unified interface for controlling

  19. NALP3 inflammasome up-regulation and CASP1 cleavage of the glucocorticoid receptor causes glucocorticoid resistance in leukemia cells

    Science.gov (United States)

    Paugh, Steven W.; Bonten, Erik J.; Savic, Daniel; Ramsey, Laura B.; Thierfelder, William E.; Gurung, Prajwal; Malireddi, R. K. Subbarao; Actis, Marcelo; Mayasundari, Anand; Min, Jaeki; Coss, David R.; Laudermilk, Lucas T.; Panetta, John C.; McCorkle, J. Robert; Fan, Yiping; Crews, Kristine R.; Stocco, Gabriele; Wilkinson, Mark R.; Ferreira, Antonio M.; Cheng, Cheng; Yang, Wenjian; Karol, Seth E.; Fernandez, Christian A.; Diouf, Barthelemy; Smith, Colton; Hicks, J. Kevin; Zanut, Alessandra; Giordanengo, Audrey; Crona, Daniel; Bianchi, Joy J.; Holmfeldt, Linda; Mullighan, Charles G.; den Boer, Monique L.; Pieters, Rob; Jeha, Sima; Dunwell, Thomas L.; Latif, Farida; Bhojwani, Deepa; Carroll, William L.; Pui, Ching-Hon; Myers, Richard M.; Guy, R. Kiplin; Kanneganti, Thirumala-Devi; Relling, Mary V.; Evans, William E.

    2015-01-01

    Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and leukemia cell resistant to glucocorticoids confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the sensitivity to prednisolone of primary leukemia cells from 444 newly diagnosed ALL patients, revealing significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases. PMID:25938942

  20. Caustic-Side Solvent-Extraction Modeling for Hanford Interim Pretreatment System

    International Nuclear Information System (INIS)

    Moyer, B.A.; Birdwell, J.F.; Delmau, L. H.; McFarlane, J.

    2008-01-01

    The purpose of this work is to examine the applicability of the Caustic-Side Solvent Extraction (CSSX) process for the removal of cesium from Hanford tank-waste supernatant solutions in support of the Hanford Interim Pretreatment System (IPS). The Hanford waste types are more challenging than those at the Savannah River Site (SRS) in that they contain significantly higher levels of potassium, the chief competing ion in the extraction of cesium. It was confirmed by use of the CSSX model that the higher levels of potassium depress the cesium distribution ratio (DCs), as validated by measurement of DCs values for four of eight specified Hanford waste-simulant compositions. The model predictions were good to an apparent standard error of ±11%. It is concluded from batch distribution experiments, physical-property measurements, equilibrium modeling, flowsheet calculations, and contactor sizing that the CSSX process as currently employed for cesium removal from alkaline salt waste at the SRS is capable of treating similar Hanford tank feeds. For the most challenging waste composition, 41 stages would be required to provide a cesium decontamination factor (DF) of 5000 and a concentration factor (CF) of 5. Commercial contacting equipment with rotor diameters of 10 in. for extraction and 5 in. for stripping should have the capacity to meet throughput requirements, but testing will be required to confirm that the needed efficiency and hydraulic performance are actually obtainable. Markedly improved flowsheet performance was calculated for a new solvent formulation employing the more soluble cesium extractant BEHBCalixC6 used with alternative scrub and strip solutions, respectively 0.1 M NaOH and 10 mM boric acid. The improved system can meet minimum requirements (DF = 5000 and CF = 5) with 17 stages or more ambitious goals (DF = 40,000 and CF = 15) with 19 stages. Potential benefits of further research and development are identified that would lead to reduced costs, greater

  1. Glucocorticoids and the regulation of memory in health and disease

    NARCIS (Netherlands)

    de Quervain, Dominique J. -F; Aerni, Amanda; Schelling, Gustav; Roozendaal, Benno

    Over the last decades considerable evidence has accumulated indicating that glucocorticoids - stress hormones released from the adrenal cortex - are crucially involved in the regulation of memory. Specifically, glucocorticoids have been shown to enhance memory consolidation of emotionally arousing

  2. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects

    NARCIS (Netherlands)

    Judd, L.L.; Schettler, P.J.; Brown, E.S.; Wolkowitz, O.M.; Sternberg, E.M.; Bender, B.G.; Bulloch, K.; Cidlowski, J.A.; Kloet, E.R. de; Fardet, L.; Joels, M.; Leung, D.Y.; McEwen, B.S.; Roozendaal, B.; Rossum, E.F. van; Ahn, J.; Brown, D.W.; Plitt, A.; Singh, G.

    2014-01-01

    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as

  3. Adverse Consequences of Glucocorticoid Medication : Psychological, Cognitive, and Behavioral Effects

    NARCIS (Netherlands)

    Judd, Lewis L.; Schettler, Pamela J.; Brown, E. Sherwood; Wolkowitz, Owen M.; Sternberg, Esther M.; Bender, Bruce G.; Bulloch, Karen; Cidlowski, John A.; de Kloet, E. Ronald; Fardet, Laurence; Joëls, Marian; Leung, Donald Y. M.; McEwen, Bruce S.; Roozendaal, Benno; Van Rossum, Elisabeth F. C.; Ahn, Junyoung; Brown, David W.; Plitt, Aaron; Singh, Gagandeep

    2014-01-01

    Glucocorticoids are the most commonly prescribed anti-inflammatory/immunosuppressant medications worldwide. This article highlights the risk of clinically significant and sometimes severe psychological, cognitive, and behavioral disturbances that may be associated with glucocorticoid use, as well as

  4. Glucocorticoids and fetal programming part 1: Outcomes.

    Science.gov (United States)

    Moisiadis, Vasilis G; Matthews, Stephen G

    2014-07-01

    Fetal development is a critical period for shaping the lifelong health of an individual. However, the fetus is susceptible to internal and external stimuli that can lead to adverse long-term health consequences. Glucocorticoids are an important developmental switch, driving changes in gene regulation that are necessary for normal growth and maturation. The fetal hypothalamic-pituitary-adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids; these effects can persist throughout the life of an organism. Dysfunction of the HPA axis as a result of fetal programming has been associated with impaired brain growth, altered behaviour and increased susceptibility to chronic disease (such as metabolic and cardiovascular disease). Moreover, the effects of glucocorticoid-mediated programming are evident in subsequent generations, and transmission of these changes can occur through both maternal and paternal lineages.

  5. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B

    2011-01-01

    of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids....... Glucocortioids affect several cellular structures and functions, which may explain the observed adverse effects. Glucocorticoids can impair neuronal glucose uptake, decrease excitability, cause atrophy of dendrites, compromise development of myelin-producing oligodendrocytes and disturb important cellular...

  6. Cardiovascular Side Effects of Atomoxetine and Its Interactions with Inhibitors of the Cytochrome P450 System

    Directory of Open Access Journals (Sweden)

    Pashtoon Murtaza Kasi

    2011-01-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is one of the most common neurobehavioral disorders of childhood and adolescence. Classically, stimulants have been used in the treatment of this condition. Atomoxetine (Strattera; Eli Lilly and Company is a selective norepinephrine reuptake inhibitor (SNRI, one of the first medications in the nonstimulant class of medications that has been approved by the FDA for the treatment of ADHD. Atomoxetine is a phenoxypropylamine derivative and is structurally related to the antidepressant fluoxetine. The common side effects reported with the use of atomoxetine include mainly GI disturbances. Cardiovascular side effects are less commonly reported. The increase in the noradrenergic tone may explain some of the side effects noted with the use of this medication. Here, we present a case of a patient who presented with syncope, orthostatic hypotension, and tachycardia and discuss the various clinical implications based on the pharmacokinetics and pharmacodynamics of the drug.

  7. DEMONSTRATION OF THE ENVIRONMENTAL AND DEMAND-SIDE MANAGEMENT BENEFITS OF GRID-CONNECTED PHOTOVOLTAIC POWER SYSTEMS

    Science.gov (United States)

    This study investigated the pollutant emission reduction and demand-side management potential of 16 photovoltaic (PV) systems installed across the U.S. in 1993 and 1994. The project was sponsored by the U.S. Environmental Protection Agency (EPA) and 11 electric utilities. This ar...

  8. Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid.

    Science.gov (United States)

    Chen, Jiao; Wang, Zhen-zhen; Zuo, Wei; Zhang, Shuai; Chu, Shi-feng; Chen, Nai-hong

    2016-02-01

    Major depression is thought to originate from maladaptation to adverse events, particularly when impairments occur in mood-related brain regions. Hypothalamus-pituitary-adrenal (HPA) axis is one of the major systems involved in physiological stress response. HPA axis dysfunction and high glucocorticoid concentrations play an important role in the pathogenesis of depression. In addition, astrocytic disability and dysfunction of neurotrophin brain-derived neurotrophin factor (BDNF) greatly influence the development of depression and anxiety disorders. Therefore, we investigated whether depressive-like and anxiety-like behaviors manifest in the absence of glucocorticoid production and circulation in adrenalectomized (ADX) rats after chronic mild stress (CMS) exposure and its potential molecular mechanisms. The results demonstrate that glucocorticoid-controlled rats showed anxiety-like behaviors but not depression-like behaviors after CMS. Molecular and cellular changes included the decreased BDNF in the hippocampus, astrocytic dysfunction with connexin43 (cx43) decreasing and abnormality in gap junction in prefrontal cortex (PFC). Interestingly, we did not find any changes in glucocorticoid receptor (GR) or its chaperone protein FK506 binding protein 51 (FKBP5) expression in the hippocampus or PFC in ADX rats subjected to CMS. In conclusion, the production and circulation of glucocorticoids are one of the contributing factors in the development of depression-like behaviors in response to CMS. In contrast, the effects of CMS on anxiety-like behaviors are independent of the presence of circulating glucocorticoids. Meanwhile, stress decreased GR expression and enhanced FKBP5 expression via higher glucocorticoid exposure. Gap junction dysfunction and changes in BDNF may be associated with anxiety-like behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Analytical Methods Development in Support of the Caustic Side Solvent Extraction System

    International Nuclear Information System (INIS)

    Maskarinec, M.P.

    2001-01-01

    The goal of the project reported herein was to develop and apply methods for the analysis of the major components of the solvent system used in the Caustic-Side Solvent Extraction Process (CSSX). These include the calix(4)arene, the modifier, 1-(2,2,3,3- tetrafluoropropoxy)-3-(4-sec-butylphenoxy)-2-propanol and tri-n-octylamine. In addition, it was an objective to develop methods that would allow visualization of other components under process conditions. These analyses would include quantitative laboratory methods for each of the components, quantitative analysis of expected breakdown products (4-see-butylphenol and di-n-octylamine), and qualitative investigations of possible additional breakdown products under a variety of process extremes. These methods would also provide a framework for process analysis should a pilot facility be developed. Two methods were implemented for sample preparation of aqueous phases. The first involves solid-phase extraction and produces quantitative recovery of the solvent components and degradation products from the various aqueous streams. This method can be automated and is suitable for use in radiation shielded facilities. The second is a variation of an established EPA liquid-liquid extraction procedure. This method is also quantitative and results in a final extract amenable to virtually any instrumental analysis. Two HPLC methods were developed for quantitative analysis. The first is a reverse-phase system with variable wavelength W detection. This method is excellent from a quantitative point of view. The second method is a size-exclusion method coupled with dual UV and evaporative light scattering detectors. This method is much faster than the reverse-phase method and allows for qualitative analysis of other components of the waste. For tri-n-octylamine and other degradation products, a GC method was developed and subsequently extended to GUMS. All methods have precision better than 5%. The combination of these methods

  10. A novel microgrid demand-side management system for manufacturing facilities

    Science.gov (United States)

    Harper, Terance J.

    Thirty-one percent of annual energy consumption in the United States occurs within the industrial sector, where manufacturing processes account for the largest amount of energy consumption and carbon emissions. For this reason, energy efficiency in manufacturing facilities is increasingly important for reducing operating costs and improving profits. Using microgrids to generate local sustainable power should reduce energy consumption from the main utility grid along with energy costs and carbon emissions. Also, microgrids have the potential to serve as reliable energy generators in international locations where the utility grid is often unstable. For this research, a manufacturing process that had approximately 20 kW of peak demand was matched with a solar photovoltaic array that had a peak output of approximately 3 KW. An innovative Demand-Side Management (DSM) strategy was developed to manage the process loads as part of this smart microgrid system. The DSM algorithm managed the intermittent nature of the microgrid and the instantaneous demand of the manufacturing process. The control algorithm required three input signals; one from the microgrid indicating the availability of renewable energy, another from the manufacturing process indicating energy use as a percent of peak production, and historical data for renewable sources and facility demand. Based on these inputs the algorithm had three modes of operation: normal (business as usual), curtailment (shutting off non-critical loads), and energy storage. The results show that a real-time management of a manufacturing process with a microgrid will reduce electrical consumption and peak demand. The renewable energy system for this research was rated to provide up to 13% of the total manufacturing capacity. With actively managing the process loads with the DSM program alone, electrical consumption from the utility grid was reduced by 17% on average. An additional 24% reduction was accomplished when the microgrid

  11. New Real-Time Market Facilitating Demand-Side Resources for System Balancing

    DEFF Research Database (Denmark)

    Feng, Donghan; Nyeng, Preben; Xie, Jun

    2011-01-01

    Many demand side resources have the potential to provide fast and low cost balancing services. Switching these devices on and off can be executed in seconds and have limited consequences for the customers if the duration is not long. With carefully designed market rules, tens of thousands...... the participation of demand-side resources. In light of the future environment of increasing intermittent renewable power and distributed energy/storage resources, stochastic time-series and Monte-Carlo simulation are used to analyze the relationship between balancing requirement and generation/demand uncertainties...

  12. Toward server-side, high performance climate change data analytics in the Earth System Grid Federation (ESGF) eco-system

    Science.gov (United States)

    Fiore, Sandro; Williams, Dean; Aloisio, Giovanni

    2016-04-01

    In many scientific domains such as climate, data is often n-dimensional and requires tools that support specialized data types and primitives to be properly stored, accessed, analysed and visualized. Moreover, new challenges arise in large-scale scenarios and eco-systems where petabytes (PB) of data can be available and data can be distributed and/or replicated (e.g., the Earth System Grid Federation (ESGF) serving the Coupled Model Intercomparison Project, Phase 5 (CMIP5) experiment, providing access to 2.5PB of data for the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5). Most of the tools currently available for scientific data analysis in the climate domain fail at large scale since they: (1) are desktop based and need the data locally; (2) are sequential, so do not benefit from available multicore/parallel machines; (3) do not provide declarative languages to express scientific data analysis tasks; (4) are domain-specific, which ties their adoption to a specific domain; and (5) do not provide a workflow support, to enable the definition of complex "experiments". The Ophidia project aims at facing most of the challenges highlighted above by providing a big data analytics framework for eScience. Ophidia provides declarative, server-side, and parallel data analysis, jointly with an internal storage model able to efficiently deal with multidimensional data and a hierarchical data organization to manage large data volumes ("datacubes"). The project relies on a strong background of high performance database management and OLAP systems to manage large scientific data sets. It also provides a native workflow management support, to define processing chains and workflows with tens to hundreds of data analytics operators to build real scientific use cases. With regard to interoperability aspects, the talk will present the contribution provided both to the RDA Working Group on Array Databases, and the Earth System Grid Federation (ESGF

  13. New type side weir discharge coefficient simulation using three novel hybrid adaptive neuro-fuzzy inference systems

    Science.gov (United States)

    Bonakdari, Hossein; Zaji, Amir Hossein

    2018-03-01

    In many hydraulic structures, side weirs have a critical role. Accurately predicting the discharge coefficient is one of the most important stages in the side weir design process. In the present paper, a new high efficient side weir is investigated. To simulate the discharge coefficient of these side weirs, three novel soft computing methods are used. The process includes modeling the discharge coefficient with the hybrid Adaptive Neuro-Fuzzy Interface System (ANFIS) and three optimization algorithms, namely Differential Evaluation (ANFIS-DE), Genetic Algorithm (ANFIS-GA) and Particle Swarm Optimization (ANFIS-PSO). In addition, sensitivity analysis is done to find the most efficient input variables for modeling the discharge coefficient of these types of side weirs. According to the results, the ANFIS method has higher performance when using simpler input variables. In addition, the ANFIS-DE with RMSE of 0.077 has higher performance than the ANFIS-GA and ANFIS-PSO methods with RMSE of 0.079 and 0.096, respectively.

  14. 29 CFR 1915.507 - Land-side fire protection systems.

    Science.gov (United States)

    2010-07-01

    ... standard for employee safety or employee protection from fire hazards in land-side facilities, including... remains hazardous to employee safety or health, or provide safeguards to prevent employees from entering... hazardous to employee safety or health; and (6) Select, install, inspect, maintain, and test all automatic...

  15. Sports teams as complex adaptive systems: manipulating player numbers shapes behaviours during football small-sided games

    OpenAIRE

    Silva, Pedro; Vilar, Lu?s; Davids, Keith; Ara?jo, Duarte; Garganta, J?lio

    2016-01-01

    Small-sided and conditioned games (SSCGs) in sport have been modelled as complex adaptive systems. Research has shown that the relative space per player (RSP) formulated in SSCGs can impact on emergent tactical behaviours. In this study we adopted a systems orientation to analyse how different RSP values, obtained through manipulations of player numbers, influenced four measures of interpersonal coordination observed during performance in SSCGs. For this purpose we calculated positional data ...

  16. Single-step simultaneous side-by-side placement of a self-expandable metallic stent with a 6-Fr delivery system for unresectable malignant hilar biliary obstruction: a feasibility study.

    Science.gov (United States)

    Kawakubo, Kazumichi; Kawakami, Hiroshi; Kuwatani, Masaki; Kudo, Taiki; Abe, Yoko; Kawahata, Shuhei; Kubo, Kimitoshi; Kubota, Yoshimasa; Sakamoto, Naoya

    2015-02-01

    Bilateral self-expandable metallic stent (SEMS) placement for the management of unresectable malignant hilar biliary obstruction (UMHBO) is technically challenging to perform using the existing metallic stents with thick delivery systems. The recently developed 6-Fr delivery systems could facilitate a single-step simultaneous side-by-side placement through the accessory channel of the duodenoscope. The aim of this study was to evaluate the feasibility of this procedure. Between May and September 2013, 13 consecutive patients with UMHBO underwent a single-step simultaneous side-by-side placement of SEMS with the 6-Fr delivery system. The technical success rate, stent patency, and rate of complications were evaluated from the prospectively collected database. Technical success was achieved in 11 (84.6%, 95% confidence interval [CI]: 57.8-95.8) patients. The median procedure time was 25 min. Early and late complications were observed in 23% (one segmental cholangitis and two liver abscesses) and 15% (one segmental cholangitis and one cholecystitis) patients, respectively. Median dysfunction free patency was 263 days (95% CI: 37-263). Five patients (38%) experienced stent occlusion that was successfully managed by endoscopic stent placement. A single-step simultaneous side-by-side placement of SEMS with a 6-Fr delivery system was feasible for the management of UMHBO. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  17. Glucocorticoid resistance as a major drive in sepsis pathology.

    Science.gov (United States)

    Dendoncker, Karen; Libert, Claude

    2017-06-01

    Sepsis is an acute systemic inflammatory disease. Glucocorticoids (GCs), which function by binding to the GC receptor GR have very powerful anti-inflammatory activities, yet they are hardly useful in sepsis. We can thus consider sepsis as a GC resistant disease. We here review the literature which has investigated this GC resistance, and summarize the mechanisms of GC resistance that have been observed in other diseases and in experimental models. We also discuss the importance of GC resistance in sepsis, in terms of the contribution of this phenomenon to the pathogenesis of sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. D-Side: A Facility and Workforce Planning Group Multi-criteria Decision Support System for Johnson Space Center

    Science.gov (United States)

    Tavana, Madjid

    2005-01-01

    "To understand and protect our home planet, to explore the universe and search for life, and to inspire the next generation of explorers" is NASA's mission. The Systems Management Office at Johnson Space Center (JSC) is searching for methods to effectively manage the Center's resources to meet NASA's mission. D-Side is a group multi-criteria decision support system (GMDSS) developed to support facility decisions at JSC. D-Side uses a series of sequential and structured processes to plot facilities in a three-dimensional (3-D) graph on the basis of each facility alignment with NASA's mission and goals, the extent to which other facilities are dependent on the facility, and the dollar value of capital investments that have been postponed at the facility relative to the facility replacement value. A similarity factor rank orders facilities based on their Euclidean distance from Ideal and Nadir points. These similarity factors are then used to allocate capital improvement resources across facilities. We also present a parallel model that can be used to support decisions concerning allocation of human resources investments across workforce units. Finally, we present results from a pilot study where 12 experienced facility managers from NASA used D-Side and the organization's current approach to rank order and allocate funds for capital improvement across 20 facilities. Users evaluated D-Side favorably in terms of ease of use, the quality of the decision-making process, decision quality, and overall value-added. Their evaluations of D-Side were significantly more favorable than their evaluations of the current approach. Keywords: NASA, Multi-Criteria Decision Making, Decision Support System, AHP, Euclidean Distance, 3-D Modeling, Facility Planning, Workforce Planning.

  19. Are BDNF and glucocorticoid activities calibrated?

    Science.gov (United States)

    Jeanneteau, Freddy; Chao, Moses V.

    2012-01-01

    One hypothesis to account for the onset and severity of neurological disorders is the loss of trophic support. Indeed, changes in the levels and activities of brain-derived neurotrophic factor (BDNF) occur in numerous neurodegenerative and neuropsychiatric diseases. A deficit promotes vulnerability whereas a gain of function facilitates recovery by enhancing survival, synapse formation and synaptic plasticity. Implementation of ‘BDNF therapies’, however, faces numerous methodological and pharmacokinetic issues. Identifying BDNF mimetics that activate the BDNF receptor or downstream targets of BDNF signaling represent an alternative approach. One mechanism that shows great promise is to study the interplay of BDNF and glucocorticoid hormones, a major class of natural steroid secreted during stress reactions and in synchrony with circadian rhythms. While small amounts of glucocorticoids support normal brain function, excess stimulation by these steroid hormones precipitate stress-related affective disorders. To date, however, because of the paucity of knowledge of underlying cellular mechanisms, deleterious effects of glucocorticoids are not prevented following extreme stress. In the present review, we will discuss the complementary roles share by BDNF and glucocorticoids in synaptic plasticity, and delineate possible signaling mechanisms mediating these effects. PMID:23022538

  20. Glucocorticoid Regulation of the Vitamin D Receptor

    Science.gov (United States)

    Hidalgo, Alejandro A.; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    Many studies indicate calcitriol has potent anti-tumor activity in different types of cancers. However, high levels of vitamin D can produce hypercalcemia in some patients. Glucocorticoids are used to ameliorate hypercalcemia and to enhance calcitriol anti-tumor activity. Calcitriol in combination with the glucocorticoid dexamethasone (Dex) increased vitamin D receptor (VDR) protein levels and ligand binding in squamous cell carcinoma VII (SCC). In this study we found that both calcitriol and Dex induce VDR- and glucocorticoid receptor (GR)-mediated transcription respectively, indicating both hormone receptors are active in SCC. Pre-treatment with Dex increases VDR-mediated transcription at the human CYP24A1 promoter. Whereas, pre-treatment with other steroid hormones, including dihydrotestosterone and R1881, has no effect on VDR-mediated transcription. Real-time PCR indicates treatment with Dex increases Vdr transcripts in a time-dependent manner, suggesting Dex may directly regulate expression of Vdr. Numerous putative glucocorticoid response elements (GREs) were found in the Vdr gene. Chromatin immunoprecipitation (ChIP) assay demonstrated GR binding at several putative GREs located within the mouse Vdr gene. However, none of the putative GREs studied increase GR-mediated transcription in luciferase reporter assays. In an attempt to identify the response element responsible for Vdr transcript regulation, future studies will continue to analyze newly identified GREs more distal from the Vdr gene promoter. PMID:20398752

  1. Activation of glucocorticoid receptors in Müller glia is protective to retinal neurons and suppresses microglial reactivity

    OpenAIRE

    Gallina, Donika; Zelinka, Christopher Paul; Cebulla, Colleen; Fischer, Andy J.

    2015-01-01

    Reactive microglia and macrophages are prevalent in damaged retinas. Glucocorticoid signaling is known to suppress inflammation and the reactivity of microglia and macrophages. In the vertebrate retina, the glucocorticoid receptor (GCR) is known to be activated and localized to the nuclei of Müller glia (Gallina et al., 2014). Accordingly, we investigated how signaling through GCR influences the survival of neurons using the chick retina in vivo as a model system. We applied intraocular injec...

  2. Coverage Extension via Side-Lobe Transmission in Multibeam Satellite System

    OpenAIRE

    Gharanjik, Ahmad; Kmieciak, Jarek; Shankar, Bhavani; Ottersten, Björn

    2017-01-01

    In this paper, we study feasibility of coverage extension of a multibeam satellite network by providing low-rate communications to terminals located outside the coverage of main beams. Focusing on the MEO satellite network, and using realistic link budgets from O3b networks, we investigate the performance of both forward and return-links for terminals stationed in the side lobes of the main beams. Particularly, multi-carrier transmission for forward-link and single carrier transmission for re...

  3. Glucocorticoid induced TNFR-related protein (GITR as marker of human regulatory T cells: expansion of the GITR+CD25- cell subset in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    E. Bartoloni Bocci

    2011-06-01

    Full Text Available Objectives: Regulatory T cells (TREG represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/ inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR is a well known marker of murine TREG cells, but little is known in humans. The aim of this study was to investigate the characteristics of TREG cells in systemic lupus erythematosus (SLE and the potential role of GITR as marker of human TREG. Methods: Nineteen SLE patients and 15 sex- and age-matched normal controls (NC were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR using TaqMan probes. Results: The CD25highGITRhigh subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05. On the opposite, the CD25-GITRhigh cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01. Interestingly, FoxP3 at mRNA level was expressed in both CD25- GITRhigh and CD25highGITRhigh cells, suggesting that both cell subsets have regulatory activity. Conclusions: CD4+CD25-GITRhigh cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset.

  4. Glucocorticoids for the treatment of post-traumatic stress disorder and phobias: a novel therapeutic approach.

    Science.gov (United States)

    de Quervain, Dominique J-F; Margraf, Jürgen

    2008-04-07

    Post-traumatic stress disorder (PTSD) and phobias belong to the most common anxiety disorders and to the most common psychiatric illnesses in general. In both disorders, aversive memories are thought to play an important role in the pathogenesis and symptomatology. Previously, we have reported that elevated glucocorticoid levels inhibit memory retrieval in animals and healthy humans. We therefore hypothesized that the administration of glucocorticoids might also inhibit the retrieval of aversive memory, thereby reducing symptoms in patients with PTSD and phobias. In recent clinical studies, we found first evidence to support this hypothesis. In patients with PTSD, low-dose cortisol treatment for one month reduced symptoms of traumatic memories without causing adverse side effects. Furthermore, we found evidence for a prolonged effect of the cortisol treatment. Persistent retrieval and reconsolidation of traumatic memories is a process that keeps these memories vivid and thereby the disorder alive. By inhibiting memory retrieval, cortisol may weaken the traumatic memory trace, and thus reduce symptoms even beyond the treatment period. In patients with social phobia, we found that a single oral administration of cortisone 1 h before a socio-evaluative stressor significantly reduced self-reported fear during the anticipation-, exposure-, and recovery phase of the stressor. In subjects with spider phobia, repeated oral administration of cortisol 1 h before exposure to a spider photograph induced a progressive reduction of stimulus-induced fear. This effect was maintained when subjects were exposed to the stimulus again two days after the last cortisol administration, indicating that cortisol facilitated the extinction of phobic fear. In conclusion, by a common mechanism of reducing the retrieval of aversive memories, glucocorticoids may be suited for the treatment of PTSD as well as phobias. More studies are needed to further evaluate the therapeutic efficacy of

  5. Switching Device Dead Time Optimization of Resonant Double-Sided LCC Wireless Charging System for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    2017-11-01

    Full Text Available Aiming at the reduction of the influence of the dead time setting on power level and efficiency of the inverter of double-sided LCC resonant wireless power transfer (WPT system, a dead time soft switching optimization method for metal–oxide–semiconductor field-effect transistor (MOSFET is proposed. At first, the mathematic description of double-sided LCC resonant wireless charging system is established, and the operating mode is analyzed as well, deducing the quantitative characteristic that the secondary side compensation capacitor C2 can be adjusted to ensure that the circuit is inductive. A dead time optimization design method is proposed, contributing to achieving zero-voltage switching (ZVS of the inverter, which is closely related to the performance of the WPT system. In the end, a prototype is built. The experimental results verify that dead time calculated by this optimized method can ensure the soft switching of the inverter MOSFET and promote the power and efficiency of the WPT.

  6. Probabilistic reliability analyses to detect weak points in secondary-side residual heat removal systems of KWU PWR plants

    International Nuclear Information System (INIS)

    Schilling, R.

    1984-01-01

    Requirements made by Federal German licensing authorities called for the analysis of the second-side residual heat removal systems of new PWR plants with regard to availability, possible weak points and the balanced nature of the overall system for different incident sequences. Following a description of the generic concept and the process and safety-related systems for steam generator feed and main steam discharge, the reliability of the latter is analyzed for the small break LOCA and emergency power mode incidents, weak points in the process systems are identified, remedial measures of a system-specific and test-strategic nature are presented and their contribution to improving system availability is quantified. A comparison with the results of the German Risk Study on Nuclear Power Plants (GRS) shows a distinct reduction in core meltdown frequency. (orig.)

  7. Reliability analyses to detect weak points in secondary-side residual heat removal systems of KWU PWR plants

    International Nuclear Information System (INIS)

    Schilling, R.

    1983-01-01

    Requirements made by Federal German licensing authorities called for the analysis of the secondary-side residual heat removal systems of new PWR plants with regard to availability, possible weak points and the balanced nature of the overall system for different incident sequences. Following a description of the generic concept and the process and safety-related systems for steam generator feed and main steam discharge, the reliability of the latter is analyzed for the small break LOCA and emergency power mode incidents, weak points in the process systems identified, remedial measures of a system-specific and test-strategic nature presented and their contribution to improving system availability quantified. A comparison with the results of the German Risk Study on Nuclear Power Plants (GRS) shows a distinct reduction in core meltdown frequency. (orig.)

  8. Efectos del tratamiento con glucocorticoides durante el embarazo. A propósito de un caso

    Directory of Open Access Journals (Sweden)

    Diana Machado Ramírez

    2015-06-01

    Full Text Available The use of anti-inflammatory glucocorticoids may be necessary during pregnancy to treat some maternal conditions. Its effects in pregnant women are virtually the same as those described in the general adult population. Avascular necrosis is the death of bone tissue due to the interruption of the blood supply, and is mainly associated with the use of high-dose corticosteroids for long periods. We present the case of a 21-year-old patient at 34 weeks’ gestation admitted to the Intensive Care Unit of the Enrique Cabrera Hospital because of decompensated hypertension, obesity and congenital adrenal hyperplasia treated with suppressive doses of steroids. Subsequently, she was diagnosed with an avascular necrosis of both femoral heads. Iatrogenic Cushing’s syndrome resulting from all these factors was found. The newborn developed a seborrheic dermatitis of the scalp. The purpose of this presentation is to describe the side effects of the chronic use of glucocorticoids in pregnant women.

  9. Peripheral mechanisms contributing to the glucocorticoid hypersensitivity in proopiomelanocortin null mice treated with corticosterone

    Science.gov (United States)

    Michailidou, Zoi; Coll, Anthony P; Kenyon, Christopher J; Morton, Nicholas M; O'Rahilly, Stephen; Seckl, Jonathan R; Chapman, Karen E

    2007-01-01

    Proopiomelanocortin (POMC) deficiency causes severe obesity through hyperphagia of hypothalamic origin. However, low glucocorticoid levels caused by adrenal insufficiency mitigate against insulin resistance, hyperphagia and fat accretion in Pomc−/− mice. Upon exogenous glucocorticoid replacement, corticosterone-supplemented (CORT) Pomc−/− mice show exaggerated responses, including excessive fat accumulation, hyperleptinaemia and insulin resistance. To investigate the peripheral mechanisms underlying this glucocorticoid hypersensitivity, we examined the expression levels of key determinants and targets of glucocorticoid action in adipose tissue and liver. Despite lower basal expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which generates active glucocorticoids within cells, CORT-mediated induction of 11β-HSD1 mRNA levels was more pronounced in adipose tissues of Pomc−/− mice. Similarly, CORT treatment increased lipoprotein lipase mRNA levels in all fat depots in Pomc−/− mice, consistent with exaggerated fat accumulation. Glucocorticoid receptor (GR) mRNA levels were selectively elevated in liver and retroperitoneal fat of Pomc−/− mice but were corrected by CORT in the latter depot. In liver, CORT increased phosphoenolpyruvate carboxykinase mRNA levels specifically in Pomc−/− mice, consistent with their insulin-resistant phenotype. Furthermore, CORT induced hypertension in Pomc−/− mice, independently of adipose or liver renin–angiotensin system activation. These data suggest that CORT-inducible 11β-HSD1 expression in fat contributes to the adverse cardiometabolic effects of CORT in POMC deficiency, whereas higher GR levels may be more important in liver. PMID:17592030

  10. Extending the eigCG algorithm to nonsymmetric Lanczos for linear systems with multiple right-hand sides

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Rehim, A M; Stathopoulos, Andreas; Orginos, Kostas

    2014-08-01

    The technique that was used to build the EigCG algorithm for sparse symmetric linear systems is extended to the nonsymmetric case using the BiCG algorithm. We show that, similarly to the symmetric case, we can build an algorithm that is capable of computing a few smallest magnitude eigenvalues and their corresponding left and right eigenvectors of a nonsymmetric matrix using only a small window of the BiCG residuals while simultaneously solving a linear system with that matrix. For a system with multiple right-hand sides, we give an algorithm that computes incrementally more eigenvalues while solving the first few systems and then uses the computed eigenvectors to deflate BiCGStab for the remaining systems. Our experiments on various test problems, including Lattice QCD, show the remarkable ability of EigBiCG to compute spectral approximations with accuracy comparable to that of the unrestarted, nonsymmetric Lanczos. Furthermore, our incremental EigBiCG followed by appropriately restarted and deflated BiCGStab provides a competitive method for systems with multiple right-hand sides.

  11. Demand side management for remote area power supply systems incorporating solar irradiance model

    International Nuclear Information System (INIS)

    Al-Alawi, A.; Islam, S.M.

    2004-01-01

    This paper presents a technique for generating the daily electricity load profile for remote areas in the Middle East from first principles, using diversified demand. The generated load profile includes the energy required to run a small desalination unit to provide the necessary freshwater. Demand side management (DSM) is used in this study to smooth out the daily peaks and fill valleys in the load curve to make the most efficient use of energy resources. Finally, the load profile is compared with real data for six houses collected from Safri area in the Sultanate of Oman. These data may be used as the basis to obtain load profiles of other remote areas of the Middle East since the weather and social factors are similar. The modified hourly variation factor based on weather and economic and social factors of the Middle East is obtained. (author)

  12. An Enhanced System Architecture for Optimized Demand Side Management in Smart Grid

    Directory of Open Access Journals (Sweden)

    Anzar Mahmood

    2016-04-01

    Full Text Available Demand Side Management (DSM through optimization of home energy consumption in the smart grid environment is now one of the well-known research areas. Appliance scheduling has been done through many different algorithms to reduce peak load and, consequently, the Peak to Average Ratio (PAR. This paper presents a Comprehensive Home Energy Management Architecture (CHEMA with integration of multiple appliance scheduling options and enhanced load categorization in a smart grid environment. The CHEMA model consists of six layers and has been modeled in Simulink with an embedded MATLAB code. A single Knapsack optimization technique is used for scheduling and four different cases of cost reduction are modeled at the second layer of CHEMA. Fault identification and electricity theft control have also been added in CHEMA. Furthermore, carbon footprint calculations have been incorporated in order to make the users aware of environmental concerns. Simulation results prove the effectiveness of the proposed model.

  13. Side loading vault system and method for the disposal of radioactive waste

    International Nuclear Information System (INIS)

    Meess, D.C.; Jones, B.J.; Mello, R.M.; Weiss, T.G. Jr.; Wright, J.B.

    1990-01-01

    This patent describes a method for the disposal of hazardous radioactive waste. It comprises: constructing a floor slab in the earth; constructing an elongated wall assembly over the floor slab having sidewalls and a front wall and a back wall at either end the side walls being longer than the front and back walls; providing an accessway in the front wall; constructing a ceiling slab over the wall assembly that is supported at least in part by the wall assembly to form a vault cell; inspecting the vault cell for structural defects, introducing hazardous radioactive waste through the accessway in the front wall and loading the cell with the waste from the back wall to the front wall in rows, each of which is substantially parallel to the back wall to minimize radiation exposure to workers loading the cell, and closing the accessway of the vault cell by constructing a removable wall structure within the accessway

  14. Adaptive Hysteresis Band Current Control (AHB) with PLL of Grid Side Converter-Based Wind Power Generation System

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Li, Lijuan

    2011-01-01

    Adaptive hysteresis band current control(AHB CC) is used to control the three-phase grid currents by means of grid side converter in wind power generation system in this paper. AHB has reached the good purpose with PLL (Lock phase loop). First the mathematical models of each part are given......, transformer and grid, and control parts, etc. The simulation results have verified that the control strategy is feasible to fit for control of gird currents, active power, reactive power and DC-link voltage in wind power generation system....

  15. Bone mineral density among systemic lupus erythematosus patient age 5-18 years with glucocorticoid treatment in child and adolescent outpatient clinic, Cipto Mangunkusumo Hospital, Jakarta

    Science.gov (United States)

    Indriyani, N.; Tridjaja, B.; Medise, B. E.; Kurniati, N.

    2017-08-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease affecting children; its morbidity and mortality rates are significant. One risk factor for morbidity is chronic corticosteroid use. The aim of this study is to determine the occurrence rate of low bone mineral density; discuss the characteristics, including cumulative and daily doses of corticosteroid, body mass index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), calcium, and vitamin D intake; and assess bone metabolism laboratory parameters, including serum calcium, vitamin D, alkaline phosphatase (ALP), phosphorus, and cortisol among children with SLE receiving corticosteroids. This was a descriptive, cross-sectional study involving 16 children with SLE attending the child and adolescent outpatient clinic at Cipto Mangunkusumo Hospital in November-December 2016. Low bone mineral density occurred among 7/16 patients. The mean total bone mineral density was 0.885 ± 0.09 g/cm2. Children with SLE receiving corticosteroid had low calcium (8.69 ± 0.50 mg/dl), vitamin D (19.3 ± 5.4 mg/dl), ALP (79.50 [43.00-164.00] U/l), and morning cortisol level (1.20 [0.0-10.21] ug/dl), as well as calcium (587.58 ± 213.29 mg/d) and vitamin D (2.9 [0-31.8] mcg/d) intake. The occurrence of low bone mineral density was observed among children with SLE receiving corticosteroid treatment. Low bone mineral density tends to occur among patients with higher cumulative doses and longer duration of corticosteroid treatments.

  16. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

    NARCIS (Netherlands)

    Campolongo, Patrizia; Roozendaal, Benno; Trezza, Viviana; Hauer, Daniela; Schelling, Gustav; McGaugh, James L.; Cuomo, Vincenzo

    2009-01-01

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors,

  17. First report of the successful operation of a side stream supersaturation hypolimnetic oxygenation system in a eutrophic, shallow reservoir.

