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Sample records for pituitary-adrenal function tests

  1. Use of the Dexamethasone-Corticotrophin Releasing Hormone Test to Assess Hypothalamic-Pituitary-Adrenal Axis Function in Rheumatoid Arthritis

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    Eman A. Hasan

    2009-01-01

    Full Text Available Objectives. Hypothalamic-Pituitary-Adrenal axis function may be abnormal in rheumatoid arthritis (RA. A pilot study in 7 patients suggested impaired glucocorticoid feedback in some patients after the dexamethasone-corticotrophin releasing hormone (CRH test. This study aimed to investigate the dexamethasone-corticotrophin releasing factor test in a larger group of patients and relate the results to characteristics of the disease. Methods. Outpatients with active RA (≥3 swollen and tender joints and C-reactive protein > 10 mg/L took dexamethasone (1.5 mg at 23:00 hour in the evening. Next day, baseline saliva and plasma samples were collected, CRH was infused at 11:00 hour, and 4 serial blood and saliva samples were collected. Plasma samples were stored at −80∘C and a radioimmunoassay performed for saliva and plasma cortisol. Results. All 20 participants showed normal dexamethasone suppression and mounted no response to the CRH challenge. In samples with measurable cortisol, there was a strong correlation between saliva and plasma values (r = 0.876, n = 26, P<.01. Conclusion. No abnormalities were found in the Dexamethasone-CRH test in RA patients in contrast to a previous pilot study. Salivary cortisol measurement may offer an alternative noninvasive technique to plasma cortisol in RA patients in future studies.

  2. Childhood Parental Loss and Adult Hypothalamic-Pituitary-Adrenal Function

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    Tyrka, Audrey R.; Wier, Lauren; Price, Lawrence H.; Ross, Nicole; Anderson, George M.; Wilkinson, Charles W.; Carpenter, Linda L.

    2009-01-01

    Background Several decades of research link childhood parental loss with risk for major depression and other forms of psychopathology. A large body of preclinical work on maternal separation and some recent studies of humans with childhood parental loss have demonstrated alterations of hypothalamic-pituitary-adrenal (HPA) axis function which could predispose to the development of psychiatric disorders. Methods Eighty-eight healthy adults with no current Axis I psychiatric disorder participated in this study. Forty-four participants experienced parental loss during childhood, including 19 with a history of parental death and 25 with a history of prolonged parental separation. The loss group was compared to a matched group of individuals who reported no history of childhood parental separation or childhood maltreatment. Participants completed diagnostic interviews and questionnaires and the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Repeated measures general linear models were used to test the effects of parental loss, a measure of parental care, sex, and age on the hormone responses to the Dex/CRH test. Results Parental loss was associated with increased cortisol responses to the test, particularly in males. The effect of loss was moderated by levels of parental care; participants with parental desertion and very low levels of care had attenuated cortisol responses. ACTH responses to the Dex/CRH test did not differ significantly as a function of parental loss. Conclusions These findings are consistent with the hypothesis that early parental loss induces enduring changes in neuroendocrine function. PMID:18339361

  3. Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence

    NARCIS (Netherlands)

    Laceulle, O.M.; Nederhof, Esther; van Aken, M.A.G.; Ormel, Johan

    2017-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during

  4. Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

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    Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

    2017-06-01

    Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Chronic stress and pituitary-adrenal function in female pigs

    NARCIS (Netherlands)

    Janssens, C.J.J.G.

    1994-01-01

    Introduction

    The main purpose of the studies described in this thesis was to gain more insight in the regulation of the hypothalamic-pituitary-adrenocorticaI (HPA) system and the mechanisms underlying adaptation to chronic stress in female pigs. The function of the HPA axis, which

  6. Toxic stress history and hypothalamic-pituitary-adrenal axis function in a social stress task: Genetic and epigenetic factors.

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    Lapp, Hannah E; Ahmed, Sarah; Moore, Celia L; Hunter, Richard G

    2018-02-21

    Histories of early life stress (ELS) or social discrimination can reach levels of severity characterized as toxic to mental and physical health. Such toxic social stress during development has been linked to altered acute hypothalamic-pituitary-adrenal (HPA) response to social stress in adulthood. However, there are important individual differences in the size and direction of these effects. We explored developmental, genetic, epigenetic, and contextual sources of individual differences in the relationship between ELS, discrimination, and adult responses to acute social stress in a standard laboratory test. Additional measures included perceived status, social support, background activity of HPA axis, and genetic variants in aspects of the stress response system. Participants (n = 90) answered questions about historical and ongoing stress, provided a DNA sample to examine genetic polymorphisms and epigenetic marks, and underwent the Trier Social Stress Test (TSST) during which three saliva samples were collected to assess HPA function. Individuals who reported high levels of childhood adversity had a blunted salivary cortisol response to the TSST. Childhood adversity, discrimination experiences, and FKBP5 genotype were found to predict pretest cortisol levels. Following up on recent observations that the glucocorticoid receptor directly interacts with the mitochondrial genome, particularly the NADH dehydrogenase 6 (MT-ND6) gene, individuals who reported high childhood adversity were also found to have higher percent methylation across six CpG sites upstream of MT-ND6. These findings suggest multiple contributions across psychological, genetic, epigenetic, and social domains to vulnerability and resilience in hypothalamic-pituitary-adrenal axis regulation. Further study to examine how these multiple contributors affect developmental endpoints through integrated or independent pathways will be of use. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Metabolomics: A Window for Understanding Long Term Physical Consequences of Distrubed Sleep and Hypothalamic Pituitary Adrenal Function in Posttraumatic Stress

    Science.gov (United States)

    2017-09-01

    Hypothalamic-Pituitary-Adrenal Function in Posttraumatic Stress PRINCIPAL INVESTIGATOR: Sabra Inslicht, Ph.D. RECIPIENT: Northern California Institute...Posttraumatic Stress 5b. GRANT NUMBER W81XWH-16-1-0313 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sabra Inslicht, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER...ABSTRACT Post-traumatic stress (PTS) is a common psychiatric condition that may result after combat exposure and can have a profound effect on sleep

  8. Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence. The trails study.

    Science.gov (United States)

    Laceulle, Odilia M; Nederhof, Esther; van Aken, Marcel A G; Ormel, Johan

    2017-11-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during adolescence (N=141). HPA-axis functioning (basal cortisol, cortisol awakening response, anticipation of, reaction to and recovery after a stress task) was measured twice, at age 16 and 19. Adversity (i.e., social defeat and loss/illness) since age 16 was measured extensively with the Life Stress Interview at age 19. Adolescents who reported being exposed to social defeat showed increases in basal cortisol (ɳ 2 =0.029) and decreases in reaction to the stress task (ɳ 2 =0.030) from age 16-19, compared to their peers in the loss/illness and no stress group. The current study provides unique longitudinal data on the role of adversity in HPA-axis functioning. Evidence is provided that adversity can affect the body's neuroendocrine response to stress, dependent on the nature of both the HPA-measures and adverse events under study. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory.

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    McCormick, Cheryl M; Mathews, Iva Z

    2010-06-30

    Chronic exposure to stress is known to affect learning and memory in adults through the release of glucocorticoid hormones by the hypothalamic-pituitary-adrenal (HPA) axis. In adults, glucocorticoids alter synaptic structure and function in brain regions that express high levels of glucocorticoid receptors and that mediate goal-directed behaviour and learning and memory. In contrast to relatively transient effects of stress on cognitive function in adulthood, exposure to high levels of glucocorticoids in early life can produce enduring changes through substantial remodeling of the developing nervous system. Adolescence is another time of significant brain development and maturation of the HPA axis, thereby providing another opportunity for glucocorticoids to exert programming effects on neurocircuitry involved in learning and memory. These topics are reviewed, as is the emerging research evidence in rodent models highlighting that adolescence may be a period of increased vulnerability compared to adulthood in which exposure to high levels of glucocorticoids results in enduring changes in adult cognitive function. Copyright 2009 Elsevier Inc. All rights reserved.

  10. Translational relevance of rodent models of hypothalamic-pituitary-adrenal function and stressors in adolescence

    Directory of Open Access Journals (Sweden)

    Cheryl M. McCormick

    2017-02-01

    Full Text Available Elevations in glucocorticoids that result from environmental stressors can have programming effects on brain structure and function when the exposure occurs during sensitive periods that involve heightened neural development. In recent years, adolescence has gained increasing attention as another sensitive period of development, a period in which pubertal transitions may increase the vulnerability to stressors. There are similarities in physical and behavioural development between humans and rats, and rats have been used effectively as an animal model of adolescence and the unique plasticity of this period of ontogeny. This review focuses on benefits and challenges of rats as a model for translational research on hypothalamic-pituitary-adrenal (HPA function and stressors in adolescence, highlighting important parallels and contrasts between adolescent rats and humans, and we review the main stress procedures that are used in investigating HPA stress responses and their consequences in adolescence in rats. We conclude that a greater focus on timing of puberty as a factor in research in adolescent rats may increase the translational relevance of the findings.

  11. Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

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    Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

    2015-01-01

    Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

  12. Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children

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    Lopez-Duran, Nestor L.; Olson, Sheryl L.; Hajal, Nastassia J.; Felt, Barbara T.; Vazquez, Delia M.

    2009-01-01

    The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to…

  13. The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

    NARCIS (Netherlands)

    P.C. Guest (Paul); D. Martins-de-Souza (Daniel); H. Rahmoune (Hassan); S. Bahn (Sabine); P.C. Guest (Paul)

    2013-01-01

    textabstractOver the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in

  14. Predicting mental disorders from hypothalamic-pituitary-adrenal axis functioning: a 3-year follow-up in the TRAILS study.

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    Nederhof, E; van Oort, F V A; Bouma, E M C; Laceulle, O M; Oldehinkel, A J; Ormel, J

    2015-08-01

    Hypothalamic-pituitary-adrenal axis functioning, with cortisol as its major output hormone, has been presumed to play a key role in the development of psychopathology. Predicting affective disorders from diurnal cortisol levels has been inconclusive, whereas the predictive value of stress-induced cortisol concentrations has not been studied before. The aim of this study was to predict mental disorders over a 3-year follow-up from awakening and stress-induced cortisol concentrations. Data were used from 561 TRAILS (TRacking Adolescents' Individual Lives Survey) participants, a prospective cohort study of Dutch adolescents. Saliva samples were collected at awakening and half an hour later and during a social stress test at age 16. Mental disorders were assessed 3 years later with the Composite International Diagnostic Interview (CIDI). A lower cortisol awakening response (CAR) marginally significantly predicted new disorders [odds ratio (OR) 0.77, p = 0.06]. A flat recovery slope predicted disorders with a first onset after the experimental session (OR 1.27, p = 0.04). Recovery revealed smaller, non-significant ORs when predicting new onset affective or anxiety disorders, major depressive disorder, or dependence disorders in three separate models, corrected for all other new onsets. Our results suggest that delayed recovery and possibly reduced CAR are indicators of a more general risk status and may be part of a common pathway to psychopathology. Delayed recovery suggests that individuals at risk for mental disorders perceived the social stress test as less controllable and less predictable.

  15. Association of IL-6, hypothalamus-pituitary-adrenal axis function, and depression in patients with cancer.

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    Jehn, Christian Friedrich; Kühnhardt, Dagmar; Bartholomae, Andrea; Pfeiffer, Sebastian; Schmid, Peter; Possinger, Kurt; Flath, Bernd Christian; Lüftner, Diana

    2010-09-01

    Evidence suggests that cytokines (IL-6) and alteration of the hypothalamic-pituitary-adrenal (HPA) axis play a crucial role in the etiology of depression. Patients with cancer show elevated prevalence rates for depression. The objective of this cross-sectional study was to investigate the associations between these abnormalities and depression. Plasma concentrations of IL-6 and cortisol were measured in cancer patients with (N = 31) and without depression (N = 83). The relative diurnal variation of cortisol (cortisol VAR), expressed in percentage, was calculated. There was a significant difference in median plasma concentration of IL-6 between the patients with depression and those without (18.7 vs 2.7 pg/mL; P cancer is associated with increased plasma IL-6 concentrations and dysfunction of the HPA axis.

  16. Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

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    Kempke, Stefan; Luyten, Patrick; De Coninck, Sarah; Van Houdenhove, Boudewijn; Mayes, Linda C; Claes, Stephan

    2015-02-01

    There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses. A total of 40 female patients diagnosed with CFS were asked to provide morning saliva cortisol samples (after awakening, 30min later, and 1h later) for seven consecutive days as a measure of cortisol activity. In addition, patients were exposed to the Trier Social Stress Test, a well-validated stress test, to investigate the relationship between early childhood trauma and cortisol stress reactivity. Before the start of the study, patients completed the Childhood Trauma Questionnaire-Short form (CTQ-SF) as a measure of early childhood trauma (i.e. sexual, physical and emotional traumatic experiences). SCP was measured with the Depressive Experiences Questionnaire (DEQ). Data were analyzed by calculating several indices of cortisol secretion (i.e. Cortisol Awakening Response and Area Under the Curve). There was no association between early childhood trauma and cortisol as measured over the 7-day period. However, emotional neglect was significantly negatively related to cortisol reactivity in the TSST. SCP did not significantly mediate this association. Findings of this study suggest that emotional neglect is associated with blunted HPA axis reactivity, congruent with the assumption that CFS may reflect loss of adaptability of the neuroendocrine stress response system in at least a subgroup of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Perturbing the Hypothalamic Pituitary Adrenal Axis:A Mathematical Model for Interpreting PTSDAssessment Tests

    Science.gov (United States)

    2017-08-15

    Suppression Test (DST) The dexamethasone suppression test (DST) is a pharmacological challenge test typically used to identify the cause of abnormal ...suppres- sion is in effect. One way to further probe the system is to combine a nonpharmacological, psychological stressor with the DST. The ensuing...second stage of our proposed test, we assume Iext(t) to be a positive constant when the external ( psychological ) stressor is on, and zero while off. In

  18. Basal activity of the hypothalamic-pituitary-adrenal axis and cognitive function in anorexia nervosa.

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    Seed, J A; Dixon, R A; McCluskey, S E; Young, A H

    2000-01-01

    Anorexia nervosa is associated with abnormalities in neuroendocrine function including sustained hypercortisolism, which has been shown elsewhere to be associated with impairment of function in learning, memory and attention. Cognitive impairment has also been observed in anorexia nervosa. These effects may be mediated in part through cortisol effects on the hippocampus, which is dense with glucocorticoid receptors. We investigated the association between cortisol levels and cognitive function in anorexia nervosa by measuring both 24-hour urinary cortisol counts and performance on tasks of learning, memory and attention in patients suffering from the disorder. Cortisol secretion was shown to be significantly higher in the patient group than in a matched control group and patients were also shown to be impaired in memory and attention. However, no correlations were found between the cognitive deficits and cortisol measures. It is suggested that more sensitive profiling of cortisol levels throughout the circadian cycle may be useful in future studies of cognitive function in anorexia nervosa.

  19. Pre-receptor Regulation of Cortisol in Hypothalamic-Pituitary-Adrenal Axis Functioning an Metabolism

    NARCIS (Netherlands)

    M.J.H.J. Dekker (Marieke)

    2011-01-01

    textabstractGlucocorticoids (GCs) are ubiquitous, nuclear hormones, which are essential for life. In man, the main GC is cortisol, produced by the adrenals, endocrine glands that are situated on top of the kidneys. Cortisol exerts its functions in nearly all tissues and is crucial in the

  20. Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle.

    Science.gov (United States)

    Kapoor, Amita; Matthews, Stephen G

    2008-12-01

    Prenatal stress is associated with altered behavior and hypothalamic-pituitary-adrenal (HPA) axis function postnatally. Recent studies suggest that these outcomes are dependent on the timing of the prenatal stress. The majority of these studies have been carried out in male offspring. We hypothesized that a short period of prenatal stress would result in female offspring that exhibit differences in open-field behavior and HPA axis activity, but the outcome would depend on the timing of the prenatal stress and the stage of the reproductive cycle. Pregnant guinea pigs were exposed to a strobe light during the fetal brain growth spurt [gestational d 50-52 (PS50)] or during the period of rapid brain myelination [gestational d 60-62 (PS60)]. Open-field activity was assessed in juvenile and adult female offspring. HPA axis function was tested in adult offspring. All tests in adulthood were carried out during the estrous and luteal phases of the reproductive cycle to determine the effect of stage on HPA axis programming. Tissues were collected upon completion of the study for analysis by in situ hybridization. PS60 offspring exhibited decreased activity in an open field during the estrous phase of the reproductive cycle compared with control offspring. Both PS50 and PS60 offspring exhibited a lower salivary cortisol response to a stressor, only during the estrous phase. Consistent with the behavioral and endocrine data, PS60 females exhibited lower plasma estradiol levels, reduced ovary weight, and increased glucocorticoid receptor mRNA in the paraventricular nucleus. In conclusion, we have demonstrated that there are effects of prenatal stress on behavior and HPA axis functioning in female offspring but that the outcomes are dependent on the timing of the prenatal stress together with the status of the reproductive cycle.

  1. Salivary cortisol assessment in the evaluation of hypothalamic-pituitary-adrenal function

    International Nuclear Information System (INIS)

    Kahn, S.E.; Maxwell, J.U.; Barron, J.L.

    1984-01-01

    A simple, short and sensitive direct radio-immunoassay technique for the determination of salivary cortisol concentration was employed to assess saliva as a medium for evaluating cortisol response during endocrine testing in 9 controls and 40 patients. Results in controls suggested that an adequate salivary cortisol response to insulin hypoglycaemia was an increase of 150% above the basal value with a minimum peak of 15 nmol/l. Thirty-three patients were classified as being either good or poor responders to insulin hypoglycaemia on the basis of criteria for plasma cortisol levels. When the defined salivary cortisol response was used for assessment, all 33 patients were correctly categorized into the same response groups. The salivary cortisol response to intramuscular tetracosactin in 3 patients and an intravenous dexamethasone infusion in 4 patients confirmed the value of saliva as an assay medium. These studies show that the salivary cortisol response parallels that of total plasma cortisol in all cases. However, with sampling at short intervals a lag in secretion of the free fraction from the plasma into the saliva becomes apparent. The relative change in cortisol levels from the basal value is greater in saliva than in plasma

  2. Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis

    NARCIS (Netherlands)

    Gardner, M.P.; Lightman, S.; Sayer, A.A.; Cooper, C.; Cooper, R.; Deeg, D.J.H.; Ebrahim, S.; Gallacher, J.; Kivimaki, M.; Kumari, M.; Kuh, D; Martin, R.M.; Peeters, G.; Ben-Shlomoa, Y.

    2013-01-01

    The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is

  3. Investigation of the hypothalamo-pituitary-adrenal axis (HPA) by 1 microg ACTH test and metyrapone test in patients with primary fibromyalgia syndrome.

    Science.gov (United States)

    Calis, M; Gökçe, C; Ates, F; Ulker, S; Izgi, H B; Demir, H; Kirnap, M; Sofuoglu, S; Durak, A C; Tutus, A; Kelestimur, F

    2004-01-01

    Primary fibromyalgia syndrome (PFS) is characterized by widespread chronic pain that affects the musculoskeletal system, fatigue, anxiety, sleep disturbance, headache and postural hypotension. The pathophysiology of PFS is unknown. The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in PFS. Both hyperactivity and hypoactivity of the HPA axis have been reported in patients with PFS. In this study we assessed the HPA axis by 1 microg ACTH stimulation test and metyrapone test in 22 patients with PFS and in 15 age-, sex-, and body mass index (BMI)- matched controls. Metyrapone (30 mg/kg) was administered orally at 23:00 h and blood was sampled at 08:30 h the following morning for 11-deoxycortisol. ACTH stimulation test was carried out by using 1 microg (iv) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. Peak cortisol level (659.4 +/- 207.2 nmol/l) was lower in the patients with PFS than peak cortisol level (838.7 +/- 129.6 nmol/l) in the control subjects (p < 0.05). Ten patients (45%) with PFS had peak cortisol responses to 1 microg ACTH test lower than the lowest peak cortisol detected in healthy controls. After metyrapone test 11-deoxycortisol level was 123.7 +/- 26 nmol/l in patients with PFS and 184.2 +/- 17.3 nmol/l in the controls (p < 0.05). Ninety five percent of the patients with PFS had lower 11-deoxycortisol level after metyrapone than the lowest 11-deoxycortisol level after metyrapone detected in healthy controls. We also compared the adrenal size of the patients with that of the healthy subjects and we found that the adrenal size between the groups was similar. This study clearly shows that HPA axis is underactivated in PFS, rather than overactivated.

  4. A longitudinal study of disturbances of the hypothalamic-pituitary-adrenal axis in women with progestin-negative functional hypothalamic amenorrhea.

    Science.gov (United States)

    Kondoh, Y; Uemura, T; Murase, M; Yokoi, N; Ishikawa, M; Hirahara, F

    2001-10-01

    To longitudinally evaluate disturbances of the hypothalamic-pituitary-adrenal (HPA) axis in women with secondary progestin-negative hypothalamic amenorrhea. Retrospective cohort study. Yokohama City University, Yokohama, Japan. Twenty-four women with progestin-negative hypothalamic amenorrhea. Administration of human corticotropin-releasing hormone (hCRH) and treatment with a combination of estrogen and progesterone. Plasma cortisol and ACTH concentrations and period required for recovery from amenorrhea. Plasma ACTH concentrations 30 and 60 minutes after injection of hCRH and the percent maximum increment (%Cmax) of ACTH were significantly lower in the amenorrheic patients compared with the control group patients. The basal cortisol was significantly higher, and the %Cmax of cortisol was significantly lower. In the 16 patients who recovered from amenorrhea, there was a significant positive correlation (Y = 1.93X-10.8, r = 0.629) between the basal cortisol concentrations (X) and the period for recovery (Y). The serum E2 gradually increased before recovery, and this E2 increase was preceded by changes in the plasma cortisol concentration and the %Cmax values of cortisol and ACTH. The CRH test might be useful for evaluating the roles of stress and for estimating the period required for recovery in hypothalamic amenorrhea.

  5. Combined receptor antagonist stimulation of the hypothalamic-pituitary-adrenal axis test identifies impaired negative feedback sensitivity to cortisol in obese men.

    Science.gov (United States)

    Mattsson, Cecilia; Reynolds, Rebecca M; Simonyte, Kotryna; Olsson, Tommy; Walker, Brian R

    2009-04-01

    Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie disorders including obesity, depression, cognitive decline, and the metabolic syndrome. Conventional tests of HPA axis negative feedback rely on glucocorticoid receptor (GR) agonists such as dexamethasone but do not test feedback by endogenous cortisol, potentially mediated by both GR and mineralocorticoid receptors (MR). The objective of the study was to use a combination of GR (RU38486, mifepristone) and MR (spironolactone) antagonists to explore the poorly understood activation of the HPA axis that occurs in obesity. This was a double-blind, placebo-controlled, randomized, crossover study. The study was conducted at a clinical research facility. Participants included 15 lean (body mass index 22.0 +/- 1.6 kg/m(2)) and 16 overweight/obese (body mass index 30.1 +/- 3.5 kg/m(2)) men. Subjects attended on four occasions for blood and saliva sampling every 30 min between 1800 and 2200 h. At 1100 and 1600 h before visits, subjects took 200 mg spironolactone, 400 mg RU38486, 200 mg spironolactone + 400 mg RU38486, or placebo orally. Serum cortisol levels after drug or placebo were measured. Cortisol levels did not differ between lean and obese after placebo. Spironolactone and RU38486 alone had modest effects, increasing cortisol by less than 50% in both groups. However, combined spironolactone plus RU38486 elevated cortisol concentrations substantially, more so in lean than obese men [2.9- (0.3) vs. 2.2 (0.3)-fold elevation, P = 0.002]. Combined receptor antagonist stimulation of the HPA axis reveals redundancy of MR and GR in negative feedback in humans. Obese men have impaired responses to combined receptor antagonist stimulation, suggesting impaired negative feedback by endogenous cortisol. Such an approach may be useful to dissect abnormal HPA axis control in neuropsychiatric and other disorders.

  6. Effects of experimentally induced hyperthyroidism on central hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies.

    Science.gov (United States)

    Johnson, Elizabeth O; Calogero, Aldo E; Konstandi, Maria; Kamilaris, Themis C; La Vignera, Sandro; Vignera, Sandro La; Chrousos, George P

    2013-06-01

    Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.

  7. Effects of denial of reward through maternal contact in the neonatal period on adult hypothalamic-pituitary-adrenal axis function in the rat.

    Science.gov (United States)

    Diamantopoulou, Anastasia; Raftogianni, Androniki; Stamatakis, Antonios; Oitzl, Melly S; Stylianopoulou, Fotini

    2013-06-01

    Emotional behavioral traits associated with stress response are well documented to be affected by early life events. In the present work, we used a novel paradigm of neonatal experience, in which pups were trained in a T-maze and either received (RER rats) or were denied (DER) the reward of maternal contact, during postnatal days 10-13. We then evaluated stress coping and key factors controlling the function of the hypothalamic-pituitary-adrenal axis in adulthood. Adult male DER rats exposed to a single session of forced swim stress (FSS) showed increased immobility, while RER rats exhibited increased escape attempts. The corticosterone response following this stressor was higher although not prolonged in the DER rats. Their CRH mRNA levels in the PVN were increased up to 2h after the forced swim. However, basal levels of these hormones did not differ among groups. In addition, the DER neonatal experience induced an increase in hippocampal GR but a decrease in CRH-R1 immunopositive cells in the CA1 area of the hippocampus and the central amygdala. Overall, these data show a distinct stress response profile in the DER male rats, characterized by passive coping during the forced swim, increased hormonal response following stress, increased inhibitory control through GR and an indirect contribution of CRH-R1, the latter two factors resulting in a modified regulation of the response termination. It thus appears that DER rats have an enhanced potential for appropriate reactivity upon an incoming challenge, while maintaining in parallel an adequate control of the duration of their stress responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Antidepressant-Like Effects of Shuyusan in Rats Exposed to Chronic Stress: Effects on Hypothalamic-Pituitary-Adrenal Function

    Directory of Open Access Journals (Sweden)

    Liping Chen

    2012-01-01

    Full Text Available This study was to investigate antidepressant activities of Shuyusan (a Chinese herb, using a rats model of depression induced by unpredictable chronic mild stress (UCMS. The administration groups were treated with Shuyusan decoction for 3 weeks and compared with fluoxetine treatment. In order to understand the potential antidepressant-like activities of Shuyusan, tail suspension test (TST and forced swimming test (FST were used as behavioral despair study. The level of corticotropin-releasing factor (CRH, adrenocorticotropic hormone (ACTH, corticosterone (CORT and hippocampus glucocorticoid receptor expression were examined. After modeling, there was a significant prolongation of immobility time in administration groups with the TST and FST. High-dose Shuyusan could reduce the immobility time measured with the TST and FST. The immobility time in high-dose herbs group and fluoxetine group was increased significantly compared with the model group. After 3 weeks herbs fed, the serum contents level of CRH, ACTH, and CORT in high-dose herb group was significantly decreased compared to the model group. The result indicated that Shuyusan had antidepressant activity effects on UCMS model rats. The potential antidepressant effect may be related to decreasing glucocorticoid levels activity, regulating the function of HPA axis, and inhibiting glucocorticoid receptor expression in hippocampus.