    Science.gov (United States)

    Gerling, Alexandra B; Browne, Richard G; Gantzer, Paul A; Mobley, Mark H; Little, John C; Carey, Cayelan C

    2014-12-15

    Controlling hypolimnetic hypoxia is a key goal of water quality management. Hypoxic conditions can trigger the release of reduced metals and nutrients from lake sediments, resulting in taste and odor problems as well as nuisance algal blooms. In deep lakes and reservoirs, hypolimnetic oxygenation has emerged as a viable solution for combating hypoxia. In shallow lakes, however, it is difficult to add oxygen into the hypolimnion efficiently, and a poorly designed hypolimnetic oxygenation system could potentially result in higher turbidity, weakened thermal stratification, and warming of the sediments. As a result, little is known about the viability of hypolimnetic oxygenation in shallow bodies of water. Here, we present the results from recent successful tests of side stream supersaturation (SSS), a type of hypolimnetic oxygenation system, in a shallow reservoir and compare it to previous side stream deployments. We investigated the sensitivity of Falling Creek Reservoir, a shallow (Zmax = 9.3 m) drinking water reservoir located in Vinton, Virginia, USA, to SSS operation. We found that the SSS system increased hypolimnetic dissolved oxygen concentrations at a rate of ∼1 mg/L/week without weakening stratification or warming the sediments. Moreover, the SSS system suppressed the release of reduced iron and manganese, and likely phosphorus, from the sediments. In summary, SSS systems hold great promise for controlling hypolimnetic oxygen conditions in shallow lakes and reservoirs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Glucocorticoid Availability in Colonic Inflammation of Rat

    Czech Academy of Sciences Publication Activity Database

    Ergang, Peter; Leden, Pavel; Bryndová, Jana; Žbánková, Šárka; Mikšík, Ivan; Kment, M.; Pácha, Jiří

    2008-01-01

    Roč. 53, č. 8 (2008), s. 2160-2167 ISSN 0163-2116 R&D Projects: GA MZd(CZ) NR8576; GA ČR GA305/07/0328 Grant - others:Univerzita Karlova(CZ) 77/2006C Institutional research plan: CEZ:AV0Z50110509 Keywords : glucocorticoids * 11beta hydroxisteroid dehydrogenase 1 Subject RIV: ED - Physiology Impact factor: 1.583, year: 2008

  19. REDUCTION IN CUTS SPEED AT THE BEGINNING OF A SORTING SIDINGS, EQUIPPED WITH QUASI-CONTINUOUS SPEED CONTROL SYSTEM

    Directory of Open Access Journals (Sweden)

    O. A. Nazarov

    2016-08-01

    Full Text Available Purpose. Clear and uninterrupted operation of humps depends on the quality of technical equipment and control technology of cuts speed. Technology of interval and purposive regulation of cuts speed is used at most humps. The article discusses ways to reduce the cuts rolling speed to a safe level at the beginning of the sorting sidings equipped with quasi-continuous speed control system. Methodology. It proposed three fundamentally different ways to reduce the cuts rolling speed at the beginning of the sorting siding. The analysis of the ways to reduce cuts rolling speed to a safe level at the beginning of the sorting sidings was conducted using simulation the process of cuts rolling from humps equipped with quasi-continuous speed control. Findings. As a result of analysis, the inappropriateness of opposite elevation using on the roll-out part of the hump after the last separation switch point. Spot regulators of cars speed can be used to reduce the cuts rolling speed at the beginning of the sorting siding, but this leads to a division conditions deterioration on the last separating switch points of long cuts with the following after them short cuts. Reducing the cuts rolling speed at the beginning of the sorting siding can be carried out using the beam on a stationary wagon retarders park brake position. Control Algorithm park brake position is quite simple. All produce should be unhooked from it at a safe speed. If the accuracy of the implementation of the set speed output to unhook from the park brake position is low, it is possible to eliminate the error of point regulators cars speed. Originality. The question where to start location point of wagon retarders zone to reduce speed to cut level requires additional research. Reducing rolling cut the speed at the beginning of the sorting sidings can be carried out using the beam on a stationary wagon retarders park brake position. Practical value. Control Algorithm park brake position is quite

  20. Biochemical endpoints of glucocorticoid hormone action

    Energy Technology Data Exchange (ETDEWEB)

    Young, D.A.; Nicholson, M.L.; Guyette, W.A.; Giddings, S.J.; Mendelsohn, S.L.; Nordeen, S.K.; Lyons, R.T.

    1978-01-01

    Both the rapidly evolving metabolic effects of glucocorticoids and the more slowly developing lethal actions appear to be initiated via the synthesis of new mRNAs and proteins. The chronic suppression of cell growth may be the consequence of suppression of overall rates of protein synthesis (and probably RNA and DNA synthesis as well) that in turn may represent the cellular response to the small changes in ratios of adenine nucleotides that result from the suppression of oxidative ATP production. The inhibition of glucose transport may also play a role here to prevent a compensatory increase in glycolytic ATP production. Some other hormone actions, the decrease in the ability of cells to concentrate AIB and the increase in nuclear fragility are unrelated to, and evolve separately from, the hormonal inhibitions on energy production. Cell killing is not the result of suppression of protein synthesis, nor of hormone-induced increases in calcium uptake. While the mechanisms are unknown, the increase in nuclear fragility appears to be the earliest measure of their operation. In tumor cells resistance to lethal actions of glucocorticoids may emerge via the selection of cells with hardier membranes, that are better able to withstand the intracellular destructive events set in motion by high levels of glucocorticoids.

  1. An Economic Evalution of Demand-side Energy Storage Systems by using a Multi-agent based Electricity Market

    Science.gov (United States)

    Furusawa, Ken; Sugihara, Hideharu; Tsuji, Kiichiro

    Opened wholesale electric power market in April 2005, deregulation of electric power industry in Japan has faced a new competitive environment. In the new environment, Independent Power Producer (: IPP), Power Producer and Supplier (: PPS), Load Service Entity (: LSE) and electric utility can trade electric energy through both bilateral contracts and single-price auction at the electricity market. In general, the market clearing price (: MCP) is largely changed by amount of total load demand in the market. The influence may cause price spike, and consequently the volatility of MCP will make LSEs and their customers to face a risk of revenue and cost. DSM is attracted as a means of load leveling, and has effect on decreasing MCP at peak load period. Introducing Energy Storage systems (: ES) is one of DSM in order to change demand profile at customer-side. In case that customers decrease their own demand at jumped MCP, a bidding strategy of generating companies may be changed their strategy. As a result, MCP is changed through such complex mechanism. In this paper the authors evaluate MCP by multi-agent. It is considered that customer-side ES has an effect on MCP fluctuation. Through numerical examples, this paper evaluates the influence on MCP by controlling customer-side ES corresponding to variation of MCP.

  2. Cytokine modulation by glucocorticoids: mechanisms and actions in cellular studies.

    Science.gov (United States)

    Brattsand, R; Linden, M

    1996-01-01

    Glucocorticoids inhibit the expression and action of most cytokines. This is part of the in vivo feed-back system between inflammation-derived cytokines and CNS-adrenal produced corticosteroids with the probable physiological relevance to balance parts of the host defence and anti-inflammatory systems of the body. Glucocorticoids modulate cytokine expression by a combination of genomic mechanisms. The activated glucocorticoid-receptor complex can (i) bind to and inactivate key proinflammatory transcription factors (e.g. AP-1, NF kappa B). This takes place at the promotor responsive elements of these factors, but has also been reported without the presence of DNA; (ii) via glucocorticoid responsive elements (GRE), upregulate the expression of cytokine inhibitory proteins, e.g. I kappa B, which inactivates the transcription factor NF kappa B and thereby the secondary expression of a series of cytokines; (iii) reduce the half-life time and utility of cytokine mRNAs. In studies with triggered human blood mononuclear cells in culture, glucocorticoids strongly diminish the production of the 'initial phase' cytokines IL-1 beta and TNF-alpha and the 'immunomodulatory' cytokines IL-2, IL-3, IL-4, IL-5, IL-10, IL-12 and IFN-gamma, as well as of IL-6, IL-8 and the growth factor GM-CSF. While steroid treatment broadly attenuates cytokine production, it cannot modulate it selectively, e.g. just the TH0, the TH1 or the TH2 pathways. The production of the 'anti-inflammatory' IL-10 is also inhibited. The exceptions of steroid down-regulatory activity on cytokine expression seem to affect 'repair phase' cytokines like TGF-beta and PDGF. These are even reported to be upregulated, which may explain the rather weak steroid dampening action on healing and fibrotic processes. Some growth factors, e.g. G-CSF and M-CSF, are only weakly affected. In addition to diminishing the production of a cytokine, steroids can also often inhibit its subsequent actions. Because cytokines work in

  3. Life-threatening and disabling injuries in car-to-car side impacts--implications for development of protective systems.

    Science.gov (United States)

    Håland, Y; Lövsund, P; Nygren, A

    1993-04-01

    Improvements to the passive safety of cars in lateral collisions are of great importance. This study of injuries in car side collisions in Sweden by the use of two evaluation methods has been performed to establish the basis for future development of protective systems for this type of accident. The Folksam car accident data file has been used. Injuries were found to be twice as common for near-side than for far-side* occupants in car to car impacts. Serious to fatal (AIS 3-6) injuries to belted front seat occupants in near side impacts (10% of all injuries) were compared with the estimated number of injuries to different parts of the body with risk of serious consequences (RSC)--either deaths or permanent disabilities (4.5% of all injuries). The two injury evaluation methods resulted in different ranking orders. AIS 3-6 injuries were received by the chest (37%), abdomen/pelvis (25%), and the head (15%). The RSC method gave a ranking order of head (25%), neck (21%), leg (15%), chest (14%), and abdomen/pelvis (11%). The method of evaluating AIS 3-6 injuries emphasizes only the threat to life. The RSC method also takes into account the risk of disabilities. Injuries to the neck and the leg were found to be most disabling, whilst the injuries to the head, chest, and abdomen/pelvis were the most life threatening. The study also shows that elderly people receive significantly more chest injuries (relative to the number of head injuries), on average four times more than young people.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. New conditions on synchronization of networks of linearly coupled dynamical systems with non-Lipschitz right-hand sides.

    Science.gov (United States)

    Liu, Bo; Lu, Wenlian; Chen, Tianping

    2012-01-01

    In this paper, we study synchronization of networks of linearly coupled dynamical systems. The node dynamics of the network can be very general, which may not satisfy the QUAD condition. We derive sufficient conditions for synchronization, which can be regarded as extensions of previous results. These results can be employed to networks of coupled systems, of which, in particular, the node dynamics have non-Lipschitz or even discontinuous right-hand sides. We also give several corollaries where the synchronization of some specific non-QUAD systems can be deduced. As an application, we propose a scheme to realize synchronization of coupled switching systems via coupling the signals which drive the switchings. Examples with numerical simulations are also provided to illustrate the theoretical results. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Removal time and efficacy of Riddell Quick Release Face Guard Attachment System side clips during 1 football season.

    Science.gov (United States)

    Gruppen, Tonia; Smith, Molly; Ganss, Andrea

    2012-01-01

    In the National Athletic Trainers' Association position statement, "Acute Management of the Cervical Spine-Injured Athlete," the technique recommended for face-mask (FM) removal is one that "creates the least head and neck motion, is performed most quickly, is the least difficult, and carries the least chance of failure." Industrial and technological advances in football helmet design and FM attachment systems might influence the efficacy of emergency FM removal. To examine the removal times and success rates of the Quick Release (QR) Face Guard Attachment System (Riddell Sports, Inc, Elyria, OH) throughout and at the conclusion of 1 season of play by a National Collegiate Athletic Association Division III football team competing in the Midwest. Controlled laboratory study. College laboratory. A total of 69 randomly selected Revolution IQ (Riddell Sports, Inc) football helmets fitted with the QR system were used. Each helmet was secured to a spine board, and investigators attempted to remove both of the QR side clips from the helmet with the Riddell insertion tool. Dependent variables included total time for removal of both QR side clips from the FM and success rate for removal of both side clips. The overall success rate for removal of both clips was 94.8% (164/173), whereas the mean times for removal of both clips ranged from 9.92 ± 12.06 seconds to 16.65 ± 20.97 seconds over 4 trial sessions. We found no differences among mean times for trial sessions throughout the season of play among the same helmets or among different helmets (P > .05). Removal time and success rate of the Riddell QR were satisfactory during and after 1 season of play despite use in various temperatures and precipitation.

  6. Removal Time and Efficacy of Riddell Quick Release Face Guard Attachment System Side Clips During 1 Football Season

    Science.gov (United States)

    Gruppen, Tonia; Smith, Molly; Ganss, Andrea

    2012-01-01

    Context In the National Athletic Trainers' Association position statement, “Acute Management of the Cervical Spine-Injured Athlete,” the technique recommended for face-mask (FM) removal is one that “creates the least head and neck motion, is performed most quickly, is the least difficult, and carries the least chance of failure.” Industrial and technological advances in football helmet design and FM attachment systems might influence the efficacy of emergency FM removal. Objective To examine the removal times and success rates of the Quick Release (QR) Face Guard Attachment System (Riddell Sports, Inc, Elyria, OH) throughout and at the conclusion of 1 season of play by a National Collegiate Athletic Association Division III football team competing in the Midwest. Design Controlled laboratory study. Setting College laboratory. Patients or Other Participants A total of 69 randomly selected Revolution IQ (Riddell Sports, Inc) football helmets fitted with the QR system were used. Intervention(s) Each helmet was secured to a spine board, and investigators attempted to remove both of the QR side clips from the helmet with the Riddell insertion tool. Main Outcome Measure(s) Dependent variables included total time for removal of both QR side clips from the FM and success rate for removal of both side clips. Results The overall success rate for removal of both clips was 94.8% (164/173), whereas the mean times for removal of both clips ranged from 9.92 ± 12.06 seconds to 16.65 ± 20.97 seconds over 4 trial sessions. We found no differences among mean times for trial sessions throughout the season of play among the same helmets or among different helmets (P > .05). Conclusions Removal time and success rate of the Riddell QR were satisfactory during and after 1 season of play despite use in various temperatures and precipitation. PMID:22889658

  7. Glucocorticoid actions on L6 muscle cells in culture

    International Nuclear Information System (INIS)

    Max, S.R.; Konagaya, M.; Konagaya, Y.

    1986-01-01

    Glucocorticoids exert striking catabolic effects on skeletal muscle. The mechanism of these effects remains poorly understood. They employed L6 muscle cells in culture to ascertain whether intracellular glucocorticoid receptors are involved. Studies in vitro permit exploration of glucocorticoid effects in the absence of other hormonal influences. L6 myoblasts were induced to form differentiated myotubes by growth in 1% serum. L6 myotubes were found to possess a high-affinity, limited capacity intracellular glucocorticoid receptor (apparent K/sub D/ = 5 x 10 -10 M; B/sub max/ = 711 pmols/g protein) with ligand specificity similar to that of glucocorticoid receptors from classical glucocorticoid target tissues. Further, [ 3 H] triamcinolone acetonide specific binding to L6 cell homogenates was blocked by a glucocorticoid antagonist, RU38486 (11β-(4-dimethyl-aminophenyl)-17β-hydroxy-17α-(prop-l-ynyl)-estra-4,9-dien-3-one). Dexamethasone (10 -5 M) caused a 10-fold increase in the activity of gluatmine synthetase in L6 myotubes; this increase was prevented by RU38486. Similarly, dexamethasone (10 -5 M) caused a 20% decrease in [ 12 C] leucine incorporation into protein. This effect also was blocked by RU38486. Thus, induction of glutamine synthetase and diminution of protein synthesis by dexamethasone require intracellular glucocorticoid receptors. L6 cells should prove particularly valuable for further studies of glucocorticoid actions on skeletal muscle

  8. Modeling and Control of Grid Side Converter in Wind Power Generation System Based on Synchronous VFDPC with PLL

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Li, Lijuan

    2011-01-01

    Virtual flux oriented direct power control (VFDPC) is combined space vector modulation (SVM) with PI of DC-link voltage, active power and reactive power to control the grid side converter in wind power generation system in this paper. VFDPC has reached good performances with PLL (phase lock loop......, LCL filter, transformer grid, and control parts, such as PI controllers of DC-link voltage, active power, reactive power, and SVM, and so on. The simulation results have verified that the control strategy is feasible to fit for control of gird currents, active power, reactive power and DC-link voltage...

  9. GlobePort Faces Global Business Challenges--Assessing the Organizational Side of Information Systems Projects

    Science.gov (United States)

    Ghosh, Biswadip

    2011-01-01

    Published studies have reported that Information System (IS) projects succeed or fail based on how effectively the organizational issues were understood and addressed in the specification, development and implementation stages of the project. This is particularly true in the design and delivery of Inter-Organizational Systems (IOS) that can affect…

  10. Stress, glucocorticoid hormones, and hippocampal neural progenitor cells: implications to mood disorders.

    Science.gov (United States)

    Kino, Tomoshige

    2015-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis and its end-effectors glucocorticoid hormones play central roles in the adaptive response to numerous stressors that can be either internal or external. Thus, this system has a strong impact on the brain hippocampus and its major functions, such as cognition, memory as well as behavior, and mood. The hippocampal area of the adult brain contains neural stem cells or more committed neural progenitor cells, which retain throughout the human life the ability of self-renewal and to differentiate into multiple neural cell lineages, such as neurons, astrocytes, and oligodendrocytes. Importantly, these characteristic cells contribute significantly to the above-indicated functions of the hippocampus, while various stressors and glucocorticoids influence proliferation, differentiation, and fate of these cells. This review offers an overview of the current understanding on the interactions between the HPA axis/glucocorticoid stress-responsive system and hippocampal neural progenitor cells by focusing on the actions of glucocorticoids. Also addressed is a further discussion on the implications of such interactions to the pathophysiology of mood disorders.

  11. Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

    Directory of Open Access Journals (Sweden)

    Jaime M. Ross

    2015-08-01

    Full Text Available Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing.

  12. The BL-QMR algorithm for non-Hermitian linear systems with multiple right-hand sides

    Energy Technology Data Exchange (ETDEWEB)

    Freund, R.W. [AT& T Bell Labs., Murray Hill, NJ (United States)

    1996-12-31

    Many applications require the solution of multiple linear systems that have the same coefficient matrix, but differ in their right-hand sides. Instead of applying an iterative method to each of these systems individually, it is potentially much more efficient to employ a block version of the method that generates iterates for all the systems simultaneously. However, it is quite intricate to develop robust and efficient block iterative methods. In particular, a key issue in the design of block iterative methods is the need for deflation. The iterates for the different systems that are produced by a block method will, in general, converge at different stages of the block iteration. An efficient and robust block method needs to be able to detect and then deflate converged systems. Each such deflation reduces the block size, and thus the block method needs to be able to handle varying block sizes. For block Krylov-subspace methods, deflation is also crucial in order to delete linearly and almost linearly dependent vectors in the underlying block Krylov sequences. An added difficulty arises for Lanczos-type block methods for non-Hermitian systems, since they involve two different block Krylov sequences. In these methods, deflation can now occur independently in both sequences, and consequently, the block sizes in the two sequences may become different in the course of the iteration, even though they were identical at the beginning. We present a block version of Freund and Nachtigal`s quasi-minimal residual method for the solution of non-Hermitian linear systems with single right-hand sides.

  13. A semi-distributed electric demand-side management system with PV generation for self-consumption enhancement

    International Nuclear Information System (INIS)

    Castillo-Cagigal, M.; Gutierrez, A.; Monasterio-Huelin, F.; Caamano-Martin, E.; Masa, D.; Jimenez-Leube, J.

    2011-01-01

    Highlights: → We have developed a DSM system with PV electricity and battery storage. → To implement the DSM system, we have developed a modular architecture. → Simulations and real experiments have been executed for different weather conditions. → The use of theses technologies increase the self-consumed energy. -- Abstract: This paper presents the operation of an Electrical Demand-Side Management (EDSM) system in a real solar house. The use of EDSM is one of the most important action lines to improve the grid electrical efficiency. The combination between the EDSM and the PV generation performs a new control level in the local electric behavior and allows new energy possibilities. The solar house used as test-bed for the EDSM system owns a PV generator, a lead-acid battery storage system and a grid connection. The electrical appliances are controllable from an embedded computer. The EDSM is implemented by a control system which schedules the tasks commanded by the user. By using the control system, we define the house energy policy and improve the energy behavior with regard to a selected energy criterion, self-consumption. The EDSM system favors self-consumption with regard to a standard user behavior and reduces the energy load from the grid.

  14. Building America Case Study: Side-by-Side Testing of Water Heating Systems: Results from 2013-2014 Evaluation Final Report, Cocoa, FL

    Energy Technology Data Exchange (ETDEWEB)

    Rothgeb, Stacey K [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Colon, C. [BA-PIRC; Martin, E. [BA-PIRC

    2017-08-24

    The Florida Solar Energy Center (FSEC) has completed a fourth year-long evaluation on residential hot water heating systems in a laboratory environment (east central Florida, hot-humid climate). This report contains a summary of research activities regarding the evaluation of two residential electric heat pump water heaters (HPWHs), a solar thermal system utilizing a polymer glazed absorber and a high efficiency natural gas system.

  15. Building America Case Study: Side-by-Side Testing of Water Heating Systems: Results from the 2013–2014 Evaluation Final Report

    Energy Technology Data Exchange (ETDEWEB)

    C. Colon and E. Martin

    2017-08-24

    The Florida Solar Energy Center (FSEC) has completed a fourth year-long evaluation on residential hot water heating systems in a laboratory environment (east central Florida, hot-humid climate). This report contains a summary of research activities regarding the evaluation of two residential electric heat pump water heaters (HPWHs), a solar thermal system utilizing a polymer glazed absorber and a high efficiency natural gas system.

  16. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

    Directory of Open Access Journals (Sweden)

    Diego M Presman

    2014-03-01

    Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

  17. How to fit demand side management (DSM) into current Chinese electricity system reform?

    International Nuclear Information System (INIS)

    Yu Yongzhen

    2012-01-01

    DSM is one of the best and most practical policy tools available to China for balancing environmental protection and economic growth. The new round of electricity system reform provides a good opportunity to consolidate and integrate DSM policy and expedite its development and implementation. DSM policy can be upgraded by incorporating it into the current electricity system reform. Comparing the potential acceleration of electricity price reform with the possibility of imposing a System Benefit Charge (SBC), the author argues that support for a SBC would be much easier to gather among policymakers and stakeholders in a short time and would have a much better policy effect in the current situation. The author discusses three kinds of price discrimination related to the DSM development in China: time-based electricity pricing, electricity price discrimination for industrial structure adjustment in China (Fujian Province as a case), and direct power purchases by large customers and preferential tariff policy. These can be well designed to be combined with DSM and energy efficiency policy. - Highlights: ► Elements of DSM have been in place since 1993, but without even and reinforced policy. ► DSM can be upgraded by fitting it into current Chinese electricity system reform. ► Both electricity price reform and SBC would mean increases in electricity payment. ►Imposing SBC is much easier and better than speeding up electricity price reform. ► Three kinds of price discrimination can be well designed to be combined with DSM.

  18. Towards a demand-side smart domestic electrical energy management system

    CSIR Research Space (South Africa)

    Dlodlo, N

    2013-01-01

    Full Text Available systems that could assist the end-user in achieving this goal. This paper addresses the issue of electrical energy conservation in the home through the adoption of smart technologies (one instantiation of smart technologies). Smart objects are everyday...

  19. Comparing supply-side specifications in models of global agriculture and the food system

    NARCIS (Netherlands)

    Robinson, S.; Meijl, van J.C.M.; Willenbockel, D.; Valin, H.; Fujimori, S.; Masui, T.; Sands, R.; Wise, M.; Calvin, K.V.; Mason d'Croz, D.; Tabeau, A.A.; Kavallari, A.; Schmitz, C.; Dietrich, J.P.; Lampe, von M.

    2014-01-01

    This article compares the theoretical and functional specification of production in partial equilibrium (PE) and computable general equilibrium (CGE) models of the global agricultural and food system included in the AgMIP model comparison study. The two model families differ in their scope—partial

  20. Early Life Stress Effects on the Glucocorticoid - BDNF interplay in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Nikolaos P Daskalakis

    2015-11-01

    Full Text Available Early life stress (ELS is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid and/or neurotrophin signaling pathways. Glucocorticoid (GC signaling mediates the regulation of the stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and glucocorticoid signaling pathways co-exist throughout the central nervous system (CNS, particularly in the hippocampus, which has high expression of glucocorticoid and mineralocorticoid receptors (GR and MR as well as brain-derived neurotrophic factor (BDNF and its receptor, tropomyosin-related kinase receptor B (TrkB. This review addresses the effects of ELS paradigms on GC- and BDNF- dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders.

  1. Quality assurance of double-sided silicon microstrip sensors for the silicon tracking system in the CBM experiment at FAIR

    Energy Technology Data Exchange (ETDEWEB)

    Larionov, Pavel [Goethe Universitaet, Frankfurt (Germany); Collaboration: CBM-Collaboration

    2015-07-01

    The Silicon Tracking System (STS) is the core tracking detector of the CBM experiment at FAIR. The system's task is to reconstruct the trajectories of the charged particles produced in the beam-target interactions, provide their momentum determination, and enable the detection of decay topologies. The STS will comprise 1220 double-sided silicon microstrip sensors. After production each sensor will go through a number of Quality Assurance procedures to verify their validity for performance in the STS and also to confirm the manufacturer's data. In this talk, results of the quality assurance procedures that are being applied to the latest STS prototype sensors, including detailed tests of the quality of each single strip, long-term stability and preparations for volume tests during series production, are presented.

  2. Portable double-sided pulsed laser heating system for time-resolved geoscience and materials science applications.

    Science.gov (United States)

    Aprilis, G; Strohm, C; Kupenko, I; Linhardt, S; Laskin, A; Vasiukov, D M; Cerantola, V; Koemets, E G; McCammon, C; Kurnosov, A; Chumakov, A I; Rüffer, R; Dubrovinskaia, N; Dubrovinsky, L

    2017-08-01

    A portable double-sided pulsed laser heating system for diamond anvil cells has been developed that is able to stably produce laser pulses as short as a few microseconds with repetition frequencies up to 100 kHz. In situ temperature determination is possible by collecting and fitting the thermal radiation spectrum for a specific wavelength range (particularly, between 650 nm and 850 nm) to the Planck radiation function. Surface temperature information can also be time-resolved by using a gated detector that is synchronized with the laser pulse modulation and space-resolved with the implementation of a multi-point thermal radiation collection technique. The system can be easily coupled with equipment at synchrotron facilities, particularly for nuclear resonance spectroscopy experiments. Examples of applications include investigations of high-pressure high-temperature behavior of iron oxides, both in house and at the European Synchrotron Radiation Facility using the synchrotron Mössbauer source and nuclear inelastic scattering.

  3. Benefits of Demand Side Response in Providing Frequency Response Service in the Future GB Power System

    Directory of Open Access Journals (Sweden)

    Fei eTeng

    2015-08-01

    Full Text Available The demand for ancillary service is expected to increase significantly in the future GB electricity system due to high penetration of wind. In particular, the need for frequency response, required to deal with sudden frequency drops following a loss of generator, will increase because of the limited inertia capability of wind plants. This paper quantifies the requirements for primary frequency response and analyses the benefits of frequency response provision from DSR. The results show dramatic changes in frequency response requirements driven by high penetration of wind. Case studies carried out by using an advanced stochastic generation scheduling model suggest that the provision of frequency response from DSR could greatly reduce the system operation cost, wind curtailment and carbon emissions in the future GB system characterised by high penetration of wind. Furthermore, the results demonstrate that the benefit of DSR shows significant diurnal and seasonal variation, whereas an even more rapid (instant delivery of frequency response from DSR could provide significant additional value. Our studies also indicate that the competing technologies to DSR, namely battery storage and more flexible generation could potentially reduce its value by up to 35%, still leaving significant room to deploy DSR as frequency response provider.

  4. Anti-Inflammatory Modulation of Microglia via CD163-Targeted Glucocorticoids Protects Dopaminergic Neurons in the 6-OHDA Parkinson's Disease Model

    DEFF Research Database (Denmark)

    Tentillier, Noemie; Etzerodt, Anders; Olesen, Mads N

    2016-01-01

    intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia...

  5. A side-by-side comparison of two systems of sequencing coupled reactors for anaerobic digestion of the organic fraction of municipal solid waste.

    Science.gov (United States)

    Poggi-Varaldo, Héctor M; Alzate-Gaviria, Liliana M; Pérez-Hernández, Antonino; Nevarez-Morillón, Virginia G; Rinderknecht-Seijas, Noemí

    2005-06-01

    The objective of this work was to compare the performance of two laboratory-scale, mesophilic systems aiming at the anaerobic digestion of the organic fraction of municipal solid wastes (OFMSW). The first system consisted of two coupled reactors packed with OFMSW (PBR1.1-PBR1.2) and the second system consisted of an upflow anaerobic sludge bed reactor (UASB) coupled to a packed reactor (UASB2.1-PBR2.2). For the start-up phase, both reactors PBR 1.1 and the UASB 2.1 (also called leading reactors) were inoculated with a mixture of non-anaerobic inocula and worked with leachate and effluent full recirculation, respectively. Once a full methanogenic regime was achieved in the leading reactors, their effluents were fed to the fresh-packed reactors PBR1.2 and PBR2.2, respectively. The leading PBR 1.1 reached its full methanogenic regime after 118 days (Tm, time to achieve methanogenesis) whereas the other leading UASB 2.1 reactor reached its full methanogenesis regime after only 34 days. After coupling the leading reactors to the corresponding packed reactors, it was found that both coupled anaerobic systems showed similar performances regarding the degradation of the OFMSW. Removal efficiencies of volatile solids and cellulose and the methane pseudo-yield were 85.95%, 80.88% and 0.109 NL CH4 g(-1) VS(fed) in the PBR-PBR system; and 88.75%, 82.61% and 0.115 NL CH4 g(-1) VS(fed0 in the UASB-PBR system [NL, normalized litre (273 degrees K, 1 ata basis)]. Yet, the second system UASB-PBR system showed a faster overall start-up.

  6. New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention.

    Science.gov (United States)

    Kolodziejczyk, Patrycjusz; Gromotowicz-Poplawska, Anna; Aleksiejczuk, Michal; Chabielska, Ewa; Tutka, Piotr; Miltyk, Wojciech

    2018-03-26

    Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although, this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important important as a local messenger in the pathology of cardiovascular diseases (CVD). In the last few years, the attention was focused on the correlation between raised aldosterone level and increased risk of cardiovascular events. It has been demonstrated that aldosterone contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic disordes, and oxidative stress leading to CVD development and progression. It used to be thought that the effects of aldosterone are mediated via classic nuclear receptors - mineralocorticoid receptors (MR). Now we know that the mechanism of aldosterone action in cardiovascular system is much more complex, since experimental and clinical studies indicate that MR blockade may be not sufficient to abolish aldosterone-incuced harmful effects in the cardiovascular system. Therefore, the involvement of some other than MR, receptors and factors is suggested. Moreover, in addition to the generally known genomic action of aldosterone, which involves MR activation, the nongenomic pathways are postulated in the mode of hormone action. More and more attention is focused on the membrane-coupled receptors, which mediate the rapid effects of aldosterone and have been already confirmed in different cells and tissues of a cardiovascular system. The confirmation of multiple mechanisms of aldosterone action opens a new perspective for more effective therapeutic intervention in aldosterone-related CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. The Segmented Aperture Interferometric Nulling Testbed (SAINT) I: overview and air-side system description

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter; Ballard, Marlin; Bolcar, Matthew R.; Bolognese, Jeff; Clampin, Mark; Dogoda, Peter; Dworzanski, Daniel; Helmbrecht, Michael A.; Koca, Corina; Shiri, Ron

    2016-07-01

    This work presents an overview of the Segmented Aperture Interferometric Nulling Testbed (SAINT), a project that will pair an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC). SAINT will incorporate the VNC's demonstrated wavefront sensing and control system to refine and quantify end-to-end high-contrast starlight suppression performance. This pathfinder testbed will be used as a tool to study and refine approaches to mitigating instabilities and complex diffraction expected from future large segmented aperture telescopes.

  8. Glucocorticoids facilitate the retention of acquired immobility during forced swimming

    NARCIS (Netherlands)

    Veldhuis, H D; De Korte, C C; De Kloet, E R

    1985-01-01

    The adrenalectomy-induced decrease in the level of immobility during a 5 min retest period in the Porsolt swimming test could be reversed by glucocorticoids administered s.c. 15 min after the initial forced swimming exposure. The synthetic glucocorticoids dexamethasone and RU 28362 were active in

  9. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Kroon, Jan; Puhr, M.; Buijs, J.T.; van der Horst, G.; Hemmer, D.M.; Marijt, K.A.; Hwang, M.S.; Masood, M.; Grimm, S.; Storm, Gerrit; Metselaar, Josbert Maarten; Meijer, O.C.; Culig, Z.; van der Pluijm, M.

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

  10. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan; Puhr, Martin; Buijs, Jeroen T.; Van Der Horst, Geertje; Lemhemmer, Daniël; Marijt, Koen A.; Hwang, Ming S.; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M.|info:eu-repo/dai/nl/244207690; Meijer, Onno C.; Culig, Zoran; Van Der Pluijm, Gabri

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCA). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance.

  11. Using fecal glucocorticoids for stress assessment in Mourning Doves

    Science.gov (United States)

    Washburn, Brian E.; Millspaugh, Joshua J.; Schulz, John H.; Jones, Susan B.; Mong, T.

    2003-01-01

    Fecal glucocorticoid assays provide a potentially useful, noninvasive means to study physiological responses of wildlife to various stressors. The objective of our study was to validate a method for measuring glucocorticoid metabolites in Mourning Dove (Zenaida macroura) feces. We validated the assay using standard procedures (e.g., parallelism, recovery of exogenous corticosterone) to demonstrate that the assay accurately and precisely measured glucocorticoid metabolites in Mourning Dove fecal extracts. We conducted adrenocorticotropin (ACTH) challenge experiments to validate the assay's ability to determine biologically important changes in fecal glucocorticoids. Fecal glucocorticoid levels increased significantly approximately 2-3 hr after administration of ACTH at 50 IU per kg body mass to wild Mourning Doves held in captivity. In contrast, fecal glucocorticoid metabolites did not increase in control birds, birds that received saline injections, or a lower dose of ACTH (1 IU per kg body mass). Variation in overall fecal glucocorticoid metabolite levels may have been influenced by season and the length of time birds were held in captivity. Non-invasive fecal glucocorticoid metabolite analyses, in combination with demographic information, may have considerable utility for monitoring the effects of natural and anthropogenic disturbances on Mourning Dove populations.

  12. Morphodynamic assessment of side channel systems using a simple one-dimensional bifurcation model and a comparison with aerial images

    NARCIS (Netherlands)

    van Denderen, R. Pepijn; Schielen, Ralph M.J.; Blom, Astrid; Hulscher, Suzanne J.M.H.; Kleinhans, Maarten G.

    2017-01-01

    Side channel construction is a common intervention applied to increase a river's conveyance capacity and to increase its ecological value. Past modelling efforts suggest two mechanisms affecting the morphodynamic change of a side channel: (1) a difference in channel slope between the side channel

  13. Morphodynamic assessment of side channel systems using a simple one-dimensional bifurcation model and a comparison with aerial images

    NARCIS (Netherlands)

    van Denderen, R. Pepijn; Schielen, Ralph M.J.; Blom, A.; Hulscher, Suzanne J.M.H.; Kleinhans, Maarten G.

    2017-01-01

    Side channel construction is a common intervention applied to increase a river's conveyance capacity and to increase its ecological value. Past modelling efforts suggest two mechanisms affecting the morphodynamic change of a side channel: (1) a difference in channel slope between the side channel

  14. Morphodynamic assessment of side channel systems using a simple one-dimensional bifurcation model and a comparison with aerial images

    NARCIS (Netherlands)

    Van Denderen, R. Pepijn; Schielen, Ralph Mathias Johannes; Blom, Astrid; Hulscher, Suzanne J.M.H.; Kleinhans, Maarten G.

    2018-01-01

    Side channel construction is a common intervention applied to increase the river's conveyance capacity and to increase its ecological value. Past modelling efforts suggest two mechanisms affecting the morphodynamic change of a side channel: 1) a difference in channel slope between the side channel

  15. Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    S. Lukacs

    2013-01-01

    Full Text Available Intravesical Bacilli Calmette-Guérin (BCG immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin, he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

  16. Exogenous glucocorticoids and adverse cerebral effects in children

    DEFF Research Database (Denmark)

    Damsted, Sara K.; Born, A P; Paulson, Olaf B

    2011-01-01

    of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids...... reduces neurogenesis and cerebral volume, impairs memory and increases the incidence of cerebral palsy. Cerebral effects of glucocorticoids in later childhood have been less thoroughly studied, but apparent brain atrophy, reduced size of limbic structures and neuropsychiatric symptoms have been reported....... Glucocortioids affect several cellular structures and functions, which may explain the observed adverse effects. Glucocorticoids can impair neuronal glucose uptake, decrease excitability, cause atrophy of dendrites, compromise development of myelin-producing oligodendrocytes and disturb important cellular...

  17. Managing hypertriglyceridemia in children with systemic lupus erythematosus: Two sides of the same coin.

    Science.gov (United States)

    Basu, Biswanath; Babu, Binu George; Bhattacharyya, Suman

    Hypertriglyceridemia is common in children with systemic lupus erythematosus (SLE). A retrospective analysis of the baseline clinical-pathological presentation and treatment outcome (status of lipid profiles) was performed in two children with SLE, who presented with extreme hypertriglyceridemia over a follow-up period of four weeks. The children were treated with prednisolone, mycophenolate mofetil (MMF), hydroxychloroquine and hypolipidemic agents, depending on their disease status. On serial follow-up, the first child showed a significantly raised serum triglyceride level after receiving one week of oral prednisolone therapy. Anti-lipoprotein-lipase (LPL) autoantibody was absent. Lipid profile levels of this child gradually improved after replacing oral prednisolone with another immunosuppressant, namely MMF. The second child presented with extreme hypertriglyceridemia with positive anti-LPL autoantibody. She responded to plasmapheresis followed by increasing the dose of immunosuppressant. So, extreme hypertriglyceridemia in children with SLE may be steroid induced or due to presence of anti-LPL auto antibody. Management should be individualized depending on the etiology. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  18. Voltammetry and coulometry of indium in two-side thin-layer system

    International Nuclear Information System (INIS)

    Eliseeva, L.V.; Kabanova, O.L.

    1980-01-01

    An electrochemical behaviour of In and possibilities for its determination have been investigated, using halide background solutions, by voltametry in the thin solution layer thin mercury film system. It has been shown that the maximum current of indium (3) is directly proportional to its concentration over a range of 1x10 -4 - 5x10 -3 M and the maximum current of indium oxidation from the amalgam over a range of 5x10 -7 - 1x10 -4 M. Examined were the effects of halide ion concentration, pH, electrode potential change rate on current maximum value, product efficiency of reducing indium (3) and oxidizing its amalgam, on maximum current potential and half-peak width. The analytical signal has been found to be directly proportional to chloride ion concentration over a range of 0.1 - 3.0 M, bromide and iodide ion concentration over a range of 0.1 - 1.0 M. This makes it possible to use the method for determination of halide ions

  19. The visual system in migraine: from the bench side to the office.

    Science.gov (United States)

    Kowacs, Pedro A; Utiumi, Marco A; Piovesan, Elcio J

    2015-02-01

    Throughout history, migraine-associated visual symptoms have puzzled patients, doctors, and neuroscientists. The visual aspects of migraine extend far beyond the aura phenomena, and have several clinical implications. A narrative review was conducted, beginning with migraine mechanisms, then followed by pertinent aspects of the anatomy of visual pathways, clinical features, implications of the visual system on therapy, migraine on visually impaired populations, treatment of visual auras and ocular (retinal) migraine, effect of prophylactic migraine treatments on visual aura, visual symptoms induced by anti-migraine or anti-headache drugs, and differential diagnosis. A comprehensive narrative review from both basic and clinical standpoints on the visual aspects of migraine was attained; however, the results were biased to provide any useful information for the clinician. This paper achieved its goals of addressing and condensing information on the pathophysiology of the visual aspects of migraine and its clinical aspects, especially with regards to therapy, making it useful not only for those unfamiliar to the theme but to experienced physicians as well. © 2015 American Headache Society.

  20. Inflammation in Parkinson’s disease: Role of glucocorticoids

    Directory of Open Access Journals (Sweden)

    Maria Trinidad eHerrero

    2015-04-01

    Full Text Available Chronic inflammation is a major characteristic feature of Parkinson’s disease (PD. Studies in PDpatients show evidence of augmented levels of potent pro-inflammatory molecules e.g. TNF-α, iNOS,IL-1β whereas in experimental Parkinsonism it has been consistently demonstrated that dopaminergicneurons are particularly vulnerable to activated glia releasing these toxic factors. Recent geneticstudies point to the role of immune system in the etiology of PD, thus in combination withenvironmental factors, both peripheral and CNS-mediated immune responses could play importantroles in onset and progression of PD. Whereas microglia, astrocytes and infiltrating T cells are knownto mediate chronic inflammation, the roles of other immune-competent cells are less well understood.Inflammation is a tightly controlled process. One major effector system of regulation is HPA axis.Glucocorticoids released from adrenal glands upon stimulation of HPA axis, in response to either cellinjury or presence of pathogen, activate their receptor, GR. GR regulates inflammation both throughdirect transcriptional action on target genes and by indirectly inhibiting transcriptional activities oftranscriptional factors such as NF-kB, AP-1 or interferon regulatory factors. In PD patients, the HPAaxis is unbalanced and the cortisol levels are significantly increased, implying a deregulation of GRfunction in immune cells. In experimental Parkinsonism, the activation of microglial GR has a crucialeffect in diminishing microglial cell activation and reducing dopaminergic degeneration. Moreover,glucocorticoids are also known to regulate human brain vasculature as well as blood brain barrierpermeability, any dysfunction in their actions may influence infiltration of cytotoxic moleculesresulting in increased vulnerability of dopamine neurons in PD. Overall, deregulation ofGR actions is likely important in dopamine neuron degeneration throughestablishment of chronic inflammation.