  9. Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study.

    Science.gov (United States)

    Giesbrecht, Gerald F; Ejaredar, Maede; Liu, Jiaying; Thomas, Jenna; Letourneau, Nicole; Campbell, Tavis; Martin, Jonathan W; Dewey, Deborah

    2017-05-19

    Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are lacking. In humans, prenatal BPA exposure is associated with sex-specific behavioural problems in children, and HPA axis dysregulation may be a biological mechanism. The objective of the current study was to examine sex differences in associations between prenatal maternal urinary BPA concentration and HPA axis function in 3 month old infants. Mother-infant pairs (n = 132) were part of the Alberta Pregnancy Outcomes and Nutrition study, a longitudinal birth cohort recruited (2010-2012) during pregnancy. Maternal spot urine samples collected during the 2nd trimester were analyzed for total BPA and creatinine. Infant saliva samples collected prior to and after a blood draw were analyzed for cortisol. Linear growth curve models were used to characterize changes in infant cortisol as a function of prenatal BPA exposure. Higher maternal BPA was associated with increases in baseline cortisol among females (β = 0.13 log μg/dL; 95% CI: 0.01, 0.26), but decreases among males (β = -0.22 log μg/dL; 95% CI: -0.39, -0.05). In contrast, higher BPA was associated with increased reactivity in males (β = .30 log μg/dL; 95% CI: 0.04, 0.56) but decreased reactivity in females (β = -0.15 log μg/dL; 95% CI: -0.35, 0.05). Models adjusting for creatinine yielded similar results. Prenatal BPA exposure is associated with sex-specific changes in infant HPA axis function. The biological plausibility of these findings is supported by their consistency with evidence in rodent models. Furthermore, these data support the hypotheses that sexually dimorphic changes in children's behaviour following prenatal BPA exposure are mediated by sexually dimorphic changes in HPA axis function.

  10. Gonadal Steroid Hormones and the Hypothalamo-Pituitary-Adrenal Axis

    OpenAIRE

    Handa, Robert J.; Weiser, Michael J.

    2013-01-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, pr...

  11. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

    Science.gov (United States)

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-01-01

    Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

  12. Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms : A longitudinal cohort study in the general population

    NARCIS (Netherlands)

    Tak, Lineke M.; Bakker, Stephan J. L.; Rosmalen, Judith G. M.

    In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute

  13. Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users.

    Science.gov (United States)

    Wetherell, Mark A; Montgomery, Catharine

    2014-04-01

    Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.

  14. Early-life social experiences in mice affect emotional behaviour and hypothalamic-pituitary-adrenal axis function.

    Science.gov (United States)

    Ros-Simó, Clara; Valverde, Olga

    2012-09-01

    Early-life stressful experiences are associated to alterations in behavioural responses and development of psychiatric and neurodegenerative diseases. In rodents, individual housing is considered as a stressful condition whilst enriched environment can protect against stress and its negative consequences. Neuroendocrine responses to stress can also be altered by early-life experiences and seem to contribute to behavioural alterations induced by changes in housing conditions. To develop an improved procedure of social isolation throughout development (from pre-adolescence to adulthood) in CD1 mice and to elucidate its effects on behavioural parameters related to stress and neuroendocrine responses compared to enriched or social conditions. CD1 male mice (PND 21) were housed in social/standard conditions, enriched conditions or isolated conditions during seven weeks. After that, different relevant behaviours were evaluated, including locomotor activity, anxiety-like and despair behaviour. Levels of plasma corticosterone were also analysed before and after a stressful event. CD1 mice exposed to an isolated environment exhibited higher locomotion and anxiety-like responses than animals exposed to social or enriched conditions. In addition, isolated animals showed lower basal plasma corticosterone than social or enriched ones but after a stressful event the elevation of plasma corticosterone was higher, suggesting an enhanced response of the HPA axis to a novel and stressful situation. Social interaction is an important feature to display an appropriate behavioural and neuronal development. Habituation to novel stimuli is impaired in subjects exposed to social isolation and induces increased excitability response to stressful events. Social deprivation increases the possibility of altered neuronal function and could facilitate the development of neuropsychiatric disorders in adulthood. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Enhancing offspring hypothalamic-pituitary-adrenal (HPA regulation via systematic neonatal novelty exposure: the influence of maternal HPA function

    Directory of Open Access Journals (Sweden)

    Sarah M. Dinces

    2014-06-01

    Full Text Available In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother’s ability to mount a rapid corticosterone (CORT response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring HPA regulation. Using a 2x2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel daily during infancy (PND1-21 and the other half of the litter remained in the home cage (Neo_Home; we further exposed half of these two groups to early adulthood (PND54-63 novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB and the ability to mount a large rapid CORT response (CORTE to the onset of an acute stressor. Assessment of adult offspring’s ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring’s ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the context of maternal

  16. Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function.

    Science.gov (United States)

    Haj-Mirzaian, A; Amiri, S; Kordjazy, N; Momeny, M; Razmi, A; Rahimi-Balaei, M; Amini-Khoei, H; Haj-Mirzaian, A; Marzban, H; Mehr, S E; Ghaffari, S H; Dehpour, A R

    2016-02-19

    The neuroimmune-endocrine dysfunction has been accepted as one of fundamental mechanisms contributing to the pathophysiology of psychiatric disorders including depression and anxiety. In this study, we aimed to evaluate the involvement of hypothalamic-pituitary-adrenal (HPA) axis, interleukin-1β, and nitrergic system in mediating the negative behavioral impacts of juvenile social isolation stress (SIS) in male mice. We also investigated the possible protective effects of lithium on behavioral and neurochemical changes in socially isolated animals. Results showed that experiencing 4-weeks of juvenile SIS provoked depressive and anxiety-like behaviors that were associated with hyper responsiveness of HPA axis, upregulation of interleukin-1β, and nitric oxide (NO) overproduction in the pre-frontal cortex and hippocampus. Administration of lithium (10 mg/kg) significantly attenuated the depressant and anxiogenic effects of SIS in behavioral tests. Lithium also restored the negative effects of SIS on cortical and hippocampal interleukin-1β and NO as well as HPA axis deregulation. Unlike the neutralizing effects of l-arginine (NO precursor), administration of l-NAME (3 mg/kg) and aminoguanidine (20 mg/kg) potentiated the positive effects of lithium on the behavioral and neurochemical profile of isolated mice. In conclusion, our results revealed that juvenile SIS-induced behavioral deficits are associated with abnormalities in HPA-immune function. Also, we suggest that alleviating effects of lithium on behavioral profile of isolated mice may be partly mediated by mitigating the negative impact of NO on HPA-immune function. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Barr, C S; Newman, T K; Lindell, S; Becker, M L; Shannon, C; Champoux, M; Suomi, S J; Higley, J D

    2004-07-01

    Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

  18. Mindful Parenting Predicts Mothers' and Infants' Hypothalamic-Pituitary-Adrenal Activity during a Dyadic Stressor

    Science.gov (United States)

    Laurent, Heidemarie K.; Duncan, Larissa G.; Lightcap, April; Khan, Faaiza

    2017-01-01

    Mindfulness in the parenting relationship has been proposed to help both parents and children better regulate stress, though this has not yet been shown at the physiological level. In this study, we tested relations between maternal mindfulness in parenting and both mothers' and their infants' hypothalamic-pituitary-adrenal (HPA) axis activity…

  19. Influence of early life stress on later hypothalamic-pituitary-adrenal axis functioning and its covariation with mental health symptoms: a study of the allostatic process from childhood into adolescence.

    Science.gov (United States)

    Essex, Marilyn J; Shirtcliff, Elizabeth A; Burk, Linnea R; Ruttle, Paula L; Klein, Marjorie H; Slattery, Marcia J; Kalin, Ned H; Armstrong, Jeffrey M

    2011-11-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

  20. The association between the hypothalamic pituitary adrenal axis and tryptophan metabolism in persons with recurrent major depressive disorder and healthy controls

    NARCIS (Netherlands)

    Sorgdrager, F. J. H.; Doornbos, B.; Penninx, B. W. J. H.; de Jonge, P.; Kema, I. P.

    2017-01-01

    Objectives: Persistent changes in serotonergic and hypothalamic pituitary adrenal (HPA) axis functioning are implicated in recurrent types of major depressive disorder (MDD). Systemic tryptophan levels, which influence the rate of serotonin synthesis, are regulated by glucocorticoids produced along

  1. Antidepressant-like Effect of Bacopaside I in Mice Exposed to Chronic Unpredictable Mild Stress by Modulating the Hypothalamic-Pituitary-Adrenal Axis Function and Activating BDNF Signaling Pathway.

    Science.gov (United States)

    Zu, Xianpeng; Zhang, Mingjian; Li, Wencai; Xie, Haisheng; Lin, Zhang; Yang, Niao; Liu, Xinru; Zhang, Weidong

    2017-11-01

    Preliminary studies conducted in our laboratory have confirmed that Bacopaside I (BS-I), a saponin compound isolated from Bacopa monnieri, displayed antidepressant-like activity in the mouse behavioral despair model. The present investigation aimed to verify the antidepressant-like action of BS-I using a mouse model of behavioral deficits induced by chronic unpredictable mild stress (CUMS) and further probe its underlying mechanism of action. Mice were exposed to CUMS for a period of 5 consecutive weeks to induce depression-like behavior. Then, oral gavage administrations with vehicle (model group), fluoxetine (12 mg/kg, positive group) or BS-I (5, 15, 45 mg/kg, treated group) once daily were started during the last two weeks of CUMS procedure. The results showed that BS-I significantly ameliorated CUMS-induced depression-like behaviors in mice, as characterized by an elevated sucrose consumption in the sucrose preference test and reduced immobility time without affecting spontaneous locomotor activity in the forced swimming test, tail suspension test and open field test. It was also found that BS-I treatment reversed the increased level of plasma corticosterone and decreased mRNA and protein expressions of glucocorticoid receptor induced by CUMS exposure, indicating that hypothalamic-pituitary-adrenal (HPA) axis hyperactivity of CUMS-exposed mice was restored by BS-I treatment. Furthermore, chronic administration of BS-I elevated expression levels of brain-derived neurotrophic factor (BDNF) (mRNA and protein) and activated the phosphorylation of extracellular signal-regulated kinase and cAMP response element-binding protein in the hippocampus and prefrontal cortex in mice subjected to CUMS procedure. Taken together, these results indicated that BS-I exhibited an obvious antidepressant-like effect in mouse model of CUMS-induced depression that was mediated, at least in part, by modulating HPA hyperactivity and activating BDNF signaling pathway.

  2. Autonomic response to an experimental psychological stressor in healthy subjects: measurement of sympathetic, parasympathetic, and pituitary-adrenal parameters: test-retest reliability

    DEFF Research Database (Denmark)

    Jørgensen, L S; Christiansen, P; Raundahl, U

    1990-01-01

    A mental arithmetic test (the stressor; 15 min) significantly increased systolic and diastolic blood pressure, heart rate and plasma adrenaline by 11%, 12%, 28% and 152% respectively, with a prompt return to resting values after the test. Plasma noradrenaline and serum cortisol did not increase...... of the stressor. As a measure of parasympathetic nervous function, the beat-to-beat variation of heart rate, expressed as the mean successive square difference (MSSD), was employed. Four to 14 months later, the investigation was repeated, and resting values of all measures were found to be stable. The increments...

  3. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)

    OpenAIRE

    Lee, Richard; Sawa, Akira

    2014-01-01

    In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

  4. Monitoring performance, pituitary-adrenal hormones and mood profiles: how to diagnose non-functional over-reaching in male elite junior soccer players.

    Science.gov (United States)

    Schmikli, Sándor L; de Vries, Wouter R; Brink, Michel S; Backx, Frank Jg

    2012-11-01

    To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). A prospective case-control study using a monthly performance monitor with a standardised field test to detect the performance changes. Players with a performance decrease lasting at least 1 month were compared with control players without a performance decrease on mood scores and pre-exercise and postexercise levels of stress hormones. Sporting field and sports medical laboratory. Ninety-four young elite soccer players were monitored during the 2006-2008 seasons. Twenty-one players were invited to the laboratory, seven of whom showed a significant performance decrease. Performance change over time, scores on the profile of mood states and premaximal and postmaximal exercise serum levels of adrenocorticotropic hormone (ACTH), growth hormone (GH) and cortisol. Players with a performance decrease showed psychological and hormonal changes typical of the non-functional state of over-reaching. Scores were higher on depression and anger, whereas the resting GH levels and ACTH levels after maximal exercise were reduced. ACTH and GH were capable of classifying all but one player correctly as either NFOR or control. Performance-related criteria in field tests are capable of identifying players with worsened mood and adaptations of the endocrine system that fit the definition of NFOR. Performance, mood and hormone levels may therefore be considered as valid instruments to diagnose NFOR in young elite soccer players.

  5. Autonomic response to an experimental psychological stressor in healthy subjects: measurement of sympathetic, parasympathetic, and pituitary-adrenal parameters: test-retest reliability

    DEFF Research Database (Denmark)

    Jørgensen, L S; Christiansen, P; Raundahl, U

    1990-01-01

    A mental arithmetic test (the stressor; 15 min) significantly increased systolic and diastolic blood pressure, heart rate and plasma adrenaline by 11%, 12%, 28% and 152% respectively, with a prompt return to resting values after the test. Plasma noradrenaline and serum cortisol did not increase s...

  6. Clinical insights into the safety and utility of the insulin tolerance test (ITT) in the assessment of the hypothalamo-pituitary-adrenal axis.