  1. Experimental study on thermal-hydraulic characteristics of secondary-side passive ECRHR system of AC600

    International Nuclear Information System (INIS)

    Chen Bingde; Xiao Zejun; Zhuo Wenbin

    1998-10-01

    An integral system experimental test rig was designed to study the thermal-hydraulic characteristics of secondary-side passive emergency core residual heat removal (ECRHR) system of AC600. Total sets of 166 experimental data on steady state have been obtained and main influence factors on heat removal capacity are identified. The experimental data shows that core residual heat can be removed through natural circulation under the condition of circumstance temperature 6∼23 degree C and L th of 11 m, provided wind-speed higher than 1.5 m/s in the test parameter scope. Experimental results illustrate that short disturbance of wind-speed, power and valve opening had no significant impact on natural circulation. The system seems to tolerate to these disturbance. A correlation of two-phase natural circulation flow rate is derived from constitutive equations by using of specific system parameters and several semi-empirical formulas are obtained. Compared with the measuring data, the deviation of 98.8% data points is within +-15%. The objectives of transient experiment study is to investigate the start-up modes and transition behaviors. The results of 46 runs show the natural circulation of system can be set up by means of all three start-up modes, and its transient characteristics, especially, the system stability and transit time are determined by not only start-up modes, but also system's configuration, initial and boundary conditions, mainly. The calculating results of MISAP-PRHR code, a computer code developed for passive safety system, reveal that it can predict quantitatively the steady state characteristics, such as, pressure, flowrate, heat removal capacity and the stable transient process can be well simulated, too

  2. Economic and environmental impacts from the implementation of an intelligent demand side management system at the European level

    International Nuclear Information System (INIS)

    Papagiannis, G.; Dagoumas, A.; Lettas, N.; Dokopoulos, P.

    2008-01-01

    This paper presents the results of an analysis on the economic and environmental impacts of the application of an intelligent demand side management system, called the Energy Consumption Management System (ECMS), in the European countries. The ECMS can be applied for the control of individual, widely distributed electric loads, using the power distribution network as the command communication channel. The system can be applied in public lighting, in the tertiary and residential sectors, as well as in the industry. A top-down analysis investigates the possible penetration levels in each application area. The long-term impacts following the application of system are evaluated using the LEAP2006 platform. The WASP IV model is also used for the optimization of the power generation expansion and the corresponding calibration of LEAP2006. Several operational strategies combining variable market penetration of the ECMS and expected energy savings are examined. Results show that, under a logical market penetration, a reduction of 1-4% in primary energy, of 1.5-5% in CO 2 emissions and a 2-8% saving in investment costs for power generation expansion is to be expected for the EU-15. The results also justify that innovative devices may be attractive to end users and also help in the implementation of global energy-saving policies

  3. Sports teams as complex adaptive systems: manipulating player numbers shapes behaviours during football small-sided games.

    Science.gov (United States)

    Silva, Pedro; Vilar, Luís; Davids, Keith; Araújo, Duarte; Garganta, Júlio

    2016-01-01

    Small-sided and conditioned games (SSCGs) in sport have been modelled as complex adaptive systems. Research has shown that the relative space per player (RSP) formulated in SSCGs can impact on emergent tactical behaviours. In this study we adopted a systems orientation to analyse how different RSP values, obtained through manipulations of player numbers, influenced four measures of interpersonal coordination observed during performance in SSCGs. For this purpose we calculated positional data (GPS 15 Hz) from ten U-15 football players performing in three SSCGs varying in player numbers (3v3, 4v4 and 5v5). Key measures of SSCG system behaviours included values of (1) players' dispersion, (2) teams' separateness, (3) coupling strength and time delays between participants' emerging movements, respectively. Results showed that values of participants' dispersion increased, but the teams' separateness remained identical across treatments. Coupling strength and time delay also showed consistent values across SSCGs. These results exemplified how complex adaptive systems, like football teams, can harness inherent degeneracy to maintain similar team spatial-temporal relations with opponents through changes in inter-individual coordination modes (i.e., players' dispersion). The results imply that different team behaviours might emerge at different ratios of field dimension/player numbers. Therefore, sport pedagogists should carefully evaluate the effects of changing RSP in SSCGs as a way of promoting increased or decreased pressure on players.

  4. Physical and Clinical Comparison between a Screen-Film System and a Dual-Side Reading Mammography-Dedicated Computed Radiography System

    International Nuclear Information System (INIS)

    Rivetti, S.; Canossi, B.; Battista, R.; Vetruccio, E.; Torricelli, P.; Lanconelli, N.; Danielli, C.; Borasi, G.

    2009-01-01

    Background: Digital mammography systems, thanks to a physical performance better than conventional screen-film units, have the potential of reducing the dose to patients, without decreasing the diagnostic accuracy. Purpose: To achieve a physical and clinical comparison between two systems: a screen-film plate and a dual-side computed radiography system (CRM; FUJIFILM FCR 5000 MA). Material and Methods: A unique feature of the FCR 5000 MA system is that it has a clear support medium, allowing light emitted during the scanning process to be detected on the 'back' of the storage phosphor plate, considerably improving the system's efficiency. The system's physical performance was tested by means of a quantitative analysis, with calculation of the modulation transfer function, detective quantum efficiency, and contrast-detail analysis; subsequently, the results were compared with those achieved using a screen-film system (SFM; Eastmann Kodak MinR-MinR 2000). A receiver operating characteristic (ROC) analysis was then performed on 120 paired clinical images obtained in a craniocaudal projection with the conventional SFM system under standard exposure conditions and also with the CRM system working with a dose reduced by 35% (average breast thickness: 4.3 cm; mean glandular dose: 1.45 mGy). CRM clinical images were interpreted both in hard copy and in soft copy. Results: The ROC analysis revealed that the performances of the two systems (SFM and CRM with reduced dose) were similar (P>0.05): the diagnostic accuracy of the two systems, when valued in terms of the area underneath the ROC curve, was found to be 0.74 for the SFM, 0.78 for the CRM (hard copy), and 0.79 for the CRM (soft copy). Conclusion: The outcome obtained from our experiments shows that the use of the dual-side CRM system is a very good alternative to the screen-film system

  5. Current smoking is an independent risk factor for new-onset diabetes mellitus during highdose glucocorticoid treatment.

    Science.gov (United States)

    Sugiyama, Takao; Sugimoto, Toyohiko; Suzuki, Sawako; Sato, Yuta; Tanaka, Tomoaki; Tatsuno, Ichiro

    2015-08-01

    Although high-dose glucocorticoids have been reported to cause new-onset diabetes mellitus (glucocorticoid-induced diabetes mellitus), its risk factors have remained to be determined. We investigated the risk factors related to glucocorticoid-induced diabetes mellitus diagnosed within 2 months after the high-dose treatment (newly treated with an initial high dose of > 20 mg prednisolone (PSL) equivalent per day for at least more than 6 months) in collagen vascular diseases. A total of 2,631 patients with collagen vascular diseases was registered between 1986 and 2006 in the Chiba-Shimoshizu Rheumatic Cohort. We analyzed 681 patients newly treated with high-dose glucocorticoid who did not have diabetes mellitus and/or its previous diagnosis (age: 46.3 ± 16.7 years, PSL dose: 40.0 ± 14.1 mg/day). Glucocorticoid-induced diabetes mellitus was diagnosed by two or more glucose measurements in patients with fasting glycaemia ≥ 7 mmol/L and 120 minutes post-load glycaemia ≥ 11.1 mmol/L. Glucocorticoid-induced diabetes mellitus was observed in 26.3% of patients, and the glucocorticoid-induced diabetes mellitus group had higher age, higher BMI, lower rates of females and systemic lupus erythematosus, higher rates of smoking, alcohol use, and microscopic polyangiitis. Multivariate logistic regression analysis demonstrated that the risk of glucocorticoid-induced diabetes mellitus was independently higher in every 10-year increment of initial age with adjusted odds ratio (OR) 1.556 (95% confidence interval: 1.359 - 1.783), in every 1 kg/m2 increment of BMI with OR 1.062 (1.002 - 1.124), in current smoking with OR 1.664 (1.057 - 2.622), and in every 10 mg increment of initial dose of prednisolone with OR 1.250 (1.074 - 1.454). High-dose glucocorticoids caused diabetes mellitus with high prevalence within a short period, and current smokers should be considered at higher risk of glucocorticoidinduced diabetes mellitus in addition to age, BMI, and initial dose.

  6. Benefits of Demand-Side Response in Providing Frequency Response Service in the Future GB Power System

    Energy Technology Data Exchange (ETDEWEB)

    Teng, Fei, E-mail: fei.teng09@imperial.ac.uk; Aunedi, Marko; Pudjianto, Danny; Strbac, Goran [Department of Electrical and Electronic Engineering, Imperial College London, London (United Kingdom)

    2015-08-18

    The demand for ancillary service is expected to increase significantly in the future Great Britain (GB) electricity system due to high penetration of wind. In particular, the need for frequency response, required to deal with sudden frequency drops following a loss of generator, will increase because of the limited inertia capability of wind plants. This paper quantifies the requirements for primary frequency response and analyses the benefits of frequency response provision from demand-side response (DSR). The results show dramatic changes in frequency response requirements driven by high penetration of wind. Case studies carried out by using an advanced stochastic generation scheduling model suggest that the provision of frequency response from DSR could greatly reduce the system operation cost, wind curtailment, and carbon emissions in the future GB system characterized by high penetration of wind. Furthermore, the results demonstrate that the benefit of DSR shows significant diurnal and seasonal variation, whereas an even more rapid (instant) delivery of frequency response from DSR could provide significant additional value. Our studies also indicate that the competing technologies to DSR, namely battery storage, and more flexible generation could potentially reduce its value by up to 35%, still leaving significant room to deploy DSR as frequency response provider.

  7. Benefits of Demand-Side Response in Providing Frequency Response Service in the Future GB Power System

    International Nuclear Information System (INIS)

    Teng, Fei; Aunedi, Marko; Pudjianto, Danny; Strbac, Goran

    2015-01-01

    The demand for ancillary service is expected to increase significantly in the future Great Britain (GB) electricity system due to high penetration of wind. In particular, the need for frequency response, required to deal with sudden frequency drops following a loss of generator, will increase because of the limited inertia capability of wind plants. This paper quantifies the requirements for primary frequency response and analyses the benefits of frequency response provision from demand-side response (DSR). The results show dramatic changes in frequency response requirements driven by high penetration of wind. Case studies carried out by using an advanced stochastic generation scheduling model suggest that the provision of frequency response from DSR could greatly reduce the system operation cost, wind curtailment, and carbon emissions in the future GB system characterized by high penetration of wind. Furthermore, the results demonstrate that the benefit of DSR shows significant diurnal and seasonal variation, whereas an even more rapid (instant) delivery of frequency response from DSR could provide significant additional value. Our studies also indicate that the competing technologies to DSR, namely battery storage, and more flexible generation could potentially reduce its value by up to 35%, still leaving significant room to deploy DSR as frequency response provider.

  8. Dual chamber system providing simultaneous etch and deposition on opposing substrate sides for growing low defect density epitaxial layers

    Science.gov (United States)

    Kulkarni, Nagraj S [Knoxville, TN; Kasica, Richard J. ,

    2011-03-08

    A dual-chamber reactor can include a housing enclosing a volume having a divider therein, where the divider defines a first chamber and a second chamber. The divider can include a substrate holder that supports at least one substrate and exposes a first side of the substrate to the first chamber and a second side of the substrate to the second chamber. The first chamber can include an inlet for delivering at least one reagent to the first chamber for forming a film on the first side of the substrate, and the second chamber can include a removal device for removing material from the second side of the substrate.

  9. [Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

    Science.gov (United States)

    Yarushkina, N I; Filaretova, L P

    2015-01-01

    Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

  10. Addison disease in patients treated with glucocorticoid therapy.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Acute adrenal crisis in patients with unrecognized chronic adrenocortical failure is difficult to diagnose and potentially fatal. We describe 2 patients with acute adrenal crisis whose diagnoses were hindered because of concomitant glucocorticoid treatment. Acute adrenal insufficiency is primarily a state of mineralocorticoid deficiency. Prednisolone and prednisone, the most frequently prescribed anti-inflammatory corticosteroid agents, have minimal mineralocorticoid activity. Several conditions that may be treated with pharmacological glucocorticoids are associated with an increased risk of Addison disease. An acute adrenal crisis, against which concurrent glucocorticoid therapy does not confer adequate protection, may develop in such patients.

  11. Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

    DEFF Research Database (Denmark)

    Wang, L.; Fan, J.; Lin, Y. S.

    2015-01-01

    Glucocorticoidinduced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to boneforming and resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells...... and their responses to diverse stimuli, however, the role of autophagy in glucocorticoidinduced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy...... that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis....

  12. Neuropsychiatric findings in Cushing syndrome and exogenous glucocorticoid administration.

    Science.gov (United States)

    Starkman, Monica N

    2013-09-01

    This article reviews the neuropsychiatric presentations elicited by spontaneous hypercortisolism and exogenous supraphysiologic glucocorticoids. Patients with Cushing disease and syndrome develop a depressive syndrome: irritable and depressed mood, decreased libido, disrupted sleep and cognitive decrements. Exogenous short-term glucocorticoid administration may elicit a hypomanic syndrome with mood, sleep and cognitive disruptions. Treatment options are discussed. Brain imaging and neuropsychological studies indicate elevated cortisol and other glucocorticoids are especially deleterious to hippocampus and frontal lobe. The research findings also shed light on neuropsychiatric abnormalities in conditions that have substantial subgroups exhibiting elevated and dysregulated cortisol: aging, major depressive disorder and Alzheimer's disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Effect of single x-irradiation on glucocorticoid function of adrenal glands of adult and old rats

    International Nuclear Information System (INIS)

    Gorban', Je.M.; Topol'nyikova, N.V.

    2001-01-01

    The peculiarities of short-term (1 h, 1 day) adrenal glucocorticoid function in adult and old rats after single x-irradiation at different doses was studied. changes in the glucocorticoid function of the adrenal glands at studied terms after single x-irradiation at used doses were observed in adult but not in old animals. This testifies to an age-related decrease in the range of adaptive possibilities of this link of the organism adaptive system to x-irradiation effects

  14. Demand side management in South Africa at industrial residence water heating systems using in line water heating methodology

    International Nuclear Information System (INIS)

    Rankin, R.; Rousseau, P.G.

    2008-01-01

    The South African electrical utility, ESKOM, currently focuses its demand side management (DSM) initiatives on controlling electrical load between 18:00 and 20:00 each day, which is the utility's peak demand period. Funding is provided to energy service companies (ESCo's) to implement projects that can achieve load shifting out of this period. This paper describes how an improved in line water heating concept developed in previous studies was implemented into several real life industrial sanitary water heating systems to obtain the DSM load shift required by ESKOM. Measurements from a selection of these plants are provided to illustrate the significant load reductions that are being achieved during 18:00-20:00. The measured results also show that the peak load reduction is achieved without adversely affecting the availability of sufficient hot water to the persons using the showering and washing facilities served by the water heating system. A very good correlation also exists between these measured results and simulations that were done beforehand to predict the DSM potential of the project. The in line water heater concept provides an improved solution for DSM at sanitary water heating systems due to the stratified manner in which hot water is supplied to the tanks. This provides an improved hot water supply to users when compared to conventional in tank heating systems, even with load shifting being done. It also improves the storage efficiency of a plant, thereby allowing the available storage capacity of a plant to be utilized to its full extent for load shifting purposes

  15. Glucocorticoid Receptor-Mediated Repression of Pro-Inflammatory Genes in Rheumatoid Arthritis

    Science.gov (United States)

    2015-10-01

    Braun TP, Zhu X, Szumowski M, Scott GD, Grossberg AJ, et al. 2011. Central nervous system inflam - mation induces muscle atrophy via activation of the...glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle . Cell Metab. 13:170–82 133. Lutzner N, Kalbacher H, Krones-Herzig A, Rosl F. 2012...suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704

  16. Physiological Correlates of Multiple Parasitic Infections in Side-Blotched Lizards.

    Science.gov (United States)

    Spence, Austin R; Durso, Andrew M; Smith, Geoffrey D; Skinner, Heather M; French, Susannah S

    We investigated the presence of ectoparasites and hemoparasites in side-blotched lizards (Uta stansburiana) across a large part of their range and measured how parasitic infection related to several key physiological indicators of health. Blood samples were collected from 132 lizards from central Arizona, southern Utah, and eastern Oregon. Hemoparasites were found in 22 individuals (3.2% prevalence in Arizona, 19.1% in Utah, and 6.3% in Oregon), and ectoparasites were found on 51 individuals (56.3% prevalence in Arizona, 56.1% in Utah, and 6.7% in Oregon), with 11 individuals infected with both. Hemoparasites and ectoparasites were found in all three states. Immunocompetence was higher in individuals infected with both hemoparasites and ectoparasites. Body condition, glucocorticoid levels, and reproductive investment were not related to infection status. Our study provides evidence that parasitic infection is associated with an active immune system in wild reptiles but may not impose other costs usually associated with parasites.

  17. Glucocorticoid treatment, immobility, and constipation are associated with nutritional risk.

    Science.gov (United States)

    Gutzwiller, Jean-Pierre; Aschwanden, Josef; Iff, Samuel; Leuenberger, Michèle; Perrig, Martin; Stanga, Zeno

    2011-12-01

    The hypothesis of this clinical study was to determine whether glucocorticoid use and immobility were associated with in-hospital nutritional risk. One hundred and one patients consecutively admitted to the medical wards were enrolled. Current medical conditions, symptoms, medical history, eating and drinking habits, diagnosis, laboratory findings, medications, and anthropometrics were recorded. The Nutrition Risk Score 2002 (NRS-2002) was used as a screening instrument to identify nutritional risk. The results confirmed that glucocorticoid use and immobility are independently associated with nutritional risk determined by the NRS-2002. Constipation could be determined as an additional cofactor independently associated with nutritional risk. Glucocorticoid treatment, immobility, and constipation are associated with nutritional risk in a mixed hospitalized population. The presence of long-time glucocorticoid use, immobility, or constipation should alert the clinician to check for nutritional status, which is an important factor in mortality and morbidity.

  18. Both mineralocorticoid and glucocorticoid receptors regulate emotional memory in mice

    NARCIS (Netherlands)

    Zhou, M.; Bakker, E.H.M.; Velzing, E.; Berger, S.; Oitzl, M.; Joëls, M.; Krugers, H.J.

    2010-01-01

    Corticosteroid hormones are thought to promote optimal behavioral adaptation under fearful conditions, primarily via glucocorticoid receptors (GRs). Here, we examined - using pharmacological and genetic approaches in mice - if mineralocorticoid receptors (MRs) also play a role in fearful memory

  19. The Metabolic Implications of Glucocorticoids in a High-Fat Diet Setting and the Counter-Effects of Exercise

    Directory of Open Access Journals (Sweden)

    Emily C. Dunford

    2016-12-01

    Full Text Available Glucocorticoids (GCs are steroid hormones, naturally produced by activation of the hypothalamic-pituitary-adrenal (HPA axis, that mediate the immune and metabolic systems. Synthetic GCs are used to treat a number of inflammatory conditions and diseases including lupus and rheumatoid arthritis. Generally, chronic or high dose GC administration is associated with side effects such as steroid-induced skeletal muscle loss, visceral adiposity, and diabetes development. Patients who are taking exogenous GCs could also be more susceptible to poor food choices, but the effect that increasing fat consumption in combination with elevated exogenous GCs has only recently been investigated. Overall, these studies show that the damaging metabolic effects initiated through exogenous GC treatment are significantly amplified when combined with a high fat diet (HFD. Rodent studies of a HFD and elevated GCs demonstrate more glucose intolerance, hyperinsulinemia, visceral adiposity, and skeletal muscle lipid deposition when compared to rodents subjected to either treatment on its own. Exercise has recently been shown to be a viable therapeutic option for GC-treated, high-fat fed rodents, with the potential mechanisms still being examined. Clinically, these mechanistic studies underscore the importance of a low fat diet and increased physical activity levels when individuals are given a course of GC treatment.

  20. Niffler: A Context-Aware and User-Independent Side-Channel Attack System for Password Inference

    Directory of Open Access Journals (Sweden)

    Benxiao Tang

    2018-01-01

    Full Text Available Digital password lock has been commonly used on mobile devices as the primary authentication method. Researches have demonstrated that sensors embedded on mobile devices can be employed to infer the password. However, existing works focus on either each single keystroke inference or entire password sequence inference, which are user-dependent and require huge efforts to collect the ground truth training data. In this paper, we design a novel side-channel attack system, called Niffler, which leverages the user-independent features of movements of tapping consecutive buttons to infer unlocking passwords on smartphones. We extract angle features to reflect the changing trends and build a multicategory classifier combining the dynamic time warping algorithm to infer the probability of each movement. We further use the Markov model to model the unlocking process and use the sequences with the highest probabilities as the attack candidates. Moreover, the sensor readings of successful attacks will be further fed back to continually improve the accuracy of the classifier. In our experiments, 100,000 samples collected from 25 participants are used to evaluate the performance of Niffler. The results show that Niffler achieves 70% and 85% accuracy with 10 attempts in user-independent and user-dependent environments with few training samples, respectively.

  1. Chronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons.

    Science.gov (United States)

    Barik, Jacques; Marti, Fabio; Morel, Carole; Fernandez, Sebastian P; Lanteri, Christophe; Godeheu, Gérard; Tassin, Jean-Pol; Mombereau, Cédric; Faure, Philippe; Tronche, François

    2013-01-18

    Repeated traumatic events induce long-lasting behavioral changes that are key to organism adaptation and that affect cognitive, emotional, and social behaviors. Rodents subjected to repeated instances of aggression develop enduring social aversion and increased anxiety. Such repeated aggressions trigger a stress response, resulting in glucocorticoid release and activation of the ascending dopamine (DA) system. We bred mice with selective inactivation of the gene encoding the glucocorticoid receptor (GR) along the DA pathway, and exposed them to repeated aggressions. GR in dopaminoceptive but not DA-releasing neurons specifically promoted social aversion as well as dopaminergic neurochemical and electrophysiological neuroadaptations. Anxiety and fear memories remained unaffected. Acute inhibition of the activity of DA-releasing neurons fully restored social interaction in socially defeated wild-type mice. Our data suggest a GR-dependent neuronal dichotomy for the regulation of emotional and social behaviors, and clearly implicate GR as a link between stress resiliency and dopaminergic tone.

  2. The emerging importance of ultradian glucocorticoid rhythms within metabolic pathology.

    Science.gov (United States)

    Flynn, Benjamin P; Conway-Campbell, Becky L; Lightman, Stafford L

    2018-06-01

    Glucocorticoid (GC) hormones play significant roles within homeostasis and the chrono-dynamics of their regulatory role has become increasingly recognised within dysregulated GC pathology, particularly with metabolic phenotypes. Within this article, we will discuss the relevance of the ultradian homeostatic rhythm, how its dysregulation effects glucocorticoid receptor and RNA polymeraseII recruitment and may play a significant role within aberrant metabolic action. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  3. The role of glucocorticoids in sodium retention in cirrhotic patients

    DEFF Research Database (Denmark)

    Hansen, Martin Højmark; Kristensen, Steffen Skott; Schaffalitzky de Muckadell, Ove B

    2012-01-01

    sodium retention evident in cirrhosis. The aim was to elucidate the role of glucocorticoids in sodium retention in decompensated cirrhotic patients. Methods. A randomized, double-blind, placebo-controlled, crossover study was performed in nine patients with alcoholic cirrhosis of the liver. A washout....... Conclusion. These results indicate that endogenous glucocorticoids contribute to the sodium retention in patients with alcoholic cirrhosis of the liver....

  4. Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

    LENUS (Irish Health Repository)

    Frodl, T

    2012-01-01

    Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and\\/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

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

    Science.gov (United States)

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

    2015-01-22

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

  6. Glucocorticoid-Induced Avascular Bone Necrosis: Diagnosis and Management

    Science.gov (United States)

    Chan, KL; Mok, CC

    2012-01-01

    Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty. PMID:23115605

  7. Glucocorticoid-induced avascular bone necrosis: diagnosis and management.

    Science.gov (United States)

    Chan, K L; Mok, C C

    2012-01-01

    Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty.

  8. Expression and regulation of glucocorticoid-induced leucine zipper in the developing anterior pituitary gland.

    Science.gov (United States)

    Ellestad, Laura E; Malkiewicz, Stefanie A; Guthrie, H David; Welch, Glenn R; Porter, Tom E

    2009-02-01

    The expression profile of glucocorticoid-induced leucine zipper (GILZ) in the anterior pituitary during the second half of embryonic development in the chick is consistent with in vivo regulation by circulating corticosteroids. However, nothing else has been reported about the presence of GILZ in the neuroendocrine system. We sought to characterize expression and regulation of GILZ in the chicken embryonic pituitary gland and determine the effect of GILZ overexpression on anterior pituitary hormone levels. Pituitary GILZ mRNA levels increased during embryogenesis to a maximum on the day of hatch, and decreased through the first week after hatch. GILZ expression was rapidly upregulated by corticosterone in embryonic pituitary cells. To determine whether GILZ regulates hormone gene expression in the developing anterior pituitary, we overexpressed GILZ in embryonic pituitary cells and measured mRNA for the major pituitary hormones. Exogenous GILZ increased prolactin mRNA above basal levels, but not as high as that in corticosterone-treated cells, indicating that GILZ may play a small role in lactotroph differentiation. The largest effect we observed was a twofold increase in FSH beta subunit in cells transfected with GILZ but not treated with corticosterone, suggesting that GILZ may positively regulate gonadotroph development in a manner not involving glucocorticoids. In conclusion, this is the first report to characterize avian GILZ and examine its regulation in the developing neuroendocrine system. We have shown that GILZ is upregulated by glucocorticoids in the embryonic pituitary gland and may regulate expression of several pituitary hormones.

  9. Reaction mechanisms in the radiolysis of peptides, polypeptides and proteins II reactions at side-chain loci in model systems

    International Nuclear Information System (INIS)

    Garrison, W.M.

    1983-11-01

    The major emphasis in radiation biology at the molecular level has been on the nucleic acid component of the nucleic acid-protein complex because of its primary genetic importance. But there is increasing evidence that radiation damage to the protein component also has important biological implications. Damage to capsid protein now appears to be a major factor in the radiation inactivation of phage and other viruses. And, there is increasing evidence that radiation-chemical change in the protein component of chromation leads to changes in the stability of the repressor-operator complexes involved in gene expression. Knowledge of the radiation chemistry of protein is also of importance in other fields such as the application of radiation sterilization to foods and drugs. Recent findings that a class of compounds, the α,α'-diaminodicarboxylic acids, not normally present in food proteins, are formed in protein radiolysis is of particular significance since certain of their peptide derivatives have been showing to exhibit immunological activity. The purpose of this review is to bring together and to correlate our present knowledge of products and mechanisms in the radiolysis of peptides, polypeptides and proteins both aqueous and solid-state. In part 1 we presented a discussion of the radiation-induced reactions of the peptide main-chain in model peptide and polypeptide systems. Here in part 2 the emphasis is on the competing radiation chemistry at side-chain loci of peptide derivatives of aliphatic, aromatic-unsaturated and sulfur-containing amino acids in similar systems. Information obtained with the various experimental techniques of product analysis, competition kinetics, spin-trapping, pulse radiolysis, and ESR spectroscopy are included

  10. Glucocorticoid enhancement of dorsolateral striatum-dependent habit memory requires concurrent noradrenergic activity.

    Science.gov (United States)

    Goodman, J; Leong, K-C; Packard, M G

    2015-12-17

    Previous findings indicate that post-training administration of glucocorticoid stress hormones can interact with the noradrenergic system to enhance consolidation of hippocampus- or amygdala-dependent cognitive/emotional memory. The present experiments were designed to extend these findings by examining the potential interaction of glucocorticoid and noradrenergic mechanisms in enhancement of dorsolateral striatum (DLS)-dependent habit memory. In experiment 1, different groups of adult male Long-Evans rats received training in two DLS-dependent memory tasks. In a cued water maze task, rats were released from various start points and were reinforced to approach a visibly cued escape platform. In a response-learning version of the water plus-maze task, animals were released from opposite starting positions and were reinforced to make a consistent egocentric body-turn to reach a hidden escape platform. Immediately post-training, rats received peripheral injections of the glucocorticoid corticosterone (1 or 3 mg/kg) or vehicle solution. In both tasks, corticosterone (3 mg/kg) enhanced DLS-dependent habit memory. In experiment 2, a separate group of animals received training in the response learning version of the water plus-maze task and were given peripheral post-training injections of corticosterone (3 mg/kg), the β-adrenoreceptor antagonist propranolol (3 mg/kg), corticosterone and propranolol concurrently, or control vehicle solution. Corticosterone injections again enhanced DLS-dependent memory, and this effect was blocked by concurrent administration of propranolol. Propranolol administration by itself (3 mg/kg) did not influence DLS-dependent memory. Taken together, the findings indicate an interaction between glucocorticoid and noradrenergic mechanisms in DLS-dependent habit memory. Propranolol administration may be useful in treating stress-related human psychopathologies associated with a dysfunctional DLS-dependent habit memory system. Copyright © 2015

  11. Modulation strategies of integrated HVAC systems used in residential buildings for demand-side management at different scales

    OpenAIRE

    Georges, Emeline

    2017-01-01

    The integration of renewable energy sources in the electricity production mix has an important impact on the management of the electricity grid, due to their intermittency. In particular, to ensure grid balancing, there is a rising need for flexibility, both on the supply and demand sides. A possible solution to help achieve grid balancing is the smart modulation of the electrical load in a "demand following supply" scheme through demand-side management. In this context, the objective of...

  12. Operation and Control of a Direct-Driven PMSG-Based Wind Turbine System with an Auxiliary Parallel Grid-Side Converter

    Directory of Open Access Journals (Sweden)

    Jiawei Chu

    2013-07-01

    Full Text Available In this paper, based on the similarity, in structure and principle, between a grid-connected converter for a direct-driven permanent magnet synchronous generator (D-PMSG and an active power filter (APF, a new D-PMSG-based wind turbine (WT system configuration that includes not only an auxiliary converter in parallel with the grid-side converter, but also a coordinated control strategy, is proposed to enhance the low voltage ride through (LVRT capability and improve power quality. During normal operation, the main grid-side converter maintains the DC-link voltage constant, whereas the auxiliary grid-side converter functions as an APF with harmonic suppression and reactive power compensation to improve the power quality. During grid faults, a hierarchical coordinated control scheme for the generator-side converter, main grid-side converter and auxiliary grid-side converter, depending on the grid voltage sags, is presented to enhance the LVRT capability of the direct-driven PMSG WT. The feasibility and the effectiveness of the proposed system’s topology and hierarchical coordinated control strategy were verified using MATLAB/Simulink simulations.

  13. Patterns of intrafractional motion and uncertainties of treatment setup reference systems in accelerated partial breast irradiation for right- and left-sided breast cancer.

    Science.gov (United States)

    Yue, Ning J; Goyal, Sharad; Kim, Leonard H; Khan, Atif; Haffty, Bruce G

    2014-01-01

    This study investigated the patterns of intrafractional motion and accuracy of treatment setup strategies in 3-dimensional conformal radiation therapy of accelerated partial breast irradiation (APBI) for right- and left-sided breast cancers. Sixteen right-sided and 17 left-sided breast cancer patients were enrolled in an institutional APBI trial in which gold fiducial markers were strategically sutured to the surgical cavity walls. Daily pre- and postradiation therapy kV imaging were performed and were matched to digitally reconstructed radiographs based on bony anatomy and fiducial markers, respectively, to determine the intrafractional motion. The positioning differences of the laser-tattoo and the bony anatomy-based setups with respect to the marker-based setup (benchmark) were determined to evaluate their accuracy. Statistical differences were found between the right- and left-sided APBI treatments in vector directions of intrafractional motion and treatment setup errors in the reference systems, but less in their overall magnitudes. The directional difference was more pronounced in the lateral direction. It was found that the intrafractional motion and setup reference systems tended to deviate in the right direction for the right-sided breast treatments and in the left direction for the left-sided breast treatments. It appears that the fiducial markers placed in the seroma cavity exhibit side dependent directional intrafractional motion, although additional data may be needed to further validate the conclusion. The bony anatomy-based treatment setup improves the accuracy over laser-tattoo. But it is inadequate to rely on bony anatomy to assess intrafractional target motion in both magnitude and direction. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  14. Systematic review of the clinical effect of glucocorticoids on nonhematologic malignancy

    Directory of Open Access Journals (Sweden)

    Keith Bruce D

    2008-03-01

    Full Text Available Abstract Background Glucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy. Methods A systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO and other resources were used. Data was extracted using a standard form. There was quality assessment of each study. There was a narrative synthesis of information, with presentation of results in tables. Where appropriate, meta-analyses were performed using data from published reports and a fixed effect model. Results Fifty four randomized controlled trials (RCTs, one meta-analysis, four phase l/ll trials and four case series met the eligibility criteria. Clinical trials of glucocorticoid monotherapy in breast and prostate cancer showed modest response rates. In advanced breast cancer meta-analyses, the addition of glucocorticoids to either chemotherapy or other endocrine therapy resulted in increased response rate, but not increased survival. In GI cancer, there was one RCT each of glucocorticoids vs. supportive care and chemotherapy +/- glucocorticoids; glucocorticoid effect was neutral. The only RCT found of chemotherapy +/- glucocorticoids, in which the glucocorticoid arm did worse, was in lung cancer. In glucocorticoid monotherapy, meta-analysis found that continuous high dose glucocorticoids had a detrimental effect on survival. The only other evidence, for a detrimental effect of glucocorticoid monotherapy, was in one of the two trials in lung cancer. Conclusion Glucocorticoid monotherapy has some benefit in breast and prostate cancer. In advanced breast cancer, the addition of glucocorticoids to other

  15. Salivary cortisol day curves in assessing glucocorticoid replacement therapy in Addison's disease.

    Science.gov (United States)

    Smans, Lisanne; Lentjes, Eef; Hermus, Ad; Zelissen, Pierre

    2013-01-01

    Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL). Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) × magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed. At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased. Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease.

  16. Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

    Directory of Open Access Journals (Sweden)

    Kate Kosmac

    2013-03-01

    Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

  17. Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats.

    Science.gov (United States)

    Boero, Giorgia; Pisu, Maria Giuseppina; Biggio, Francesca; Muredda, Laura; Carta, Gianfranca; Banni, Sebastiano; Paci, Elena; Follesa, Paolo; Concas, Alessandra; Porcu, Patrizia; Serra, Mariangela

    2018-05-01

    We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors.

    Directory of Open Access Journals (Sweden)

    Nadège Sarrazin

    Full Text Available The Glucocorticoid Receptor (GR is a transcription factor ubiquitously expressed in the brain. Activation of brain GRs by high levels of glucocorticoid (GC hormones modifies a large variety of physiological and pathological-related behaviors. Unfortunately the specific cellular targets of GR-mediated behavioral effects of GC are still largely unknown. To address this issue, we generated a mutated form of the GR called DeltaGR. DeltaGR is a constitutively transcriptionally active form of the GR that is localized in the nuclei and activates transcription without binding to glucocorticoids. Using the tetracycline-regulated system (Tet-OFF, we developed an inducible transgenic approach that allows the expression of the DeltaGR in specific brain areas. We focused our study on a mouse line that expressed DeltaGR almost selectively in the glutamatergic neurons of the dentate gyrus (DG of the hippocampus. This restricted expression of the DeltaGR increased anxiety-related behaviors without affecting other behaviors that could indirectly influence performance in anxiety-related tests. This behavioral phenotype was also associated with an up-regulation of the MAPK signaling pathway and Egr-1 protein in the DG. These findings identify glutamatergic neurons in the DG as one of the cellular substrate of stress-related pathologies.

  19. Glucocorticoid up-regulation of high-affinity interleukin 6 receptors on human epithelial cells

    International Nuclear Information System (INIS)

    Snyers, L.; De Wit, L.; Content, J.

    1990-01-01

    Interleukin 6 (IL-6) is a potent pleiotropic cytokine, known, among others, to stimulate immunoglobulin production by B cells and to trigger acute-phase protein synthesis by hepatocytes. Similar to IL-1, it is produced by monocytes and macrophages following an inflammatory challenge. Analysis of IL-6 receptor (IL-6R) expression on different human cell lines indicates that dexamethasone could up-regulate the number of IL-6R on one epithelial cell line (UAC) and on two hepatoma cell lines (HepG2 and Hep3B). This effect was confirmed by Scatchard analysis of binding experiments, using [ 35 S]methionine and [ 35 S]cysteine metabolically labeled IL-6. It was confirmed at the level of mRNA expression by Northern blot analysis. These results provide evidence for a link between IL-6 and glucocorticoids. They could represent an example of a system in which one role of glucocorticoids is to define more accurately the target of cytokines, and they could explain, at least partly, the frequently observed synergy between IL-6 and glucocorticoids, notably in the case of hepatocytes

  20. Glucocorticoid effects on object recognition memory require training-associated emotional arousal.

    Science.gov (United States)

    Okuda, Shoki; Roozendaal, Benno; McGaugh, James L

    2004-01-20

    Considerable evidence implicates glucocorticoid hormones in the regulation of memory consolidation and memory retrieval. The present experiments investigated whether the influence of these hormones on memory depends on the level of emotional arousal induced by the training experience. We investigated this issue in male Sprague-Dawley rats by examining the effects of immediate posttraining systemic injections of the glucocorticoid corticosterone on object recognition memory under two conditions that differed in their training-associated emotional arousal. In rats that were not previously habituated to the experimental context, corticosterone (0.3, 1.0, or 3.0 mg/kg, s.c.) administered immediately after a 3-min training trial enhanced 24-hr retention performance in an inverted-U shaped dose-response relationship. In contrast, corticosterone did not affect 24-hr retention of rats that received extensive prior habituation to the experimental context and, thus, had decreased novelty-induced emotional arousal during training. Additionally, immediate posttraining administration of corticosterone to nonhabituated rats, in doses that enhanced 24-hr retention, impaired object recognition performance at a 1-hr retention interval whereas corticosterone administered after training to well-habituated rats did not impair 1-hr retention. Thus, the present findings suggest that training-induced emotional arousal may be essential for glucocorticoid effects on object recognition memory.

  1. Glucocorticoid regulation of astrocytic fate and function.

    Directory of Open Access Journals (Sweden)

    Shuang Yu

    Full Text Available Glial loss in the hippocampus has been suggested as a factor in the pathogenesis of stress-related brain disorders that are characterized by dysregulated glucocorticoid (GC secretion. However, little is known about the regulation of astrocytic fate by GC. Here, we show that astrocytes derived from the rat hippocampus undergo growth inhibition and display moderate activation of caspase 3 after exposure to GC. Importantly, the latter event, observed both in situ and in primary astrocytic cultures is not followed by either early- or late-stage apoptosis, as monitored by stage I or stage II DNA fragmentation. Thus, unlike hippocampal granule neurons, astrocytes are resistant to GC-induced apoptosis; this resistance is due to lower production of reactive oxygen species (ROS and a greater buffering capacity against the cytotoxic actions of ROS. We also show that GC influence hippocampal cell fate by inducing the expression of astrocyte-derived growth factors implicated in the control of neural precursor cell proliferation. Together, our results suggest that GC instigate a hitherto unknown dialog between astrocytes and neural progenitors, adding a new facet to understanding how GC influence the cytoarchitecture of the hippocampus.

  2. Osteoporosis prophylaxis in patients receiving chronic glucocorticoid therapy

    International Nuclear Information System (INIS)

    Ali, Mir Sadat; AlElq, Abdulmohsen H.; AlShafei, Badar A.; AbuJubarac, Mohammed A.; AlTurki, Haifa A.

    2009-01-01

    Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, yet few patients receive proper measures to prevent its development. We retrospectively searched prescription records to determine if patients receiving oral prednisolone were receiving prophylaxis or treatment for osteopenia and osteoporosis. Patients who were prescribed greater or equal to 7.5 milligrams of prednisolone for 6 months or longer during a 6- month period were identified through the prescription monitoring system. Demographic and clinical data were extracted from the patient records, and dual energy x-ray absorptiometry (DEXA) scans were retrieved, when available. Use of oral calcium, vitamin D and anti-resorptives was recorded. One hundred males and 65 females were receiving oral prednisolone for a mean (SD) duration of 40.4 (29.9) months in males and 41.2 (36.4) months in females. Twenty-one females (12.7%) and 5 (3%) males had bone mineral density measured by DEXA. Of those, 10 (47.6%) females and 3 (50%) males were osteoporotic and 11(52.4%) females and 2 (40%) males were osteopenic. Calcium and vitamin D were prescribed to the majority of patients (60% to 80%), but none were prescribed antiresorptive/anabolic therapy. Patients in this study were neither investigated properly nor treated according to the minimum recommendations for the management of GIOP. Physician awareness about the prevention and treatment of GIOP should be a priority for the local health care system. (author)

  3. Compact ILU-type electron accelerators as a base for industrial 4-sided irradiation systems for cable and tubes

    International Nuclear Information System (INIS)

    Auslender, V.L.; Nekhaev, V.E.; Panfilov, A.D.; Tuvik, A.A.