    LENUS (Irish Health Repository)

    Finucane, Francis M

    2008-10-01

    The insulin tolerance test (ITT) is the gold standard for assessing GH and cortisol production in pituitary disease. However, areas of uncertainty remain regarding its safety in older people, the optimal duration of the test and its performance in insulin resistant states. Whether basal cortisol concentration can reliably predict an adequate adrenal response to hypoglycaemia remains to be determined.

  7. Monitoring performance, pituitary-adrenal hormones and mood profiles : how to diagnose non-functional over-reaching in male elite junior soccer players

    NARCIS (Netherlands)

    Schmikli, Sandor L.; de Vries, Wouter R.; Brink, Michel S.; Backx, Frank J. G.

    2012-01-01

    Objective To verify if in male elite junior soccer players a minimum 1-month performance decrease is accompanied by a mood profile and hormone levels typical of non-functional over-reaching (NFOR). Design A prospective case-control study using a monthly performance monitor with a standardised field

  8. [The hypothalamic-pituitary-adrenal axis and depressive disorder: recent progress].

    Science.gov (United States)

    Kunugi, Hiroshi; Hori, Hiroaki; Numakawa, Tadahiro; Ota, Miho

    2012-08-01

    Depression is a stress-induced disorder and there is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in the disease. Chronic hyperactivity of the HPA axis and resultant excessive glucocorticoid (hypercortisolism) may be causal to depression. We demonstrated that the dexamethasone (DEX)/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities. Restoration from HPA axis abnormalities occurs with clinical responses to treatment. Brain-derived neurotrophic factor (BDNF) has also been implicated in depression. We found that glucocorticoid (DEX) suppresses BDNF-induced dendrite outgrowth and synaptic formation via blocking the MAPK pathway in early-developing cultured hippocampal neurons. Furthermore, we demonstrated that glucocorticoid receptor (GR) and TrkB (a specific receptor of BDNF) interact and that DEX acutely suppresses BDNF-induced glutamate release by affecting the PLC-gamma pathway in cultured cortical neurons, indicating a mechanism underlying the effect of excessive glucocorticoid on BDNF function and resultant damage in cortical neurons. In a macroscopic view using magnetic resonance imaging (MRI), we found that individuals with hypercortisolism detected by the DEX/CRH test demonstrated volume loss in gray matter and reduced neural network assessed with diffusion tensor imaging in several brain regions. Finally, we observed that individuals with hypocortisolism detected by the DEX/CRH test tend to present more distress symptoms, maladaptive coping styles, and schizotypal personality traits than their counterparts, which points to the important role of hypocortisolism as well as hypercortisolism in depression spectrum disorders.

  9. Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Hay-Schmidt, Anders; Kiss, Alexander

    2004-01-01

    Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these recept...

  10. Corticotropin-releasing hormone and pituitary-adrenal hormones in pregnancies complicated by chronic hypertension.

    Science.gov (United States)

    Warren, W B; Gurewitsch, E D; Goland, R S

    1995-02-01

    We hypothesized that maternal plasma corticotropin-releasing hormone levels are elevated in chronic hypertension and that elevations modulate maternal and fetal pituitary-adrenal function. Venous blood samples and 24-hour urine specimens were obtained in normal and hypertensive pregnancies at 21 to 40 weeks of gestation. Corticotropin-releasing hormone, corticotropin, cortisol, dehydroepiandrosterone sulfate, and total estriol levels were measured by radioimmunoassay. Mean hormone levels were compared by unpaired t test or two-way analysis of variance. Plasma corticotropin-releasing hormone levels were elevated early in hypertensive pregnancies but did not increase after 36 weeks. Levels of pituitary and adrenal hormones were not different in normal and hypertensive women. However, maternal plasma estriol levels were lower in hypertensive pregnancies compared with normal pregnancies. Fetal 16-hydroxy dehydroepiandrosterone sulfate, the major precursor to placental estriol production, has been reported to be lower than normal in hypertensive pregnancies, possibly explaining the decreased plasma estriol levels reported here. Early stimulation of placental corticotropin-releasing hormone production or secretion may be related to accelerated maturation of placental endocrine function in pregnancies complicated by chronic hypertension.

  11. Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression.

    Science.gov (United States)

    Kunugi, Hiroshi; Hori, Hiroaki; Adachi, Naoki; Numakawa, Tadahiro

    2010-10-01

    Although the pathophysiology of depressive disorder remains elusive, two hypothetical frameworks seem to be promising: the involvement of hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF) in the pathogenesis and in the mechanism of action of antidepressant treatments. In this review, we focused on research based on these two frameworks in relation to depression and related conditions and tried to formulate an integrated theory of the disorder. Hormonal challenge tests, such as the dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA activity (hypercortisolism) in at least a portion of patients with depression, although growing evidence has suggested that abnormally low HPA axis (hypocortisolism) has also been implicated in a variety of stress-related conditions. Several lines of evidence from postmortem studies, animal studies, blood levels, and genetic studies have suggested that BDNF is involved in the pathogenesis of depression and in the mechanism of action of biological treatments for depression. Considerable evidence has suggested that stress reduces the expression of BDNF and that antidepressant treatments increase it. Moreover, the glucocorticoid receptor interacts with the specific receptor of BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered BDNF function is involved in the structural changes and possibly impaired neurogenesis in the brain of depressed patients. Based on these findings, an integrated schema of the pathological and recovery processes of depression is illustrated. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

  12. A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome.

    Science.gov (United States)

    Kennedy, P J; Cryan, J F; Quigley, E M M; Dinan, T G; Clarke, G

    2014-10-01

    Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS. Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre- and post-exposure to the TSST. The hypothalamic-pituitary-adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups. Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

  13. Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis

    Directory of Open Access Journals (Sweden)

    Ran Huo

    2017-11-01

    Full Text Available Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA axis under stress. We tested germ-free (GF mice and specific pathogen-free (SPF mice, divided into four groups. A chronic restraint stress (CRS protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases.

  14. The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors?

    Science.gov (United States)

    Armario, Antonio

    2006-10-01

    The hypothalamic-pituitary-adrenal (HPA) axis is an extremely sensitive physiological system whose activation, with the consequent release of ACTH and glucocorticoids, is triggered by a wide range of psychological experiences and physiological perturbations (stressors). The HPA axis is also activated by a high number of pharmacological agents that markedly differ in structure and function, although the precise mechanisms remain in most cases unknown. Activation of the HPA axis is the consequence of the convergence of stimulatory inputs from different brain regions into the paraventricular nucleus of the hypothalamus (PVN), where the most important ACTH secretagogues (corticotrophin releasing factor, CRF, and arginin-vasopressin, AVP) are formed. Plasma levels of ACTH and corticosterone (the latter under more restricted conditions), are considered as good markers of stress for three main reasons: (a) their plasma levels are proportional to the intensity of emotional and systemic stressors, (b) daily repeated exposure to a stressor usually resulted in reduced ACTH response to the same stressor, that is termed adaptation or habituation; and (c) chronic exposure to stressful situations results in tonic changes in the HPA axis that can be used as indices of the accumulative impact of these situations. These changes can be evaluated under resting conditions (i.e. adrenal weight, CRF and AVP gene expression in the PVN) or after some challenges (administration of CRF, ACTH or dexamethasone) that are classical endocrinological tests. There is also evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.

  15. Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity.

    Science.gov (United States)

    Whitaker, Annie M; Gilpin, Nicholas W

    2015-08-01

    Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as 'Avoiders' or 'Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24h and 11days), anxiety-like behavior (48h and 5days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24h that persisted 11days post-stress. Both Avoiders and Non-Avoiders exhibited a heightened anxiety-like behavior at 48h and 5days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and build on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. Copyright © 2015. Published by Elsevier Inc.

  16. Beta-endorphin in the plasma: Radioimmunological determination and findings in patients showing disorders at the level of the hypothalamus-pituitary-adrenal axis

    International Nuclear Information System (INIS)

    Hoerl, A.

    1985-01-01

    Beta-endorphin and adrenocorticotropic hormone (ACTH) were determined simultaneously in the plasma using a radioimmunological procedure. It was found that in patients showing imbalances within the hypothalamus-pituitary-adrenal system (Addison's disease, Cushing's Syndrome, Nelson's Syndrome) as well as elevated levels of beta-endorphin the values of ACHT invariably were also increased. The behaviour of the plasma levels of beta-endorphin and ACTH before, during and subsequent to hypophyseal surgery gives evidence to prove the close link between the two hormones. Tests performed to examine the function of the corticotropin releasing factor (CRF) both in healthy volunteers and patients suffering from endocrinological disorders likewise pointed to a parallel behaviour pattern of the two hormones in their responding or failure to respond to stimulation. The fact that a significant correlation was established between all measured values of beta-endorphin and ACTH is further evidence in confirmation of a parallel release of these two hormones in man. (TRV) [de

  17. Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA axis

    Directory of Open Access Journals (Sweden)

    Mello Andrea de Abreu Feijó de

    2003-01-01

    Full Text Available Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology

  18. The hypothalamo-pituitary-adrenal axis in major affective disorder

    DEFF Research Database (Denmark)

    Christensen, M V; Kessing, L V

    2001-01-01

    disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only......This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective...... or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging....

  19. Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress.

    Science.gov (United States)

    Keltikangas-Järvinen, L; Ravaja, N; Räikkönen, K; Hautanen, A; Adlercreutz, H

    1998-12-01

    We examined whether the relationships between the pituitary-adrenal hormones (corticotropin [ACTH) and cortisol), insulin, and glucose differ as a function of psychosocial stress defined in terms of vital exhaustion (VE) and depressive behavior (DB). The participants were 69 normotensive and 21 unmedicated borderline hypertensive (BH) middle-aged men whose work is stressful. Hormonal and metabolic variables were measured during an oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone (DXM) suppression and intravenous ACTH stimulation was also measured. We found that the basal ACTH level during the OGTT was positively associated with the cortisol response to ACTH at 60 minutes, the fasting insulin level, and the insulin to glucose ratio among exhausted and high DB men, while the reverse was true for nonexhausted and low DB men. Also, a high cortisol response to ACTH, a low cortisol level during the OGTT, and a high ratio of these cortisol determinations (cortisol ratio) were associated with high fasting insulin and glucose levels, the summed insulin values, and the insulin to glucose ratio only among nonexhausted and low DB men; among exhausted and high DB men, these associations were less pronounced, absent, or in the opposite direction. The findings suggest that VE and DB have a moderating influence on the relationships among the hormonal and metabolic parameters studied. Psychosocial stress may affect the pituitary-adrenocortical system in complex ways, contributing thereby to insulin resistance, hyperinsulinemia, and coronary heart disease (CHD) risk.

  20. Investigating the effect of acute sleep deprivation on hypothalamic-pituitary-adrenal-axis response to a psychosocial stressor.

    Science.gov (United States)

    Vargas, Ivan; Lopez-Duran, Nestor

    2017-05-01

    The hypothalamic-pituitary-adrenal (HPA) axis has been previously identified as one potential mechanism that may explain the link between sleep deprivation and negative health outcomes. However, few studies have examined the direct association between sleep deprivation and HPA-axis functioning, particularly in the context of stress. Therefore, the aim of the current study was to investigate the relationship between acute sleep deprivation and HPA-axis reactivity to a psychosocial stressor. Participants included 40 healthy, young adults between the ages of 18-29. The current protocol included spending two nights in the laboratory. After an adaptation night (night 1), participants were randomized into either a sleep deprivation condition (29 consecutive hours awake) or a control condition (night 2). Following the second night, all participants completed the Trier Social Stress Test (TSST). Salivary cortisol was collected before, during, and after the TSST. Results indicated that there were significant group differences in cortisol stress reactivity. Specifically, compared to participants in the control condition, participants in the sleep deprivation condition had greater baseline (i.e., pre-stress) cortisol, yet a blunted cortisol response to the TSST. Taken together, a combination of elevated baseline cortisol (and its subsequent effect on HPA-axis regulatory processes) and a relative 'ceiling' on the amount of cortisol a laboratory stressor can produce may explain why participants in the sleep deprivation condition demonstrated blunted cortisol responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Early developmental and temporal characteristics of stress-induced secretion of pituitary-adrenal hormones in prenatally stressed rat pups.

    Science.gov (United States)

    Takahashi, L K; Kalin, N H

    1991-08-30

    Previous experiments revealed that 14-day-old prenatally stressed rats have significantly elevated concentrations of plasma adrenocorticotrophic hormone (ACTH) and corticosterone suggesting these animals have an overactive hypothalamic-pituitary-adrenal (HPA) system. In these studies, however, stress-induced hormone levels were determined only immediately after exposure to an acute stressor. Therefore, in the current study, we examined in postnatal days 7, 14 and 21 prenatally stressed rats the stress-induced time course of this pituitary-adrenal hormone elevation. Plasma ACTH and corticosterone were measured in the basal state and at 0.0, 0.5, 1.0, 2.0 and 4.0 h after a 10-min exposure period to foot shocks administered in the context of social isolation. Results indicated that at all 3 ages, plasma ACTH in prenatally stressed rats was significantly elevated. Corticosterone concentrations were also significantly higher in prenatally stressed than in control rats, especially in day 14 rats. Analysis of stress-induced hormone fluctuations over time indicated that by 14 days of age, both prenatally stressed than in control and control rats had significant increases in plasma ACTH and corticosterone after exposure to stress. Furthermore, although prenatally stressed rats had significantly higher pituitary-adrenal hormone concentrations than control animals, the post-stress temporal patterns of decline in ACTH and corticosterone levels were similar between groups. Results suggest that throughout the preweaning period, prenatal stress produces an HPA system that functions in a manner similar to that of controls but at an increased level.

  2. Perioperative management of the hypothalamic-pituitary-adrenal axis in patients with pituitary adenomas: an Australasian survey.