    1999-01-01

    The ILU-type industrial electron accelerators are developed in BINP sins 1967. Their energy range is 0.7-4.0 MeV at beam power of 20-50 kW. The comparison of the irradiation results after bilateral and four-sided irradiation of cables and tubes is given. It is shown that the required electron energy and beam power in the case of four-sided irradiation are sufficiently lower than in the case of bilateral irradiation, resulting in an increase of productive rate of the process and improvement of treatment quality. The installations for four-sided irradiation of cables and tubes are based on the industrial electron accelerators type ILU

  4. DEMONSTRATION OF THE ENVIRONMENTAL AND DEMAND-SIDE MANAGEMENT BENEFITS OF GRID-CONNECTED PHOTOVOLTAIC POWER SYSTEMS SITED ON MILITARY BASES

    Science.gov (United States)

    The report gives results of an investigation into the pollutant emission reduction and demand-side management potential of three photovoltaic (PV) systems installed at Ft. Huachuca, AZ, Ft. Dix, NJ, and Hickam Air Force Base, HI, which began operation between January and July 199...

  5. Synthesis of NCA 11,17β-dihydroxy-6-methyl-17α-(3-[18F]fluoroprop-1-ynyl)androsta-1,4,6-trien-3-one as a potential glucocorticoid receptor ligand for neuro-PET studies

    International Nuclear Information System (INIS)

    DaSilva, J.N.; Crouzel, C.

    1990-01-01

    Glucocorticoids appear to exert physiologic, biochemical and behavioral effects on the central nervous system (1). The presence of glucocorticoid binding sites have been demonstrated in human brain by autoradiographic studies (2). In order to visualize the brain glucocorticoid binding sites by PET, the authors have synthesized n.c.a. 11,17β-dihydroxy-6-methyl-17α-(3-[ 18 F]fluoroprop-1-ynyl)androsta-1,4,6-trien-3-one, a fluorine-18 analog of the selective type II glucocorticoid receptor agonist RU 28362 (3). Biodistribution studies in mature male rats and in vivo distribution of 2 by PET on a baboon are in progress

  6. Travoprost with sofZia® preservative system lowered intraocular pressure of Japanese normal tension glaucoma with minimal side effects

    Directory of Open Access Journals (Sweden)

    Mizoue S

    2014-02-01

    Full Text Available Shiro Mizoue,1 Tadashi Nakano,2 Nobuo Fuse,3 Aiko Iwase,4 Shun Matsumoto,5 Keiji Yoshikawa6 On behalf of the IOP CHANGE Study Group7 1Department of Ophthalmology, Ehime University Graduate School of Medicine, Ehime, Japan; 2Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan; 3Department of Integrative Genomics, Tohoku Medical Megabank Organization, Miyagi, Japan; 4Tajimi Iwase Eye Clinic, Gifu, Japan; 5Department of Ophthalmology, Tokyo Teishin Hospital, 6Yoshikawa Eye Clinic, Tokyo, Japan; 7IOP CHecked and Assessed in Normal tension Glaucoma by Exceptional Glaucomatologists Study Group, Japan Background: This study aimed to evaluate the effect of travoprost with sofZia® preservative system for lowering the intraocular pressure (IOP of Japanese normal tension glaucoma (NTG patients. Methods: In this prospective, multicenter, open-label study, Japanese NTG patients with baseline IOPs <20 mmHg were enrolled after three consecutive time measurements taken at screening and baseline visits. Travoprost with sofZia® was instilled once daily. Lowering effect on IOP, conjunctival hyperemia, superficial punctate keratopathy, and adverse events were examined at week 4, 8, and 12 after drug instillation. Results: One-hundred and three of the 107 enrolled patients (baseline IOP =15.2±2.0 mmHg [mean ± standard deviation] completed the study. The mean IOP value as well as percent reduction was significantly reduced at each visit after travoprost with sofZia® initiation (P<0.0001. The conjunctival hyperemia score was 1 or less throughout the study, though it increased significantly over time. No significant change was observed in superficial punctate keratopathy. The cumulative incidence of side effects such as eyelash changes, eyelid pigmentation, and deepening of the upper lid was 47.6%, 27.2%, and 16.5%, respectively. Conclusion: Travoprost preserved with sofZia® effectively lowered the IOP of Japanese NTG patients. It was

  7. Altered placental development in undernourished rats: role of maternal glucocorticoids

    Directory of Open Access Journals (Sweden)

    Chen Chun-Hung

    2011-08-01

    Full Text Available Abstract Maternal undernutrition (MUN during pregnancy may lead to fetal intrauterine growth restriction (IUGR, which itself predisposes to adult risk of obesity, hypertension, and diabetes. IUGR may stem from insufficient maternal nutrient supply or reduced placental nutrient transfer. In addition, a critical role for maternal stress-induced glucocorticoids (GCs has been suggested to contribute to both IUGR and the ensuing risk of adult metabolic syndrome. While GC-induced fetal organ defects have been examined, there have been few studies on placental responses to MUN-induced maternal stress. Therefore, we hypothesize that 50% MUN associates with increased maternal GC levels and decreased placental HSD11B. This in turn leads to decreased placental and fetal growth, hence the need to investigate nutrient transporters. We measured maternal serum levels of corticosterone, and the placental basal and labyrinth zone expression of glucocorticoid receptor (NR3C1, 11-hydroxysteroid dehydrogenase B 1 (HSD11B-1 predominantly activates cortisone to cortisol and 11-dehydrocorticosterone (11-DHC to corticosterone, although can sometimes drive the opposing (inactivating reaction, and HSD11B-2 (only inactivates and converts corticosterone to 11-DHC in rodents in control and MUN rats at embryonic day 20 (E20. Moreover, we evaluated the expression of nutrient transporters for glucose (SLC2A1, SLC2A3 and amino acids (SLC38A1, 2, and 4. Our results show that MUN dams displayed significantly increased plasma corticosterone levels compared to control dams. Further, a reduction in fetal and placental weights was observed in both the mid-horn and proximal-horn positions. Notably, the placental labyrinth zone, the site of feto-maternal exchange, showed decreased expression of HSD11B1-2 in both horns, and increased HSD11B-1 in proximal-horn placentas, but no change in NR3C1. The reduced placental GCs catabolic capacity was accompanied by downregulation of SLC2A3, SLC

  8. Current control methods for grid-side three-phase PWM voltage-source inverter in distributed generation systems

    DEFF Research Database (Denmark)

    Lar, Ionut Andrei; Radulescu, Mircea; Ritchie, Ewen

    2012-01-01

    A comparison between two current control methods of grid side inverter, PI current control and Robust Forward control is made. PI control is implemented in d-q synchronous frame while Forward is implemented in abc stationary frames.The report contains both simulations and experimental test wich...

  9. Evaluation of flexible demand-side load-following reserves in power systems with high wind generation penetration

    NARCIS (Netherlands)

    Paterakis, N.G.; Catalao, J.P.S.; Ntomaris, A.V.; Erdinc, O.

    2015-01-01

    In this study, a two-stage stochastic programming joint energy and reserve day-ahead market structure is proposed in order to procure the required load-following reserves to tackle with wind power production uncertainty. Reserves can be procured both from generation and demand-side. Responsive

  10. Melatonin protects chondrocytes from impairment induced by glucocorticoids via NAD+-dependent SIRT1.

    Science.gov (United States)

    Yang, Wei; Kang, Xiaomin; Qin, Na; Li, Feng; Jin, Xinxin; Ma, Zhengmin; Qian, Zhuang; Wu, Shufang

    2017-10-01

    Intra-articular injection of glucocorticoids is used to relieve pain and inflammation in osteoarthritis patients, which is occasionally accompanied with the serious side effects of glucocorticoids in collagen-producing tissue. Melatonin is the major hormone released from the pineal gland and its beneficial effects on cartilage has been suggested. In the present study, we investigated the protective role of melatonin on matrix degeneration in chondrocytes induced by dexamethasone (Dex). The chondrocytes isolated from mice knee joint were treated with Dex, melatonin, EX527 and siRNA targeted for SIRT6, respectively. Dex treatment induced the loss of the extracellular matrix, NAD + /NADH ratio and NADPH concentration in chondrocytes. Melatonin alone have no effect on the quantity of proteoglycans and collagen type IIa1, however, the pretreatment of melatonin reversed the negative effects induced by Dex. Meanwhile, the significant decrease in NAD + /NADH ratio and NADPH concentration in Dex group were up-regulated by pretreatment of melatonin. Furthermore, it was revealed that inhibition of SIRT1 blocked the protective effects of melatonin. The enhancement of NAD + -dependent SIRT1 activity contributes to the chondroprotecfive effects of melatonin, which has a great benefit to prevent dexamethasone-induced chondrocytes impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Fructose, Glucocorticoids and Adipose Tissue: Implications for the Metabolic Syndrome.

    Science.gov (United States)

    Legeza, Balázs; Marcolongo, Paola; Gamberucci, Alessandra; Varga, Viola; Bánhegyi, Gábor; Benedetti, Angiolo; Odermatt, Alex

    2017-04-26

    The modern Western society lifestyle is characterized by a hyperenergetic, high sugar containing food intake. Sugar intake increased dramatically during the last few decades, due to the excessive consumption of high-sugar drinks and high-fructose corn syrup. Current evidence suggests that high fructose intake when combined with overeating and adiposity promotes adverse metabolic health effects including dyslipidemia, insulin resistance, type II diabetes, and inflammation. Similarly, elevated glucocorticoid levels, especially the enhanced generation of active glucocorticoids in the adipose tissue due to increased 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, have been associated with metabolic diseases. Moreover, recent evidence suggests that fructose stimulates the 11β-HSD1-mediated glucocorticoid activation by enhancing the availability of its cofactor NADPH. In adipocytes, fructose was found to stimulate 11β-HSD1 expression and activity, thereby promoting the adipogenic effects of glucocorticoids. This article aims to highlight the interconnections between overwhelmed fructose metabolism, intracellular glucocorticoid activation in adipose tissue, and their metabolic effects on the progression of the metabolic syndrome.

  12. The role of glucocorticoids in emotional memory reconsolidation.

    Science.gov (United States)

    Meir Drexler, Shira; Wolf, Oliver T

    2017-07-01

    Glucocorticoids are secreted following exposure to stressful events. Their modulating role on memory reconsolidation, a post-retrieval process of re-stabilization, has been investigated only recently, at times with conflicting results. The goal of this review is twofold. First, to establish the modulating role of glucocorticoids on memory reconsolidation. Second, to point the potential factors and confounds that might explain the seemingly paradoxical findings. Here we review recent pharmacological studies, conducted in rodents and humans, which suggest a critical role of glucocorticoids in this post-retrieval process. In particular, the activation of glucocorticoid receptors in the amygdala and hippocampus is suggested to be involved in emotional memories reconsolidation, pointing to a similarity between post-retrieval reconsolidation and initial memory consolidation. In addition, based on the general reconsolidation literature, we suggest several factors that might play a role in determining the direction and strength of the reconsolidation effect following glucocorticoids treatment: memory-related factors, manipulation-related factors, and individual differences. We conclude that only when taking these additional factors into account can the paradox be resolved. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Glucocorticoid effects on hippocampal protein synthesis

    International Nuclear Information System (INIS)

    Schlatter, L.K.

    1988-01-01

    Following subcutaneous injection of rats with 5 mg corticosterone, hippocampal slices in vitro show increased [ 35 S]-methionine labeling of a cytosolic protein with an apparent molecular weight (M r ) of 35,000 and an isoelectric point (IEP) of 6.6. This labeling is temporally consistent with a transcriptional event, and is steroid- and tissue-specific. The pear serum concentration of steroid occurs one hour or less following the injection. Maximal labeling of this protein is reached whenever serum corticosterone values are approximately 100 ng/ml. When endogenous corticosterone levels are elevated to 100 ng/ml through stressors or exogenous ACTH injections the same maximal increase in synthesis of the 35,000 M r protein is observed. Adrenalectomy prevents the observed response from occurring following stressor application or ACTH injections. Comparison of the increases observed after administration of the type 2 receptor agonist RU 28362 and aldosterone, which has a higher affinity for the type 1 receptor, shows a 50-fold greater sensitivity of the response to the type 2 receptor agonist. Synthesis of this protein following serum increases of steroid possibly correlates to the theorized function of the type 2 receptor feedback regulation. The similar protein in the liver has an IEP of 6.8 and a slightly higher M r . A second hippocampal protein with an M r of 46,000 and an IEP of 6.2 is also increased in labeling. Two additional liver proteins, one of Mr 53,000 (IEP of 6.2) and the other with an M r of 45,000 (IEP of 8.7-7.8) are increased in the liver following glucocorticoid administration

  14. Adrenal Insufficiency Caused by Locally Applied Glucocorticoids-Myth or Fact?

    DEFF Research Database (Denmark)

    Dinsen, Stina; Klose, Marianne; Rasmussen, Åse Krogh

    2015-01-01

    Case-reports have made it evident that both inhaled, percutaneous, intranasal, intraarticular and ophthalmic administered glucocorticoids have the potential to cause life threatening adrenal insufficiency. With few and sometimes conflicting data and study methodology the prevalence of adrenal...... insufficiency secondary to locally applied glucocorticoids is not clear. Adrenal insufficiency can only be correctly evaluated by a stimulation test, and has by this procedure been reported in up to 40-50% of patients treated with high-dose inhaled glucocorticoids. Medium- to low-dose inhaled glucocorticoids...... have been shown to cause adrenal suppression in 0-16% of patients. Glucocorticoid creams and nasal glucocorticoids can cause adrenal insufficiency, also when used within prescribed doses, but the frequency seems to be less than with inhaled glucocorticoids. Intraarticularly administered glucocorticoids...

  15. Treatment of frozen shoulder with subcutaneous TNF-alpha blockade compared with local glucocorticoid injection

    DEFF Research Database (Denmark)

    Schydlowsky, Pierre; Szkudlarek, Marcin; Madsen, Ole Rintek

    2012-01-01

    We compared the effect of subcutaneous adalimumab injections with intraarticular glucocorticoid injections on frozen shoulder of 18 patients with unilateral joint involvement. Ten patients were randomised to subcutaneous injections with adalimumab and eight to intraarticular glucocorticoid inject...

  16. Effective use of thermal energy at both hot and cold side of thermoelectric module for developing efficient thermoelectric water distillation system

    International Nuclear Information System (INIS)

    Al-Madhhachi, Hayder; Min, Gao

    2017-01-01

    Highlights: • New distillation process using thermoelectric to assist evaporation/condensation. • Novel thermoelectric distillation system with reduced specific energy consumption. • Freshwater production by thermoelectrically assisted evaporation and condensation. - Abstract: An efficient thermoelectric distillation system has been designed and constructed for production of drinkable water. The unique design of this system is to use the heat from hot side of the thermoelectric module for water evaporation and the cold side for vapour condensation simultaneously. This novel design significantly reduces energy consumption and improves the system performance. The results of experiments show that the average water production is 28.5 mL/h with a specific energy consumption of 0.00114 kW h/mL in an evaporation chamber filled with 10 × 10 × 30 mm"3 of water. This is significantly lower than the energy consumption required by other existing thermoelectric distillation systems. The results also show that a maximum temperature difference between the hot and cold side of the thermoelectric module is 42.3 °C, which led to temperature increases of 26.4 °C and 8.4 °C in water and vapour, respectively.

  17. The study of lymphocytes glucocorticoid receptor in severe head injury

    International Nuclear Information System (INIS)

    Li Dapei; Wang Haodan; Zhao Qihuang

    1994-01-01

    Glucocorticoid receptors (GCR) of peripheral lymphocytes from 14 patients with severe head injury and 11 normal volunteers are studied by means of single point method of radioligand binding assay. All these patients receive surgical therapy and glucocorticoid of routine dosage. The results show that the GCR level of these patients is lower than that of the normal, while the plasma cortisol level is much higher. These changes correlate closely to the patients' clinical outcome. It is indicated that the GCR level can reflect the degree of stress of these patients and their response to glucocorticoid therapy. Using peripheral lymphocytes instead of the brain biopsy for the measurement of GCR can reflect the GCR changes of brain tissue, it's more convenient to get the sample and more acceptable to the patients

  18. Glucocorticoid receptor polymorphism in obesity and glucose homeostasis.

    Science.gov (United States)

    Majer-Łobodzińska, Agnieszka; Adamiec-Mroczek, Joanna

    2017-01-01

    Glucocorticoid receptor (GR) activity plays a significant role in the etiology of obesity and is essential for glucose homeostasis, the development of hyperinsulinaemia and subsequent increased fat deposition. Several polymorphisms in the GR gene have been described, and at least three of them seem to be associated with altered glucocorticoid sensitivity and changes in glucose homeostasis, and other metabolic parameters. The N363S polymorphism has been associated with increased sensitivity to glucocorticoides, increased insulin response to dexamethasone and increased plasma glucose level. BclI polymorphism is associated with increased abdominal obesity, hyperinsulinaemia and increased insulin resistance. Another polymorphism, ER22/23EK, in contrast to the others, is associated with relative resistance to glucocoricides actions and more beneficial metabolic profile-lower insulin resistance level, decreased lower cardiovascular risk and subseuent prolongation of life time. More research is still needed to understand the mechanisms behind these associations at the molecular level.

  19. Osteoporosis secundaria y Osteoporosis inducida por glucocorticoides (OIG

    Directory of Open Access Journals (Sweden)

    Elías Forero Illera

    2006-01-01

    Full Text Available La osteoporosis es un problema de salud pública importante a nivel mundial, y su prevalencia está aumentando. La osteoporosis secundaria se puede producir por varias patologías y el uso de ciertos medicamentos. Los glucocorticoides son un grupo de fármacos usados extensamente en la práctica médica debido a su indiscutible utilidad. La osteoporosis inducida por glucocorticoides es un problema de salud pública. Aunque la patogénesis de la pérdida producida por los glucocorticoides en el hueso no se conoce totalmente, investigaciones recientes han proporcionado nuevas conocimientos en los mecanismos de estos fármacos a nivel celular y molecular. Diversas guías han sido propuestas por diversos grupos para el tratamiento de la OIG; desafortunadamente, las guías del tratamiento no se utilizan adecuadamente en los pacientes.

  20. Glucocorticoid receptors in monocytes in type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Damm, P; Binder, C

    1989-01-01

    Glucocorticoid receptor binding characteristics were investigated in 8 males with poorly controlled Type 1 diabetes mellitus and 14 healthy males. The cell type studied was monocytes, and a method for correction for heterogeneity in glucocorticoid binding in a mononuclear leucocyte population...... or with HbA1c. In conclusion, no major abnormalities in glucocorticoid receptor binding characteristics could be demonstrated in Type 1 diabetes mellitus....... was introduced. The number of receptors and the dissociation constant KD were, respectively, 13,699 and 2.93 X 10(-8) mol/l for the control group and 15,788 and 2.75 X 10(-8) mol/l for diabetics (p greater than 0.05). In diabetics, KD correlated negatively with blood glucose (r = 0.762, p less than 0...

  1. Medications and Side Effects

    Science.gov (United States)

    ... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

  2. Low-dose glucocorticoids in hyperandrogenism Efecto de bajas dosis de glucocorticoides en el hiperandrogenismo

    Directory of Open Access Journals (Sweden)

    Leonardo Rizzo

    2007-06-01

    Full Text Available To investigate the effect of low-doses of glucocorticoids on androgen and cortisol secretion during the course of the day, we evaluated clinical signs of hyperandrogenism and total, free and bioavailable testosterone, SHBG, and cortisol following two different protocols: A fourteen patients received betamethasone 0.6 mg/day (n=8 or methylprednisolone 4 mg/day (n=6, as single daily oral dose at 11.00 PM, during 30 days, B fourteen patients were evaluated under betamethasone 0.3 mg in a single daily dose at 11.00 PM during six months, 11 out of whom were re-evaluated six months later. Twenty eight women with hyperandrogenism were included and seven normal females were used as control. Blood samples were taken in follicular phase at 8 AM and 7 PM to determine SHBG, cortisol, total, free and bioavailable testosterone. In both protocols, a significant morning and evening decrease in cortisol and testosterone (pCon el objetivo de investigar el efecto de bajas dosis de glucocorticoides sobre la secreción de andrógenos y cortisol en el curso del día, evaluamos signos de hiperandrogenismo, testosterona total, libre y biodisponible y cortisol según dos protocolos diferentes: A catorce pacientes recibieron betametasona 0.6 mg/día (n= 8 o metilprednisolona 4 mg/día (n= 6 en dosis única cotidiana, a las 23 h, durante 30 días, B catorce pacientes fueron evaluadas bajo betametasona 0.3 mg en dosis única cotidiana a la 23 h, administrada durante 6 meses; de ellas, 11 pacientes fueron re-evaluadas 6 meses más tarde. Se incluyeron 28 mujeres con hiperandrogenismo y 7 controles normales. Se obtuvieron muestras de sangre en fase folicular a las 08:00 y 9:00 h para determinar SHBG, cortisol, testosterona total, libre y biodisponible. En ambos protocolos se observó una disminución significativa de cortisol y testosterona (p<0.05 a <0.01, más importante con betametasona (p<0.05. En el protocolo B, los niveles matutinos de SHBG aumentaron

  3. Glucocorticoid-induced myopathy in the intensive care unit

    DEFF Research Database (Denmark)

    Eddelien, Heidi Shil; Hoffmeyer, Henrik Westy; Lund, Eva Charlotte Løbner

    2015-01-01

    Glucocorticoids (GC) are used for intensive care unit (ICU) patients on several indications. We present a patient who was admitted to the ICU due to severe respiratory failure caused by bronchospasm requiring mechanical ventilation and treated with methylprednisolone 240 mg/day in addition...... to antibiotics and bronchiolytics. When the sedation was lifted on day 10, the patient was awake but quadriplegic. Blood samples revealed elevated muscle enzymes, electromyography showed myopathy, and a muscle biopsy was performed. Glucocorticoid-induced myopathy was suspected, GC treatment was tapered...

  4. Glucocorticoid receptor beta increases migration of human bladder cancer cells.

    Science.gov (United States)

    McBeth, Lucien; Nwaneri, Assumpta C; Grabnar, Maria; Demeter, Jonathan; Nestor-Kalinoski, Andrea; Hinds, Terry D

    2016-05-10

    Bladder cancer is observed worldwide having been associated with a host of environmental and lifestyle risk factors. Recent investigations on anti-inflammatory glucocorticoid signaling point to a pathway that may impact bladder cancer. Here we show an inverse effect on the glucocorticoid receptor (GR) isoform signaling that may lead to bladder cancer. We found similar GRα expression levels in the transitional uroepithelial cancer cell lines T24 and UMUC-3. However, the T24 cells showed a significant (p bladder cancer cells. Therefore, GRβ may have a significant role in bladder cancer, and possibly serve as a therapeutic target for the disease.

  5. Midlife stress alters memory and mood-related behaviors in old age: Role of locally activated glucocorticoids.

    Science.gov (United States)

    Wheelan, Nicola; Kenyon, Christopher J; Harris, Anjanette P; Cairns, Carolynn; Al Dujaili, Emad; Seckl, Jonathan R; Yau, Joyce L W

    2018-03-01

    Chronic exposure to stress during midlife associates with subsequent age-related cognitive decline and may increase the vulnerability to develop psychiatric conditions. Increased hypothalamic-pituitary-adrenal (HPA) axis activity has been implicated in pathogenesis though any causative role for glucocorticoids is unestablished. This study investigated the contribution of local glucocorticoid regeneration by the intracellular enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), in persisting midlife stress-induced behavioral effects in mice. Middle-aged (10 months old) 11β-HSD1-deficient mice and wild-type congenic controls were randomly assigned to 28 days of chronic unpredictable stress or left undisturbed (non-stressed). All mice underwent behavioral testing at the end of the stress/non-stress period and again 6-7 months later. Chronic stress impaired spatial memory in middle-aged wild-type mice. The effects, involving a wide spectrum of behavioral modalities, persisted for 6-7 months after cessation of stress into early senescence. Enduring effects after midlife stress included impaired spatial memory, enhanced contextual fear memory, impaired fear extinction, heightened anxiety, depressive-like behavior, as well as reduced hippocampal glucocorticoid receptor mRNA expression. In contrast, 11β-HSD1 deficient mice resisted both immediate and enduring effects of chronic stress, despite similar stress-induced increases in systemic glucocorticoid activity during midlife stress. In conclusion, chronic stress in midlife exerts persisting effects leading to cognitive and affective dysfunction in old age via mechanisms that depend, at least in part, on brain glucocorticoids generated locally by 11β-HSD1. This finding supports selective 11β-HSD1 inhibition as a novel therapeutic target to ameliorate the long-term consequences of stress-related psychiatric disorders in midlife. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Fatigue and gene expression in human leukocytes: Increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue

    Science.gov (United States)

    Bower, Julienne E.; Ganz, Patricia A.; Irwin, Michael R.; Arevalo, Jesusa M.G.; Cole, Steve W.

    2013-01-01

    Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n = 11) and non-fatigued controls (n = 10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p < .05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors. PMID:20854893

  7. Molecular mechanisms of glucocorticoid receptor signaling Mecanismos moleculares de señalización del receptor de glucocorticoides

    Directory of Open Access Journals (Sweden)

    Marta Labeur

    2010-10-01

    Full Text Available This review highlights the most recent findings on the molecular mechanisms of the glucocorticoid receptor (GR. Most effects of glucocorticoids are mediated by the intracellular GR which is present in almost every tissue and controls transcriptional activation via direct and indirect mechanisms. Nevertheless the glucocorticoid responses are tissue -and gene- specific. GR associates selectively with corticosteroid ligands produced in the adrenal gland in response to changes of humoral homeostasis. Ligand interaction with GR promotes either GR binding to genomic glucocorticoid response elements, in turn modulating gene transcription, or interaction of GR monomers with other transcription factors activated by other signalling pathways leading to transrepression. The GR regulates a broad spectrum of physiological functions, including cell differentiation, metabolism and inflammatory responses. Thus, disruption or dysregulation of GR function will result in severe impairments in the maintenance of homeostasis and the control of adaptation to stress.Esta revisión destaca los más recientes hallazgos sobre los mecanismos moleculares del receptor de glucocorticoides (GR. La mayoría de los efectos de los glucocorticoides son mediados por los GR intracelulares presentes en casi todos los tejidos y controlan la activación transcripcional por mecanismos directos e indirectos. Las respuestas a los glucocorticoides son específicas para cada gen y tejido. Los GR se asocian en forma selectiva con ligandos producidos en la glándula adrenal, corticosteroides, en respuesta a cambios neuroendocrinos. La interacción del ligando con el GR promueve: a la unión del GR a elementos genómicos de respuesta a glucocorticoides, modulando la transcripción; b la interacción de monómeros del GR con otros factores de transcripción activados por otras vías, llevando a la transrepresión. El GR regula un amplio espectro de funciones fisiológicas, incluyendo la

  8. RGD(F/S/V-Dex: towards the development of novel, effective, and safe glucocorticoids

    Directory of Open Access Journals (Sweden)

    Jiang X

    2016-03-01

    Full Text Available Xueyun Jiang,1 Ming Zhao,1,2 Yuji Wang,1 Haimei Zhu,1 Shurui Zhao,1 Jianhui Wu,1 Yuanbo Song,3 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Guangxi Pusen Biotechnology Co. Ltd., Nanning, Guangxi, People’s Republic of China Abstract: Dexamethasone (Dex is an effective glucocorticoid in treating inflammation and preventing rejection reaction. However, the side effects limit its clinical application. To improve its druggable profile, the conjugates of RGD-peptide-modified Dex were presented and their enhanced anti-inflammation activity, minimized osteoporotic action, and nanoscaled assembly were explored. (RGD stands for Arg-Gly-Asp. Standard single letter biochemical abbreviations for amino acids have been used throughout this paper. In respect of the rejection reaction, the survival time of the implanted myocardium of the mice treated with 1.43 µmol/kg/d of the conjugates for 15 consecutive days was significantly longer than that of the mice treated with 2.5 µmol/kg/d of Dex, and the conjugates, but not Dex, exhibited no toxic action. At a single dose of 14.3 µmol/kg (100 times minimal effective dose, 0.143 µmol/kg, the conjugates induced no liver, kidney, or systemic toxicity. At the dose of 1.43 µmol/kg, the conjugates, but not Dex, prolonged the bleeding time of the mice, and inhibited the thrombosis of the rats. In water and rat plasma, the conjugates formed nanoparticles of 14–250 and 101–166 nm in diameter, respectively. Since the nanoparticles of ~100 nm in size cannot be entrapped by macrophages in the circulation, RGDF-Dex would particularly be worthy

  9. Psychosocial animal model of PTSD produces a long-lasting traumatic memory, an increase in general anxiety and PTSD-like glucocorticoid abnormalities.

    Science.gov (United States)

    Zoladz, Phillip R; Fleshner, Monika; Diamond, David M

    2012-09-01

    Post-traumatic stress disorder (PTSD) is characterized by a pathologically intense memory for a traumatic experience, persistent anxiety and physiological abnormalities, such as low baseline glucocorticoid levels and increased sensitivity to dexamethasone. We have addressed the hypothesis that rats subjected to chronic psychosocial stress would exhibit PTSD-like sequelae, including traumatic memory expression, increased anxiety and abnormal glucocorticoid responses. Adult male Sprague-Dawley rats were exposed to a cat on two occasions separated by 10 days, in conjunction with chronic social instability. Three weeks after the second cat exposure, the rats were tested for glucocorticoid abnormalities, general anxiety and their fear-conditioned memory of the two cat exposures. Stressed rats exhibited reduced basal glucocorticoid levels, increased glucocorticoid suppression following dexamethasone administration, heightened anxiety and a robust fear memory in response to cues that were paired with the two cat exposures. The commonalities in endocrine and behavioral measures between psychosocially stressed rats and traumatized people with PTSD provide the opportunity to explore mechanisms underlying psychological trauma-induced changes in neuroendocrine systems and cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Glucocorticoid stimulates expression of corticotropin-releasing hormone gene in human placenta

    International Nuclear Information System (INIS)

    Robinson, B.G.; Emanuel, R.L.; Frim, D.M.; Majzoub, J.A.

    1988-01-01

    Primary cultures of purified human cytotrophoblasts have been used to examine the expression of the corticotropin-releasing hormone (CRH) gene in placenta. The authors report here that glucocorticoids stimulate placental CRH synthesis and secretion in primary cultures of human placenta. This stimulation is in contrast to the glucocorticoid suppression of CRH expression in hypothalamus. The positive regulation of CRH by glucocorticoids suggests that the rise in CRH preceding parturition could result from the previously described rise in fetal glucocorticoids. Furthermore, this increase in placental CRH could stimulate, via adrenocorticotropic hormone, a further rise in fetal glucocorticoids, completing a positive feedback loop that would be terminated by delivery

  11. The Glucocorticoid Receptor Controls Hepatic Dyslipidemia through Hes1

    NARCIS (Netherlands)

    Lemke, U.; Krones-Herzig, A.; Berriel Diaz, M.; Narvekar, P.; Ziegler, A.; Vegiopoulos, A.; Cato, A.C.B.; Bohl, S.; Klingmüller, U.; Screaton, R.A.; Müller-Decker, K.; Kersten, A.H.; Herzig, S.

    2008-01-01

    Aberrant accumulation of lipids in the liver (¿fatty liver¿ or hepatic steatosis) represents a hallmark of the metabolic syndrome and is tightly associated with obesity, type II diabetes, starvation, or glucocorticoid (GC) therapy. While fatty liver has been connected with numerous abnormalities of

  12. Glucocorticoids and inhibition of bone formation induced by skeletal unloading

    International Nuclear Information System (INIS)

    Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E.

    1988-01-01

    Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of 45 Ca and [ 3 H]proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly

  13. Uso de glucocorticoides en enfermedades alérgicas

    Directory of Open Access Journals (Sweden)

    M Rodríguez-González

    2017-01-01

    Full Text Available Los glucocorticoides son análogos sintéticos de las hormonas adrenocorticales, de uso común, de gran utilidad en la práctica clínica del pediatra y se consideran la piedra angular del tratamiento farmacológico de enfermedades alérgicas.

  14. Glucocorticoid management in rheumatoid arthritis: morning or night low dose?

    Directory of Open Access Journals (Sweden)

    Sabrina Paolino

    2017-08-01

    Full Text Available Morning symptoms of rheumatoid arthritis (RA are linked to circadian increase of night inflammation, supported by inadequate cortisol secretion in active disease. Therefore, exogenous glucocorticoid administration in RA is recommended by EULAR and ACR from the beginning of the diagnosis, since may partially act like a “replacement therapy”. In addition, the prevention/treatment of the night up-regulation of the immune/inflammatory reaction has been shown more effective when exogenous glucocorticoid administration is managed with a night-time-release formulation. Despite a considerably higher cost than conventional prednisone (immediate release, chronotherapy with night-time-release prednisone has been recognized a cost-effective option for RA patients not on glucocorticoids who are eligible for therapy with biologic disease-modifying antirheumatic drugs (DMARDs. Interestingly, since different cell populations involved in the inflammatory process are particularly activated during the night (i.e. monocytes, macrophages, other therapeutical approaches used in RA, such as conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs should follow the same concepts of glucocorticoid chronotherapy. Therefore, bedtime methotrexate chronotherapy was found to better manage RA symptoms, and several available NSAIDs (i.e. indomethacin, aceclofenac, ketoprofen, flurbiprofen, lornoxicam have been recently modified in their formulation, in order to obtain more focused night action.

  15. The effect of early administration of glucocorticoids on learning and ...

    African Journals Online (AJOL)

    It has been observed that steroids administered postnatally may have transient retarding effect on learning and memory functions, and that animal age and sex may modify such effects. This study aims to illustrate the effect of early administration of glucocorticoids on learning and spatial memory. Wistar rat pups were ...

  16. Chronic Glucocorticoid Hypersecretion in Cushing's Syndrome Exacerbates Cognitive Aging

    Science.gov (United States)

    Michaud, Kathy; Forget, Helene; Cohen, Henri

    2009-01-01

    Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by…

  17. Postreactivation glucocorticoids impair recall of established fear memory.

    Science.gov (United States)

    Cai, Wen-Hui; Blundell, Jacqueline; Han, Jie; Greene, Robert W; Powell, Craig M

    2006-09-13

    Pavlovian fear conditioning provides one of the best rodent models of acquired anxiety disorders, including posttraumatic stress disorder. Injection of a variety of drugs after training in fear-conditioning paradigms can impair consolidation of fear memories. Indeed, early clinical trials suggest that immediate administration of such drugs after a traumatic event may decrease the risk of developing posttraumatic stress disorder in humans (Pitman et al., 2002; Vaiva et al., 2003). The use of such a treatment is limited by the difficulty of treating every patient at risk and by the difficulty in predicting which patients will experience chronic adverse consequences. Recent clinical trials suggest that administration of glucocorticoids may have a beneficial effect on established posttraumatic stress disorder (Aerni et al., 2004) and specific phobia (Soravia et al., 2006). Conversely, glucocorticoid administration after training is known to enhance memory consolidation (McGaugh and Roozendaal, 2002; Roozendaal, 2002). From a clinical perspective, enhancement of a fear memory or a reactivated fear memory would not be desirable. We report here that when glucocorticoids are administered immediately after reactivation of a contextual fear memory, subsequent recall is significantly diminished. Additional experiments support the interpretation that glucocorticoids not only decrease fear memory retrieval but, in addition, augment consolidation of fear memory extinction rather than decreasing reconsolidation. These findings provide a rodent model for a potential treatment of established acquired anxiety disorders in humans, as suggested by others (Aerni et al., 2004; Schelling et al., 2004), based on a mechanism of enhanced extinction.

  18. Why glucocorticoid withdrawal may sometimes be as dangerous as the treatment itself

    DEFF Research Database (Denmark)

    Dinsen, Stina; Baslund, Bo; Klose, Marianne

    2013-01-01

    Glucocorticoid therapy is widely used, but withdrawal from glucocorticoids comes with a potential life-threatening risk of adrenal insufficiency. Recent case reports document that adrenal crisis after glucocorticoid withdrawal remains a serious problem in clinical practice. Partly due...... to difficulties in inter-study comparison the true prevalence of glucocorticoid-induced adrenal insufficiency is unknown, but it might be somewhere between 46 and 100% 24h after glucocorticoid withdrawal, 26-49% after approximately one week, and some patients show prolonged suppression lasting months to years....... Adrenal insufficiency might therefore be underdiagnosed in clinical practice. Clinical data do not permit accurate estimates of a lower limit of glucocorticoid dose and duration of treatment, where adrenal insufficiency will not occur. Due to individual variation, neither the glucocorticoid dose nor...

  19. Glucocorticoid receptors in anorexia nervosa and Cushing's disease.

    Science.gov (United States)

    Invitti, C; Redaelli, G; Baldi, G; Cavagnini, F

    1999-06-01

    Patients with anorexia nervosa do not display cushingoid features in spite of elevated cortisol plasma levels. Whether a cortisol resistance or a reduced availability of the metabolic substrates necessary to develop the effect of glucocorticoids is responsible for this has not been established. Twenty-two patients with severe restrictive anorexia nervosa, 10 patients with active Cushing's disease, and 24 healthy volunteers without psychiatric disorders or mood alterations were investigated. Glucocorticoid receptor characteristics were examined on mononuclear leukocytes by measuring [3H]dexamethasone binding and the effect of dexamethasone on [3H]thymidine incorporation, which represents an index of DNA synthesis. The number of glucocorticoid receptors on mononuclear leukocytes (MNL) was comparable in patients with anorexia nervosa, patients with active Cushing's disease, and normal subjects (binding capacity 3.3 +/- 0.23 vs. 3.7 +/- 0.30 and 3.5 +/- 0.20 fmol/10(6) cells). Conversely, glucocorticoid receptor affinity was significantly decreased in anorexia nervosa as well as in Cushing's patients compared to control subjects (dissociation constant 4.0 +/- 0.31 and 4.1 +/- 0.34 vs. 2.9 +/- 0.29 nmol/L, p Cushing's patients compared to control subjects (p Cushing's disease. In patients with anorexia nervosa, the incorporation of [3H]thymidine into the MNL was inversely correlated with urinary free cortisol levels. These data indicate that the lack of cushingoid features in patients with anorexia nervosa is not ascribable to a reduced sensitivity to glucocorticoids but is more likely due to the paucity of metabolic substrates.

  20. Preadmission Use of Glucocorticoids and 30-Day Mortality After Stroke.

    Science.gov (United States)

    Sundbøll, Jens; Horváth-Puhó, Erzsébet; Schmidt, Morten; Dekkers, Olaf M; Christiansen, Christian F; Pedersen, Lars; Bøtker, Hans Erik; Sørensen, Henrik T

    2016-03-01

    The prognostic impact of glucocorticoids on stroke mortality remains uncertain. We, therefore, examined whether preadmission use of glucocorticoids is associated with short-term mortality after ischemic stroke, intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). We conducted a nationwide population-based cohort study using medical registries in Denmark. We identified all patients with a first-time inpatient diagnosis of stroke between 2004 and 2012. We categorized glucocorticoid use as current use (last prescription redemption ≤90 days before admission), former use, and nonuse. Current use was further classified as new or long-term use. We used Cox regression to compute 30-day mortality rate ratios with 95% confidence intervals (CIs), controlling for confounders. We identified 100 042 patients with a first-time stroke. Of these, 83 735 patients had ischemic stroke, 11 779 had ICH, and 4528 had SAH. Absolute mortality risk was higher for current users compared with nonusers for ischemic stroke (19.5% versus 10.2%), ICH (46.5% versus 34.4%), and SAH (35.0% versus 23.2%). For ischemic stroke, the adjusted 30-day mortality rate ratio was increased among current users compared with nonusers (1.58, 95% CI: 1.46-1.71), driven by the effect of glucocorticoids among new users (1.80, 95% CI: 1.62-1.99). Current users had a more modest increase in the adjusted 30-day mortality rate ratio for hemorrhagic stroke (1.26, 95% CI: 1.09-1.45 for ICH and 1.40, 95% CI: 1.01-1.93 for SAH) compared with nonusers. Former use was not substantially associated with mortality. Preadmission use of glucocorticoids was associated with increased 30-day mortality among patients with ischemic stroke, ICH, and SAH. © 2016 American Heart Association, Inc.