    Science.gov (United States)

    Joseph, S P; Ho, J T; Doogue, M P; Burt, M G

    2012-10-01

    There is limited consensus regarding optimal glucocorticoid administration for pituitary surgery to prevent a potential adrenal crisis. To assess the investigation and management of the hypothalamic-pituitary-adrenal (HPA) axis in patients undergoing trans-sphenoidal hypophysectomy in Australasia. A questionnaire was sent to one endocrinologist at each of 18 centres performing pituitary surgery in Australasia. Using hypothetical case vignettes, respondents were asked to describe their investigation and management of the HPA axis for a patient with a: non-functioning macroadenoma and intact HPA axis, non-functioning macroadenoma and HPA deficiency and growth hormone secreting microadenoma undergoing trans-sphenoidal hypophysectomy. Responses were received from all 18 centres. Seventeen centres assess the HPA axis preoperatively by measuring early morning cortisol or a short synacthen test. Preoperative evaluation of the HPA status influenced glucocorticoid prescription by 10 centres, including 2/18 who would not prescribe perioperative glucocorticoids for a patient with a macroadenoma and an intact HPA axis. Tumour size influenced glucocorticoid prescribing patterns at 7/18 centres who prescribe a lower dose or no glucocorticoids for a patient with a microadenoma. Choice of investigations for definitive postoperative assessment of the HPA axis varied with eight centres requesting an insulin tolerance test, four centres a 250 µg short synacthen test and six centres requesting other tests. There is wide variability in the investigation and management of perioperative glucocorticoid requirements for patients undergoing pituitary surgery in Australasia. This may reflect limited evidence to define optimal management and that further well-designed studies are needed. © 2011 The Authors; Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

  3. Stress responsiveness of the hypothalamic-pituitary-adrenal axis: age-related features of the vasopressinergic regulation

    Directory of Open Access Journals (Sweden)

    Nadezhda Dmitrievna Goncharova

    2013-03-01

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH and arginine vasopressin (AVP into pituitary portal system; CRH and AVP stimulate ACTH release through specific G protein-coupled membrane receptors on pituitary corticotrophs, CRH1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates.

  4. Hair cortisol as a hypothalamic-pituitary-adrenal axis biomarker in pregnant women with asthma: a retrospective observational study.

    Science.gov (United States)

    Smy, Laura; Shaw, Kaitlyn; Amstutz, Ursula; Smith, Anne; Berger, Howard; Carleton, Bruce; Koren, Gideon

    2016-07-20

    Cortisol is a hormone involved in many physiological functions including fetal maturation and epigenetic programming during pregnancy. This study aimed to use hair cortisol as a biomarker of chronic inhaled corticosteroid (ICS) exposure and assess the potential effects of asthma on the hypothalamic-pituitary-adrenal (HPA) axis in pregnant women. We hypothesized that pregnant women with asthma treated with ICS would exhibit lower hair cortisol concentrations, indicative of adrenal suppression, compared to women with asthma not using ICS and women who do not have asthma. We performed an observational retrospective cohort study. Hair samples were analyzed from pregnant women with asthma, with (n = 56) and without (n = 31) ICS treatment, and pregnant women without asthma (n = 31). Hair samples were segmented based on the growth rate of 1 cm/month and analyzed by enzyme immunoassay to provide cortisol concentrations corresponding to preconception, trimesters 1-3, and postpartum. Hair cortisol concentrations were compared within and among the groups using non-parametric statistical tests. Hair cortisol concentrations increased across trimesters for all three groups, but this increase was dampened in women with asthma (P = 0.03 for Controls vs. ICS Treated and Controls vs. No ICS). ICS Treated women taking more than five doses per week had hair cortisol concentrations 47 % lower in third trimester than Controls. Linear regression of the third trimester hair cortisol results identified asthma as a significant factor when comparing consistent ICS use or asthma as the predictor (F(1, 25) = 9.7, P = 0.005, R(2) adj = 0.257). Hair cortisol successfully showed the expected change in cortisol over the course of pregnancy and may be a useful biomarker of HPA axis function in pregnant women with asthma. The potential impact of decreased maternal cortisol in women with asthma on perinatal outcomes remains to be determined.

  5. Effects of Carbenoxolone on the Canine Pituitary-Adrenal Axis.

    Science.gov (United States)

    Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Nakamura, Yumi; Koyama, Hidekazu

    2015-01-01

    Cushing's disease caused by pituitary corticotroph adenoma is a common endocrine disease in dogs. A characteristic biochemical feature of corticotroph adenomas is their relative resistance to suppressive negative feedback by glucocorticoids. The abnormal expression of 11beta-hydroxysteroid dehydrogenase (11HSD), which is a cortisol metabolic enzyme, is found in human and murine corticotroph adenomas. Our recent studies demonstrated that canine corticotroph adenomas also have abnormal expression of 11HSD. 11HSD has two isoforms in dogs, 11HSD type1 (HSD11B1), which converts cortisone into active cortisol, and 11HSD type2 (HSD11B2), which converts cortisol into inactive cortisone. It has been suggested that glucocorticoid resistance in corticotroph tumors is related to the overexpression of HSD11B2. Therefore it was our aim to investigate the effects of carbenoxolone (CBX), an 11HSD inhibitor, on the healthy dog's pituitary-adrenal axis. Dogs were administered 50 mg/kg of CBX twice each day for 15 days. During CBX administration, no adverse effects were observed in any dogs. The plasma adrenocorticotropic hormone (ACTH), and serum cortisol and cortisone concentrations were significantly lower at day 7 and 15 following corticotropin releasing hormone stimulation. After completion of CBX administration, the HSD11B1 mRNA expression was higher, and HSD11B2 mRNA expression was significantly lower in the pituitaries. Moreover, proopiomelanocortin mRNA expression was lower, and the ratio of ACTH-positive cells in the anterior pituitary was also significantly lower after CBX treatment. In adrenal glands treated with CBX, HSD11B1 and HSD11B2 mRNA expression were both lower compared to normal canine adrenal glands. The results of this study suggested that CBX inhibits ACTH secretion from pituitary due to altered 11HSD expressions, and is potentially useful for the treatment of canine Cushing's disease.

  6. Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

    Science.gov (United States)

    Demiraslan, Hayati; Şimşek, Yasin; Tanriverdi, Fatih; Doğanay, Mehmet; Keleştemur, Hasan Fahrettin

    2015-01-01

    To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

  7. Can variation in hypothalamic-pituitary-adrenal (HPA-axis activity explain the relationship between depression and cognition in bipolar patients?

    Directory of Open Access Journals (Sweden)

    Marieke J van der Werf-Eldering

    Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning.In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition.As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

  8. Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity

    Directory of Open Access Journals (Sweden)

    Marcella Balbo

    2010-01-01

    Full Text Available The daily rhythm of cortisol secretion is relatively stable and primarily under the influence of the circadian clock. Nevertheless, several other factors affect hypothalamo-pituitary-adrenal (HPA axis activity. Sleep has modest but clearly detectable modulatory effects on HPA axis activity. Sleep onset exerts an inhibitory effect on cortisol secretion while awakenings and sleep offset are accompanied by cortisol stimulation. During waking, an association between cortisol secretory bursts and indices of central arousal has also been detected. Abrupt shifts of the sleep period induce a profound disruption in the daily cortisol rhythm, while sleep deprivation and/or reduced sleep quality seem to result in a modest but functionally important activation of the axis. HPA hyperactivity is clearly associated with metabolic, cognitive and psychiatric disorders and could be involved in the well-documented associations between sleep disturbances and the risk of obesity, diabetes and cognitive dysfunction. Several clinical syndromes, such as insomnia, depression, Cushing's syndrome, sleep disordered breathing (SDB display HPA hyperactivity, disturbed sleep, psychiatric and metabolic impairments. Further research to delineate the functional links between sleep and HPA axis activity is needed to fully understand the pathophysiology of these syndromes and to develop adequate strategies of prevention and treatment.

  9. 注意力缺陷多动障碍儿童下丘脑-垂体-肾上腺轴的功能研究%Function of the hypothalamus-pituitary-adrenal axis in children with attention deficit hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    陈燕惠; 陈辉; 刘艳艳; 林桂秀; 韦立新; 陈丹玲

    2009-01-01

    目的 通过研究注意力缺陷多动障碍(ADHD)儿童下丘脑-垂体-肾上腺轴(HPA)的功能状态,探讨HPA轴在ADHD发生中的作用.方法 128例6~14岁ADHD男童根据DSM-IV ADHD诊断和分型标准,其中注意缺陷为主型(ADHD-I)44例,多动-冲动为主型(ADHD-HI)32例,混合型(ADHD-C)52例,对照组为年龄匹配健康男童30名,于8:00 am空腹采血.分别采用全自动微粒酶免疫分析法及电化学发光法检测血浆皮质醇及促肾上腺皮质激素(ACTH),智力测验采用瑞文标准推理测验.结果 ADHD组IQ(84.5±11.3)低于对照组(94.6±12.4,P<0.01),ADHD 3个亚型组间比较差异有显著性(P<0.01),ADHD-I和ADHD-C两个亚组IQ水低于对照组(P<0.01),ADHD-HI组与对照组比较差异无显著性.ADHD组血浆皮质醇水平(226.5±129.1 mnol/L)较对照组(384.5±141.4 nmol/L)明显降低(P<0.01),ADHD-HI组(154.4±71.6 nmol/L)下降程度较ADHD-I组(219.4±117.7 nmol/L)及ADHD-C组(258.3±136.4 nmol/L)为著(P<0.01),而ADHD各组血浆ACTH水平与对照组比较差异无显著性.结论 在非应激状态下ADHD儿童存在着HPA轴调节功能障碍,这可能系HPA轴低反应性所致.低血浆皮质醇对认知行为影响较小,而与注意缺陷、多动、冲动行为关系更为密切.%Objective To study the function of the hypothalamus-pituitary-adrenal (HPA) axis in children with attention deficit hyperactivity disorder (ADHD). Methods One hundred and twenty-eight boys with ADHD at ages of 6 to 14 years were enrolled. The diagnosis and grouping of ADHD were based on the Diagnostic and Statistical Manual of Mental Disorders ( DSM-IV) : ADHD-predominantly inattention type (ADHD-I, n =44), ADHD-predominantly hyperactive impulsivetype (ADHD-HI, n = 32) and ADHD-combined type (ADHD-C, n =52). Thirty healthy boys served as the control group. Plasma levels of cortisol and adrenocorticotropic hormone ( ACTH) were measured by automatic particle enzyme immunoassay and electrochemiluminescence

  10. Longitudinal changes in pituitary-adrenal hormones in South African women with burnout.

    Science.gov (United States)

    Moch, Shirra L; Panz, Vanessa R; Joffe, Barry I; Havlik, Ivan; Moch, Jonathan D

    2003-08-01

    The authors' goal was to document baseline pituitary-adrenal hormonal and related metabolic variables in 16 female patients with burnout. Then, following stress management intervention, to compare the changes with an equal number of untreated control subjects. At monthly intervals for 4 mo, 24-h urine samples were obtained for determination of free cortisol excretion. In addition, fasting blood samples were analyzed for levels of cortisol, dehydroepiandrosterone sulfate (DHEAS), ACTH, aldosterone, and catecholamines. Other biochemical measurements included growth hormone, prolactin, insulin, glucose, and lipid components. The Maslach Burnout Inventory, General Health Questionnaire- 28, and Zung depression rating scale were completed on each consecutive visit. The most striking finding was the reduction of urine free-cortisol excretion in the patients compared with controls. Initial urinary free cortisol was significantly lower in the patients (mean +/- SEM = 47.2 +/- 11.0 vs 79.0 +/- 6.8 nmol/L, p = 0.02) and remained significantly reduced at 4 mo (mean +/- SEM = 44.0 +/- 6.1 vs 91.1 +/- 8.8 nmol/L, p = 0.0001). There were no significant changes in the other hormonal and biochemical data. We conclude that there is functional hypocortisolism in burnout, which is not immediately restored on stress management intervention despite clinical and psychological improvement.

  11. Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome.

    Science.gov (United States)

    Armario, Antonio

    2010-07-01

    Addictive drugs (opiates, ethanol, cannabinoids (CBs), nicotine, cocaine, amphetamines) induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, with the subsequent release of adrenocorticotropic hormone and glucocorticoids. The sequence of events leading to HPA activation appears to start within the brain, suggesting that activation is not secondary to peripheral homeostatic alterations. The precise neurochemical mechanisms and brain pathways involved are markedly dependent on the particular drug, although it is assumed that information eventually converges into the hypothalamic paraventricular nucleus (PVN). Whereas some drugs may act on the hypothalamus or directly within PVN neurons (i.e. ethanol), others exert their primary action outside the PVN (i.e. CBs, nicotine, cocaine). Corticotropin-releasing hormone (CRH) has a critical role in most cases, but the changes in c-fos and CRH gene expression in the PVN also reveal differences among drugs. More studies are needed to understand how addictive drugs act on this important neuroendocrine system and their functional consequences. Copyright 2010 Elsevier Ltd. All rights reserved.

  12. Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

    Directory of Open Access Journals (Sweden)

    A.M.O. Leal

    1997-12-01

    Full Text Available Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or" zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states

  13. Sex-dependent effects of restraint on nociception and pituitary-adrenal hormones in the rat.

    Science.gov (United States)

    Aloisi, A M; Steenbergen, H L; van de Poll, N E; Farabollini, F

    1994-05-01

    The sex-dependent effects of acute restraint (RT) on nociceptive and pituitary-adrenal responses were investigated in the rat. In a first experiment, the effect of 30 min RT on pain sensitivity was evaluated through repeated use of the tail withdrawal test during and after treatment. RT induced an increase in the nociceptive threshold, i.e., analgesia, in males and females, but the duration and time-course of this effect varied between sexes. The latencies returned to approximately control values in females in the second half of RT, but in males they remained higher for the whole period of RT and immediately afterwards. Twenty-four hours later, males displayed longer latencies than controls in response to simple reexposure to the environment. In a second experiment, ACTH and corticosterone plasma levels were measured immediately after 15 or 30 min of RT. ACTH and corticosterone were higher in restrained animals than in controls after both periods of treatment, and in both sexes; however, females showed higher basal and stress corticosterone levels than males. The role played by corticosteroids in the nociceptive responses of the two sexes is discussed.

  14. Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis

    NARCIS (Netherlands)

    Dekkers, J. C.; Geenen, R.; Godaert, G. L.; Glaudemans, K. A.; Lafeber, F. P.; van Doornen, L. J.; Bijlsma, J. W.

    2001-01-01

    There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1

  15. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  16. Bile acids modulate glucocorticoid metabolism and the hypothalamic-pituitary-adrenal axis in obstructive jaundice

    DEFF Research Database (Denmark)

    McNeilly, Alison D; Macfarlane, David P; O'Flaherty, Emmett

    2010-01-01

    Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5bet...

  17. Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use: the TRAILS study

    NARCIS (Netherlands)

    Prince van Leeuwen, A.; Creemers, H.E.; Greaves-Lord, K.; Verhulst, F.C.; Ormel, J.; Huizink, A.C.

    2011-01-01

    Aims: To investigate the relationship of life-time and repeated cannabis use with hypothalamic-pituitary-adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents. Design: Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco

  18. Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use : the TRAILS study

    NARCIS (Netherlands)

    van Leeuwen, Andrea Prince; Creemers, Hanneke E.; Greaves-Lord, Kirstin; Verhulst, Frank C.; Ormel, Johan; Huizink, Anja C.

    Aims To investigate the relationship of life-time and repeated cannabis use with hypothalamic-pituitary-adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents. Design Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco use

  19. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    NARCIS (Netherlands)

    Meerlo, P; Koehl, M; van der Borght, K; Turek, FW

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine

  20. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  1. The recovery of the hypothalamo-pituitary-adrenal axis after transsphenoidal operation in three patients with Cushing's disease

    International Nuclear Information System (INIS)

    Lamberts, S.W.J.; Klijn, J.G.M.; Jong, F.H. de; Birkenhager, J.C.

    1981-01-01

    The recovery of the hypothalamo-pituitary-adrenal axis after selective transsphenoidal adenomectomy was studied in 3 patients with Cushing's disease by measuring basal plasma ACTH and cortisol concentrations, cortisol secretion rate, the diurnal rhythm of cortisol, and the reaction of cortisol to lysine vasopressin (LVP), of compound S to metyrapone and of cortisol and growth hormone to an insulin-induced hypoglycaemia. The third patient had been treated previously by external pituitary irradiation. In 2 patients basal plasma ACTH levels returned within normal values before plasma cortisol, but no supra-physiological plasma concentrations of ACTH were seen as has been observed after withdrawal of exogenous glucocorticoids. With regard to the different stimulation tests: at first the normal reaction of plasma cortisol to LVP returned after 3 months, at the same time as the restoration of growth hormone secretion in response to hypoglycaemia. A normalization of the reaction to metyrapone was seen thereafter while finally the reaction of cortisol to an insulin-induced hypoglycaemia and the diurnal rhythm of plasma cortisol returned 15 to 18 months after operation in the first patient and after 12 months in the second patient. Selective adenomectomy had also been carried out in the third patient, as evidenced by normal TSH, LH and FSH secretion. Hypocortisolism, and a deficient ACTH and growth hormone secretion in response to the stimuli mentioned, however, did not normalize up till 22 months after operation. The restoration of the hypothalamo-pituitary-adrenal axis after selective pituitary adenomectomy in Cushing's disease was prevented in this patient by prior external pituitary irradiation. (author)

  2. Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder.

    Science.gov (United States)

    Martinac, Marko; Pehar, Davor; Karlović, Dalibor; Babić, Dragan; Marcinko, Darko; Jakovljević, Miro

    2014-03-01

    Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but

  3. Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity.

    Science.gov (United States)

    Naert, G; Zussy, C; Tran Van Ba, C; Chevallier, N; Tang, Y-P; Maurice, T; Givalois, L

    2015-11-01

    Brain-derived neurotrophic factor (BDNF) appears to be highly involved in hypothalamic-pituitary-adrenal (HPA) axis regulation during adulthood, playing an important role in homeostasis maintenance. The present study aimed to determine the involvement of BDNF in HPA axis activity under basal and stress conditions via partial inhibition of this endogenous neurotrophin. Experiments were conducted in rats and mice with two complementary approaches: (i) BDNF knockdown with stereotaxic delivery of BDNF-specific small interfering RNA (siRNA) into the lateral ventricle of adult male rats and (ii) genetically induced knockdown (KD) of BDNF expression specifically in the central nervous system during the first ontogenesis in mice (KD mice). Delivery of siRNA in the rat brain decreased BDNF levels in the hippocampus (-31%) and hypothalamus (-35%) but not in the amygdala, frontal cortex and pituitary. In addition, siRNA induced no change of the basal HPA axis activity. BDNF siRNA rats exhibited decreased BDNF levels and concomitant altered adrenocortoctrophic hormone (ACTH) and corticosterone responses to restraint stress, suggesting the involvement of BDNF in the HPA axis adaptive response to stress. In KD mice, BDNF levels in the hippocampus and hypothalamus were decreased by 20% in heterozygous and by 60% in homozygous animals compared to wild-type littermates. Although, in heterozygous KD mice, no significant change was observed in the basal levels of plasma ACTH and corticosterone, both hormones were significantly increased in homozygous KD mice, demonstrating that robust cerebral BDNF inhibition (60%) is necessary to affect basal HPA axis activity. All of these results in both rats and mice demonstrate the involvement and importance of a robust endogenous pool of BDNF in basal HPA axis regulation and the pivotal function of de novo BDNF synthesis in the establishment of an adapted response to stress. © 2015 British Society for Neuroendocrinology.

  4. Model-based therapeutic correction of hypothalamic-pituitary-adrenal axis dysfunction.

    Directory of Open Access Journals (Sweden)

    Amos Ben-Zvi

    2009-01-01

    Full Text Available The hypothalamic-pituitary-adrenal (HPA axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS. At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning.

  5. The hypothalamic- pituitary -adrenal -leptin axis and metabolic health: A systems approach to resilience, robustness and control

    NARCIS (Netherlands)

    Aschbacher, K.; Rodriguez-Fernandez, M.; Wietmarschen, H. van; Tomiyama, A.; Jain, S.; Epel, E.; Doyle III, F.J.; Greef, J. van der

    2014-01-01

    Glucocorticoids contribute to obesity and metabolic syndrome; however, the mechanisms are unclear, and prognostic measures are unavailable. A systems level understanding of the hypothalamic-pituitary-adrenal (HPA) -leptin axis may reveal novel insights. Eighteen obese premenopausal women provided

  6. Hypothalamic-Pituitary-Adrenal Axis Dysfunction and Illness Progression in Bipolar Disorder

    Science.gov (United States)

    Vasconcelos-Moreno, Mirela Paiva; Gubert, Carolina; dos Santos, Bárbara Tietböhl Martins Quadros; Sartori, Juliana; Eisele, Bárbara; Ferrari, Pamela; Fijtman, Adam; Rüegg, Joëlle; Gassen, Nils Christian; Kapczinski, Flávio; Rein, Theo; Kauer-Sant’Anna, Márcia

    2015-01-01

    Background: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. Methods: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). Results: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. Conclusions: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness. PMID:25522387

  7. Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress

    Science.gov (United States)

    Meerlo, P.; Koehl, M.; van der Borght, K.; Turek, F. W.

    2002-01-01

    Chronic sleep restriction is an increasing problem in many countries and may have many, as yet unknown, consequences for health and well being. Studies in both humans and rats suggest that sleep deprivation may activate the hypothalamic-pituitary-adrenal (HPA) axis, one of the main neuroendocrine stress systems. However, few attempts have been made to examine how sleep loss affects the HPA axis response to subsequent stressors. Furthermore, most studies applied short-lasting total sleep deprivation and not restriction of sleep over a longer period of time, as often occurs in human society. Using the rat as our model species, we investigated: (i) the HPA axis activity during and after sleep deprivation and (ii) the effect of sleep loss on the subsequent HPA response to a novel stressor. In one experiment, rats were subjected to 48 h of sleep deprivation by placing them in slowly rotating wheels. Control rats were placed in nonrotating wheels. In a second experiment, rats were subjected to an 8-day sleep restriction protocol allowing 4 h of sleep each day. To test the effects of sleep loss on subsequent stress reactivity, rats were subjected to a 30-min restraint stress. Blood samples were taken at several time points and analysed for adrenocorticotropic hormone (ACTH) and corticosterone. The results show that ACTH and corticosterone concentrations were elevated during sleep deprivation but returned to baseline within 4 h of recovery. After 1 day of sleep restriction, the ACTH and corticosterone response to restraint stress did not differ between control and sleep deprived rats. However, after 48 h of total sleep deprivation and after 8 days of restricted sleep, the ACTH response to restraint was significantly reduced whereas the corticosterone response was unaffected. These results show that sleep loss not only is a mild activator of the HPA axis itself, but also affects the subsequent response to stress. Alterations in HPA axis regulation may gradually appear under

  8. [Correlations between the hypothalamo-pituitary-adrenal axis and the metabolic syndrome].

    Science.gov (United States)

    Góth, Miklós; Hubina, Erika; Korbonits, Márta

    2005-01-09

    The metabolic syndrome has several similarities with Cushing's syndrome (impaired glucose tolerance, hypertension, dyslipidemia, central obesity) suggesting that abnormalities in the regulation of the hypothalamic-pituitary-adrenal axis may have a link with the metabolic syndrome. Several studies suggested an association between the clinical signs of the metabolic syndrome and the increased hypothalamic-pituitary-adrenal axis activity based on increased cortisol concentration at 09.00 a.m. and increased cortisol response to corticotropin. According to the Barker hypothesis the fetal malnutrition could determine adult cardiovascular diseases (coronary heart disease, hypertension), some endocrine and metabolic disorders (obesity, type 2 diabetes and hyperlipidemia). The suggested mechanism of the phenomenon is that the suboptimal fetal nutrition results in glucocorticoid overproduction. The 11beta-hydroxysteroid dehydrogenase (converts biological inactive cortisone to cortisol and vice versa) is an important enzyme in cortisol metabolism. The increased expression of 11beta-hydroxysteroid dehydrogenase type 1 in fat tissue could lead to central obesity and impaired glucose tolerance. The hypothesis that increased corticotropin-releasing hormone production drives the overactive hypothalamo-pituitary-adrenal axis was not proven. Further investigations are needed to identify additional pathogenetic factors and to find new therapeutic possibilities.

  9. Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

    Science.gov (United States)

    van Bodegom, Miranda; Homberg, Judith R.; Henckens, Marloes J. A. G.

    2017-01-01

    Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA

  10. The hypothalomo-pituitary-adrenal system in liquidators of the Chernobyl accident consequences: summing up the seven-year follow-up

    International Nuclear Information System (INIS)

    Mitryaeva, N.A.

    1996-01-01

    The function of the hypothalamo-pituitary-adrenal system was studied over time (1986-1993) in 500 liquidators of the Chernobyl accident consequences with external exposure dose of 250 mSv. The concentrations of hydrocortisone, ACTH, and β-endorphine in the peripheral blood were radioimmunoassayed at rest and during functional loading. Glucocorticoids were measured in the urine by thin-layer chromatography. The number of glucocorticoid receptors in peripheral blood lymphocytes was assessed by the radioreceptor method. Stable hypercorticalism in the presence of reduced β-endorphine and increased ACTH levels was observed in the majority of examinees during the first years after the accident. Six years after the accident the above parameters were normal at rest, although during functional loading disorders in the reserve potential of the hypothalamo-pituitary-adrenal system were observed, which deteriorated its adaptation to changes int he environment. It is advisable to single out high risk groups of subjects with disadaptation disorders for regular check-ups among the liquidators. 10 refs.; 3 figs.; 4 tabs

  11. Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

    Directory of Open Access Journals (Sweden)

    Jong-Ho Lee

    2014-06-01

    Full Text Available BackgroundThis study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF during adolescence on the adverse behavioral outcome of neonatal maternal separation.MethodsMale Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS or left undisturbed (nonhandled, NH. Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF. Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay.ResultsDaily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it.ConclusionProlonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA axis.

  12. Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review.

    Science.gov (United States)

    Incollingo Rodriguez, Angela C; Epel, Elissa S; White, Megan L; Standen, Erin C; Seckl, Jonathan R; Tomiyama, A Janet

    2015-12-01

    Although there is substantial evidence of differential hypothalamic-pituitary-adrenal (HPA) axis activity in both generalized and abdominal obesity, consistent trends in obesity-related HPA axis perturbations have yet to be identified. To systematically review the existing literature on HPA activity in obesity, identify possible explanations for inconsistencies in the literature, and suggest methodological improvements for future study. Included papers used Pubmed, Google Scholar, and the University of California Library search engines with search terms body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, sagittal diameter, abdominal versus peripheral body fat distribution, body fat percentage, DEXA, abdominal obesity, and cortisol with terms awakening response, slope, total daily output, reactivity, feedback sensitivity, long-term output, and 11β-HSD expression. Empirical research papers were eligible provided that they included at least one type of obesity (general or abdominal), measured at least one relevant cortisol parameter, and a priori tested for a relationship between obesity and cortisol. A general pattern of findings emerged where greater abdominal fat is associated with greater responsivity of the HPA axis, reflected in morning awakening and acute stress reactivity, but some studies did show underresponsiveness. When examined in adipocytes, there is a clear upregulation of cortisol output (due to greater expression of 11β-HSD1), but in hepatic tissue this cortisol is downregulated. Overall obesity (BMI) appears to also be related to a hyperresponsive HPA axis in many but not all studies, such as when acute reactivity is examined. The reviewed literature contains numerous inconsistencies and contradictions in research methodologies, sample characteristics, and results, which partially precluded the development of clear and reliable patterns of dysregulation in each investigated cortisol parameter. The literature to date is

  13. Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder

    NARCIS (Netherlands)

    Kallen, V. L.; Tulen, J. H. M.; Utens, E. M. W. J.; Treffers, P. D. A.; de Jong, F. H.; Ferdinand, R. F.