  1. Glucocorticoid programming of the fetal male hippocampal epigenome.

    Science.gov (United States)

    Crudo, Ariann; Suderman, Matthew; Moisiadis, Vasilis G; Petropoulos, Sophie; Kostaki, Alisa; Hallett, Michael; Szyf, Moshe; Matthews, Stephen G

    2013-03-01

    The late-gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems. As a result, synthetic glucocorticoids (sGCs) are administered to pregnant women at risk of delivering preterm. However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring. Here, we test the hypothesis that prenatal GC exposure resulting from the fetal cortisol surge or after sGC exposure results in promoter-specific epigenetic changes in the hippocampus. Fetal guinea pig hippocampi were collected before (gestational day [GD52]) and after (GD65) the fetal plasma cortisol surge (Term∼GD67) and 24 hours after (GD52) and 14 days after (GD65) two repeat courses of maternal sGC (betamethasone) treatment (n = 3-4/gp). We identified extensive genome-wide alterations in promoter methylation in late fetal development (coincident with the fetal cortisol surge), whereby the majority of the affected promoters exhibited hypomethylation. Fetuses exposed to sGC in late gestation exhibited substantial differences in DNA methylation and histone h3 lysine 9 (H3K9) acetylation in specific gene promoters; 24 hours after the sGC treatment, the majority of genes affected were hypomethylated or hyperacetylated. However, 14 days after sGC exposure these differences did not persist, whereas other promoters became hypermethylated or hyperacetylated. These data support the hypothesis that the fetal GC surge is responsible, in part, for significant variations in genome-wide promoter methylation and that prenatal sGC treatment profoundly changes the epigenetic landscape, affecting both DNA methylation and H3K9 acetylation. This is important given the widespread use of sGC in the management of women in preterm labor.

  2. FBXW7 regulates glucocorticoid response in T-cell acute lymphoblastic leukaemia by targeting the glucocorticoid receptor for degradation.

    Science.gov (United States)

    Malyukova, A; Brown, S; Papa, R; O'Brien, R; Giles, J; Trahair, T N; Dalla Pozza, L; Sutton, R; Liu, T; Haber, M; Norris, M D; Lock, R B; Sangfelt, O; Marshall, G M

    2013-04-01

    Loss of function mutation in FBXW7, an E3 ubiquitin ligase, is associated with good prognosis and early glucocorticoid treatment response in childhood T-cell acute lymphoblastic leukemia (T-ALL) by unknown mechanisms. Here, we show that FBXW7 targets the glucocorticoid receptor α (GRα) for ubiquitylation and proteasomal degradation in a manner dependent on glycogen synthase kinase 3 β-mediated phsophorylation. FBXW7 inactivation caused elevated GRα levels, and enhanced the transcriptional response to glucocorticoids. There was significant enhancement of GR transcriptional responses in FBXW7-deficient cell lines and primary T-ALL samples, in particular, for those pro-apoptotic regulatory proteins, BIM and PUMA. Reduced FBXW7 expression or function promoted glucocorticoid sensitivity, but not sensitivity to other chemotherapeutic agents used in T-ALL. Moreover, this was a general feature of different cancer cell types. Taken together, our work defines GRα as a novel FBXW7 substrate and demonstrates that favorable patient prognosis in T-ALL is associated with FBXW7 mutations due to enhanced GRα levels and steroid sensitivity. These findings suggest that inactivation of FBXW7, a putative tumor suppressor protein, may create a synthetic lethal state in the presence of specific anticancer therapies.

  3. Development of a one side automatic TIG arc welding system in horizontal position for annular vessels in nuclear fuel cycle factory

    International Nuclear Information System (INIS)

    Ohtsuka, Takao; Ohsawa, Morihiko; Nakashima, Hiroyuki; Habuta, Susumu; Hori, Tomiji; Fujiwara, Katsusi; Kitaguchi, Yoshihisa.

    1995-01-01

    Various annular vessels are planned to be equipped as a part of the plutonium refining facility in the nuclear fuel cycle factory. For manufacturing the high quality vessels, a one side automatic TIG arc welding system which is applied to the circumferencial joints in horizontal welding position have been completed. The automatic welding system is confirmed to be effective for improving the joint qualities and saving the manufacturing cost by our Mockup test. The main points of our welding system are as follows. (1) Low pulsed TIG arc welding process with a mixed shielding gas of Ar+5%H 2 is being employed. (2) Mechanical seam trucking system for the carriage and welding torch is equipped in the welding machine. (3) Arc voltage controlling system is employed for stabilizing the welding condition. (4) Magnetic wheels are equipped at the carriage for travelling without rails. The weight of this welding machine is designed to be less than 15 kg. (author)

  4. Influencia de los glucocorticoides inhalados sobre la densidad mineral ósea y el metabolismo óseo Inhaled glucocorticoids: influence on bone mineral density and bone metabolism

    Directory of Open Access Journals (Sweden)

    Fernando D. Saraví

    2000-04-01

    Full Text Available Los glucocorticoides inhalados (GCI constituyen hoy un tratamiento de primera línea del asma bronquial. Los efectos sistémicos de los GCI, como la supresión del eje hipotalámico- hipofisario-adrenal, son en general menores que los de los glucocorticoides orales. Sin embargo, existe el riesgo de efectos adversos sobre el hueso a largo plazo. El objetivo del presente trabajo fue revisar los datos publicados acerca de los efectos de los GCI sobre los marcadores del metabolismo óseo y la densidad mineral ósea en adultos y en pacientes pediátricos. Aunque los estudios examinados no proporcionan resultados uniformes, en términos generales sugieren que los GCI pueden afectar al metabolismo y a la densidad mineral ósea, en particular 1 cuando se administran a dosis elevadas (más de 400 µg/día en niños y más de 800 µg/día en adultos; 2 en pacientes pediátricos, en los que también pueden afectar al crecimiento en estatura; 3 en pacientes cuya ingesta de calcio y vitamina D es inadecuada, y 4 en mujeres postmenopáusicas sin terapia de reposición hormonal. En general, a dosis terapéuticamente equivalentes, la beclometasona tiene mayor efecto deletéreo sobre el hueso que la budesonida, y esta mayor que la fluticasona. Además de la precaución obvia de utilizar la menor dosis eficaz, se proponen como medidas preventivas: 1 la adecuada instrucción sobre el uso de los aerosoles; 2 el uso de cámaras de inhalación; 3 el enjuague bucal tras la administración de GCI, y 4 ajustes o suplementos dietéticos para asegurar una adecuada ingesta de calcio y vitamina D.Inhaled glucocorticoids (IGs are today the first-line treatment for bronchial asthma. The systemic effects of inhaled glucocorticoids, such as suppressing the hypothalamic-pituitary-adrenal axis, are generally less than those with oral glucocorticoids. However, there is a long-term risk of adverse effects on bone. The objective of this piece was to review the published data on the

  5. The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer.

    Science.gov (United States)

    Patel, Meera; McSorley, Stephen T; Park, James H; Roxburgh, Campbell S D; Edwards, Joann; Horgan, Paul G; McMillan, Donald C

    2018-03-06

    There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer. Clinicopathological characteristics were extracted from a prospective database. MMR and BRAF status was determined using immunohistochemistry. The tumour microenvironment was assessed using routine H&E pathological sections. SIR was assessed using modified Glasgow Prognostic Score (mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and lymphocyte:monocyte ratio (LMR). Overall, 972 patients were included. The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right-sided tumour location was associated with older age (P=0.001), deficient MMR (P=0.005), higher T stage (Plocation was consistently associated with a high SIR, mGPS (Plocation, adjuvant chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275 patients who received adjuvant chemotherapy, right-sided location was not associated with the MMR status (P=0.509) but was associated with higher T stage (P=0.001), venous invasion (P=0.036), CD3 + at the invasive margin (P=0.033) and CD3 + within cancer nests (P=0.012). There was no relationship between tumour location, SIR or CSS in the adjuvant group. Right-sided tumour location was associated with an elevated tumour lymphocytic infiltrate and an elevated SIR. There was no association between tumour location and

  6. Expression of glucocorticoid receptor and glucose transporter-1 during placental development in the diabetic rat

    Directory of Open Access Journals (Sweden)

    Ramazan Demir

    2011-07-01

    Full Text Available In various tissues, glucocorticoids (GCs are known to downregulate glucose transport systems; however, their effects on glucose transporters (GLUTs in the placenta of a diabetic rat are unknown. Glucocorticoid hormone action within the cell is regulated by the glucocorticoid receptor (GR. Thus, this study was designed to investigate the relationship between GR and glucose transporter expression in the placenta of the diabetic rat. Our immunohistochemical results indicated that GR and glucose transporter protein 1 (GLUT 1 are expressed ubiquitously in the trophoblast and endothelial cells of the labyrinthine zone, where maternal fetal transport takes place in the rat placenta. Expression of GR in the junctional zone of the rat placenta was detected in giant cells, and in some spongiotrophoblast cells, but not in the glycogen cells. GLUT 1 was present, especially in glycogen cells during early pregnancy, and in the spongiotrophoblast cells of the junctional zone during late pregnancy. Amounts of GR and GLUT 1 protein were increased towards the end of gestation both in the control and the diabetic placenta. However, at days 17 and 19 of gestation, only the placental GR protein was significantly increased in the streptozotocin-induced diabetic rats compared to control rats. Diabetes led to a significant decrease in placental weight at gestation day 15. In contrast, at gestational days 17 and 21, the weights of the diabetic placenta were significantly increased as compared with the controls. Moreover, diabetes induced fetus intrauterine growth retardation at gestational days 13, 17 and 21. In conclusion, the localization pattern of GR and GLUT 1 proteins in the same cell types led us to believe that there might be a relationship between GR and GLUT 1 expressions at the cellular level. GLUT 1 does not play a pivotal role in diabetic pregnancies. However, placental growth abnormalities during diabetic pregnancy may be related to the amount of GR

  7. SU-E-T-317: The Development of a DIBH Technique for Left Sided Breast Patients Undergoing Radiation Therapy Utilizing Varians RPM System in a Community Hospital

    International Nuclear Information System (INIS)

    Hasson, B; Young, M; Workie, D; Geraghty, C

    2014-01-01

    Purpose: To develop and implement a Deep Inhalation Breath Hold program (DIBH) for treatment of patients with Left-sided breast cancer in a community hospital. Methods: All patients with left sided breast cancer underwent a screening free breathing CT. Evaluation of the conventional tangent treatment fields and the heart was conducted. If the heart would not be excluded using tangents, the patient then received DIBH breathe coaching. The patients returned for a 4D CT simulation. The patients breathing cycle was monitored using the Varian Real-Time position ManagementTM (RPM) system to assess duration of DIBH, amplitude, phase and recovery time to normal breathing. Then a DIBH CT was obtained at the desired amplitude. Duplicate plans were developed for both free breathing and DIBH on the Eclipse planning system and comparison DVH's were created. The plan that provided the prescribed treatment coverage and the least doses to the OAR (heart, Lt. Lung) was determined. Those patients selected to receive treatment with DIBH were set up for treatment, and breathing was monitored using the RPM system. Practice trials were used to confirm that the amplitude, phase and recovery were consistent with findings from simulation. Results: 10 patients have been treated using the DIBH procedure in our clinic. The DIBH patients had an average increase of 80% lung volume on DIBH, decreased lung volume receiving 50% of the dose, and decreases in the V20 dose. Significant reduction in the maximum and mean dose to the heart, as well as the dose to 1CC of the volume for the DIBH plans. Conclusion: Using the RPM system already available in the clinic, staff training, and patient coaching a simple DIBH program was setup. The use of DIBH has shown promise in reducing doses to the critical organs while maintaining PTV coverage for left sided breast treatments

  8. SU-E-T-317: The Development of a DIBH Technique for Left Sided Breast Patients Undergoing Radiation Therapy Utilizing Varians RPM System in a Community Hospital

    Energy Technology Data Exchange (ETDEWEB)

    Hasson, B; Young, M; Workie, D; Geraghty, C [Anne Arundel Medical Center, Annapolis, MD (United States)

    2014-06-01

    Purpose: To develop and implement a Deep Inhalation Breath Hold program (DIBH) for treatment of patients with Left-sided breast cancer in a community hospital. Methods: All patients with left sided breast cancer underwent a screening free breathing CT. Evaluation of the conventional tangent treatment fields and the heart was conducted. If the heart would not be excluded using tangents, the patient then received DIBH breathe coaching. The patients returned for a 4D CT simulation. The patients breathing cycle was monitored using the Varian Real-Time position ManagementTM (RPM) system to assess duration of DIBH, amplitude, phase and recovery time to normal breathing. Then a DIBH CT was obtained at the desired amplitude. Duplicate plans were developed for both free breathing and DIBH on the Eclipse planning system and comparison DVH's were created. The plan that provided the prescribed treatment coverage and the least doses to the OAR (heart, Lt. Lung) was determined. Those patients selected to receive treatment with DIBH were set up for treatment, and breathing was monitored using the RPM system. Practice trials were used to confirm that the amplitude, phase and recovery were consistent with findings from simulation. Results: 10 patients have been treated using the DIBH procedure in our clinic. The DIBH patients had an average increase of 80% lung volume on DIBH, decreased lung volume receiving 50% of the dose, and decreases in the V20 dose. Significant reduction in the maximum and mean dose to the heart, as well as the dose to 1CC of the volume for the DIBH plans. Conclusion: Using the RPM system already available in the clinic, staff training, and patient coaching a simple DIBH program was setup. The use of DIBH has shown promise in reducing doses to the critical organs while maintaining PTV coverage for left sided breast treatments.

  9. Inhibition of dehydration-induced water intake by glucocorticoids is associated with activation of hypothalamic natriuretic peptide receptor-A in rat.

    Directory of Open Access Journals (Sweden)

    Chao Liu

    Full Text Available Atrial natriuretic peptide (ANP provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A, is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of

  10. Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: implications for glucocorticoid neurotoxicity.

    Science.gov (United States)

    Virgin, C E; Ha, T P; Packan, D R; Tombaugh, G C; Yang, S H; Horner, H C; Sapolsky, R M

    1991-10-01

    Glucocorticoids (GCs), the adrenal steroid hormones secreted during stress, can damage the hippocampus and impair its capacity to survive coincident neurological insults. This GC endangerment of the hippocampus is energetic in nature, as it can be prevented when neurons are supplemented with additional energy substrates. This energetic endangerment might arise from the ability of GCs to inhibit glucose transport into both hippocampal neurons and astrocytes. The present study explores the GC inhibition in astrocytes. (1) GCs inhibited glucose transport approximately 15-30% in both primary and secondary hippocampal astrocyte cultures. (2) The parameters of inhibition agreed with the mechanisms of GC inhibition of glucose transport in peripheral tissues: A minimum of 4 h of GC exposure were required, and the effect was steroid specific (i.e., it was not triggered by estrogen, progesterone, or testosterone) and tissue specific (i.e., it was not triggered by GCs in cerebellar or cortical cultures). (3) Similar GC treatment caused a decrease in astrocyte survival during hypoglycemia and a decrease in the affinity of glutamate uptake. This latter observation suggests that GCs might impair the ability of astrocytes to aid neurons during times of neurologic crisis (i.e., by impairing their ability to remove damaging glutamate from the synapse).

  11. Effect of Side Chain Functional Group on Interactions in Ionic Liquid Systems: Insights from Infinite Dilution Thermodynamic Data.

    Science.gov (United States)

    Paduszyński, Kamil; Królikowska, Marta

    2017-11-02

    Measurements of infinite dilution activity coefficients of 48 molecular solutes (including alkanes, alkenes, alkynes, aromatics, ethers, alcohols, water, ketones, pyridine, thiophene, acetonitrile, and 1-nitropropane) in two ionic liquids (ILs), namely, 1-(2-hydroxyethyl)-3-methylimidazolium dicyanamide and 1-(2-chloroethyl)-3-methylimidazolium dicyanamide, are reported in the temperature range from T = 308.15 to 358.15 K. Comparative analysis of an effect of OH/Cl substitution of terminal carbon in side chains of imidazolium cations is presented and discussed in terms of different types of intermolecular forces acting between ILs and solutes. The new data also are confronted to those published previously for a "plain" counterpart of the studied ILs, namely, 1-ethyl-3-methylimidazolium dicyanamide. Infinite dilution capacity and selectivity of the studied ILs are presented to evaluate them as separating agents in extraction of aromatics from alkanes and sulfur compounds from alkanes. Three modeling approaches, namely, linear solvation energy relationship (LSER), regular solution theory, and conductor-like screening model for real solvents (COSMO-RS), are tested for their capabilities of capturing the substitution effects detected experimentally.

  12. [Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].

    Science.gov (United States)

    Xiang, Shu-lin; He, Li-ping; Ran, Xing-wu; Tian, Hao-ming; Li, Xiu-jun; Liang, Jin-zhong

    2008-09-01

    he still had obvious hirsutism. No side effect of DEX was found. PGRS may present with pseudo-precocious puberty and galactorrhea. The aim of treatment in glucocorticoid resistance is to suppress the excessive secretion of ACTH and the increased production of adrenal androgens. The administration of synthetic GC with minimal intrinsic mineralocorticoid activity, such as DEX, provides a rational treatment for PGRS. Long-term DEX treatment should be individualized and carefully titrated based on the clinical manifestations and biochemical profile in order to control the clinical manifestations of the disease.

  13. Side Effects (Management)

    Science.gov (United States)

    ... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

  14. Energy Storage System by Means of Improved Thermal Performance of a 3 MW Grid Side Wind Power Converter

    DEFF Research Database (Denmark)

    Qin, Zian; Liserre, Marco; Blaabjerg, Frede

    2013-01-01

    method of the energy storage system. Then the conventional thermal evaluation approach is simplified for evaluation with long term wind profile. The case studies are done to address the optimal power size and capacity of the energy storage system by comparing the improvement of the thermal performance....... Also, the two promising candidates, ultracapacitors and batteries, are compared....

  15. Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells.

    Science.gov (United States)

    Dong, Hongli; Carlton, Michael E; Lerner, Adam; Epstein, Paul M

    2015-01-01

    Stimulation of cAMP signaling induces apoptosis in glucocorticoid-sensitive and resistant CEM leukemic and MM.1 multiple myeloma cell lines, and this effect is enhanced by dexamethasone in both glucocorticoid-sensitive cell types and in glucocorticoid-resistant CEM cells. Expression of the mRNA for the glucocorticoid receptor alpha (GR) promoters 1A3, 1B and 1C, expression of mRNA and protein for GR, and the BH3-only proapoptotic proteins, Bim and Bad, and the phosphorylation state of Bad were examined following stimulation of the cAMP and glucocorticoid signaling pathways. Expression levels of GR promoters were increased by cAMP and glucocorticoid signaling, but GR protein expression was little changed in CEM and decreased in MM.1 cells. Stimulation of these two signaling pathways induced Bim in CEM cells, induced Bad in MM.1 cells, and activated Bad, as indicated by its dephosphorylation on ser112, in both cell types. This study shows that leukemic and multiple myeloma cells, including those resistant to glucocorticoids, can be induced to undergo apoptosis by stimulating the cAMP signaling pathway, with enhancement by glucocorticoids, and the mechanism by which this occurs may be related to changes in Bim and Bad expression, and in all cases, to activation of Bad.

  16. Radiation Therapy Side Effects

    Science.gov (United States)

    Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

  17. Simple models of district heating systems for load and demand side management and operational optimisation; Simple modeller for fjernvarmesystemer med henblik pae belastningsudjaevning og driftsoptimering

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, B. [Technical Univ. of Denmark, Dept. of Mechanical Engineering, Kgs. Lyngby (Denmark); Larsen, H.V. [Risoe National Lab., System Analysis Dept., Roskilde (DK)

    2004-12-01

    The purpose of this research project has been to further develop and test simple (aggregated) models of district heating (DH) systems for simulation and operational optimization, and to investigate the influence of Load Management and Demand Side Management (DMS) on the total operational costs. The work is based on physical-mathematical modelling and simulation of DH systems, and is a continuation of previous EFP-96 work. In the present EFP-2001 project the goals have been to improve the Danish method of aggregation by addressing the problem of aggregation of pressure losses, and to test the methods on a much larger data set than in the EFP-1996 project. In order to verify the models it is crucial to have good data at disposal. Full information on the heat loads and temperatures not only at the DH plant but also at every consumer (building) is needed, and therefore only a few DH systems in Denmark can supply such data. (BA)

  18. Mono-(2-ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11β-hydroxysteroid dehydrogenase 2 in murine gonadotrope cells

    International Nuclear Information System (INIS)

    Hong, Dun; Li, Xing-Wang; Lian, Qing-Quan; Lamba, Pankaj; Bernard, Daniel J.; Hardy, Dianne O.; Chen, Hai-Xiao; Ge, Ren-Shan

    2009-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) have been classified as toxicants to the reproductive system at the testis level and DEHP may also impair reproductive axis function at the pituitary levels. However, MEHP is 10-fold more potent than DEHP in toxicity and little is known about the toxicological effect of MEHP on pituitary. In this study, we demonstrated that 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), not 11β-HSD1, is strongly expressed in murine gonadotrope LβT2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11β-HSD2 enzyme activity in LβT2 cells at as low as 10 -7 M. Corticosterone (CORT) at a concentration of 10 -6 M significantly inhibited LβT2 cell proliferation after 2-day culture, and 10 -6 M RU486, an antagonist of glucocorticoid receptor (GR), reversed this inhibition. However, in the presence of 10 -5 or 10 -4 M MEHP, the minimal concentration of CORT to inhibit the proliferation of LβT2 cells was lowered to 10 -7 M, and 10 -6 M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11β-HSD2 may have a key role in glucocorticoid metabolism in LβT2 cells. MEHP may participate in the glucocorticoid metabolism in LβT2 cells through inhibition of 11β-HSD2 enzyme activity. Such perturbation may be of pathological significance as MEHP may interfere with the reproductive system at pituitary level through regulation of glucocorticoid metabolism, especially in neonates with higher risk of phthalates exposure.

  19. A radioreceptor assay for measurement of plasma glucocorticoid binding activity

    International Nuclear Information System (INIS)

    Fan Jie

    1990-01-01

    A radioreceptor assay (RRA) for plasma glucocorticoid binding activity (GCBA) has been developed using glucocorticoid receptor in rat thymocytes. Unlike other assays for natural and certain synthetic corticosteroids, RRA measures the GCBA of all natural and synthetic GC in plasma. The range of standard curve was 0 ∼ 1.00 mg/L. The sensitivity was 0.01 mg/l. The recovery rate was 92.1%, and the intra and inter assay CV was 0.7% (n = 3) and 4.4% (n = 3) respectively. The level of corticosterone in 9 rat plasma samples was determined by RRA and CBG-isotope binding assay. There was a general correlation over a wide range between the values determined by the two assays (r = 0.95; P < 0.001). The measuring condition was described in detail

  20. The transcriptomics of glucocorticoid receptor signaling in developing zebrafish.

    Directory of Open Access Journals (Sweden)

    Dinushan Nesan

    Full Text Available Cortisol is the primary corticosteroid in teleosts that is released in response to stressor activation of the hypothalamus-pituitary-interrenal axis. The target tissue action of this hormone is primarily mediated by the intracellular glucocorticoid receptor (GR, a ligand-bound transcription factor. In developing zebrafish (Danio rerio embryos, GR transcripts and cortisol are maternally deposited into the oocyte prior to fertilization and influence early embryogenesis. To better understand of the molecular mechanisms involved, we investigated changes in the developmental transcriptome prior to hatch, in response to morpholino oligonucleotide knockdown of GR using the Agilent zebrafish microarray platform. A total of 1313 and 836 mRNA transcripts were significantly changed at 24 and 36 hours post fertilization (hpf, respectively. Functional analysis revealed numerous developmental processes under GR regulation, including neurogenesis, eye development, skeletal and cardiac muscle formation. Together, this study underscores a critical role for glucocorticoid signaling in programming molecular events essential for zebrafish development.

  1. Effect of glucocorticoids and gamma radiation on epidermal Langerhans cells

    International Nuclear Information System (INIS)

    Belsito, D.V.; Baer, R.L.; Thorbecke, G.J.; Gigli, I.

    1984-01-01

    The effect of 750 rads of gamma radiation on the rate of return of epidermal Langerhans cells (LC) following suppressive doses of topical glucorticoids was studied in guinea pigs. Gamma radiation alone had no effect on the LC as assessed by staining for cell membrane ATPase activity and Ia antigen. It did, however, delay the expected return of Ia but not ATPase surface markers on the LC after perturbation with glucocorticoids. The delayed return of surface Ia antigen is possibly related to a radiation-induced defect in the production of a required lymphokine and/or in intracellular Ia transport. Although our data do not rule out a cytolytic effect of steroids on the LC, they do strongly suggest that, at least in part, glucocorticoids act on the LC by altering cell surface characteristics

  2. Gastroprotective role of glucocorticoids during NSAID-induced gastropathy.

    Science.gov (United States)

    Filaretova, Ludmila

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) make significant contributions to gastric ulcer disease which remains widespread. Although several factors have been postulated as pathogenic elements of the gastric injury induced by NSAIDs, it is, however believed that prostaglandin deficiency plays a critical role in the pathogenesis of this injury. During prostaglandin deficiency, other defensive mechanisms might operate to attenuate NSAID-induced gastropathy. According to our results, NSAIDs, similar to stress, induce an increase in glucocorticoid production that in turn helps the gastric mucosa to resist the harmful actions of these drugs. In this article, we review our experimental data suggesting that glucocorticoids may play a role as natural defensive factors in maintaining the integrity of the gastric mucosa during NSAID therapy and might operate to attenuate NSAID-induced gastropathy.

  3. Locomotor therapy with extended-release crystalline glucocorticoids

    Directory of Open Access Journals (Sweden)

    Vladimir Vasilyevich Badokin

    2013-01-01

    Full Text Available Topical glucocorticoid (GC therapy for locomotor diseases is an extremely important component of a comprehensive program to treat inflammatory and, to a lesser extent, degenerative diseases. It reduces the time of hospitalization by 5—10 days in this category of patients, has a prompt and potent anti-inflammatory effect, and shows predictable efficiency. This therapy shows good tolerability and high safety and prevents serious adverse reactions to GC treatment.

  4. Early adverse experience and substance addiction: dopamine, oxytocin, and glucocorticoid pathways

    Science.gov (United States)

    Kim, Sohye; Kwok, Stephanie; Mayes, Linda C.; Potenza, Marc N.; Rutherford, Helena J. V.; Strathearn, Lane

    2016-01-01

    Substance addiction may follow a chronic, relapsing course and critically undermine the physical and psychological well-being of the affected individual and the social units of which the individual is a member. Despite the public health burden associated with substance addiction, treatment options remain suboptimal, with relapses often seen. The present review synthesizes growing insights from animal and human research to shed light upon developmental and neurobiological pathways that may increase susceptibility to addiction. We examine the dopamine system, the oxytocin system, and the glucocorticoid system, as they are particularly relevant to substance addiction. Our aim is to delineate how early adverse experience may induce long-lasting alterations in each of these systems at molecular, neuroendocrine, and behavioral levels and ultimately lead to heightened vulnerability to substance addiction. We further discuss how substance addiction in adulthood may increase the risk of suboptimal caregiving for the next generation, perpetuating the intergenerational cycle of early adverse experiences and addiction. PMID:27508337

  5. The Adsorption Langmuir Model of Transfer Metal Ti, V and Mn on System Water-Sediment in Along Side Code River, Yogyakarta

    International Nuclear Information System (INIS)

    Rini Jati Wardani; Muzakky; Agus Taftazani

    2007-01-01

    The adsorption langmuir model of transfer metal Ti, V and Mn on system water-sediment in along side Code river, Yogyakarta has been studied. For that purpose, the study is to make prediction about adsorption langmuir model of identified metal Ti, V and Mn from upstream until downstream samples water and sediment in along side Code river. The factor influenced of langmuir adsorption on transfer metal Ti, V and Mn in system water-sediment is Total Suspended Solid (TSS). The analysis showed that between TSS with metal concentration in sediment have linear correlation. The result of calculation from curve of langmuir isotherm, showed for Ti has R 2 = 0.8006 with capacities of adsorption = 0.5 mol/l and energy of adsorption = 13.286 J/mol, V has R 2 = 0.9883 with capacities of adsorption = 0.0137 mol/l and energy of adsorption = 16.64 J/mol, Mn has R 2 = 0.9624 with capacities of adsorption 0.152 mol/l and energy of adsorption = 10.51 J/mol. The conclusion from this topic about adsorption langmuir for metal Ti, V and Mn according to energy of langmuir adsorption by chemisorption process above 10 J/mo. (author)

  6. Right-sided superior vena cava draining into the left atrium: a rare anomaly of systemic venous return

    International Nuclear Information System (INIS)

    Aminololama-Shakeri, Shadi; Wootton-Gorges, Sandra L.; Reyes, Melissa; Moore, Elizabeth H.; Pretzlaff, Robert K.

    2007-01-01

    The most commonly encountered systemic thoracic venous anomaly is a persistent left superior vena cava that drains into the right atrium via the coronary sinus. A much rarer systemic venous anomaly is that of isolated anomalous drainage of a normally positioned right superior vena cava (RSVC) into the left atrium (LA). This has been reported in approximately 20 patients with the diagnosis usually being made by cardiac catheterization. We report the case of a toddler with asymptomatic hypoxemia resulting from anomalous drainage of a normal RSVC into his LA. This was diagnosed non-invasively by contrast-enhanced chest CT. (orig.)

  7. Social Regulation of Leukocyte Homeostasis: The Role of Glucocorticoid Sensitivity

    Science.gov (United States)

    Cole, Steve W.

    2010-01-01

    Recent small-scale genomics analyses suggest that physiologic regulation of pro-inflammatory gene expression by endogenous glucocorticoids may be compromised in individuals who experience chronic social isolation. This could potentially contribute to the elevated prevalence of inflammation-related disease previously observed in social isolates. The present study assessed the relationship between leukocyte distributional sensitivity to glucocorticoid regulation and subjective social isolation in a large population-based sample of older adults. Initial analyses confirmed that circulating neutrophil percentages were elevated, and circulating lymphocyte and monocyte percentages were suppressed, in direct proportion to circulating cortisol levels. However, leukocyte distributional sensitivity to endogenous glucocorticoids was abrogated in individuals reporting either occasional or frequent experiences of subjective social isolation. This finding held in both nonparametric univariate analyses and in multivariate linear models controlling for a variety of biological, social, behavioral, and psychological confounders. The present results suggest that social factors may alter immune cell sensitivity to physiologic regulation by the hypothalamic-pituitary-adrenal axis in ways that could ultimately contribute to the increased physical health risks associated with social isolation. PMID:18394861

  8. CHLORPYRIFOS DEVELOPMENTAL NEUROTOXICITY: INTERACTION WITH GLUCOCORTICOIDS IN PC12 CELLS

    Science.gov (United States)

    Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

    2012-01-01

    Prenatal coexposures to glucocorticoids and organophosphate pesticides are widespread. Glucocorticoids are elevated by maternal stress and are commonly given in preterm labor; organophosphate exposures are virtually ubiquitous. We used PC12 cells undergoing neurodifferentiation in order to assess whether dexamethasone enhances the developmental neurotoxicity of chlorpyrifos, focusing on concentrations relevant to human exposures. By themselves, each agent reduced the number of cells and the combined exposure elicited a correspondingly greater effect than with either agent alone. There was no general cytotoxicity, as cell growth was actually enhanced, and again, the combined treatment evoked greater cellular hypertrophy than with the individual compounds. The effects on neurodifferentiation were more complex. Chlorpyrifos alone had a promotional effect on neuri to genesis whereas dexamethasone impaired it; combined treatment showed an overall impairment greater than that seen with dexamethasone alone. The effect of chlorpyrifos on differentiation into specific neurotransmitter phenotypes was shifted by dexamethasone. Either agent alone promoted differentiation into the dopaminergic phenotype at the expense of the cholinergic phenotype. However, in dexamethasone-primed cells, chlorpyrifos actually enhanced cholinergic neurodifferentiation instead of suppressing this phenotype. Our results indicate that developmental exposure to glucocorticoids, either in the context of stress or the therapy of preterm labor, could enhance the developmental neurotoxicity of organophosphates and potentially of other neurotoxicants, as well as producing neurobehavioral outcomes distinct from those seen with either individual agent. PMID:22796634

  9. Regulation of NAD(P)H:quininone oxidoreductase by glucocorticoids

    International Nuclear Information System (INIS)

    Pinaire, J.A.; Xiao, G.-H.; Falkner, K.C.; Prough, R.A.

    2004-01-01

    Previous studies in neonatal and adolescent rats as well as adrenalectomized rats have demonstrated that glucocorticoids regulate the expression of the rat NAD(P)H:quinone oxidoreductase gene (QOR). We used primary cultures of rat adult hepatocytes to document that added glucorticoids repress both the basal and 1,2-benzanthracene-induced expression of QOR mRNA by 65-70%. QOR enzyme activity and protein were concomitantly suppressed as well. The monotonic concentration response for repression of QOR gene products up to 100 μM DEX concentration demonstrated that the glucocorticoid receptor (GR) was most likely involved in this process. The lack of effect at higher concentration rules out a role for the Pregnane X receptor in this regulation by DEX. In addition, the anti-glucorticoid RU38486 blocked this negative regulation and the protein synthesis inhibitor cycloheximide had no effect on this repression process. Similar results of GR dependence were observed using a luciferase reporter construct containing the 5'-flanking region of the human QOR gene using HepG2 cells. Collectively, these results demonstrate that GR must directly participate in the negative regulation of QOR gene expression by dexamethasone and other glucocorticoids in vivo

  10. Effects of Social Isolation on Glucocorticoid Regulation in Social Mammals

    Science.gov (United States)

    Hawkley, Louise C.; Cole, Steve W.; Capitanio, John P.; Norman, Greg J.; Cacioppo, John T.

    2012-01-01

    The regulation and function of the hypothalamic-pituitary-adrenocortical (HPA) axis and glucocorticoids have been well conserved across vertebrate species. Glucocorticoids influence a wide range of physiological functions that include glucose regulation, metabolism, inflammatory control, as well as cardiovascular, reproductive, and neuronal effects. Some of these are relatively quick-acting non-genomic effects, but most are slower-acting genomic effects. Thus, any stimulus that affects HPA function has the potential to exert wide-ranging short-term and long-term effects on much of vertebrate physiology. Here, we review the effects of social isolation on the functioning of the HPA axis in social species, and on glucocorticoid physiology in social mammals in particular. Evidence indicates that objective and perceived social isolation alter HPA regulation, although the nature and direction of the HPA response differs among species and across age. The inconsistencies in the direction and nature of HPA effects have implications for drawing cross-species conclusions about the effects of social isolation, and are particularly problematic for understanding HPA-related physiological processes in humans. The animal and human data are incommensurate because, for example, animal studies of objective isolation have typically not been modeled on, or for comparability with, the subjective experience of isolation in humans. An animal model of human isolation must be taken more seriously if we want to advance our understanding of the mechanisms for the effects of objective and perceived isolation in humans. PMID:22663934

  11. The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl Christian; Overgaard, Søren

    2011-01-01

    of 3 months without treatment. Group 3 was left untreated and served as controls. All sheep received a restricted diet with low calcium and phosphorus. At sacrifice, cortical bone samples from the femur midshaft of each sheep were harvested, micro-CT scanned and subjected to three-point bending...... and tensile strength testing. Bone collagen and mineral were determined. Cortical porosity was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Apparent density was significantly decreased in the glucocorticoid-2 compared with the glucocorticoid-1 group....... Collagen content was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Bone mineral content did not differ between the groups. Neither the three-point bending mechanical properties nor the tensile mechanical properties differed significantly between...

  12. Dark Side of Information Systems and Protection of Children Online: Examining Predatory Behavior and Victimization of Children within Social Media

    Science.gov (United States)

    Albert, Connie S.

    2014-01-01

    Protecting children online from sexual predators has been a focus of research in psychiatry, sociology, computer science, and information systems (IS) for many years. However, the anonymity afforded by social media has made finding a solution to the problem of child protection difficult. Pedophiles manipulate conversation (discourse) with children…

  13. Elucidation and modulation of glucocorticoid-induced apoptosis in acute lymphoblastic leukemia cells

    International Nuclear Information System (INIS)

    Eberhart, K.

    2011-01-01

    This thesis deals with the elucidation of the synergistic effect of the glucocorticoid dexamethasone and the metabolic modulator 2-deoxyglucose on apoptosis induction in two in vitro model systems of childhood acute lymphoblastic leukemia. 2-deoxyglucose accelerated the kinetics of, and increased the sensitivity to, glucocorticoid-induced apoptosis in two leukemia cell lines. In primary lymphocytes from healthy donors, in contrast, 2-deoxyglucose and dexamethasone did not act synergistically on apoptosis induction. To elucidate the molecular basis of the synergistic effect, glycolysis by means of glucose uptake, lactate production, ATP levels, glucose transporter and hexokinase expression and mitochondrial oxygen consumption was analyzed in treated vs. untreated cells. The study revealed a downregulation of gene expression of the glucose transporter GLUT1 and hexokinase 2 (HK2), release of HK2 from the outer mitochondrial membrane, as well as reduced glycolysis and mitochondrial respiration. Moreover, the analysis of the mitochondrial proteome by 2 dimensional differential gel electrophoresis after treatment with 2-deoxyglucose and dexamethasone revealed the regulation of several interesting candidate proteins involved in treatment related apoptosis. (author)

  14. Microarray analyses of glucocorticoid and vitamin D3 target genes in differentiating cultured human podocytes.

    Directory of Open Access Journals (Sweden)

    Xiwen Cheng

    Full Text Available Glomerular podocytes are highly differentiated epithelial cells that are key components of the kidney filtration units. Podocyte damage or loss is the hallmark of nephritic diseases characterized by severe proteinuria. Recent studies implicate that hormones including glucocorticoids (ligand for glucocorticoid receptor and vitamin D3 (ligand for vitamin D receptor protect or promote repair of podocytes from injury. In order to elucidate the mechanisms underlying hormone-mediated podocyte-protecting activity from injury, we carried out microarray gene expression studies to identify the target genes and corresponding pathways in response to these hormones during podocyte differentiation. We used immortalized human cultured podocytes (HPCs as a model system and carried out in vitro differentiation assays followed by dexamethasone (Dex or vitamin D3 (VD3 treatment. Upon the induction of differentiation, multiple functional categories including cell cycle, organelle dynamics, mitochondrion, apoptosis and cytoskeleton organization were among the most significantly affected. Interestingly, while Dex and VD3 are capable of protecting podocytes from injury, they only share limited target genes and affected pathways. Compared to VD3 treatment, Dex had a broader and greater impact on gene expression profiles. In-depth analyses of Dex altered genes indicate that Dex crosstalks with a broad spectrum of signaling pathways, of which inflammatory responses, cell migration, angiogenesis, NF-κB and TGFβ pathways are predominantly altered. Together, our study provides new information and identifies several new avenues for future investigation of hormone signaling in podocytes.

  15. Type 1 plaminogen activator inhibitor gene: Functional analysis and glucocorticoid regulation of its promoter

    International Nuclear Information System (INIS)

    Van Zonneveld, A.J.; Curriden, S.A.; Loskutoff, D.J.

    1988-01-01

    Plasminogen activator inhibitor type 1 is an important component of the fibrinolytic system and its biosynthesis is subject to complex regulation. To study this regulation at the level of transcription, the authors have identified and sequenced the promoter of the human plasminogen activator inhibitor type 1 gene. Nuclease protection experiments were performed by using endothelial cell mRNA and the transcription initiation (cap) site was established. Sequence analysis of the 5' flanking region of the gene revealed a perfect TATA box at position -28 to position -23, the conserved distance from the cap site. Comparative functional studies with the firefly luciferase gene as a reporter gene showed that fragments derived from this 5' flanking region exhibited high promoter activity when transfected into bovine aortic endothelial cells and mouse Ltk - fibroblasts but were inactive when introduced into HeLa cells. These studies indicate that the fragments contain the plasminogen activator inhibitor type 1 promoter and that it is expressed in a tissue-specific manner. Although the fragments were also silent in rat FTO2B hepatoma cells, their promoter activity could be induced up to 40-fold with the synthetic glucocorticoid dexamethasone. Promoter deletion mapping experiments and studies involving the fusion of promoter fragments to a heterologous gene indicated that dexamethasone induction is mediated by a glucocorticoid responsive element with enhancer-like properties located within the region between nucleotides -305 and +75 of the plasminogen activator inhibitor type 1 gene

  16. Hepatocyte growth factor limits autoimmune neuroinflammation via glucocorticoid-induced leucine zipper expression in dendritic cells.