    2008-01-01

    The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were

  14. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

    Directory of Open Access Journals (Sweden)

    Jereme G. Spiers

    2015-01-01

    Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

  15. Relation of anterior cingulate cortex metabolic characteristics to hypothalamic-pituitary -adrenal axis functional in depressive patients: A 1H-magnetic resonance spectroscope study%抑郁症患者前扣带回代谢特征与下丘脑-垂体-肾上腺轴活性水平的氢质子波谱研究

    Institute of Scientific and Technical Information of China (English)

    彭红军; 李凌江; 贺忠

    2013-01-01

    目的:用磁共振氢质子波谱的方法探讨抑郁症患者前扣带回(ACC)代谢特征与下丘脑-垂体-肾上腺轴(HPA轴)功能活性的关系.方法:选取68例符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的抑郁症患者及30例正常对照,采用磁共振扫描检测前扣带回氢质子波谱N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、谷氨酸复合物(Glx)及肌醇(mI)等5种代谢物的含量,计算NAA/Cr、Glx/Cr、Cho/Cr、mI/Cr比值.用皮质醇醒觉反应(CAR)检测HPA轴活性,定义为连续2天醒后30 min觉醒时皮质醇浓度差值的均值.根据抑郁症组HPA轴活性均值将抑郁症组分为HPA轴高活性组35例(>6.6 nmol/L)及HPA轴低活性组33例(≤6.6nmol/L).结果:与正常对照相比,抑郁症患者两侧ACC的NAA/Cr[左侧(1.6±0.5)vs.(2.0±0.5),右侧(1.7±0.4)vs.(2.2±0.5)]和Glx/Cr[左侧(0.1±0.03) vs.(0.1 ±0.03),右侧(0.1±0.01) vs.(0.2±0.04)]较低(均P<0.05),右侧Cho/Cr较高[(1.5±0.9)vs.(0.9±0.3),P<0.01];与低HPA轴活性组相比,高HPA轴活性组左侧NAA/Cr较低[(1.6±0.4)vs.(1.7±0.4),P<0.05],右侧Cho/Cr较高[(1.7±0.2)vs.(1.2±0.1),P<0.01].结论:抑郁症患者可能存在双侧前扣带回N-乙酰天门冬氨酸、谷氨酸及胆碱等代谢紊乱,高HPA轴活性可能与部分代谢物质存在相关.%Objective:To investigate the relationship between metabolic characteristics and hypothalamic-pituitary-adrenal axis (HPA) in anterior cingulate lobes (ACC) in depressive patients with 1H-magnetic resonance spectroscope (1H-MRS).Methods:Totally 68 patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-Ⅳ) and 30 healthy controls were scanned by magnetic resonance and 1 H-MRS data were collected.The bilateral anterior cingulate lobes were selected as region of interest.The levels of N-acetyl aspartic acid (NAA),choline (Cho),creatine (Cr),glutamic acid

  16. The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats.

    Science.gov (United States)

    Merlo, Eduardo; Podratz, Priscila L; Sena, Gabriela C; de Araújo, Julia F P; Lima, Leandro C F; Alves, Izabela S S; Gama-de-Souza, Letícia N; Pelição, Renan; Rodrigues, Lívia C M; Brandão, Poliane A A; Carneiro, Maria T W D; Pires, Rita G W; Martins-Silva, Cristina; Alarcon, Tamara A; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

    2016-08-01

    Tributyltin chloride (TBT) is an environmental contaminant that is used as a biocide in antifouling paints. TBT has been shown to induce endocrine-disrupting effects. However, studies evaluating the effects of TBT on the hypothalamus-pituitary-adrenal (HPA) axis are especially rare. The current study demonstrates that exposure to TBT is critically responsible for the improper function of the mammalian HPA axis as well as the development of abnormal morphophysiology in the pituitary and adrenal glands. Female rats were treated with TBT, and their HPA axis morphophysiology was assessed. High CRH and low ACTH expression and high plasma corticosterone levels were detected in TBT rats. In addition, TBT leads to an increased in the inducible nitric oxide synthase protein expression in the hypothalamus of TBT rats. Morphophysiological abnormalities, including increases in inflammation, a disrupted cellular redox balance, apoptosis, and collagen deposition in the pituitary and adrenal glands, were observed in TBT rats. Increases in adiposity and peroxisome proliferator-activated receptor-γ protein expression in the adrenal gland were observed in TBT rats. Together, these data provide in vivo evidence that TBT leads to functional dissociation between CRH, ACTH, and costicosterone, which could be associated an inflammation and increased of inducible nitric oxide synthase expression in hypothalamus. Thus, TBT exerts toxic effects at different levels on the HPA axis function.

  17. Effects of oral megestrol acetate administration on the hypothalamic-pituitary-adrenal axis of male bottlenose dolphins (Tursiops truncatus).

    Science.gov (United States)

    Houser, Dorian S; Champagne, Cory D; Jensen, Eric D; Smith, Cynthia R; Cotte, Lara S; Meegan, Jenny M; Booth, Rebecca K; Wasser, Samuel K

    2017-07-15

    OBJECTIVE To evaluate the impact of oral megestrol acetate (MA) administration on adrenal function in male bottlenose dolphins (Tursiops truncatus). DESIGN Serial cross-sectional study. ANIMALS 8 adult male dolphins, all of which were receiving MA at various daily doses (range, 0 to 60 mg, PO) for the control of reproductive behavior. PROCEDURES Blood samples were collected every 2 weeks for 1 year from dolphins trained to voluntarily provide them. Cortisol, ACTH, and other hormone concentrations were measured in serum or plasma via radioimmunoassay or ELISA. Fecal samples, also provided by dolphins voluntarily, were assayed for glucocorticoid metabolite concentrations. Effects of daily MA dose on hormone concentrations were evaluated. RESULTS Daily MA doses as low as 10 mg strongly suppressed cortisol secretion in nearly all dolphins, and except for a single measurement, no dolphin had measurable serum concentrations at doses ≥ 20 mg. Variations in serum cortisol concentration were unrelated to season but were directly related to ACTH concentrations, suggesting primary effects upstream of the adrenal gland. Cessation of MA administration resulted in almost immediate restoration of measurable serum cortisol concentrations, although concentrations continued to rise in a few dolphins over the following weeks to months. CONCLUSIONS AND CLINICAL RELEVANCE Caution should be exercised when administering MA to control reproductive behavior in male dolphins. Because the hypothalamic-pituitary-adrenal axis appeared to be sensitive to even small doses of MA in dolphins, duration of treatment may be the most critical consideration.

  18. Relational victimization, friendship, and adolescents' hypothalamic-pituitary-adrenal axis responses to an in vivo social stressor.

    Science.gov (United States)

    Calhoun, Casey D; Helms, Sarah W; Heilbron, Nicole; Rudolph, Karen D; Hastings, Paul D; Prinstein, Mitchell J

    2014-08-01

    Adolescents' peer experiences may have significant associations with biological stress-response systems, adding to or reducing allostatic load. This study examined relational victimization as a unique contributor to reactive hypothalamic-pituitary-adrenal (HPA) axis responses as well as friendship quality and behavior as factors that may promote HPA recovery following a stressor. A total of 62 adolescents (ages 12-16; 73% female) presenting with a wide range of life stressors and adjustment difficulties completed survey measures of peer victimization and friendship quality. Cortisol samples were collected before and after a lab-based interpersonally themed social stressor task to provide measures of HPA baseline, reactivity, and recovery. Following the stressor task, adolescents discussed their performance with a close friend; observational coding yielded measures of friends' responsiveness. Adolescents also reported positive and negative friendship qualities. Results suggested that higher levels of adolescents' relational victimization were associated with blunted cortisol reactivity, even after controlling for physical forms of victimization and other known predictors of HPA functioning (i.e., life stress or depressive symptoms). Friendship qualities (i.e., low negative qualities) and specific friendship behaviors (i.e., high levels of responsiveness) contributed to greater HPA regulation; however, consistent with theories of rumination, high friend responsiveness in the context of high levels of positive friendship quality contributed to less cortisol recovery. Findings extend prior work on the importance of relational victimization and dyadic peer relations as unique and salient correlates of adaptation in adolescence.

  19. Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

    Directory of Open Access Journals (Sweden)

    Alya Annabi

    2015-11-01

    Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

  20. Differential effects of mineralocorticoid blockade on the hypothalamo-pituitary-adrenal axis in pregnant and nonpregnant ewes

    Science.gov (United States)

    Lingis, Melissa; Richards, Elaine M.

    2011-01-01

    During pregnancy, plasma ACTH and cortisol are chronically increased; this appears to occur through a reset of hypothalamo-pituitary-adrenal (HPA) activity. We have hypothesized that differences in mineralocorticoid receptor activity in pregnancy may alter feedback inhibition of the HPA axis. We tested the effect of MR antagonism in pregnant and nonpregnant ewes infused for 4 h with saline or the MR antagonist canrenoate. Pregnancy significantly increased plasma ACTH, cortisol, angiotensin II, and aldosterone. Infusion of canrenoate increased plasma ACTH, cortisol, and aldosterone in both pregnant and nonpregnant ewes; however, the temporal pattern of these responses differed between these two reproductive states. In nonpregnant ewes, plasma ACTH and cortisol transiently increased at 1 h of infusion, whereas in pregnant ewes the levels gradually increased and were significantly elevated from 2 to 4 h of infusion. MR blockade increased plasma aldosterone from 2 to 4 h in the pregnant ewes but only at 4 h in the nonpregnant ewes. In both pregnant and nonpregnant ewes, the increase in plasma aldosterone was significantly related to the timing and magnitude of the increase in plasma potassium. The results indicate a differential effect of MR activity in pregnant and nonpregnant ewes and suggest that the slow changes in ACTH, cortisol, and aldosterone are likely to be related to blockade of MR effects in the kidney rather than to effects of MR blockade in hippocampus or hypothalamus. PMID:21205934

  1. Hypothalamic-Pituitary-Adrenal Reactivity to Acute Stress: an Investigation into the Roles of Perceived Stress and Family Resources.

    Science.gov (United States)

    Obasi, Ezemenari M; Shirtcliff, Elizabeth A; Cavanagh, Lucia; Ratliff, Kristen L; Pittman, Delishia M; Brooks, Jessica J

    2017-11-01

    Rurally situated African Americans suffer from chronic exposure to stress that may have a deleterious effect on health outcomes. Unfortunately, research on potential mechanisms that underlie health disparities affecting the African American community has received limited focus in the scientific literature. This study investigated the relationship between perceived stress, family resources, and cortisol reactivity to acute stress. A rural sample of African American emerging adults (N = 60) completed a battery of assessments, the Trier Social Stress Test (TSST), and provided four samples of salivary cortisol: prior to receiving TSST instructions, prior to conducting the speech task, immediately following the TSST, and 15-20 min following the TSST. As predicted, cortisol levels increased in response to a controlled laboratory inducement of acute stress. Moreover, diminished levels of family resources were associated with blunted cortisol reactivity to acute stress. Of note, higher levels of perceived stress over the past month and being male were independently associated with lower levels of cortisol at baseline. Lack of family resources had a blunting relationship on the hypothalamic-pituitary-adrenal axis reactivity. These findings provide biomarker support for the relationship between family resources-an indicator associated with social determinants of health-and stress physiology within a controlled laboratory experiment. Identifying mechanisms that work toward explanation of within-group differences in African American health disparities is both needed and informative for culturally informed prevention and intervention efforts.

  2. Developmental changes in hypothalamus-pituitary-adrenal activity over the transition to adolescence: normative changes and associations with puberty.

    Science.gov (United States)

    Gunnar, Megan R; Wewerka, Sandi; Frenn, Kristin; Long, Jeffrey D; Griggs, Christopher

    2009-01-01

    Home baseline and laboratory stressor (Trier Social Stress Test for Children) measures of salivary cortisol were obtained from 82 participants (40 girls) aged 9, 11, 13, and 15 years. Measures of pubertal development, self-reported stress, parent reports of child depressive symptoms and fearful temperament, and cardiac measures of sympathetic and parasympathetic activity were also obtained. Significant increases in the home cortisol baselines were found with age and pubertal development. Cortisol stress reactivity differed by age group with 11-year-olds and 13-year-old boys showing blunted reactivity and 9-year-olds, 13-year-old girls, and 15-year-olds showing significant cortisol reactions. Cortisol reactivity correlated marginally with sexual maturation. Measures of sympathetic activity revealed increased sympathetic modulation with age. Higher sympathetic tone was associated with more fearful temperament, whereas greater cortisol reactivity was associated with more anxious and depressed symptoms for girls. The importance of these findings for the hypothesis that puberty-associated increases in hypothalamic-pituitary-adrenal axis activity heightens the risk of psychopathology is discussed.

  3. What can we know from pituitary-adrenal hormones about the nature and consequences of exposure to emotional stressors?