    Science.gov (United States)

    Benkhoucha, Mahdia; Molnarfi, Nicolas; Dunand-Sauthier, Isabelle; Merkler, Doron; Schneiter, Gregory; Bruscoli, Stefano; Riccardi, Carlo; Tabata, Yasuhiko; Funakoshi, Hiroshi; Nakamura, Toshikazu; Reith, Walter; Santiago-Raber, Marie-Laure; Lalive, Patrice H

    2014-09-15

    Autoimmune neuroinflammation, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity, is believed to result from immune tolerance dysfunction leading to demyelination and substantial neurodegeneration. We previously showed that CNS-restricted expression of hepatocyte growth factor (HGF), a potent neuroprotective factor, reduced CNS inflammation and clinical deficits associated with EAE. In this study, we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response. RNA interference-directed neutralization of GILZ expression by DCs suppressed the induction of tolerance caused by HGF. Finally, adoptive transfer of HGF-treated DCs from wild-type but not GILZ gene-deficient mice potently mediated functional recovery in recipient mice with established EAE through effective modulation of autoaggressive T cell responses. Altogether, these results show that by inducing GILZ in DCs, HGF reproduces the mechanism of immune regulation induced by potent immunomodulatory factors such as IL-10, TGF-β1, and glucocorticoids and therefore that HGF therapy may have potential in the treatment of autoimmune dysfunctions. Copyright © 2014 by The American Association of Immunologists, Inc.

  17. The Principle of Non-Refoulement and Access to Asylum System: Two Sides of the Same Coin

    Directory of Open Access Journals (Sweden)

    Goranka Lalić Novak

    2015-12-01

    Full Text Available The European Union and other countries on the Balkan route for migrants have recorded a large increase in the number of asylum seekers. In parallel with the increased number of refugees trying to enter the territory of the EU, measures for migration management have tightened, and the right to asylum at the level of the Member States has been interpreted more and more restrictive. Search for protection from persecution has become a reason for closing borders and disabling access to territory and asylum system. However, access to asylum system is the first step in the realization of the right to asylum as guaranteed by international, European and national law. In addition to allowing access to territory and asylum system, which implies an obligation of states to accept refugees in order to confirm the need for international protection in a fair and efficient procedure, the states are obliged to respect the principle of non-refoulement. The aim of this paper is to clarify the connection between providing access to asylum system and respect for the principle of non-refoulement. Analysis in the paper was done by legal-dogmatic method of research and interpretation of legal acts and other authorities, as well as of UNHCR relevant recommendations and documents. The assumption is that without the provision of access to territory and asylum system the principle of non-refoulement cannot be respected. Apart from the international refugee law and doctrinal interpretations, it derives from the practice of the European Court of Human Rights regarding the prohibition of torture or other inhuman treatment or punishment guaranteed by the Convention for the Protection of Human Rights and Fundamental Freedoms. The conclusion is that the states must take into account international and European standards regarding the protection of the principle of non-refoulement when considering the introduction of new measures to manage migration movements.

  18. Highly efficient end-side-pumped Nd:YAG solar laser by a heliostat-parabolic mirror system.

    Science.gov (United States)

    Almeida, J; Liang, D; Vistas, C R; Guillot, E

    2015-03-10

    We report a large improvement in the collection and slope efficiency of an Nd:YAG solar laser pumped by a heliostat-parabolic mirror system. A conical fused silica lens was used to further concentrate the solar radiation from the focal zone of a 2 m diameter primary concentrator to a Nd:YAG single-crystal rod within a conical pump cavity, which enabled multipass pumping to the active medium. A 56 W cw laser power was measured, corresponding to 21.1  W/m2 record-high solar laser collection efficiency with the heliostat-parabolic mirror system. 4.9% slope efficiency was calculated, corresponding to 175% enhancement over our previous result.

  19. Performance analysis of a small regenerative gas turbine system adopting steam injection and side-wall in finned tube evaporator

    International Nuclear Information System (INIS)

    Kang, Soo Young; Lee, Jong Jun; Kim, Tong Seop

    2009-01-01

    Small gas turbines in power range of several MWs are quite suitable for application in distributed generation as well as Community Energy Systems (CES). Humidification is an effective way to improve gas turbine performance, and steam injection is the most general and practically feasible method. This study intended to examine the effect of steam injection on the performance of several MW class gas turbines. A primary concern is given to the regenerative cycle gas turbine. The steam injection effect on the performance of a system without the regenerator (i.e. a simple cycle) is also examined. In addition, the influence of bypass of some of the exhaust gas on the performance of the gas turbine, especially the regenerative cycle gas turbine, is evaluated.

  20. Science review: Mechanisms of impaired adrenal function in sepsis and molecular actions of glucocorticoids

    OpenAIRE

    Prigent, Hélène; Maxime, Virginie; Annane, Djillali

    2004-01-01

    This review describes current knowledge on the mechanisms that underlie glucocorticoid insufficiency in sepsis and the molecular action of glucocorticoids. In patients with severe sepsis, numerous factors predispose to glucocorticoid insufficiency, including drugs, coagulation disorders and inflammatory mediators. These factors may compromise the hypothalamic–pituitary axis (i.e. secondary adrenal insufficiency) or the adrenal glands (i.e. primary adrenal failure), or may impair glucocorticoi...

  1. Assignment of the human gene for the glucocorticoid receptor to chromosome 5.

    OpenAIRE

    Gehring, U; Segnitz, B; Foellmer, B; Francke, U

    1985-01-01

    Human lymphoblastic leukemia cells of line CEM-C7 are glucocroticoid-sensitive and contain glucocorticoid receptors of wild-type characteristics. EL4 mouse lymphoma cells are resistant to lysis by glucocorticoids due to mutant receptors that exhibit abnormal DNA binding. Hybrids between the two cell lines were prepared and analyzed with respect to glucocorticoid responsiveness and to receptor types by DNA-cellulose chromatrography. Sensitive hybrid cell clones contained the CEM-C7-specific re...

  2. Comparative product testing of children's restraint systems, with inclusion of side-collision tests

    Energy Technology Data Exchange (ETDEWEB)

    Goerlitz, H. [Stiftung Warentest, Berlin (Germany); Noeske, V. [DEKRA Dresden (Germany)

    2001-07-01

    Stiftung Warentest has conducted comparative product testing for Group 0.. III child car seats to evaluate accident protection, handling, comfort of the seats, and safety against faulty use. The tests that were conducted were intended to provide assessment of product quality. Owing to great reader interest, tests conducted on child car seats have become well established for a considerable number of years now. They enjoy esteemed status, for example, in our magazine test. Stiftung Warentest conducted its first tests on children's restraint system many years ago: in May of 1968. The great interest in this topic, as evidenced by widespread feedback from readers, justifies the high costs occasioned by the dynamic testing of children's restraint systems. The popularity of this topic leads to greater sales of the particular issues of the magazine test - which carries no advertising - and at least compensates for most of the added costs necessary for dynamic collision testing. It is not generally well known that Stiftung Warentest covers approximately 90% of its budget from the sales of its two magazines test and Finanztest, and of its other special publications. The annual subsidy by the German government is relatively small. The national subsidy is intended to compensate for the loss of revenue from the exclusion of advertising. (orig.)

  3. Raised urinary glucocorticoid and adrenal androgen precursors in the urine of young hypertensive patients: possible evidence for partial glucocorticoid resistance

    Science.gov (United States)

    Shamim, W; Yousufuddin, M; Francis, D; Gualdiero, P; Honour, J; Anker, S; Coats, A

    2001-01-01

    OBJECTIVE—To evaluate urinary glucocorticoid excretion profiles in a cohort of recently diagnosed young hypertensive patients.
METHODS—After excluding patients with secondary causes, 60 individuals with premature hypertension were recruited (diagnosed by ambulatory blood pressure monitoring before the age of 36 years). In addition, 30 older hypertensive controls (age of onset > 36 years, "middle aged hypertensive controls"), and 30 normal controls (age matched to the young hypertensive group) were studied. All provided 24 hour urine collections for mass spectrometry for total cortisol metabolites and total androgen metabolites by gas chromatography.
RESULTS—Among male patients, those with premature hypertension had higher total urinary excretion of cortisol metabolites (mean (SD), 13 332 (6472) µg/day) than age matched normal controls (7270 (1788) µg/day; p = 0.00001) or middle aged hypertensive controls (8315 (3565) µg/day; p = 0.002). A similar increase was seen among the female patients, although the absolute concentrations were lower. There was no significant difference between middle aged hypertensive patients and normal controls. Urinary total androgen excretion profiles in female patients also showed an unusual increase in the premature hypertension group (2958 (1672) µg/day) compared with the other groups (middle aged hypertensive controls, 1373 (748) µg/day, p = 0.0003; normal controls, 1687 (636) µg/day, p = 0.002). In all subjects, serum sodium and creatinine concentrations were within the normal range; serum potassium concentrations were found to be low before the start of treatment.
CONCLUSIONS—Individuals presenting with premature hypertension have an abnormally high excretion of glucocorticoid metabolites in the urine. While the mechanism remains uncertain, these findings are compatible with partial resistance of the glucocorticoid receptors, with a compensatory increase in cortisol and androgen

  4. The electronics, trigger and data acquisition system for the liquid argon time projection chamber of the DarkSide-50 search for dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Agnes, P.; Albuquerque, I. F. M.; Alexander, T.; Alton, A. K.; Arisaka, K.; Asner, D. M.; Ave, M.; Back, H. O.; Baldin, B.; Biery, K.; Bocci, V.; Bonfini, G.; Bonivento, W.; Bossa, M.; Bottino, B.; Brigatti, A.; Brodsky, J.; Budano, F.; Bussino, S.; Cadeddu, M.; Cadoni, M.; Calaprice, F.; Canci, N.; Candela, A.; Cao, H.; Caravati, M.; Cariello, M.; Carlini, M.; Catalanotti, S.; Cataudella, V.; Cavalcante, P.; Chepurnov, A.; Cicaló, C.; Cocco, A. G.; Covone, G.; Crippa, L.; D' Angelo, D.; D' Incecco, M.; Davini, S.; de Candia, A.; Cecco, S. De; Deo, M. De; Filippis, G. De; Rosa, G. De; Vincenzi, M. De; Derbin, A.; Devoto, A.; Eusanio, F. Di; Dionisi, C.; Pietro, G. Di; Edkins, E.; Empl, A.; Fan, A.; Fiorillo, G.; Fomenko, K.; Forster, G.; Franco, D.; Gabriele, F.; Galbiati, C.; Giagu, S.; Giganti, C.; Giovanetti, G. K.; Goretti, A. M.; Granato, F.; Grandi, L.; Gromov, M.; Guan, M.; Guardincerri, Y.; Hackett, B. R.; Herner, K. R.; Hughes, D.; Humble, P.; Hungerford, E. V.; Ianni, A.; Ianni, A.; James, I.; Johnson, T. N.; Keeter, K.; Kendziora, C. L.; Kobychev, V.; Koh, G.; Korablev, D.; Korga, G.; Kubankin, A.; Li, X.; Lissia, M.; Loer, B.; Lombardi, P.; Longo, G.; Luitz, S.; Ma, Y.; Machado, A.; Machulin, I. N.; Mandarano, A.; Mari, S. M.; Maricic, J.; Marini, L.; Martoff, C. J.; Meyers, P. D.; Miletic, T.; Milincic, R.; Montanari, D.; Monte, A.; Montuschi, M.; Monzani, M. E.; Mosteiro, P.; Mount, B. J.; Muratova, V. N.; Musico, P.; Agasson, A. Navrer; Nelson, A.; Odrowski, S.; Oleinik, A.; Orsini, M.; Ortica, F.; Pagani, L.; Pallavicini, M.; Pantic, E.; Parmeggiano, S.; Pelczar, K.; Pelliccia, N.; Pocar, A.; Pordes, S.; Pugachev, D. A.; Qian, H.; Randle, K.; Ranucci, G.; Razeti, M.; Razeto, A.; Reinhold, B.; Renshaw, A. L.; Rescigno, M.; Riffard, Q.; Romani, A.; Rossi, B.; Rossi, N.; Rountree, S. D.; Sablone, D.; Saggese, P.; Saldanha, R.; Sands, W.; Sangiorgio, S.; Savarese, C.; Schlitzer, B.; Segreto, E.; Semenov, D. A.; Shields, E.; Singh, P. N.; Skorokhvatov, M. D.; Smirnov, O.; Sotnikov, A.; Stanford, C.; Suvorov, Y.; Tartaglia, R.; Tatarowicz, J.; Testera, G.; Tonazzo, A.; Trinchese, P.; Unzhakov, E. V.; Verducci, M.; Vishneva, A.; Vogelaar, R. B.; Wada, M.; Walker, S.; Wang, H.; Wang, Y.; Watson, A. W.; Westerdale, S.; Wojcik, M. M.; Xiang, X.; Xiao, X.; Xu, J.; Yang, C.; Yoo, J.; Zavatarelli, S.; Zec, A.; Zhong, W.; Zhu, C.; Zuzel, G.

    2017-12-01

    The DarkSide-50 experiment at the Laboratori Nazionali del Gran Sasso is a search for dark matter using a dual phase time projection chamber with 50 kg of low radioactivity argon as target. Light signals from interactions in the argon are detected by a system of 38 photo-multiplier tubes (PMTs), 19 above and 19 below the TPC volume inside the argon cryostat. We describe the electronics which processes the signals from the photo-multipliers, the trigger system which identifies events of interest, and the data-acquisition system which records the data for further analysis. The electronics include resistive voltage dividers on the PMTs, custom pre-amplifiers mounted directly on the PMT voltage dividers in the liquid argon, and custom amplifier/discriminators (at room temperature). After amplification, the PMT signals are digitized in CAEN waveform digitizers, and CAEN logic modules are used to construct the trigger, the data acquisition system for the TPC is based on the Fermilab "artdaq" software. The system has been in operation since early 2014.

  5. An Efficient Demand Side Management System with a New Optimized Home Energy Management Controller in Smart Grid

    Directory of Open Access Journals (Sweden)

    Hafiz Majid Hussain

    2018-01-01

    Full Text Available The traditional power grid is inadequate to overcome modern day challenges. As the modern era demands the traditional power grid to be more reliable, resilient, and cost-effective, the concept of smart grid evolves and various methods have been developed to overcome these demands which make the smart grid superior over the traditional power grid. One of the essential components of the smart grid, home energy management system (HEMS enhances the energy efficiency of electricity infrastructure in a residential area. In this aspect, we propose an efficient home energy management controller (EHEMC based on genetic harmony search algorithm (GHSA to reduce electricity expense, peak to average ratio (PAR, and maximize user comfort. We consider EHEMC for a single home and multiple homes with real-time electricity pricing (RTEP and critical peak pricing (CPP tariffs. In particular, for multiple homes, we classify modes of operation for the appliances according to their energy consumption with varying operation time slots. The constrained optimization problem is solved using heuristic algorithms: wind-driven optimization (WDO, harmony search algorithm (HSA, genetic algorithm (GA, and proposed algorithm GHSA. The proposed algorithm GHSA shows higher search efficiency and dynamic capability to attain optimal solutions as compared to existing algorithms. Simulation results also show that the proposed algorithm GHSA outperforms the existing algorithms in terms of reduction in electricity cost, PAR, and maximize user comfort.

  6. MBE growth of compounds on the copper rich side of the (Sr,Ca)CuO system

    Energy Technology Data Exchange (ETDEWEB)

    Eustache, B. [Ecole Superieure de Physique et Chimie Industrielles, Paris (France). Lab. Surfaces et Supraconducteurs]|[Wintici S.A., 17 Rue Jean Moulin, 94300, Paris (France); Beuran, F.C.; Hatterer, C.J.; Mairet, V.; Partiot, C.; Xu, X.Z.; Germain, P.; Lagues, M. [Ecole Superieure de Physique et Chimie Industrielles, Paris (France). Lab. Surfaces et Supraconducteurs; Deville Cavellin, C. [Universite Paris XII, 61 Avenue du General de Gaulle, 94010 Creteil, Paris (France)

    1997-04-01

    Thin films belonging to the copper rich family in the (Sr,Ca)-Cu-O system have been synthesized using molecular beam epitaxy (MBE) deposition. The growth conditions have been optimized on two different substrates, MgO (100) and SrTiO{sub 3} (100). We discuss in this paper the variations of the electron diffraction pattern (RHEED) during the growth. The films obtained present a single orientation with good crystallization. The average composition measured by Rutherford backscattering spectroscopy (RBS) is (Sr,Ca){sub 0.6}CuO{sub z}. This stoichiometry is close to the composition expected for the first members of the spin ladders homologous series Sr{sub n-1}Cu{sub n+1}O{sub 2n}. High resolution electron microscopy (HREM) and X-ray diffraction measurements on a four circles diffractometer are in progress. Preliminary results confirm that the structure is consistent with spin-ladders structures. Typical room temperature resistivity is of the order of 0.5 m{Omega} cm. The search for superconducting properties in these compounds is discussed. (orig.)

  7. Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes.

    Science.gov (United States)

    Hoffman, Eric P; Riddle, Valerie; Siegler, Maxime A; Dickerson, Daniel; Backonja, Miroslav; Kramer, William G; Nagaraju, Kanneboyina; Gordish-Dressman, Heather; Damsker, Jesse M; McCall, John M

    2018-06-01

    Glucocorticoid drugs are highly effective anti-inflammatory agents, but chronic use is associated with extensive pharmacodynamic safety concerns that have a considerable negative impact on patient quality of life. Vamorolone (VBP15) is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties. Pre-clinical data in multiple mouse models of inflammation showed retention of anti-inflammatory efficacy, but loss of most or all side effects. We report first-in-human Phase 1 clinical trials (86 healthy adult males), with single ascending doses (0.1-20.0 mg/kg), and multiple ascending doses (1.0-20 mg/kg/day; 14 days treatment). Vamorolone was well-tolerated at all dose levels. Vamorolone showed pharmacokinetic and metabolism profiles similar to prednisone. Biomarker studies showed loss of side effects of traditional glucocorticoid drugs (bone fragility, metabolic disturbance, immune suppression). Suppression of the adrenal axis was 10-fold less than prednisone. The crystallographic structure of vamorolone was solved, and compared to prednisone and dexamethasone. There was overlap in structure, but differences in conformation at the C-ring where glucocorticoids interact with Asn564 of the glucocorticoid receptor. The predicted loss of Asn564 binding to vamorolone may underlie the loss of gene transcriptional activity. Vamorolone is a dissociative steroid that retains high affinity binding and nuclear translocation of both glucocorticoid (agonist) and mineralocorticoid (antagonist) receptors, but does not show pharmacodynamic safety concerns of existing glucocorticoid drugs at up to 20 mg/kg/day. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Single-sided NMR

    CERN Document Server

    Casanova, Federico; Blümich, Bernhard

    2011-01-01

    Single-Sided NMR describes the design of the first functioning single-sided tomograph, the related measurement methods, and a number of applications. One of the key advantages to this method is the speed at which the images are obtained.

  9. Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

    Science.gov (United States)

    Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno

    2016-05-01

    Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress

  10. Glucocorticoid administration for Graves' hyperthyroidism treated by radioiodine. A questionnaire survey among members of the European Thyroid Association

    NARCIS (Netherlands)

    Lazarus, J. H.; Bartalena, L.; Marcocci, C.; Kahaly, G. J.; Krassas, G.; Wiersinga, W. M.; Baldeschi, L.; Boboridis, K.; Boschi, A.; Currò, N.; Daumerie, C.; Dickinson, A. J.; Eckstein, A.; Kendall-Taylor, P.; Lane, C. M.; Ludgate, M. E.; Mann, K.; Marinò, M.; Mourits, M. P.; Nardi, M.; Neoh, C.; Orgiazzi, J.; Pearce, S.; Perros, P.; Pinchera, A.; Pitz, S.; Salvi, M.; Sivelli, P.; Stahl, M.; von Arx, G.

    2010-01-01

    Background: Glucocorticoid prophylaxis is required in some instances after radioiodine (RAI) treatment for Graves' hyperthyroidism to prevent progression of Graves' orbitopathy (GO). However, no randomized clinical trial has been performed to ascertain the optimum glucocorticoid therapy. Aim and

  11. Glucocorticoid Effects on Memory Consolidation Depend on Functional Interactions between the Medial Prefrontal Cortex and Basolateral Amygdala

    NARCIS (Netherlands)

    Roozendaal, Benno; McReynolds, Jayme R.; Van der Zee, Eddy A.; Lee, Sangkwan; McGaugh, James L.; McIntyre, Christa K.

    2009-01-01

    Considerable evidence indicates that the basolateral complex of the amygdala (BLA) interacts with efferent brain regions in mediating glucocorticoid effects on memory consolidation. Here, we investigated whether glucocorticoid influences on the consolidation of memory for emotionally arousing

  12. Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study.

    Science.gov (United States)

    Tseng, C-L; Chen, Y-T; Huang, C-J; Luo, J-C; Peng, Y-L; Huang, D-F; Hou, M-C; Lin, H-C; Lee, F-Y

    2015-09-01

    Controversy exists regarding glucocorticoids therapy and the risk of peptic ulcer bleeding (PUB). The present study was undertaken to determine whether short-term use of glucocorticoids is associated with the occurrence of peptic ulcer bleeding. The records of adult patients hospitalised for newly diagnosed peptic ulcer bleeding from 2000 to 2012 were retrieved from the Taiwan National Health Insurance Research Database, a nationwide population-based registry system. The association between systemic glucocorticoids usage and peptic ulcer bleeding was determined with a conditional logistic regression model comparing cases and controls during time windows of 7, 14 and 28 days using a case-crossover design. Of the 8894 enrolled patients, the adjusted self-matched odds ratios for peptic ulcer bleeding after exposure to the glucocorticoids were 1.37 (95% CI: 1.12-1.68, P = 0.003) for the 7-day window, 1.66 (95% CI: 1.38-2.00, P peptic ulcer bleeding. Concomitant use of a nonselective nonsteroidal anti-inflammatory drug (NSAID) or aspirin further elevated the risk. However, it does not eliminate the effect of underlying diseases flare-up that may have placed the patients at risk for peptic ulcer bleeding in this kind of study design. Short-term (7-28 days) exposure to glucocorticoids is significantly associated with peptic ulcer bleeding; this risk seems dose-dependent and is higher when nonselective NSAIDs or aspirin are used concurrently. © 2015 John Wiley & Sons Ltd.

  13. Physiological and skill demands of 'on-side' and 'off-side' games.

    Science.gov (United States)

    Gabbett, Tim J; Jenkins, David G; Abernethy, Bruce

    2010-11-01

    This study investigated the physiological and skill demands of 'on-side' and 'off-side' games in elite rugby league players. Sixteen male rugby league players participated in 'on-side' and 'off-side' games. Both small-sided games were played in a 40- × 40-m playing area. The 'off-side' game permitted players to have 3 'plays' while in possession of the ball. Players were permitted to pass backward or forward (to an 'off-side' player). The 'on-side' game also permitted players to have 3 'plays' while in possession of the ball. However, players were only permitted to pass backward to players in an 'on-side' position. Heart rate and movement patterns (via global positioning system) were recorded continuously throughout both games. Data were collected on the distance covered, number of high-acceleration and velocity efforts, and recovery between efforts. Video footage was also taken to track the performance of the players. Post hoc inspection of the footage was undertaken to count the number of possessions and the number and quality of disposals. In comparison to 'on-side' games, 'off-side' games had a greater number of involvements ("touches"), passes, and effective passes. However, the cognitive demands of 'on-side' games were greater than 'off-side' games. 'Off-side' games resulted in a greater total distance covered, greater distance covered in mild and moderate accelerations, and greater distance covered in low, moderate, and high-velocity efforts. There were also a greater number of short duration recovery periods between efforts in 'off-side' games. The results of this study demonstrate that 'off-side' games provide greater physiological and skill demands than 'on-side' games. 'Off-side' games may provide a practical alternative to 'on-side' games for the development of skill and fitness in elite rugby league players.

  14. Glucocorticoid receptor gene polymorphism and juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Scheplyagina Larisa A

    2011-01-01

    Full Text Available Abstract Background The glucocorticoid receptor gene (NR3C1 has been suggested as a candidate gene affecting juvenile idiopathic arthritis (JIA course and prognosis. The purpose of this study is to investigate the glucocorticoid receptor gene BclI polymorphism (rs41423247 in JIA patients, the gene's role in susceptibility to juvenile idiopathic arthritis, and its associations with JIA activity, course and bone mineralization. Methods One hundred twenty-two Caucasian children with JIA and 143 healthy ethnically matched controls were studied. We checked markers of clinical and laboratory activity: morning stiffness, Ritchie Articular Index (RAI, swollen joint count (SJC, tender joint count (TJC, physician's visual analog scale (VAS, hemoglobin level (Hb, leukocyte count (L, platelet count (Pl, Westergren erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, albumin, DAS and DAS28. Bone mineralization was measured by dual-energy X-ray absorptiometry (DXA of lumbar spine L1-L4. Assessments of bone metabolism included osteocalcin, C-terminal telopeptide (CTT, parathyroid hormone (PTH, total and ionized calcium, inorganic phosphate and total alkaline phosphatase (TAP. BclI polymorphism was genotyped by polymerase chain reaction restriction fragment length polymorphism. Results No association was observed between glucocorticoid receptor gene polymorphism and the presence or absence of JIA. In girls with JIA, the presence of the G allele was associated with an unfavorable arthritis course, a younger age of onset of arthritis (p = 0.0017, and higher inflammatory activity. The higher inflammatory activity was demonstrated by the following: increased time of morning stiffness (p = 0.02, VAS (p = 0.014, RAI (p = 0.048, DAS (p = 0.035, DAS28 (p = 0.05, Pl (p = 0.003, L (p = 0.046, CRP (p = 0.01. In addition, these patients had bone metabolism disturbances as follows: decreased BA (p = 0.0001, BMC (p = 0.00007, BMD (0.005 and Z score (p = 0.002; and

  15. Behavioral neuroadaptation to alcohol : from glucocorticoids to histone acetylation

    Directory of Open Access Journals (Sweden)

    Daniel Beracochea

    2016-10-01

    Full Text Available A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic-pituitary-adrenal (HPA axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit including the prefrontal cortex, the hippocampus and the amygdala. These structures are implicated in learning and memory processes as well as in orchestrating neuroadaptive responses to stress and anxiety responses. Thus, potentiation of anxiety-related neuroadaptation by alcohol is characterized by an abnormally amygdala hyperactivity coupled with a hypofunction of the prefrontal cortex and the hippocampus. This review describes research on molecular and epigenetic mechanisms by which alcohol causes distinct region-specific adaptive changes in gene expression patterns and ultimately, leads to a variety of cognitive and behavioral impairments on prefrontal- and hippocampal-based tasks. Alcohol-induced neuroadaptations involve the dysregulation of numerous signaling cascades, leading to long-term changes in transcriptional profiles of genes, through the actions of transcription factors such as CREB (cAMP response element binding protein and chromatin remodeling due to post-translational modifications of histone proteins. We describe the role of prefrontal-hippocampus-amygdala circuit in mediating the effects of acute and chronic alcohol on learning and memory, and region-specific molecular and epigenetic mechanisms involved in this process. This review first discusses the importance of brain region-specific dysregulation of glucocorticoid concentration in the development of alcohol dependence and describes on how persistently increased glucocorticoid levels in prefrontal cortex may be involved in

  16. Withdrawal of inhaled glucocorticoids and exacerbations of COPD

    DEFF Research Database (Denmark)

    Magnussen, Helgo; Disse, Bernd; Rodriguez-Roisin, Roberto

    2014-01-01

    fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric......-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid...

  17. Glucocorticoids Enhance Taste Aversion Memory via Actions in the Insular Cortex and Basolateral Amygdala

    Science.gov (United States)

    Miranda, Maria Isabel; Quirarte, Gina L.; Rodriguez-Garcia, Gabriela; McGaugh, James L.; Roozendaal, Benno

    2008-01-01

    It is well established that glucocorticoid hormones strengthen the consolidation of hippocampus-dependent spatial and contextual memory. The present experiments investigated glucocorticoid effects on the long-term formation of conditioned taste aversion (CTA), an associative learning task that does not depend critically on hippocampal function.…

  18. Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition

    NARCIS (Netherlands)

    S.W.J. Lamberts (Steven); E.F.C. van Rossum (Liesbeth)

    2004-01-01

    textabstractMost actions of glucocorticoids (GCs) are mediated by the glucocorticoid receptor (GR). The interindividual response to GCs varies considerably, as demonstrated by a variable suppressive response to 0.25-mg dexamethasone (DEX). Several polymorphisms in the gene coding

  19. Pulsatile thyrotropin secretion in patients with Addison's disease during variable glucocorticoid therapy

    DEFF Research Database (Denmark)

    Hangaard, J; Andersen, M; Grodum, E

    1996-01-01

    , increasing significantly (P glucocorticoids, when the pulse frequency was also significantly reduced (P ... of glucocorticoids on the TSH response to TRH, our data indicate that even physiological serum levels of cortisol have an influence on endogenous TSH secretion, probably caused by regulation of the pituitary sensitivity to TRH....

  20. Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor

    DEFF Research Database (Denmark)

    Presman, Diego M; Ogara, M Florencia; Stortz, Martín

    2014-01-01

    Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR) transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation wi...

  1. Fecal glucocorticoid response to environmental stressors in green iguanas (Iguana iguana)

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Timm, Jeanette; Ibsen, Ida

    2012-01-01

    Quantification of glucocorticoid metabolites in feces has been shown to be a powerful tool in evaluating well-being in vertebrates. Little is known however about the hypothalamic–pituitary–adrenal axis response to stressors, and consequent glucocorticoid excretion, in reptiles. In a longitudinal...

  2. Glucocorticoid metabolites in newborns: A marker for traffic noise related stress?

    DEFF Research Database (Denmark)

    Lech Cantuaria, Manuella; Usermann, Jakob; Proietti, Elena

    2018-01-01

    Traffic noise has been associated with an increased risk for several non-auditory health effects, which may be explained by a noise-induced release of stress hormones (e.g. glucocorticoids). Although several studies in children and adults have indicated an increased secretion of glucocorticoids...

  3. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors.

    Science.gov (United States)

    Lehrner, Amy; Bierer, Linda M; Passarelli, Vincent; Pratchett, Laura C; Flory, Janine D; Bader, Heather N; Harris, Iris R; Bedi, Aarti; Daskalakis, Nikolaos P; Makotkine, Iouri; Yehuda, Rachel

    2014-02-01

    Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation. Published by Elsevier Ltd.

  4. The effects of glucocorticoids on the inhibition of emotional information: A dose-response study.

    Science.gov (United States)

    Taylor, Véronique A; Ellenbogen, Mark A; Washburn, Dustin; Joober, Ridha

    2011-01-01

    There is evidence that cortisol influences cognitive and affective processes such as selective attention and memory for emotional events, yet the effects of glucocorticoids on attentional inhibition in humans remain unknown. Consequently, this double-blind study examined dose-dependent effects of exogenous glucocorticoids on the inhibition of emotional information. Sixty-three university students (14 male, 49 female) ingested either a placebo pill or hydrocortisone (10mg or 40mg), and completed a negative priming task assessing the inhibition of pictures depicting angry, sad, and happy faces. The 10mg, but not the 40mg hydrocortisone dose elicited increased inhibition for angry faces relative to placebo. Thus, moderate glucocorticoid elevations may have adaptive effects on emotional information processing, whereas high glucocorticoid elevations appear to attenuate this effect, consistent with the view that there are dose-dependent effects of glucocorticoids on cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Total brain, cortical and white matter volumes in children previously treated with glucocorticoids

    DEFF Research Database (Denmark)

    Holm, Sara K; Madsen, Kathrine S; Vestergaard, Martin

    2018-01-01

    BACKGROUND: Perinatal exposure to glucocorticoids and elevated endogenous glucocorticoid-levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid-treatment during childhood on brain volumes. METHODS: Thirty children and adolescents...... with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical grey and white matter, brain, and intracranial volume, and total cortical thickness and surface area were...... were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures. CONCLUSION: Observed smaller total brain...

  6. Glucocorticoids maintain human osteoclasts in the active mode of their resorption cycle

    DEFF Research Database (Denmark)

    Søe, Kent; Delaissé, Jean-Marie

    2010-01-01

    that glucocorticoids deeply modify this resorptive behavior. First, glucocorticoids gradually induce excavations with a trenchlike morphology while reducing the time-dependent increase in excavation numbers. This indicates that glucocorticoids make osteoclasts elongate the excavations they initiated rather than...... migrating to a new resorption site, as in control conditions. Second, the round excavations in control conditions contain undegraded demineralized collagen as repeatedly reported earlier, whereas the excavations with a trenchlike morphology generated under glucocorticoid exposure appear devoid of leftovers...... of demineralized collagen. This indicates that collagenolysis proceeds generally at a lower rate than demineralization under control conditions, whereas collagenolysis rates are increased up to the level of demineralization rates in the presence of glucocorticoids. Taking these observations together leads...

  7. Instructions for producing a mouse model of glucocorticoid-induced osteoporosis

    DEFF Research Database (Denmark)

    Thiele, S.; Baschant, U.; Rauch, A.

    2014-01-01

    Glucocorticoids are effective drugs used for the treatment of inflammatory diseases such as rheumatoid arthritis or asthma. Furthermore, they regulate various physiological processes, including bone remodeling. However, long-term high- and even low-dose glucocorticoid use is associated...... with a compromised bone quality and an increased fracture risk. At the cellular level, glucocorticoids suppress bone formation and stimulate bone resorption, which leads to loss of bone mass. To investigate the underlying mechanisms and new therapeutic strategies, the in vivo model for glucocorticoid-induced bone...... loss is widely used. This protocol outlines the common procedure that is currently used for the induction of bone loss in mice using glucocorticoids. It further provides useful hints and highlights possible pitfalls to take into account before starting an experiment....

  8. A Pharmacokinetic/Pharmacodynamic Study of the Glucocorticoid Receptor Antagonist Mifepristone Combined with Enzalutamide in Castrate Resistant Prostate Cancer

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-14-1-0021 TITLE: A Pharmacokinetic/Pharmacodynamic Study of the Glucocorticoid Receptor Antagonist Mifepristone Combined...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER A Pharmacokinetic/Pharmacodynamic Study of the Glucocorticoid Receptor Antagonist Mifepristone Combined...way it adapts is by upregulating another hormone receptor, the glucocorticoid receptor (GR), which may compensate for diminished AR activity. The

  9. Expression and function of nuclear receptor coregulators in brain : understanding the cell-specific effects of glucocorticoids

    NARCIS (Netherlands)

    Laan, Siem van der

    2008-01-01

    Currently, the raising awareness of the role of glucocorticoids in the onset of numerous (neuro)-pathologies constitutes the increasing necessity of understanding the mechanisms of action of glucocorticoids in bodily processes and brain functioning. Glucocorticoids mediate their effects by binding

  10. Glucocorticoids exert context-dependent effects on cells of the joint in vitro

    DEFF Research Database (Denmark)

    Madsen, Suzi H; Andreassen, Kim V; Christensen, Søren T

    2011-01-01

    Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This st....... This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts....

  11. A membrane glucocorticoid receptor mediates the rapid/non-genomic actions of glucocorticoids in mammalian skeletal muscle fibres.

    Science.gov (United States)

    Pérez, María Hernández-Alcalá; Cormack, Jonathan; Mallinson, David; Mutungi, Gabriel

    2013-10-15

    Glucocorticoids (GCs) are steroid hormones released from the adrenal gland in response to stress. They are also some of the most potent anti-inflammatory and immunosuppressive drugs currently in clinical use. They exert most of their physiological and pharmacological actions through the classical/genomic pathway. However, they also have rapid/non-genomic actions whose physiological and pharmacological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the rapid/non-genomic effects of two widely prescribed glucocorticoids, beclomethasone dipropionate (BDP) and prednisolone acetate (PDNA), on force production in isolated, intact, mouse skeletal muscle fibre bundles. The results show that the effects of both GCs on maximum isometric force (Po) were fibre-type dependent. Thus, they increased Po in the slow-twitch fibre bundles without significantly affecting that of the fast-twitch fibre bundles. The increase in Po occurred within 10 min and was insensitive to the transcriptional inhibitor actinomycin D. Also, it was maximal at ∼250 nM and was blocked by the glucocorticoid receptor (GCR) inhibitor RU486 and a monoclonal anti-GCR, suggesting that it was mediated by a membrane (m) GCR. Both muscle fibre types expressed a cytosolic GCR. However, a mGCR was present only in the slow-twitch fibres. The receptor was more abundant in oxidative than in glycolytic fibres and was confined mainly to the periphery of the fibres where it co-localised with laminin. From these findings we conclude that the rapid/non-genomic actions of GCs are mediated by a mGCR and that they are physiologically/therapeutically beneficial, especially in slow-twitch muscle fibres.

  12. Extra-adrenal glucocorticoid synthesis: immune regulation and aspects on local organ homeostasis.

    Science.gov (United States)

    Talabér, Gergely; Jondal, Mikael; Okret, Sam

    2013-11-05

    Systemic glucocorticoids (GCs) mainly originate from de novo synthesis in the adrenal cortex under the control of the hypothalamus-pituitary-adrenal (HPA)-axis. However, research during the last 1-2 decades has revealed that additional organs express the necessary enzymes and have the capacity for de novo synthesis of biologically active GCs. This includes the thymus, intestine, skin and the brain. Recent research has also revealed that locally synthesized GCs most likely act in a paracrine or autocrine manner and have significant physiological roles in local homeostasis, cell development and immune cell activation. In this review, we summarize the nature, regulation and known physiological roles of extra-adrenal GC synthesis. We specifically focus on the thymus in which GC production (by both developing thymocytes and epithelial cells) has a role in the maintenance of proper immunological function. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Use of glucocorticoids during pregnancy and risk of attention-deficit/hyperactivity disorder in offspring

    DEFF Research Database (Denmark)

    Laugesen, Kristina; Byrjalsen, Anna; Frøslev, Trine

    2017-01-01

    OBJECTIVE: Prenatal exposure to excess endogenous glucocorticoid (GC) has been linked to attention-deficit/hyperactivity disorder (ADHD). We investigated whether prenatal exposure to exogenous GC is associated with ADHD. DESIGN: Nationwide cohort study. SETTING: A cohort of 875 996 singletons born...... ADHD risk in children prenatally exposed to GCs and in children of former GC users with risk in unexposed children of never users. We computed cumulative incidence at 10 years of age and adjusted HRs (aHRs). In addition, we compared exposed children with unexposed siblings in a sibling design. RESULTS......: We identified 875 996 children, among whom 5319 were prenatally exposed to systemic GCs and 36 780 to local/inhaled GCs. Cumulative incidences of ADHD at 10 years of age were 2.65% in prenatally exposed children and 2.03% in unexposed children of never users. At the general population level, prenatal...

  14. Multimodal Regulation of Circadian Glucocorticoid Rhythm by Central and Adrenal Clocks.

    Science.gov (United States)

    Son, Gi Hoon; Cha, Hyo Kyeong; Chung, Sooyoung; Kim, Kyungjin

    2018-05-01

    Adrenal glucocorticoids (GCs) control a wide range of physiological processes, including metabolism, cardiovascular and pulmonary activities, immune and inflammatory responses, and various brain functions. During stress responses, GCs are secreted through activation of the hypothalamic-pituitary-adrenal axis, whereas circulating GC levels in unstressed states follow a robust circadian oscillation with a peak around the onset of the active period of a day. A recent advance in chronobiological research has revealed that multiple regulatory mechanisms, along with classical neuroendocrine regulation, underlie this GC circadian rhythm. The hierarchically organized circadian system, with a central pacemaker in the suprachiasmatic nucleus of the hypothalamus and local oscillators in peripheral tissues, including the adrenal gland, mediates periodicities in physiological processes in mammals. In this review, we primarily focus on our understanding of the circadian regulation of adrenal GC rhythm, with particular attention to the cooperative actions of the suprachiasmatic nucleus central and adrenal local clocks, and the clinical implications of this rhythm in human diseases.

  15. Post-operative analgesic effects of paracetamol, NSAIDs, glucocorticoids, gabapentinoids and their combinations

    DEFF Research Database (Denmark)

    Dahl, Jørgen Berg; Nielsen, Rasmus; Wetterslev, Jørn

    2014-01-01

    , and no well-documented 'gold standards' exist. The aim of the present topical, narrative review is to provide an update of the evidence for post-operative analgesic efficacy with the most commonly used, systemic non-opioid drugs, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs)/COX-2 antagonists......, glucocorticoids, gabapentinoids, and combinations of these. The review is based on data from previous systematic reviews with meta-analyses, investigating effects of non-opioid analgesics on pain, opioid-requirements, and opioid-related adverse effects. Paracetamol, NSAIDs, COX-2 antagonists, and gabapentin....... Trials of pregabalin > 300 mg/day indicated a morphine-sparing effect of 13.4 (4, 22.8) mg morphine/24 h. Notably, though, the available evidence for additive or synergistic effects of most combination regimens was sparse or lacking. Paracetamol, NSAIDs, selective COX-2 antagonists, and gabapentin all...

  16. Glucocorticoids and laminitis in the horse.

    Science.gov (United States)

    Johnson, Philip J; Slight, Simon H; Ganjam, Venkataseshu K; Kreeger, John M

    2002-08-01

    The administration of exogenously administered GCs and syndromes associated with GC excess are both attended by increased risk for the development of laminitis in adult horses. However, there exists substantial controversy as to whether excess GCs cause laminitis de novo. If true, the pathogenesis of laminitis arising from the effects of GC excess is probably different from that associated with diseases of the gastrointestinal tract and endotoxemia. Although a satisfactory explanation for the development of laminitis as a consequence of GC action is currently lacking, numerous possible and plausible theoretical mechanisms do exist. Veterinarians must exert caution with respect to the use of GCs in adult horses. The extent to which individual horses are predisposed to laminitis as a result of GC effect cannot be predicted based on current information. However, the administration of systemic GCs to horses that have been previously affected by laminitis should be used only with extreme caution, and should be accompanied by careful monitoring for further signs of laminitis. The risk of laminitis appears to be greater during treatment using some GCs (especially dexamethasone and triamcinalone) compared with others (prednisone and prednisolone). Whenever possible, to reduce the risk of laminitis, GCs should be administered locally. For example, the risk of GC-associated laminitis is evidently considerably reduced in horses affected with chronic obstructive pulmonary disease (COPD) if GC treatment is administered via inhalation. We have hypothesized that structural changes in the equine hoof that resemble laminitis may arise as a consequence of excess GC effect. Although these changes are not painful per se, and are not associated with inflammation, they could likely predispose affected horses to the development of bona fide laminitis for other reasons. Moreover, the gross morphological appearance of the chronically GC-affected hoof resembles that of a chronically

  17. Side Effects: Sleep Problems

    Science.gov (United States)

    Sleep problems are a common side effect during cancer treatment. Learn how a polysomnogram can assess sleep problems. Learn about the benefits of managing sleep disorders in men and women with cancer.

  18. Side Effects: Fatigue

    Science.gov (United States)

    Fatigue is a common side effect of many cancer treatments such as chemotherapy, radiation therapy, immunotherapy, and surgery. Anemia and pain can also cause fatigue. Learn about symptoms and way to manage fatigue.

  19. Side Effects: Diarrhea

    Science.gov (United States)

    Diarrhea, a side effect of cancer treatment, may cause symptoms such as loose, watery stools. Diarrhea can lead to dehydration and malnutrition in cancer patients. Learn about ways to treat and manage diarrhea during cancer treatment.

  20. Side Effects: Appetite Loss

    Science.gov (United States)

    Cancer treatments may lower your appetite. Side effects such as nausea, fatigue, or mouth sores can also making eating difficult. Learn how to eat well to avoid losing weight or becoming dehydrated, so you stay strong during treatment.

  1. Side Effects: Pain

    Science.gov (United States)

    Controlling pain is an important part of your cancer treatment plan. Learn how to track levels of pain. Find out how pain, a side effect of cancer treatment, is treated using acupuncture, biofeedback, and physical therapy.

  2. Side Effects: Anemia

    Science.gov (United States)

    Anemia is a side effect of cancer treatments, including chemotherapy and radiation therapy. It can make women and men feel fatigued, dizzy, and short of breath. Learn how to manage fatigue caused by anemia during cancer treatment.

  3. Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis.

    Science.gov (United States)

    Hardy, Rowan; Juarez, Maria; Naylor, Amy; Tu, Jinwen; Rabbitt, Elizabeth H; Filer, Andrew; Stewart, Paul M; Buckley, Christopher D; Raza, Karim; Cooper, Mark S

    2012-10-18

    Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Local glucocorticoid production is also significantly increased during joint inflammation. Therefore, we investigated how locally derived glucocorticoids and inflammatory cytokines regulate DKK1 synthesis in synovial fibroblasts during inflammatory arthritis. We examined expression and regulation of DKK1 in primary cultures of human synovial fibroblasts isolated from patients with inflammatory arthritis. The effect of TNFα, IL-1β and glucocorticoids on DKK1 mRNA and protein expression was examined by real-time PCR and ELISA. The ability of inflammatory cytokine-induced expression of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to sensitise fibroblasts to endogenous glucocorticoids was explored. Global expression of Wnt signalling and target genes in response to TNFα and glucocorticoids was assessed using a custom array. DKK1 expression in human synovial fibroblasts was directly regulated by glucocorticoids but not proinflammatory cytokines. Glucocorticoids, but not TNFα, regulated expression of multiple Wnt agonists and antagonists in favour of inhibition of Wnt signalling. However, TNFα and IL-1β indirectly stimulated DKK1 production through increased expression of 11β-HSD1. These results demonstrate that in rheumatoid arthritis synovial fibroblasts, DKK1 expression is directly regulated by glucocorticoids rather than TNFα. Consequently, the links between synovial inflammation, altered Wnt signalling and bone remodelling are not direct but are dependent on local activation of endogenous glucocorticoids.

  4. Side core lifter

    Energy Technology Data Exchange (ETDEWEB)

    Edelman, Ya A

    1982-01-01

    A side core lifter is proposed which contains a housing with guide slits and a removable core lifter with side projections on the support section connected to the core receiver. In order to preserve the structure of the rock in the core sample by means of guaranteeing rectilinear movement of the core lifter in the rock, the support and core receiver sections are hinged. The device is equipped with a spring for angular shift in the core-reception part.

  5. Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis.

    Science.gov (United States)

    Herrera, Cristian; Marcos, Miguel; Carbonell, Cristina; Mirón-Canelo, José Antonio; Espinosa, Gerard; Cervera, Ricard; Chamorro, Antonio-Javier

    2018-05-01

    The human glucocorticoid receptor gene (NR3C1) is considered to play a role in the differences and sensitivities of the glucocorticoid response in individuals with autoimmune diseases. The objective of this study was to examine by means of a systematic review previous findings regarding allelic variants of NR3C1 in relation to the risk of developing systemic autoimmune diseases. Studies that analysed the genotype distribution of NR3C1 allelic variants among patients with systemic autoimmune diseases were retrieved. A meta-analysis was conducted with a random effects model. Odds ratios (ORs) and their confidence intervals (CIs) were calculated. In addition, sub-analysis by ethnicity, sensitivity analysis and tests for heterogeneity of the results were performed. Eleven studies met the inclusion criteria for meta-analysis. We found no evidence that the analysed NR3C1 polymorphisms, rs6198, rs56149945, and rs6189/rs6190, modulate the risk of developing a systemic autoimmune disease. Nonetheless, a protective role for the minor allele of rs41423247 was found among Caucasians (OR=0.78; 95% CI: 0.65, 0.92; P=0.004). A subgroup analysis according to underlying diseases revealed no significant association either for Behçet's disease or rheumatoid arthritis, while correlations between NR3C1 polymorphisms and disease activity or response to glucocorticoids could not be evaluated due to insufficient data. There is no clear evidence that the analysed NR3C1 allelic variants confer a risk for developing systemic autoimmune diseases although the minor G allele of rs41423247 may be protective among Caucasians. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Science.gov (United States)

    Parnaudeau, Sébastien; Dongelmans, Marie-louise; Turiault, Marc; Ambroggi, Frédéric; Delbes, Anne-Sophie; Cansell, Céline; Luquet, Serge; Piazza, Pier-Vincenzo; Tronche, François; Barik, Jacques

    2014-01-01

    The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs) release. GCs bind the glucocorticoid receptor (GR) a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While GR within dopamine-innervated areas drives cocaine's behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurons is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice. PMID:24574986

  7. Inherently variable responses to glucocorticoid stress among endogenous retroviruses isolated from 23 mouse strains.

    Science.gov (United States)

    Hsu, Karen; Lee, Young-Kwan; Chew, Alex; Chiu, Sophia; Lim, Debora; Greenhalgh, David G; Cho, Kiho

    2017-10-01

    Active participation of endogenous retroviruses (ERVs) in disease processes has been exemplified by the finding that the HERV (human ERV)-W envelope protein is involved in the pathogenesis of multiple sclerosis, an autoimmune disease. We also demonstrated that injury-elicited stressors alter the expression of murine ERVs (MuERVs), both murine leukemia virus-type and mouse mammary tumor virus (MMTV)-type (MMTV-MuERV). In this study, to evaluate MMTV-MuERVs' responses to stress (e.g., injury, infection)-elicited systemic glucocorticoid (GC) levels, we examined the GC-stress response of 64 MMTV-MuERV promoters isolated from the genomes of 23 mouse strains. All 64 promoters responded to treatment with a synthetic GC, dexamethasone (DEX), at a wide range from a 0.6- to 85.7-fold increase in reporter activity compared to no treatment. An analysis of the 10 lowest and 10 highest DEX responders revealed specific promoter elements exclusively present in either the three lowest or the two highest responders. Each promoter had a unique profile of transcription regulatory elements and the glucocorticoid response element (GRE) was identified in all promoters with the number of GREs ranging from 2 to 7. The three lowest DEX responders were the only promoters with two GREs. The findings from this study suggest that certain MMTV-MuERVs are more responsive to stress-elicited systemic GC elevation compared to the others. The mouse strain-specific genomic MMTV-MuERV profiles and individual MMTV-MuERVs' differential responses to GC-stress might explain, at least in part, the variable inflammatory responses to injury and/or infection, often observed among different mouse strains. This article is part of a Special Issue entitled: Immune and Metabolic Alterations in Trauma and Sepsis edited by Dr. Raghavan Raju. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Directory of Open Access Journals (Sweden)

    Sebastien eParnaudeau

    2014-02-01

    Full Text Available The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs release. GCs bind the glucocorticoid receptor (GR a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While the GR within dopamine-innervated areas drives cocaine’s behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurones is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

  9. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  10. Stabilization of glucocorticoid receptors in isolated rat hepatocytes by radioprotectants

    International Nuclear Information System (INIS)

    Karle, J.M.; Ridder, W.E.; Wright, N.; Olmeda, R.; Nielsen, C.J.

    1986-01-01

    Previous work has shown that glucocorticoid receptors in rat liver homogenate can be stabilized by the addition of MoO 4 plus the sulfhydryl-containing compounds dithiothreitol and WR 1065. The latter is the dephosphorylated, principal metabolite of the radioprotectant WR 2721 (or S-2-(3-aminopropylamino)ethanesphosphorothioic acid). The current work results from applying this knowledge to intact rat hepatocytes. Cells were isolated by collagenase perfusion and incubated in supplemented minimum essential medium at 37 0 C with various concentrations of WR 2721, WR 1065, or vehicle. Samples of these cell suspensions were analyzed at various times for steroid binding capacity by incubating homogenates (27,000 x g supernates) with 50 nM 3 H-triamcinolone acetonide in the presence or absence of excess unlabelled dexamethasone. Concentrations of 10 mM WR 2721 provided marked preservation of the binding capacity (>85% of the initial value at 5 hours) compared to control at 60% of the binding capacity. WR 1065 at 10 mM provided no such protection. This is consistent with the observation that WR 1065 does not pass cell membranes. The authors propose that supplying reducing equivalents to intracellular components such as the glucocorticoid receptor may be one mechanism of the radioprotection afforded by WR 2721

  11. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    Energy Technology Data Exchange (ETDEWEB)

    Li, Qun-Yi; Zhang, Meng [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Hallis, Tina M.; DeRosier, Therese A. [Cell Systems Division, Invitrogen, Madison, WI (United States); Yue, Jian-Min; Ye, Yang [State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China); Mais, Dale E. [The National Center for Drug Screening, Shanghai (China); MPI Research, Mattawan, MI (United States); Wang, Ming-Wei, E-mail: wangmw@mail.shcnc.ac.cn [The National Center for Drug Screening, Shanghai (China); State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai (China)

    2010-01-15

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K{sub i} = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  12. Glucocorticoid augmentation of prolonged exposure therapy: rationale and case report

    Directory of Open Access Journals (Sweden)

    Laura Pratchett

    2010-12-01

    Full Text Available Rationale: Prolonged exposure (PE therapy has been found to reduce symptoms of posttraumatic stress disorder (PTSD; however, it is difficult for many patients to engage fully in the obligatory retelling of their traumatic experiences. This problem is compounded by the fact that habituation and cognitive restructuring – the main mechanisms through which PE is hypothesized to work – are not instantaneous processes, and often require several weeks before the distress associated with imaginal exposure abates. Case reports: Two cases are described that respectively illustrate the use of hydrocortisone and placebo, in combination with PE, for the treatment of combat-related PTSD. Based on known effects of glucocorticoids on learning and memory performance, we hypothesized that augmentation with hydrocortisone would improve the therapeutic effects of PE by hastening “new” learning and facilitating decreases in the emotional impact of fear memories during the course of treatment. The veteran receiving hydrocortisone augmentation of PE displayed an accelerated and ultimately greater decline in PTSD symptoms than the veteran receiving placebo. Conclusions: While no general conclusion can be derived from comparison of two patients, the findings are consistent with the rationale for augmentation. These case reports support the potential for an appropriately designed and powered clinical trial to examine the efficacy of glucocorticoids in augmenting the effects of psychotherapy for PTSD.

  13. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    International Nuclear Information System (INIS)

    Aguilar, David; Strom, Joshua; Chen, Qin M.

    2014-01-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA

  14. Characterization of a novel non-steroidal glucocorticoid receptor antagonist

    International Nuclear Information System (INIS)

    Li, Qun-Yi; Zhang, Meng; Hallis, Tina M.; DeRosier, Therese A.; Yue, Jian-Min; Ye, Yang; Mais, Dale E.; Wang, Ming-Wei

    2010-01-01

    Selective antagonists of the glucocorticoid receptor (GR) are desirable for the treatment of hypercortisolemia associated with Cushing's syndrome, psychic depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327, a non-steroidal small molecule with potent binding affinity to GR (K i = 13.2 nM), was identified in a high-throughput screening effort. As a full GR antagonist, NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes involved in hepatic gluconeogenesis, but has a minimal effect on matrix metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene. Interestingly, the compound recruits neither coactivators nor corepressors to the GR complex but competes with glucocorticoids for the interaction between GR and a coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation, but significantly blocks Dex-induced GR transportation to the nucleus, and thus appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal compound, NC3327, may represent a new class of GR antagonists as potential therapeutics for a variety of cortisol-related endocrine disorders.

  15. Autoimmune hyperthyroidism due to secondary adrenal insufficiency: resolution with glucocorticoids.

    Science.gov (United States)

    Skamagas, Maria; Geer, Eliza B

    2011-01-01

    To describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids. We report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis. Autoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient's symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency. The hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis.

  16. Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids.

    Science.gov (United States)

    Yarnell, Kelly; Purcell, Rebecca S; Walker, Susan L

    2016-04-25

    Adrenal activity can be assessed in the equine species by analysis of feces for corticosterone metabolites. During a potentially aversive situation, corticotrophin releasing hormone (CRH) is released from the hypothalamus in the brain. This stimulates the release of adrenocorticotrophic hormone (ACTH) from the pituitary gland, which in turn stimulates release of glucocorticoids from the adrenal gland. In horses the glucocorticoid corticosterone is responsible for several adaptations needed to support equine flight behaviour and subsequent removal from the aversive situation. Corticosterone metabolites can be detected in the feces of horses and assessment offers a non-invasive option to evaluate long term patterns of adrenal activity. Fecal assessment offers advantages over other techniques that monitor adrenal activity including blood plasma and saliva analysis. The non-invasive nature of the method avoids sampling stress which can confound results. It also allows the opportunity for repeated sampling over time and is ideal for studies in free ranging horses. This protocol describes the enzyme linked immunoassay (EIA) used to assess feces for corticosterone, in addition to the associated biochemical validation.

  17. SU-E-T-532: Left-Sided Breast Cancer Irradiation Using Volumatric Modulated Arc Therapy: An Evaluation of Multiple Commercial Systems

    International Nuclear Information System (INIS)

    Liu, R; Liu, T; Qi, S

    2015-01-01

    Purposes: There has been growing interest in treating breast cancer using VMAT technique. Our goal is to compare the dosimetry and treatment delivery parameters for the left-sided breast cancer treatment using various VMAT platforms from commercially available planning systems. Methods: Five consecutive left-sided breast cancer patients initially treated with conventional 3D-conformal radiotherapy (3DCRT) were selected. Four VMAT plans using most popular treatment planning systems, including Eclipse (Version 11, Varian), Pinnacle (Version 9.8, Philips), Monaco (Version 2.03, Elekta) and helical Tomotherapy (V4.0, Accuray). The same structure set and same planning goals were used for all VMAT plans. The dosimetric parameters including target coverage and minimum/maximum/mean, dose-volume endpoints for the selected normal structures: the heart, ipsilateral-/contralateral lung and breast, were evaluated. Other dosimetric indices including heterogeneity index (HI) were evaluated. The treatment delivery parameters, such as monitor unit (MUs) and delivery time were also compared. Results: VMAT increases dose homogeneity to the treated volume and reduces the irradiated heart and left-lung volumes. Compared to the 3DCRT technique, all VMAT plans offer better heart and left-lung dose sparing; the mean heart doses were 4.5±1.6(Monaco), 1.2±0.4(Pinnacle), 1.3± (Eclipse) and 5.6±4.4(Tomo), the mean left-lung doses were 5.9±1.5(Monaco), 3.7±0.7(Pinnacle), 1.4± (Eclipse) and 5.2±1.6 (Tomo), while for the 3DCRT plan, the mean heart and left-Lung doses were 2.9±2.0, and 6.8±4.4 (Gy) respectively. The averaged contralateral-breast and lung mean doses were higher in VMAT plans than the 3DCRT plans but were not statistically significant. Among all the VMAT plans, the Pinnacle plans often yield the lowest right-lung/breast mean doses, and slightly better heterogeneity indices that are similar to Tomotherapy plans. Treatment delivery time of the VMAT plans (except helical

  18. Experimental Study on the Effect of Calcitonin in Osteoporosis Induced by the Immobilization and Long-Term Glucocorticoid

    International Nuclear Information System (INIS)

    Park, Dong Jin; Lee, Sang Rae

    1989-01-01

    It is well known that the glucocorticoid induces osteoporosis by suppression of the osteoblast, but its effect on the osteoclast has some controversy whether it activates or suppresses the osteoclast. If the calcitonin, which is known to suppress the osteoclast, prevents the osteoporosis by glucocorticoid, then the suppression of the osteoclast by the glucocorticoid is not so significant. And if the calcitonin increases the osteoblastic activity, Tc-99m MDP uptake will be increased in spite of the glucocorticoid effect on the osteoblast. The immobilization operation was performed to the right leg of male Wistar rats weighing about 200 gm each. For 16 weeks after operation, rats were injected glucocorticoid alone or glucocorticoid and calcitonin. The bone density was measured by means of photodensitometry under reference aluminum step wedge and Tc-99m MDP uptake was available to the index of the osteoblastic activity. 1. The bone density of femoral head was markedly reduced than that of femoral shaft following ratio of cancellous and cortical components in both site. 2. glucocorticoid caused decrease in bone density of spine and femur, and there is significantly increase of it when medication of glucocorticoid and calcitonin injection simultaneously than that of glucocorticoid. 3. Tc-99m MDP uptake was revealed significant reduction in medication of glucocorticoid but increase in glucocorticoid and calcitonin injection simultaneously in later experimental period. 4. There was a slight reduction in plasma osteocalcin in medication of glucocorticoid through experimental periods and an increase in its value in case of giving glucocorticoid and calcitonin simultaneously in later experimental period. From these results, we suggest that osteoporosis by immobilization is more pronounced by glucocorticoid hormone and osteoporosis induced by immobilization and glucocorticoid use is prevented by calcitonin administration with increasing osteoblastic activity.

  19. Electroretinography in healthy subjects in relation to systemic glucocorticoid intake

    DEFF Research Database (Denmark)

    Kappelgaard, Per; Hansen, Katrine B; Vilsbøll, Tina

    2012-01-01

    This study examined electroretinographic function in healthy subjects before and after prednisolone intake. To separate the effect of prednisolone on the retina from the potentially confounding hyperglycemia-inducing effect of prednisolone, electroretinography was made while fasting and at a pre-...

  20. Electroretinography in healthy subjects in relation to systemic glucocorticoid intake

    DEFF Research Database (Denmark)

    Kappelgaard, Per; Hansen, Katrine B; Vilsbøll, Tina

    2012-01-01

    .011) and post-prandial glycemia (P = 0.023). We conclude that prednisolone had no detectable effect on the ffERG in healthy lean men in this study. Retinal function may be less sensitive to changes in glycemia in healthy subjects than in people with diabetes, a characteristic that was unchanged by a short...

  1. [Psychoanalysis and Side Effect].

    Science.gov (United States)

    Shirahase, Joichiro

    2015-01-01

    A study of psychoanalysis from the perspective of side effects reveals that its history was a succession of measures to deal with its own side effects. This, however, does not merely suggest that, as a treatment method, psychoanalysis is incomplete and weak: rather, its history is a record of the growth and development of psychoanalysis that discovered therapeutic significance from phenomena that were initially regarded as side effects, made use of these discoveries, and elaborated them as a treatment method. The approach of research seen during the course of these developments is linked to the basic therapeutic approach of psychoanalysis. A therapist therefore does not draw conclusions about a patient's words and behaviors from a single aspect, but continues to make efforts to actively discover a variety of meanings and values from them, and to make the patient's life richer and more productive. This therapeutic approach is undoubtedly one of the unique aspects of psychoanalysis. I discuss the issue of psychoanalysis and side effects with the aim of clarifying this unique characteristic of psychoanalysis. The phenomenon called resistance inevitably emerges during the process of psychoanalytic treatment. Resistance can not only obstruct the progress of therapy; it also carries the risk of causing a variety of disadvantages to the patient. It can therefore be seen as an adverse effect. However, if we re-examine this phenomenon from the perspective of transference, we find that resistance is in fact a crucial tool in psychoanalysis, and included in its main effect, rather than a side effect. From the perspective of minimizing the character of resistance as a side effect and maximizing its character as a main effect, I have reviewed logical organization, dynamic evaluation, the structuring of treatment, the therapist's attitudes, and the training of therapists. I conclude by stating that psychoanalysis has aspects that do not match the perspective known as a side

  2. Sulforaphane reverses glucocorticoid-induced apoptosis in osteoblastic cells through regulation of the Nrf2 pathway

    Directory of Open Access Journals (Sweden)

    Lin H

    2014-07-01

    Full Text Available Hao Lin,1,* Bo Wei,1,* Guangsheng Li,1 Jinchang Zheng,1 Jiecong Sun,1 Jiaqi Chu,2 Rong Zeng,1 Yanru Niu21Department of Spinal Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China; 2Laboratory Institute of Minimally Invasive Orthopedic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Apoptosis of osteoblasts triggered by high-dose glucocorticoids (GCs has been identified as a major cause of osteoporosis. However, the underlying molecular mechanisms accounting for this action remain elusive, which has impeded the prevention and cure of this side effect. Sulforaphane (SFP is a naturally occurring isothiocyanate that has huge health benefits for humans. In this study, by using osteoblastic MC3T3-E1 cells as a model, we demonstrate the protective effects of SFP against dexamethasone (Dex-induced apoptosis and elucidate the underlying molecular mechanisms. The results show that SFP could effectively inhibit the Dex-induced growth inhibition and release of lactate dehydrogenase in MC3T3-E1 cells. Treatment with Dex induced caspase-dependent apoptosis in MC3T3-E1 cells, as evidenced by an increase in the Sub-G1 phase, chromatin condensation, and deoxyribonucleic acid fragmentation, which were significantly suppressed by coincubation with SFP. Mitochondria-mediated apoptosis pathway contributed importantly to Dex-induced apoptosis, as revealed by the activation of caspase-3/-9 and subsequent cleavage of poly adenosine diphosphate ribose polymerase, which was also effectively blocked by SFP. Moreover, treatments of Dex strongly induced overproduction of reactive oxygen species and inhibited the expression of nuclear factor erythroid 2-related factor 2 (Nrf2 and the downstream effectors HO1 and NQO1. However, cotreatment with SFP effectively reversed this action of Dex. Furthermore, silencing of Nrf2 by

  3. Cytokine-induced loss of glucocorticoid function: effect of kinase inhibitors, long-acting β(2-adrenoceptor [corrected] agonist and glucocorticoid receptor ligands.

    Directory of Open Access Journals (Sweden)

    Christopher F Rider

    Full Text Available Acting on the glucocorticoid receptor (NR3C1, glucocorticoids are widely used to treat inflammatory diseases. However, glucocorticoid resistance often leads to suboptimal asthma control. Since glucocorticoid-induced gene expression contributes to glucocorticoid activity, the aim of this study was to use a 2 × glucocorticoid response element (GRE reporter and glucocorticoid-induced gene expression to investigate approaches to combat cytokine-induced glucocorticoid resistance. Pre-treatment with tumor necrosis factor-α (TNF or interleukin-1β inhibited dexamethasone-induced mRNA expression of the putative anti-inflammatory genes RGS2 and TSC22D3, or just TSC22D3, in primary human airway epithelial and smooth muscle cells, respectively. Dexamethasone-induced DUSP1 mRNA was unaffected. In human bronchial epithelial BEAS-2B cells, dexamethasone-induced TSC22D3 and CDKN1C expression (at 6 h was reduced by TNF pre-treatment, whereas DUSP1 and RGS2 mRNAs were unaffected. TNF pre-treatment also reduced dexamethasone-dependent 2×GRE reporter activation. This was partially reversed by PS-1145 and c-jun N-terminal kinase (JNK inhibitor VIII, inhibitors of IKK2 and JNK, respectively. However, neither inhibitor affected TNF-dependent loss of dexamethasone-induced CDKN1C or TSC22D3 mRNA. Similarly, inhibitors of the extracellular signal-regulated kinase, p38, phosphoinositide 3-kinase or protein kinase C pathways failed to attenuate TNF-dependent repression of the 2×GRE reporter. Fluticasone furoate, fluticasone propionate and budesonide were full agonists relative to dexamethasone, while GSK9027, RU24858, des-ciclesonide and GW870086X were partial agonists on the 2×GRE reporter. TNF reduced reporter activity in proportion with agonist efficacy. Full and partial agonists showed various degrees of agonism on RGS2 and TSC22D3 expression, but were equally effective at inducing CDKN1C and DUSP1, and did not affect the repression of CDKN1C or TSC22D3

  4. Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide

    DEFF Research Database (Denmark)

    Skov, M; Main, K M; Sillesen, Ida Blok

    2002-01-01

    . Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition...

  5. Stress impairs reconsolidation of drug memory via glucocorticoid receptors in the basolateral amygdala.

    Science.gov (United States)

    Wang, Xiao-Yi; Zhao, Mei; Ghitza, Udi E; Li, Yan-Qin; Lu, Lin

    2008-05-21

    Relapse to drug taking induced by exposure to cues associated with drugs of abuse is a major challenge to the treatment of drug addiction. Previous studies indicate that drug seeking can be inhibited by disrupting the reconsolidation of a drug-related memory. Stress plays an important role in modulating different stages of memory including reconsolidation, but its role in the reconsolidation of a drug-related memory has not been investigated. Here, we examined the effects of stress and corticosterone on reconsolidation of a drug-related memory using a conditioned place preference (CPP) procedure. We also determined the role of glucocorticoid receptors (GRs) in the basolateral amygdala (BLA) in modulating the effects of stress on reconsolidation of this memory. We found that rats acquired morphine CPP after conditioning, and that this CPP was inhibited by stress given immediately after re-exposure to a previously morphine-paired chamber (a reconsolidation procedure). The disruptive effect of stress on reconsolidation of morphine related memory was prevented by inhibition of corticosterone synthesis with metyrapone or BLA, but not central amygdala (CeA), injections of the glucocorticoid (GR) antagonist RU38486 [(11,17)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one]. Finally, the effect of stress on drug related memory reconsolidation was mimicked by systemic injections of corticosterone or injections of RU28362 [11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one] (a GR agonist) into BLA, but not the CeA. These results show that stress blocks reconsolidation of a drug-related memory, and this effect is mediated by activation of GRs in the BLA.

  6. Impact of vitamin D3 on cardiovascular responses to glucocorticoid excess.

    Science.gov (United States)

    Ahmed, Mona A

    2013-06-01

    Although the cardiovascular system is not a classical target for 1,25-dihydroxyvitamin D3, both cardiac myocytes and vascular smooth muscle cells respond to this hormone. The present study aimed to elucidate the effect of active vitamin D3 on cardiovascular functions in rats exposed to glucocorticoid excess. Adult male Wistar rats were allocated into three groups: control group, dexamethasone (Dex)-treated group receiving Dex (200 μg/kg) subcutaneously for 12 days, and vitamin D3-Dex-treated group receiving 1,25-(OH)2D3 (100 ng/kg) and Dex (200 μg/kg) subcutaneously for 12 days. Rats were subjected to measurement of systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressures and heart rate. Rate pressure product (RPP) was calculated. Rats' isolated hearts were perfused in Langendorff preparation and studied for basal activities (heart rate, peaked developed tension, time to peak tension, half relaxation time, and myocardial flow rate) and their responses to isoproterenol infusion. Blood samples were collected for determination of plasma level of nitrite, nitric oxide surrogate. Dex-treated group showed significant increase in SBP, DBP, MAP, and RPP, as well as cardiac hypertrophy and enhancement of basal cardiac performance evidenced by increased heart rate, rapid and increased contractility, and accelerated lusitropy, together with impaired contractile and myocardial flow rate responsiveness to beta-adrenergic activation and depressed inotropic and coronary vascular reserves. Such alterations were accompanied by low plasma nitrite. These changes were markedly improved by vitamin D3 treatment. In conclusion, vitamin D3 is an efficacious modulator of the deleterious cardiovascular responses induced by glucocorticoid excess, probably via accentuation of nitric oxide.

  7. Glucocorticoid suppression of human lymphocyte DNA synthesis. Influence of phytohemagglutinin concentration

    International Nuclear Information System (INIS)

    Segel, G.B.; Lukacher, A.; Gordon, B.R.; Lichtman, M.A.

    1980-01-01

    Glucocorticoids have been shown to suppress lectin-stimulated lymphocyte DNA synthesis in some studies, whereas in other studies, the hormones have had little effect. We have found that the position on the PHA dose-response curve that is studied is the most important determinant of whether cortisol inhibits 3 H-thymidine incorporation into lymphocyte DNA. The proportion of monocytes in culture also influenced the cortisol effect, but it was quantitatively less important than PHA concentration. Cortisol (5 nM to 100 μM) had little effect on blastogenesis or thymidine incorporation into DNA in cultures that contained both a high concentration (14% +- 2 (S.E.)) of monocytes and a concentration of PHA (0.6 to 1.2 μg/ml) that produced maximal stimulation of mitogenesis. When monocytes were reduced from 14 to 1.4%, cortisol (5 μM) caused a 30% reduction in thymidine incorporation in cultures stimulated by 0.6 to 1.2 μg/ml PHA. Much greater cortisol suppression of thymidine incorporation occurred if the concentration of PHA was reduced. For example, reduction of the PHA concentration from 1.2 to 0.075 μg/ml resulted in an increase in suppression by 5 μM cortisol from 5 to 90% even in the presence of 14% monocytes. These data indicate that the suppressive effects of glucocorticoids on blastogenesis and thymidine incorporation in vitro depend principally on the concentration of PHA used to stimulate blastogenesis and secondarily on the proportion of monocytes in the culture system

  8. The role of the kisspeptin system in regulation of the reproductive endocrine axis and territorial behavior in male side-blotched lizards (Uta stansburiana).

    Science.gov (United States)

    Neuman-Lee, Lorin; Greives, Timothy; Hopkins, Gareth R; French, Susannah S

    2017-03-01

    The neuropeptide kisspeptin and its receptor are essential for activation of the hypothalamic-pituitary-gonadal (HPG) axis and regulating reproduction. While the role of kisspeptin in regulating the HPG axis in mammals has been well established, little is known about the functional ability of kisspeptins to activate the HPG axis and associated behavior in non-mammalian species. Here we experimentally examined the effects of kisspeptin on downstream release of testosterone and associated aggression and display behaviors in the side-blotched lizard (Uta stansburiana). We found that exogenous treatment with kisspeptin resulted in an increase in circulating testosterone levels, castration blocked the kisspeptin-induced increase in testosterone, and testosterone levels in kisspeptin-treated animals were positively related to frequency of aggressive behaviors. This evidence provides a clear link between kisspeptin, testosterone, and aggressive behavior in lizards. Thus, it is likely that kisspeptin plays an important role more broadly in non-mammalian systems in the regulation of reproductive physiology and related behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. The response of the day side magnetosphere--ionosphere system to time-varying field line reconnection at the magnetopause. II. Erosion event of March 27, 1968

    International Nuclear Information System (INIS)

    Reid, G.C.; Holzer, T.E.

    1975-01-01

    The circuit analogy for the response of the coupled magnetosphere-ionosphere system to changes in day side field line reconnection rate is applied to real conditions and is used to calculate the expected variation in magnetopause position during the erosion event described by Aubry et al. (1970). Generally good agreement between observation and theory is found. The role of the dawn-dusk electric field responsible for magnetospheric convection is examined in some detail and is treated in the circuit analogy as the field due to an external generator connected across the circuit. It is found that the erosion process requires two distinct time constants for a proper description: (1) the time needed for magnetosheath plamsa to travel down the freshly reconnected field lines to the ionosphere and (2) roughly, the time required for the foot of a reconnected field line to travel one quarter of the total noon-midnight dimension of the polar cap. The second time constant is the dominant one and is not related to the ionospheric conductivity, as has been suggested previously. Examination of high-latitude magnetograms obtained during the erosion event discussed shows that the electric field oscillations predicted by the theory and observed by the spacecraft in terms of oscillations in the magnetopause position are also reflected in osci []lations in ionospheric current flow

  10. Tumor-promoting phorbol ester amplifies the inductions of tyrosine aminotransferase and ornithine decarboxylase by glucocorticoid

    International Nuclear Information System (INIS)

    Kido, H.; Fukusen, N.; Katunuma, N.

    1987-01-01

    In adrenalectomized rats, the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) markedly enhanced the inductions of tyrosine aminotransferase (TAT) and ornithine decarboxylase by glucocorticoids, even with sufficient concentration of glucocorticoids to have a maximal effect, whereas it had no effect on TAT activity and increased ornithine decarboxylase activity only slightly in the absence of glucocorticoids. Phorbol derivatives and components of TPA such as 4β-phorbol, phorbol 12-tetradecanoate, phorbol 13-acetate, and 4-O-methylphorbol 12-tetradecanoate 13-acetate, which have no tumor-promoting activity or ability to activate protein kinase C, did not have any effect on TAT induction by glucocorticoid. TPA enhanced the induction of TAT by various glucocorticoids but had no effect on induction of TAT by glucagon or insulin and did not enhance the induction of glucose-6-phosphate dehydrogenase by 17β-estradiol. These results suggest that TPA specifically enhances the induction of TAT and ornithine decarboxylase by glucocorticoids. Similar effects of TPA on TAT induction by glucocorticoid were observed in primary cultures of adult rat hepatocytes. Another activator of protein kinase C, rac-1,2-dioctanoylglycerol, was also found to have similar effects on the cells

  11. Radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroids in man

    International Nuclear Information System (INIS)

    Ballard, P.L.; Carter, J.P.; Graham, B.S.; Baxter, J.D.

    1975-01-01

    An assay for plasma glucocorticoid activity has been developed using specific glucocorticoid receptors. Unlike other assays for cortisol and certain synthetic corticosteroids, this radioreceptor assay measures the glucocorticoid activity of all natural and synthetic steroids. Steroids extracted from as little as 0.05 ml of plasma are incubated with 3 H-dexamethasone and cytosol receptors from cultured rat hepatoma cells. From 0.5 to 50 ng of cortisol are accurately detected. Glucocorticoid activities of adult plasmas determined by the assay correlate closely with corticoid levels obtained in the CBG-isotope and fluorometric assays. Other steroids are measured in proportion to both concentration and potency as glucocorticoids. Relative activities include: cortisol 100, dexamethasone 940, prednisolone 230, prednisone 3, estradiol 1 and androstenedione 1. A similar ranking of steroids was found using receptors from a human source (fetal lung). The assay has been useful in detecting glucocorticoid activity in unidentified medications and in measuring plasma glucocorticoid levels after administration of synthetic corticosteroids. (auth)

  12. A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ram Nanik

    2012-12-01

    Full Text Available Abstract Background Familial glucocorticoid deficiency (FGD is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency in the presence of normal plasma renin and aldosterone level. Focal segmental glomerulosclerosis (FSGS is a form of glomerular disease associated with proteinuria and nephritic syndrome. This is the first case of familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. Case presentation An eight month old boy presented with increased genital pigmentation. Initial investigation revealed that he was glucocorticoid deficient and was started on hydrocortisone and fludrocortisone with a diagnosis of primary adrenal insufficiency. Later fludrocortisone was withdrawn and he was diagnosed to have isolated glucocorticoid deficiency. He later developed focal segmental glomerulosclerosis for which he underwent renal transplantation at the age of five years. Now at the age of twelve years, this boy is doing well on hydrocortisone treatment. His two siblings and a first degree cousin also had isolated glucocorticoid deficiency. One of the above two siblings died due to renal failure secondary to focal segmental glomerulosclerosis. Conclusion Patients with familial glucocorticoid deficiency should be carefully followed for development of features of nephrotic syndrome.

  13. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression.

    Science.gov (United States)

    Hinds, Terry D; Peck, Bailey; Shek, Evan; Stroup, Steven; Hinson, Jennifer; Arthur, Susan; Marino, Joseph S

    2016-02-11

    Unlike the glucocorticoid receptor α (GRα), GR β (GRβ) has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex) responsiveness. We measured GR isoform expression in C₂C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C₂C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a) mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx) and muscle ring finger 1 (MuRF1) response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

  14. Overexpression of Glucocorticoid Receptor β Enhances Myogenesis and Reduces Catabolic Gene Expression

    Directory of Open Access Journals (Sweden)

    Terry D. Hinds

    2016-02-01

    Full Text Available Unlike the glucocorticoid receptor α (GRα, GR β (GRβ has a truncated ligand-binding domain that prevents glucocorticoid binding, implicating GRα as the mediator of glucocorticoid-induced skeletal muscle loss. Because GRβ causes glucocorticoid resistance, targeting GRβ may be beneficial in impairing muscle loss as a result of GRα activity. The purpose of this study was to determine how the overexpression of GRβ affects myotube formation and dexamethasone (Dex responsiveness. We measured GR isoform expression in C2C12 muscle cells in response to Dex and insulin, and through four days of myotube formation. Next, lentiviral-mediated overexpression of GRβ in C2C12 was performed, and these cells were characterized for cell fusion and myotube formation, as well as sensitivity to Dex via the expression of ubiquitin ligases. GRβ overexpression increased mRNA levels of muscle regulatory factors and enhanced proliferation in myoblasts. GRβ overexpressing myotubes had an increased fusion index. Myotubes overexpressing GRβ had lower forkhead box O3 (Foxo3a mRNA levels and a blunted muscle atrophy F-box/Atrogen-1 (MAFbx and muscle ring finger 1 (MuRF1 response to Dex. We showed that GRβ may serve as a pharmacological target for skeletal muscle growth and protection from glucocorticoid-induced catabolic signaling. Increasing GRβ levels in skeletal muscle may cause a state of glucocorticoid resistance, stabilizing muscle mass during exposure to high doses of glucocorticoids.

  15. Working the Dark Side

    DEFF Research Database (Denmark)

    Bjering, Jens Christian Borrebye

    A few days after the terror attacks of 9/11, then Vice President Dick Cheney appeared on television with a call for “working the dark side.” While still unclear what this expression entailed at the time, Cheney's comment appears in retrospect to almost have been prophetic for the years to come....... By analyzing official reports and testimonies from soldiers partaking in the War On Terror, the dissertation's second part—dark arts—focuses on the transformation of the dark side into a productive space in which “information” and the hunt for said information overshadowed all legal, ethical, or political...

  16. To the problem of software development for two-sided communication system between an operator and computers in the automatic control system of elementary particle accelerators

    International Nuclear Information System (INIS)

    Asyaev, Yu.V.; Burtsev, V.L.; Makarov, V.V.; Nikitin, V.D.; Solov'ev, G.N.

    1975-01-01

    Principles, composition and basic characteristics of the software for a system of operators communication with minicomputers within the automatic accelerator control system are described. It is indicated that the external language of communication proposed in the system should meet the requirements for a provision of dialogue between the operator and the minicomputer operating in the real-time mode with an accelerator. There is a set of standard procedures allowing the operator to interact with the system in a sufficiently complete and flexible manner. These standard procedures are provided in the external operator's language in the form of a set of the control statements. The basic programs of the software system for communication are MONITOR, INTERPRETER and DRIVER programs. The MONITOR program algorithm employs the following principles - service of the input/output requests in the system is made on the relative priority basis: the maximum priority is assigned to operator's requests, the requests of the dispatcher and application programs are at a lower priority level

  17. The distorting effect of varying diets on fecal glucocorticoid measurements as indicators of stress

    DEFF Research Database (Denmark)

    Kalliokoski, Otto; Teilmann, A. Charlotte; Abelson, Klas S. P.

    2015-01-01

    The physiological stress response is frequently gauged in animals, non-invasively, through measuring glucocorticoids in excreta. A concern with this method is, however, the unknown effect of variations in diets on the measurements. With an energy dense diet, leading to reduced defecation, will low...... concentrations of glucocorticoids be artificially inflated? Can this effect be overcome by measuring the total output of glucocorticoids in excreta? In a controlled laboratory setting we explored the effect in mice. When standard mouse chow – high in dietary fiber – was replaced with a 17% more energy-dense diet...

  18. Influence of chronic x-ray exposure on adrenal glucocorticoid function and adrenocorticocyte membrane potential

    International Nuclear Information System (INIS)

    Gorban', Je.M.; Topol'nikova, N.V.

    1998-01-01

    The peculiarities of adrenal glucocorticoid function and membrane potential (MP) of zona fasciculata adrenocorticocyte (ACC) in rats after chronic x-ray exposure was studied. The changes of adrenal glucocorticoid function caused by chronic x-ray exposure within a relatively small period of irradiation (1.5 months) are obscure and manifest themselves only at physiological load. With the prolongation of the period (8 and 15 months), more considerable inhibition of the adrenal glucocorticoid function and disturbances in the membrane mechanisms of ACC MP level regulation are revealed

  19. OSTEOPENIA in cancellous bone of sheep induced by Glucocorticoid alone

    DEFF Research Database (Denmark)

    Ding, Ming; Cheng, L.; Bollen, Peter

    2008-01-01

    Introduction: There is a great need for suitable large animal models that closely resemble osteoporosis in humans, and that they have adequate bone size for bone prosthesis and biomaterial research. Previous investigations have shown that osteoporotic sheep model requires glucocorticoid (GC......) microarchitectural properties and mechanical properties of sheep cancellous bone after a 7 months steroid treatment; and thus to validate a large animal model for orthopaedic implant/biomaterial research. Materials and Methods: Eighteen female sheep were randomly allocated into 3 groups: group 1 (GC-1) received GC......, osteocalcin was significantly reduced after 7 months but a rebound phenomenon was observed 3 months after cessation of GC. In conclusion, this study has validated an osteopenia sheep model. Bone quality was significantly reduced following a 7 months GC-treatment and recovered after further 3 month observation...

  20. Glucocorticoid: A potential role in microgravity-induced bone loss

    Science.gov (United States)

    Yang, Jiancheng; Yang, Zhouqi; Li, Wenbin; Xue, Yanru; Xu, Huiyun; Li, Jingbao; Shang, Peng

    2017-11-01

    Exposure of animals and humans to conditions of microgravity, including actual spaceflight and simulated microgravity, results in numerous negative alterations to bone structure and mechanical properties. Although there are abundant researches on bone loss in microgravity, the explicit mechanism is not completely understood. At present, it is widely accepted that the absence of mechanical stimulus plays a predominant role in bone homeostasis disorders in conditions of weightlessness. However, aside from mechanical unloading, nonmechanical factors such as various hormones, cytokines, dietary nutrition, etc. are important as well in microgravity induced bone loss. The stress-induced increase in endogenous glucocorticoid (GC) levels is inevitable in microgravity environments. Moreover, it is well known that GCs have a detrimental effect to bone health at excess concentrations. Therefore, GC plays a potential role in microgravity-induced bone loss. This review summarizeds several studies and their prospective solutions to this hypothesis.

  1. Forskningens personlige side

    DEFF Research Database (Denmark)

    Hansen, Finn Thorbjørn

    2008-01-01

    Artiklen omhandler den ontologiske vending inden for universitetspædagogisk forskning, og redegør for hvorfor en mere personlig og eksistentiel side ved forskningen må medtænkes i universitetspædagogikken og -vejledningen. Udgivelsesdato: 24.11.08...

  2. Side loading filter apparatus

    International Nuclear Information System (INIS)

    Reynolds, K.E.

    1981-01-01

    A side loading filter chamber for use with radioactive gases is described. The equipment incorporates an inexpensive, manually operated, mechanism for aligning filter units with a number of laterally spaced wall openings and for removing the units from the chamber. (U.K.)

  3. Side insertable spacer

    International Nuclear Information System (INIS)

    Patterson, J.F.; Ewing, R.H.

    1992-01-01

    This patent describes a spacer for restraining the fuel rods of a nuclear fuel assembly, the assembly being formed of a plurality of parallel, elongated fuel rods so arranged that the assembly is bounded by a polygon having an even number of sides, the rods being so arranged as to lie in a plurality of sets of parallel rows, the rows of each set being perpendicular to one of the sides of the polygon. It comprises a number of spacer combs equal to at least half the number of the sides of the polygon, the spacer combs being superposed on each other, each of the spacer combs comprising: a single base strip having a length equal to that of one of the sides of the polygon and grid strips equal in number to the spaces between rows in one of the sets, and at least a majority of the grid strips being of a length sufficient to extend substantially the full length of the rows; the grid strips being provided with spring members positioned to engage each of the rods; the grid strips being provided with spring members positioned to engage each of the rods; the grid strips being secured to and extending at right angles to the base strip; the grid strips of different combs being positioned at angles to each other, so as to occupy the spaces between rows in different sets

  4. Methodological considerations for measuring glucocorticoid metabolites in feathers

    Science.gov (United States)

    Berk, Sara A.; McGettrick, Julie R.; Hansen, Warren K.; Breuner, Creagh W.

    2016-01-01

    In recent years, researchers have begun to use corticosteroid metabolites in feathers (fCORT) as a metric of stress physiology in birds. However, there remain substantial questions about how to measure fCORT most accurately. Notably, small samples contain artificially high amounts of fCORT per millimetre of feather (the small sample artefact). Furthermore, it appears that fCORT is correlated with circulating plasma corticosterone only when levels are artificially elevated by the use of corticosterone implants. Here, we used several approaches to address current methodological issues with the measurement of fCORT. First, we verified that the small sample artefact exists across species and feather types. Second, we attempted to correct for this effect by increasing the amount of methanol relative to the amount of feather during extraction. We consistently detected more fCORT per millimetre or per milligram of feather in small samples than in large samples even when we adjusted methanol:feather concentrations. We also used high-performance liquid chromatography to identify hormone metabolites present in feathers and measured the reactivity of these metabolites against the most commonly used antibody for measuring fCORT. We verified that our antibody is mainly identifying corticosterone (CORT) in feathers, but other metabolites have significant cross-reactivity. Lastly, we measured faecal glucocorticoid metabolites in house sparrows and correlated these measurements with corticosteroid metabolites deposited in concurrently grown feathers; we found no correlation between faecal glucocorticoid metabolites and fCORT. We suggest that researchers should be cautious in their interpretation of fCORT in wild birds and should seek alternative validation methods to examine species-specific relationships between environmental challenges and fCORT. PMID:27335650

  5. Management of glucocorticoids-induced osteoporosis: role of teriparatide

    Directory of Open Access Journals (Sweden)

    Silvia Migliaccio

    2009-04-01

    Full Text Available Silvia Migliaccio1, Marina Brama1, Nazzarena Malavolta21Dipartimento di Fisiopatologia Medica, Policlinico Umberto I, Università degli Studi Sapienza di Roma, Italy; 2Dipartimento di Medicina Interna, Policlinico S Orsola Malpighi, Bologna, ItalyAbstract: Glucocorticoids (GC-induced osteoporosis (GIOP is the most common cause of secondary osteoporosis, which leads to an increased fracture risk in patients. The normal bone turnover depends on a balance between osteoblasts and osteoclasts activity and GC can cause a rapid bone loss, decreasing bone formation and increasing bone resorption. The decreased bone formation is mainly due to the GC-induced apoptosis of both osteoblasts and osteocytes, while the increased bone resorption is due to the increased life-span of pre-existing osteoclasts. Bisphosphonates are clearly effective in preventing and treating GIOP but anabolic therapeutic strategies are the new promising therapeutic alternative. Experimental and clinical studies indicate that teriparatide, the active (1–34 parathyroid hormone (PTH molecule, is efficacious for the treatment of GIOP, being able to induce an increase in bone mass in these patients. Intermittent administration of human PTH (1–34 stimulates bone formation by increasing osteoblast number. Additionally, human PTH (1–34 modulates the level and/or activity of locally produced growth factors and cytokines. Teriparatide has been demonstrated in several clinical studies to significantly decrease the incidence of fractures in patients affected by GIOP. It has recently received an indication for GIOP and its label indication has also been expanded.Keywords: glucocorticoids, osteoblasts, osteoclasts, osteoporosis, teriparatide

  6. Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat.

    Directory of Open Access Journals (Sweden)

    Irina Bogdarina

    2010-02-01

    Full Text Available Adverse events in pregnancy may 'programme' offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11beta-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence.

  7. Mapracorat, a selective glucocorticoid receptor agonist, causes apoptosis of eosinophils infiltrating the conjunctiva in late-phase experimental ocular allergy

    Directory of Open Access Journals (Sweden)

    Baiula M

    2014-06-01

    Full Text Available Monica Baiula,1 Andrea Bedini,1 Jacopo Baldi,1 Megan E Cavet,2 Paolo Govoni,3 Santi Spampinato11Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy; 2Global Pharmaceutical R&D, Bausch & Lomb Inc., Rochester, NY, USA; 3Department of Biomedical, Biotechnological and Translational Sciences, University of Parma, Parma, ItalyBackground: Mapracorat, a novel nonsteroidal selective glucocorticoid receptor agonist, has been proposed for the topical treatment of inflammatory disorders as it binds with high affinity and selectivity to the human glucocorticoid receptor and displays a potent anti-inflammatory activity, but seems to be less effective in transactivation of a number of genes, resulting in a lower potential for side effects. Contrary to classical glucocorticoids, mapracorat displays a reduced ability to increase intraocular pressure and in inducing myocilin, a protein linked to intraocular pressure elevation. Allergic conjunctivitis is the most common form of ocular allergy and can be divided into an early phase, developing immediately after allergen exposure and driven primarily by mast cell degranulation, and a late phase, developing from 6–10 hours after the antigen challenge, and characterized by conjunctival infiltration of eosinophils and other immune cells as well as by the production of cytokines and chemokines.Methods: In this study, mapracorat was administered into the conjunctival sac of ovalbumin (OVA-sensitized guinea pigs 2 hours after the induction of allergic conjunctivitis, with the aim of investigating its activity in reducing clinical signs of the late-phase ocular reaction and to determine its mechanism of anti-allergic effects with respect to apoptosis of conjunctival eosinophils and expression of the chemokines C-C motif ligand 5 (CCL5, C-C motif ligand 11 (CCL11, and interleukin-8 (IL-8 and the proinflammatory cytokines interleukin-1β (IL-1β and tumor necrosis factor-α (TNF

  8. Decreased plasma cholesterol esterification and cholesteryl ester transfer in hypopituitary patients on glucocorticoid replacement therapy

    NARCIS (Netherlands)

    Beentjes, JAM; Van Tol, A; Sluiter, WJ; Dullaart, RPF

    Cardiovascular risk is increased in hypopituitary patients. No data are available with respect to the effect of glucocorticoid replacement therapy on high density lipoproteins (HDL) metabolism in such patients. Plasma lecithin:choresterol acyl transferase (LCAT), cholesteryl ester transfer protein

  9. The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl C; Overgaard, Søren

    2010-01-01

    The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone – Validation of large animal model for tissue engineering and biomaterial research Ming Ding,1* Carl Christian Danielsen,2 Søren Overgaard1 1Orthopaedic Research Laboratory......, Department of Orthopaedics and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark 2Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, Aarhus C, Denmark Osteopenia in sheep has been successfully induced...... by glucocorticoid treatment and the changes in properties of cancellous bone were comparable with those observed in humans after long-term glucocorticoid treatment. However, the influence on cortical bone has not been thoroughly elucidated. This study aimed to investigate the influence of glucocorticoid on sheep...

  10. Stress, glucocorticoids and memory: implications for treating fear-related disorders.

    Science.gov (United States)

    de Quervain, Dominique; Schwabe, Lars; Roozendaal, Benno

    2017-01-01

    Glucocorticoid stress hormones are crucially involved in modulating mnemonic processing of emotionally arousing experiences. They enhance the consolidation of new memories, including those that extinguish older memories, but impair the retrieval of information stored in long-term memory. As strong aversive memories lie at the core of several fear-related disorders, including post-traumatic stress disorder and phobias, the memory-modulating properties of glucocorticoids have recently become of considerable translational interest. Clinical trials have provided the first evidence that glucocorticoid-based pharmacotherapies aimed at attenuating aversive memories might be helpful in the treatment of fear-related disorders. Here, we review important advances in the understanding of how glucocorticoids mediate stress effects on memory processes, and discuss the translational potential of these new conceptual insights.

  11. Memory consolidation in human sleep depends on inhibition of glucocorticoid release.

    Science.gov (United States)

    Plihal, W; Born, J

    1999-09-09

    Early sleep dominated by slow-wave sleep has been found to be particularly relevant for declarative memory formation via hippocampo-neocortical networks. Concurrently, early nocturnal sleep is characterized by an inhibition of glucocorticoid release from the adrenals. Here, we show in healthy humans that this inhibition serves to support declarative memory consolidation during sleep. Elevating plasma glucocorticoid concentration during early sleep by administration of cortisol impaired consolidation of paired associate words, but not of non-declarative memory of visuomotor skills. Since glucocorticoid concentration was enhanced only during retention sleep, but not during acquisition or retrieval, a specific effect on the consolidation process is indicated. Blocking mineralocorticoid receptors by canrenoate did not affect memory, suggesting inactivation of glucocorticoid receptors to be the essential prerequisite for memory consolidation during early sleep.

  12. Risk of catecholaminergic crisis following glucocorticoid administration in patients with an adrenal mass: a literature review

    NARCIS (Netherlands)

    Barrett, C.; Uum, S.H. van; Lenders, J.W.M.

    2015-01-01

    BACKGROUND: Glucocorticoids as diagnostic or therapeutic agents have been reported to carry an increased risk of catecholaminergic crisis (CC) in patients with pheochromocytoma or paraganglioma (PPGL). METHODS: We searched literature databases using the following terms: pheochromocytoma,

  13. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  14. Cellular and biochemical actions of adrenal glucocorticoid hormones on rat thymic lymphocytes.

    OpenAIRE

    Young, D A; Voris, B P; Nicholson, M L

    1981-01-01

    The molecular, biochemical, and cellular effects of adrenal glucocorticoid hormones on thymic lymphocytes are reviewed, with emphasis on their relationship to the growth suppressive and lethal actions that occur in lymphoid tissues when glucocorticoids are administered to the whole animal. The data support the hypothesis that the hormonal inhibition of growth and development is a consequence of its ability to suppress cellular energy production, causing the cells to behave as though they were...

  15. Safety aspects of preoperative high-dose glucocorticoid in primary total knee replacement

    DEFF Research Database (Denmark)

    Jørgensen, C C; Pitter, F T; Kehlet, H

    2017-01-01

    Background: Preoperative single high-dose glucocorticoid may have early outcome benefits in total hip arthroplasty (THA) and knee arthroplasty (TKA), but long-term safety aspects have not been evaluated. Methods: From October 2013, the departments reporting to the prospective Lundbeck Foundation....... Conclusions: In this detailed prospective cohort study, preoperative high-dose glucocorticoid administration was not associated with LOS >4 days, readmissions or infectious complications in TKA patients without contraindications....

  16. Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis

    OpenAIRE

    Hardy, Rowan; Juarez, Maria; Naylor, Amy; Tu, Jinwen; Rabbitt, Elizabeth H; Filer, Andrew; Stewart, Paul M; Buckley, Christopher D; Raza, Karim; Cooper, Mark S

    2012-01-01

    Introduction: Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Local glucocorticoid production is also significantly increased during joint inflammation. Therefore, we investigated how locally derived glucocorticoids and inflammatory cytok...

  17. Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission.

    OpenAIRE

    Piazza, P V; Rougé-Pont, F; Deroche, V; Maccari, S; Simon, H; Le Moal, M

    1996-01-01

    An increase in the activity of mesencephalic dopaminergic neurons has been implicated in the appearance of pathological behaviors such as psychosis and drug abuse. Several observations suggest that glucocorticoids might contribute to such an increase in dopaminergic activity. The present experiments therefore analyzed the effects of corticosterone, the major glucocorticoid in the rat, both on dopamine release in the nucleus accumbens of freely moving animals by means of microdialysis, and on ...

  18. Preadmission glucocorticoid use and anastomotic leakage after colon and rectal cancer resections: a Danish cohort study

    Science.gov (United States)

    Ostenfeld, Eva Bjerre; Erichsen, Rune; Baron, John A; Thorlacius-Ussing, Ole; Iversen, Lene Hjerrild; Riis, Anders H; Sørensen, Henrik Toft

    2015-01-01

    Objective To examine whether preadmission glucocorticoid use increases the risk of anastomotic leakage after colon and rectal cancer resections. Design A population-based cohort study. Setting Denmark (2001–2011). Participants We identified patients who had undergone a primary anastomosis after a colorectal cancer resection by linking medical registries. Participants who filled their most recent glucocorticoid prescription ≤90, 91–365 and >365 days before their surgery date were categorised as current, recent and former users, respectively. Main outcome measures We calculated 30-day absolute risk of anastomotic leakage and computed ORs using logistic regression models with adjustment for potential confounders. Results Of the 18 190 patients with colon cancer, anastomotic leakage occurred in 1184 (6.5%). Glucocorticoid use overall was not associated with an increased risk of leakage (6.4% vs 6.9% among never-users; OR 1.05; 95% CI 0.89 to 1.23). Categories of oral, inhaled or intestinal-acting glucocorticoids did not greatly affect risk of leakage. Anastomotic leakage occurred in 695 (13.2%) of 5284 patients with rectal cancer. Glucocorticoid use overall slightly increased risk of leakage (14.6% vs 12.8% among never-users; OR 1.36, 95% CI 1.08 to 1.72). Results did not differ significantly within glucocorticoid categories. Conclusions Preadmission glucocorticoids modestly increased the risk of anastomotic leakage mainly after rectal cancer resection. However, absolute risk differences were small and the clinical impact of glucocorticoid use may therefore be limited. PMID:26408282

  19. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle.

    LENUS (Irish Health Repository)

    Morgan, Stuart A

    2009-11-01

    Glucocorticoid excess is characterized by increased adiposity, skeletal myopathy, and insulin resistance, but the precise molecular mechanisms are unknown. Within skeletal muscle, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone (11-dehydrocorticosterone in rodents) to active cortisol (corticosterone in rodents). We aimed to determine the mechanisms underpinning glucocorticoid-induced insulin resistance in skeletal muscle and indentify how 11beta-HSD1 inhibitors improve insulin sensitivity.

  20. Peripheral CLOCK regulates target-tissue glucocorticoid receptor transcriptional activity in a circadian fashion in man.

    Directory of Open Access Journals (Sweden)

    Evangelia Charmandari

    Full Text Available Circulating cortisol fluctuates diurnally under the control of the "master" circadian CLOCK, while the peripheral "slave" counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans.We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs as non-synchronized controls.GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo.Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night.

  1. Peripheral CLOCK Regulates Target-Tissue Glucocorticoid Receptor Transcriptional Activity in a Circadian Fashion in Man

    Science.gov (United States)

    Charmandari, Evangelia; Chrousos, George P.; Lambrou, George I.; Pavlaki, Aikaterini; Koide, Hisashi; Ng, Sinnie Sin Man; Kino, Tomoshige

    2011-01-01

    Context and Objective Circulating cortisol fluctuates diurnally under the control of the “master” circadian CLOCK, while the peripheral “slave” counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR) at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans. Design and Participants We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs) obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs) as non-synchronized controls. Results GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo. Conclusions Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night. PMID:21980503

  2. Flapping propulsion with side-by-side pitching foils

    Science.gov (United States)

    Huera-Huarte, Francisco

    2016-11-01

    Fish schools are one of the most common types of collective behaviour observed in nature. One of the reasons why fish swim in groups, is to reduce the cost of transport of the school. In this work we explore the propulsive performance of two foils flapping in a symmetric configuration, i.e. with an out-of-phase flapping motion. Direct thrust measurements and Particle Image Velocimetry (PIV) allowed a detailed examination of the forces and the wake generated by the system, for different kinematics (swept angles and frequencies) and shaft separations. For certain specific cases, volumetric PIV shows major differences on how the different structures in the wake of the system evolve, depending on the imposed kinematics and the side-by-side separation between the foils. Results obtained will be compared against data produced with isolated flapping foils with similar imposed kinematics, with the aim to better understand the interactions between both and the performance of the system as a whole. The author would like to acknowledge the financial support provided by the Spanish Ministerio de Economia y competitividad (MINECO) through Grant DPI2015-71645-P.

  3. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Shoko, E-mail: satosho@rs.tus.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp [Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Yonago 683-8503 (Japan); Tohkin, Masahiro, E-mail: tohkin@phar.nagoya-cu.ac.jp [Department of Medical Safety Science, Graduate School of Pharmaceutical Science, Nagoya City University, Nagoya 267-8603 (Japan); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Komai, Michio, E-mail: mkomai@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.

  4. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    International Nuclear Information System (INIS)

    Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Tohkin, Masahiro; Gonzalez, Frank J.; Komai, Michio

    2013-01-01

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction

  5. Testosterone supplementation, glucocorticoid milieu and bone homeostasis in the ageing male.

    Science.gov (United States)

    Ajdžanović, Vladimir Z; Filipović, Branko R; Šošić Jurjević, Branka T; Milošević, Verica Lj

    2017-08-01

    Male ageing is entwined with a continuous fall in free testosterone levels, which contributes to the pathogenesis of bone loss. Glucocorticoid excess, either dependent on the ageing process or iatrogenically induced, was found to additionally impair the bone structure and metabolism. Cautious testosterone supplementation in this respect may positively affect the glucocorticoid milieu and bone homeostasis, while testosterone-induced changes in the glucocorticoid output could serve as a determinant of bone-related therapeutic outcome. Namely, bone mineral content/density, the parameters of trabecular bone structure as well as bone strength are enhanced, serum calcitonin levels tend to increase, while serum osteocalcin, serum parathyroid hormone and urinary calcium decrease, all upon testosterone administration to the ageing male. In parallel, testosterone application decreases glucocorticoid secretion in the animal models of male ageing, while clinical data in this field are still inconsistent. Importantly, a physiological link exists between testosterone-induced changes in glucocorticoid levels and the tendency of bone status improvement in the ageing male. We believe that the assessment of circulating adrenocorticotropic hormone concentrations together with glucocorticoid levels, reflecting the hypothalamic-pituitary-adrenal axis feedback loop operativeness during testosterone supplementation, represents a well-balanced bone-related therapeutic update. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  6. Effects of a single glucocorticoid injection on propylene glycol-treated cows with clinical ketosis.

    Science.gov (United States)

    van der Drift, Saskia G A; Houweling, Martin; Bouman, Marina; Koets, Ad P; Tielens, Aloysius G M; Nielen, Mirjam; Jorritsma, Ruurd

    2015-05-01

    This study investigated the metabolic effects of glucocorticoids when administered to propylene glycol-treated cows with clinical ketosis. Clinical ketosis was defined by depressed feed intake and milk production, and a maximal score for acetoacetate in urine. All cows received 250 mL oral propylene glycol twice daily for 3 days and were randomly assigned to a single intramuscular injection with sterile isotonic saline solution (n = 14) or dexamethasone-21-isonicotinate (n = 17). Metabolic blood variables were monitored for 6 days and adipose tissue variables for 3 days. β-Hydroxybutyrate (BHBA) concentrations in blood decreased in all cows during treatment, but were lower in glucocorticoid-treated cows. Cows treated with glucocorticoids had higher plasma glucose and insulin concentrations, whereas concentrations of non-esterified fatty acids, 3-methylhistidine and growth hormone were unaffected. mRNA expression of hormone-sensitive lipase, BHBA receptor and peroxisome proliferator-activated receptor type γ in adipose tissue was not affected. This shows that lipolytic effects do not appear to be important in ketotic cows when glucocorticoids are combined with PG. Plasma 3-methyl histidine concentrations were similar in both groups, suggesting that glucocorticoids did not increase muscle breakdown and that the greater rise in plasma glucose in glucocorticoid-treated cows may not be due to increased supply of glucogenic amino acids from muscle. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Effort-reward-imbalance in healthy teachers is associated with higher LPS-stimulated production and lower glucocorticoid sensitivity of interleukin-6 in vitro.

    Science.gov (United States)

    Bellingrath, Silja; Rohleder, Nicolas; Kudielka, Brigitte M

    2013-02-01

    According to the effort-reward-imbalance (ERI) model, a lack of reciprocity between costs and gains at work increases the risk for adverse health outcomes. Inflammation has been shown to play a crucial role in a variety of stress-related diseases and alterations in immune system glucocorticoid sensitivity may help to explain the increased risk for cardiovascular disease (CVD) and depression related to chronic work stress. Changes in lipopolysaccharide (LPS)-induced interleukin (IL)-6 production and inhibition of IL-6 production by dexamethasone in reaction to the Trier Social Stress Test (TSST) were assessed in forty-six healthy school teachers to test whether chronic work stress is accompanied by alterations in inflammatory activity and glucocorticoid sensitivity of the innate immune system. High ERI was associated with an increase in pro-inflammatory potential, reflected in elevated IL-6 production before and after stress and with a lower capacity of dexamethasone to suppress IL-6 production in vitro over all measurement time points. ERI was not associated with stress-related changes in GC sensitivity. The present findings suggest a less effective anti-inflammatory regulation by glucocorticoids in teachers suffering from chronic work stress. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Activated Glucocorticoid Receptor Interacts with the INHAT Component Set/TAF-Iβ and Releases it from a Glucocorticoid-responsive Gene Promoter, Relieving Repression: Implications for the Pathogenesis of Glucocorticoid Resistance in Acute Undifferentiated Leukemia with Set-Can Translocation

    Science.gov (United States)

    Ichijo, Takamasa; Chrousos, George P.; Kino, Tomoshige

    2008-01-01

    SUMMARY Set/template-activating factor (TAF)-Iβ, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Iβ interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Iβ was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Iβ from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Iβ acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids. PMID:18096310

  9. Activated glucocorticoid receptor interacts with the INHAT component Set/TAF-Ibeta and releases it from a glucocorticoid-responsive gene promoter, relieving repression: implications for the pathogenesis of glucocorticoid resistance in acute undifferentiated leukemia with Set-Can translocation.

    Science.gov (United States)

    Ichijo, Takamasa; Chrousos, George P; Kino, Tomoshige

    2008-02-13

    Set/template-activating factor (TAF)-Ibeta, part of the Set-Can oncogene product found in acute undifferentiated leukemia, is a component of the inhibitor of acetyltransferases (INHAT) complex. Set/TAF-Ibeta interacted with the DNA-binding domain of the glucocorticoid receptor (GR) in yeast two-hybrid screening, and repressed GR-induced transcriptional activity of a chromatin-integrated glucocorticoid-responsive and a natural promoter. Set/TAF-Ibeta was co-precipitated with glucocorticoid response elements (GREs) of these promoters in the absence of dexamethasone, while addition of the hormone caused dissociation of Set/TAF-Ibeta from and attraction of the p160-type coactivator GRIP1 to the promoter GREs. Set-Can fusion protein, on the other hand, did not interact with GR, was constitutively co-precipitated with GREs and suppressed GRIP1-induced enhancement of GR transcriptional activity and histone acetylation. Thus, Set/TAF-Ibeta acts as a ligand-activated GR-responsive transcriptional repressor, while Set-Can does not retain physiologic responsiveness to ligand-bound GR, possibly contributing to the poor responsiveness of Set-Can-harboring leukemic cells to glucocorticoids.

  10. Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice.

    Science.gov (United States)

    Sefton, Charlotte; Harno, Erika; Davies, Alison; Small, Helen; Allen, Tiffany-Jayne; Wray, Jonathan R; Lawrence, Catherine B; Coll, Anthony P; White, Anne

    2016-11-01

    Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances.

  11. NPP Krsko secondary side analysis

    International Nuclear Information System (INIS)

    Fabijan, Lj.

    1987-01-01

    The purpose of this work is to analyze secondary side thermohydraulics response on steam generator tube plugging in order to ensure nominal NPP power. We had established that the additional opening of the governing valve No. 3 and 4 can compensate pressure drop caused by steam generator tube plugging. Two main steam flows with four governing valves were simulated. Steam expansion in turbine and feed water system was modeled separately. All important process point and steam moisture changes impact on nominal NPP power were analysed. (author)

  12. Exenatide improves glucocorticoid-induced glucose intolerance in mice

    Directory of Open Access Journals (Sweden)

    Ruiying Zhao

    2011-01-01

    Full Text Available Ruiying Zhao1,2*, Enrique Fuentes-Mattei1,2*, Guermarie Velazquez-Torres1,3, Chun-Hui Su1,2, Jian Chen1, Mong-Hong Lee1,2, Sai-Ching Jim Yeung4,51Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Program in Genes and Development, 3Program in Cancer Biology, Graduate School of Biomedical Sciences, University of Texas Health Science Center in Houston, Houston, TX, USA; 4Department of Endocrine Neoplasia and Hormonal Disorders, 5Department of Emergency Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA *Both authors contributed equally.Abstract: Exenatide is an incretin mimetic that is recently available in the US for the treatment of diabetes. There is a paucity of information on the effects of exenatide in glucocorticoid (GC-induced diabetes. Although the effect of continuous intravenous infusion of exenatide on GC-induced glucose intolerance has been investigated before in healthy human males receiving oral prednisolone, we investigated the efficacy of a single subcutaneous dose of exenatide (3 µg/kg in lowering blood glucose in GC-induced glucose intolerance in C57BL/6 mice. In a longitudinal experiment, the area under the curve (AUC of oral glucose tolerance tests (OGTT significantly increased after dexamethasone (P = 0.004, which was subsequently decreased by exenatide (P < 0.001. A cross-sectional experiment showed that exenatide improved glucose tolerance compared with placebo in a mouse model of dexamethasone-induced glucose intolerance. AUC of OGTT in the exenatide group were significantly (P < 0.001 lower than in the placebo group. Insulin tolerance tests (ITT demonstrated that exenatide decreased the ability of the mice to tolerate insulin compared with placebo. The AUC of ITT in the exenatide group were also significantly (P = 0.006 lower than in the placebo group. In conclusion, a single dose of exenatide was able to decrease glucose intolerance and

  13. Metabolic Side Effects of Lithium

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    M. Cagdas Eker

    2010-04-01

    Full Text Available Lithium is an alkaline ion being used since 19th century. After its widespread use in psychiatric disorders, observed side effects caused skepticism about its therapeutic efficacy. Despite several disadvantages, lithium is one of the indispensible drugs used in affective disorders, especially in bipolar disorder. It became a necessity for physicians to recognize its side effects since lithium is still accepted as a gold standard in the treatment of bipolar disorder. Adverse effects of chronic administration of lithium on several organ systems are widely known. In this article metabolic effects of lithium on thyroid and parathyroid glands, body mass index and kidneys will be discussed along with their mechanisms, clinical findings, possible risk factors and treatment. One of the most common side effect of lithium is hypothyroidism. It has the same clinical and biochemical properties as primary hypothyroidism and observed as subclinical hypothyroidism in the first place. Hypothyroidism, even its subclinical form, may be associated with non-response or inadequate response and is indicated as a risk factor for development of rapid cycling bipolar disorder. Therefore, hypothyroidism should be screened no matter how severe it is and should be treated with thyroid hormone in the presence of clinical hypothyroidism. Weight gain due to lithium administration disturbs the compliance to treatment and negatively affects the course of the illness. Increased risk for diabetes, hypertension, ischemic heart disease and stroke because of weight gain constitute other centers of problem. Indeed, it is of importance to determine the risk factors before treatment, to follow up the weight, to re-organize nutritional habits and to schedule exercises. Another frequent problematic side effect of lithium treatment is renal dysfunction which clinically present as nephrogenic diabetes insipidus with the common symptoms of polyuria and polydipsia. Nephrogenic diabetes

  14. Org 214007-0: a novel non-steroidal selective glucocorticoid receptor modulator with full anti-inflammatory properties and improved therapeutic index.

    Science.gov (United States)

    van Lierop, Marie-José C; Alkema, Wynand; Laskewitz, Anke J; Dijkema, Rein; van der Maaden, Hans M; Smit, Martin J; Plate, Ralf; Conti, Paolo G M; Jans, Christan G J M; Timmers, C Marco; van Boeckel, Constant A A; Lusher, Scott J; McGuire, Ross; van Schaik, Rene C; de Vlieg, Jacob; Smeets, Ruben L; Hofstra, Claudia L; Boots, Annemieke M H; van Duin, Marcel; Ingelse, Benno A; Schoonen, Willem G E J; Grefhorst, Aldo; van Dijk, Theo H; Kuipers, Folkert; Dokter, Wim H A

    2012-01-01

    Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects.

  15. Effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia

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    Yang Yu

    2017-10-01

    Full Text Available Objective: To study the effects of glucocorticoid combined with antibiotics on serum infection indexes, acute phase proteins and stress hormones in patients with severe pneumonia. Methods: a total of 80 patients with severe pneumonia who were hospitalized between August 2014 and January 2017 were retrospectively analyzed and divided into the routine treatment group (n=46 who received conventional antibiotic therapy and the combined treatment group (n=34 who received glucocorticoid combined with antibiotic therapy, and the differences in infection indexes, acute proteins and stress hormones were compared between the two groups of patients before and after treatment. Results: The differences in serum levels of infection indexes, acute phase proteins and stress hormones were not statistically significant between the two groups before treatment. After 1 week of treatment, serum infection indexes CRP and PCT levels of observation group were lower than those of control group; serum acute phase proteins α1-AT, α1-AG and CER levels were lower than those of control group; serum stress hormones Cor, AngⅠ and AngⅡ levels were lower than those of control group. Conclusion: Glucocorticoid combined with antibiotics can effectively inhibit systemic infection and stress and optimize the illness in patients with severe pneumonia.

  16. Control of energy balance by hypothalamic gene circuitry involving two nuclear receptors, neuron-derived orphan receptor 1 and glucocorticoid receptor.

    Science.gov (United States)

    Kim, Sun-Gyun; Lee, Bora; Kim, Dae-Hwan; Kim, Juhee; Lee, Seunghee; Lee, Soo-Kyung; Lee, Jae W

    2013-10-01

    Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-derived orphan receptor 1 (NOR1) and glucocorticoid receptor (GR), which directs the regulated expression of orexigenic neuropeptides agouti-related peptide (AgRP) and neuropeptide Y (NPY) in response to peripheral signals. Our results suggest that the anorexigenic signal leptin induces NOR1 expression likely via the transcription factor cyclic AMP response element-binding protein (CREB), while the orexigenic signal glucocorticoid mobilizes GR to inhibit NOR1 expression by antagonizing the action of CREB. Also, NOR1 suppresses glucocorticoid-dependent expression of AgRP and NPY. Consistently, relative to wild-type mice, NOR1-null mice showed significantly higher levels of AgRP and NPY and were less responsive to leptin in decreasing the expression of AgRP and NPY. These results identify mutual antagonism between NOR1 and GR to be a key rheostat for peripheral metabolic signals to centrally control energy balance.

  17. Age-related synthesis of glucocorticoids in thymocytes

    International Nuclear Information System (INIS)

    Qiao Shengjun; Chen Liying; Okret, Sam; Jondal, Mikael

    2008-01-01

    Glucocorticoids (GCs) are primarily synthesized in the adrenal glands but an ectopic production has also been reported in the brain, the gastrointestinal tract and in thymic epithelial cells (TEC). Here we show that thymocytes express genes encoding for all enzymes required for de novo GC synthesis and produce the hormone as demonstrated by both a GC specific reporter assay and a corticosterone specific ELISA assay. Interestingly, GC synthesis is detectable in cells from young mice (4 weeks) and thereafter increases during aging (14-22 weeks) together with an increased gene expression of the rate-limiting enzymes StAR and CYP11A1. Hormone production occurred at a thymocyte differentiation stage characterized by being double positive for the CD4 and CD8 surface markers but was found to be unrelated to CD69 expression, a marker for thymocytes undergoing positive selection. No GC synthesis was found in resting or anti-CD3 activated CD4 and CD8 positive T cells isolated from the spleen. Thymocyte-derived GC had an anti-proliferative effect on a GR-transfected cell line and induced apoptosis in thymocytes. The age- and differentiation stage-related GC synthesis in thymocytes may play a role in the involution process that the thymus gland undergoes

  18. Combined Effects of Glucocorticoid and Noradrenergic Activity on Loss Aversion.

    Science.gov (United States)

    Margittai, Zsofia; Nave, Gideon; Van Wingerden, Marijn; Schnitzler, Alfons; Schwabe, Lars; Kalenscher, Tobias

    2018-01-01

    Loss aversion is a well-known behavioral regularity in financial decision making, describing humans' tendency to overweigh losses compared to gains of the same amount. Recent research indicates that stress and associated hormonal changes affect loss aversion, yet the underlying neuroendocrine mechanisms are still poorly understood. Here, we investigated the causal influence of two major stress neuromodulators, cortisol and noradrenaline, on loss aversion during financial decision making. In a double-blind, placebo-controlled between-subject design, we orally administered either the α2-adrenergic antagonist yohimbine (increasing noradrenergic stimulation), hydrocortisone, both substances, or a placebo to healthy young men. We tested the treatments' influence on a financial decision-making task measuring loss aversion and risk attitude. We found that both drugs combined, relative to either drug by itself, reduced loss aversion in the absence of an effect on risk attitude or choice consistency. Our data suggest that concurrent glucocorticoid and noradrenergic activity prompts an alignment of reward- with loss-sensitivity, and thus diminishes loss aversion. Our results have implications for the understanding of the susceptibility to biases in decision making.

  19. Glucocorticoids and Type 2 Diabetes: From Physiology to Pathology

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    Guido Di Dalmazi

    2012-01-01

    Full Text Available Type 2 diabetes mellitus is the result of interaction between genetic and environmental factors, leading to heterogeneous and progressive pancreatic β-cell dysfunction. Overweight and obesity are major contributors to the development of insulin resistance and impaired glucose tolerance. The inability of β cells to secrete enough insulin produces type 2 diabetes. Abnormalities in other hormones such as reduced secretion of the incretin glucagon-like peptide 1 (GLP-1, hyperglucagonemia, and raised concentrations of other counterregulatory hormones also contribute to insulin resistance, reduced insulin secretion, and hyperglycaemia in type 2 diabetes. Clinical-overt and experimental cortisol excess is associated with profound metabolic disturbances of intermediate metabolism resulting in abdominal obesity, insulin resistance, and low HDL-cholesterol levels, which can lead to diabetes. It was therefore suggested that subtle abnormalities in cortisol secretion and action are one of the missing links between insulin resistance and other features of the metabolic syndrome. The aim of this paper is to address the role of glucocorticoids on glucose homeostasis and to explain the relationship between hypercortisolism and type 2 diabetes.

  20. Genetic, functional and molecular features of glucocorticoid receptor binding.

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    Francesca Luca

    Full Text Available Glucocorticoids (GCs are key mediators of stress response and are widely used as pharmacological agents to treat immune diseases, such as asthma and inflammatory bowel disease, and certain types of cancer. GCs act mainly by activating the GC receptor (GR, which interacts with other transcription factors to regulate gene expression. Here, we combined different functional genomics approaches to gain molecular insights into the mechanisms of action of GC. By profiling the transcriptional response to GC over time in 4 Yoruba (YRI and 4 Tuscans (TSI lymphoblastoid cell lines (LCLs, we suggest that the transcriptional response to GC is variable not only in time, but also in direction (positive or negative depending on the presence of specific interacting transcription factors. Accordingly, when we performed ChIP-seq for GR and NF-κB in two YRI LCLs treated with GC or with vehicle control, we observed that features of GR binding sites differ for up- and down-regulated genes. Finally, we show that eQTLs that affect expression patterns only in the presence of GC are 1.9-fold more likely to occur in GR binding sites, compared to eQTLs that affect expression only in its absence. Our results indicate that genetic variation at GR and interacting transcription factors binding sites influences variability in gene expression, and attest to the power of combining different functional genomic approaches.