    Science.gov (United States)

    Armario, Antonio; Daviu, Núria; Muñoz-Abellán, Cristina; Rabasa, Cristina; Fuentes, Silvia; Belda, Xavier; Gagliano, Humberto; Nadal, Roser

    2012-07-01

    Exposure to stress induces profound physiological and behavioral changes in the organisms and some of these changes may be important regarding stress-induced pathologies and animal models of psychiatric diseases. Consequences of stress are dependent on the duration of exposure to stressors (acute, chronic), but also of certain characteristics such as intensity, controllability, and predictability. If some biological variables were able to reflect these characteristics, they could be used to predict negative consequences of stress. Among the myriad of physiological changes caused by stress, only a restricted number of variables appears to reflect the intensity of the situation, mainly plasma levels of ACTH and adrenaline. Peripheral hypothalamic-pituitary-adrenal (HPA) hormones (ACTH and corticosterone) are also able to reflect fear conditioning. In contrast, the activation of the HPA axis is not consistently related to anxiety as evaluated by classical tests such as the elevated plus-maze. Similarly, there is no consistent evidence about the sensitivity of the HPA axis to psychological variables such as controllability and predictability, despite the fact that: (a) lack of control over aversive stimuli can induce behavioral alterations not seen in animals which exert control, and (b) animals showed clear preference for predictable versus unpredictable stressful situations. New studies are needed to re-evaluate the relationship between the HPA axis and psychological stress characteristics using ACTH instead of corticosterone and taking advantages of our current knowledge about the regulation of this important stress system.

  4. Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress.

    Science.gov (United States)

    Sanchís-Ollé, Maria; Ortega-Sánchez, Juan A; Belda, Xavier; Gagliano, Humberto; Nadal, Roser; Armario, Antonio

    2017-04-03

    We have recently demonstrated that adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated exposure to a stressor does not follow the rules of habituation and can be fully expressed after a single experience with severe stressors. In the present work we tested the hypothesis that adaptation could be impaired if animals experience malaise during initial exposure to the stressor. To this end, animals were allowed to drink saccharin for 30min before being exposed for 3h to immobilization on boards (IMO), a severe stressor; then they were given either saline or lithium ip after the first hour of IMO. Stress-naïve rats followed exactly the same procedure except IMO. Exposure to IMO caused a strong activation of the HPA axis whereas the effect of lithium was modest. Both IMO and lithium administration resulted in conditioned taste aversion to saccharin when evaluated 4days later. When all animals were exposed to IMO 6days later, reduced HPA response and less impact on body weight was observed in the two groups previously exposed to IMO as compared with stress-naïve rats. Therefore, lithium administration during the first IMO exposure did not affect adaptation of the HPA axis and weight gain. These results indicate that malaise per se only weakly activated the HPA axis and argue against the hypothesis that signs of physical malaise during exposure to the stressor could impair HPA adaptation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Pituitary-Adrenal Axis in Prader Willi Syndrome

    Directory of Open Access Journals (Sweden)

    Olivia S. Edgar

    2016-01-01

    Full Text Available Purpose: Prader Willi syndrome (PWS is a rare genetic condition that has concurrent endocrinological insufficiencies. The presence of growth hormone deficiency has been well documented, but adrenal insufficiency (AI is not widely reported. A review was conducted to investigate its prevalence and relevance in PWS in both adults and children. Methodology: A literature review was performed with the search terms “Prader-Willi syndrome” and “adrenal insufficiency”. Results: The review found studies disagree on the prevalence and method of investigation of AI in PWS. Case studies demonstrate that patients with PWS are at risk of premature death, often secondary to respiratory infections. The possibility that this may be the result of the inability to mount an effective cortisol response has been studied, with some evidence confirming AI in PWS patients. Most reports agreed AI is present in PWS, however, Farholt et al. showed no HPA axis dysfunction in adults, suggesting that perhaps it is rare in adults, and children should be the focus of further studies. Conclusion: AI is present in some patients with PWS. Further research is required to ensure optimal treatment can be implemented and to prevent premature deaths related to adrenal insufficiency. Clinicians should have a low threshold for testing the adrenal axis and considering treatment for adrenal insufficiency in PWS patients.

  6. Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia The effects of stress on hypothalamic-pituitary-adrenal (HPA axis function in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Francesca L. Guest

    2013-01-01

    Full Text Available Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA. Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.

  7. Effects of Parental Depressive Symptoms on Child Adjustment Moderated by Hypothalamic Pituitary Adrenal Activity: Within- and between-Family Risk

    Science.gov (United States)

    Laurent, Heidemarie K.; Leve, Leslie D.; Neiderhiser, Jenae M.; Natsuaki, Misaki N.; Shaw, Daniel S.; Fisher, Philip A.; Marceau, Kristine; Harold, Gordon T.; Reiss, David

    2013-01-01

    Child hypothalamic pituitary adrenal (HPA) activity was investigated as a moderator of parental depressive symptom effects on child behavior in an adoption sample ("n" = 210 families). Adoptive parents' depressive symptoms and child internalizing and externalizing were assessed at 18, 27, and 54 months, and child morning and evening HPA…

  8. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2012-01-01

    Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

  9. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2015-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  10. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2017-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  11. Hypothalamic-pituitary-adrenal axis abnormalities in response to deletion of 11beta-HSD1 is strain-dependent

    NARCIS (Netherlands)

    Carter, R. N.; Paterson, J. M.; Tworowska, U.; Stenvers, D. J.; Mullins, J. J.; Seckl, J. R.; Holmes, M. C.

    2009-01-01

    Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity underlie differential vulnerability to neuropsychiatric and metabolic disorders, although the basis of this variation is poorly understood. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has previously been

  12. The relation between hypothalamic-pituitary-adrenal (HPA) axis activity and age of onset of alcohol use

    NARCIS (Netherlands)

    Evans, B.E.; Greaves-Lord, K.; Euser, A.S.; Franken, I.H.A.; Huizink, A.C.

    2012-01-01

    Aims: Hypothalamic-pituitary-adrenal (HPA) axis activity may prove a viable biomarker for identifying those susceptible to alcohol use disorders. The purpose of this study was to examine the relation of the age at which adolescents begin drinking with diurnal and stress cortisol. Design:

  13. Association analyses of depression and genes in the hypothalamus-pituitary-adrenal axis

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Krogh, Jesper; Nielsen, Marit Nyholm

    2017-01-01

    OBJECTIVE: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in depression. The aim was to investigate the potential association between depression and seven genes regulating or interfering with the HPA axis, including the gene encoding angiotensin converting enzyme......) was investigated. RESULTS: After quality control, 68 genetic variants were left for analyses. Four of nine variants within ACE were nominally associated with depression and a gene-wise association was likewise observed. However, none of the SNPs located within AVP, CRH, CRHR1, CRHR2, FKBP5 or NC3C1 were associated...... with depression. One nominally significant interaction, most likely due to chance, was identified. CONCLUSION: The results indicate that ACE could be a potential candidate gene for depression....

  14. Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

    DEFF Research Database (Denmark)

    Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A

    2015-01-01

    OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...

  15. Anatomy of melancholia: focus on hypothalamic-pituitary-adrenal axis overactivity and the role of vasopressin.

    LENUS (Irish Health Repository)

    Dinan, Timothy G

    2012-02-03

    Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA\\/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

  16. Role of the Hypothalamic-Pituitary-Adrenal Axis in Developmental Programming of Health and Disease

    Science.gov (United States)

    Xiong, Fuxia; Zhang, Lubo

    2012-01-01

    Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth. PMID:23200813

  17. Differential flatness properties and adaptive control of the hypothalamic-pituitary-adrenal axis model

    Science.gov (United States)

    Rigatos, Gerasimos

    2016-12-01

    It is shown that the model of the hypothalamic-pituitary-adrenal gland axis is a differentially flat one and this permits to transform it to the so-called linear canonical form. For the new description of the system's dynamics the transformed control inputs contain unknown terms which depend on the system's parameters. To identify these terms an adaptive fuzzy approximator is used in the control loop. Thus an adaptive fuzzy control scheme is implemented in which the unknown or unmodeled system dynamics is approximated by neurofuzzy networks and next this information is used by a feedback controller that makes the state variables (CRH - corticotropin releasing hormone, adenocortocotropic hormone - ACTH, cortisol) of the hypothalamic-pituitary-adrenal gland axis model converge to the desirable levels (setpoints). This adaptive control scheme is exclusively implemented with the use of output feedback, while the state vector elements which are not directly measured are estimated with the use of a state observer that operates in the control loop. The learning rate of the adaptive fuzzy system is suitably computed from Lyapunov analysis, so as to assure that both the learning procedure for the unknown system's parameters, the dynamics of the observer and the dynamics of the control loop will remain stable. The performed Lyapunov stability analysis depends on two Riccati equations, one associated with the feedback controller and one associated with the state observer. Finally, it is proven that for the control scheme that comprises the feedback controller, the state observer and the neurofuzzy approximator, an H-infinity tracking performance can be succeeded.

  18. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

    Science.gov (United States)

    Oyola, Mario G; Handa, Robert J

    2017-09-01

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  19. Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in Hypothalamic-Pituitary Adrenal Axis Modulation

    Directory of Open Access Journals (Sweden)

    Jeremy D Coplan

    2015-07-01

    Full Text Available Background: Chronic stress may conceivably require plasticity of maternal physiology and behavior to cope with the conflicting primary demands of infant rearing and foraging for food. In addition, social rank may play a pivotal role in mandating divergent homeostatic adaptations in cohesive social groups. We examined cerebrospinal fluid (CSF oxytocin (OT levels and hypothalamic pituitary adrenal (HPA axis regulation in the context of maternal social stress and assessed the contribution of social rank to dyadic-distance as reflective of distraction from normative maternal-infant interaction. Methods: Twelve socially-housed mother-infant bonnet macaque dyads were studied after variable foraging demand (VFD exposure compared to 11 unstressed dyads. Dyadic-distance was determined by behavioral observation. Social ranking was performed blindly by two observers. Post-VFD maternal plasma cortisol and CSF OT were compared to corresponding measures in non-VFD exposed mothers. Results: High social rank was associated with increased dyadic-distance only in VFD-exposed dyads and not in control dyads. In mothers unexposed to VFD, social rank was not related to maternal cortisol levels whereas VFD-exposed dominant versus subordinate mothers exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus subordinate mothers. VFD-exposed mothers with high cortisol specifically exhibited CSF OT elevations in comparison to control groups. Conclusions: Pairing of maternal social rank to dyadic-distance in VFD presumably reduces maternal contingent responsivity, with ensuing long-term sequelae. VFD-exposure dichotomizes maternal HPA axis response as a function of social rank with relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer during maternal stress exposure.

  20. Repeated exposure to immobilization or two different footshock intensities reveals differential adaptation of the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Rabasa, Cristina; Muñoz-Abellán, Cristina; Daviu, Núria; Nadal, Roser; Armario, Antonio

    2011-05-03

    Factors involved in adaptation to repeated stress are not well-characterized. For instance, acute footshock (FS) of high intensity appears to be less severe than immobilization (IMO) in light of the speed of post-stress recovery of the hypothalamic-pituitary-adrenal (HPA) axis and other physiological variables. However, repeated exposure to IMO consistently resulted in reduction of the HPA response to the same stressor (adaptation), whereas failure to adapt has been usually reported after FS. Thus, in the present work we directly compared the activation of HPA axis and other physiological changes in response to both acute and repeated exposure to IMO and two intensities of FS (medium and high) in adult male rats. Control rats were exposed to the FS boxes but they did not receive shocks. Daily repeated exposure to IMO resulted in significant adaptation of the overall ACTH and corticosterone responses to the stressor. Such a reduction was also observed with repeated exposure to FS boxes and FS-medium, whereas repeated exposure to FS-high only resulted in a small reduction of the corticosterone response during the post-stress period. This suggests that some properties of FS-high make adaptation to it difficult. Interestingly, overall changes in food intake and body weight gain throughout the week of exposure to the stressors reveal a greater impact of IMO than FS-high, indicating that factors other than the intensity of a stressor, at least when evaluated in function of the above physiological variables, can influence HPA adaptation. Since FS exposure is likely to cause more pain than IMO, activation of nociceptive signals above a certain level may negatively affect HPA adaptation to repeated stressors. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. DMPD: The role of macrophages in the hypothalamic-pituitary-adrenal activation inresponse to endotoxin (LPS). [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available response to endotoxin (LPS). Derijk RH, van Rooijen N, Berkenbosch F. Res Immunol. 1992 Feb;143(2):224-9. (....e hypothalamic-pituitary-adrenal activation inresponse to endotoxin (LPS). Authors Derijk RH, van Rooijen N, Berk

  2. Hypothalamic-pituitary-adrenal axis activity is not elevated in a songbird (Junco hyemalis) preparing for migration.

    Science.gov (United States)

    Bauer, Carolyn M; Needham, Katie B; Le, Chuong N; Stewart, Emily C; Graham, Jessica L; Ketterson, Ellen D; Greives, Timothy J

    2016-06-01

    During spring, increasing daylengths stimulate gonadal development in migratory birds. However, late-stage reproductive development is typically postponed until migration has been completed. The hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids, which have been associated with pre-migratory hyperphagia and fattening. The HPA-axis is also known to suppress the hypothalamic-pituitary-gonadal (HPG) axis, suggesting the possibility that final transition into the breeding life history stage may be slowed by glucocorticoids. We hypothesized that greater HPA-axis activity in individuals preparing for migration may foster preparation for migration while simultaneously acting as a "brake" on the development of the HPG-axis. To test this hypothesis, we sampled baseline corticosterone (CORT), stress-induced CORT, and negative feedback efficacy of Dark-eyed Juncos (Junco hyemalis) in an overwintering population that included both migratory (J.h. hyemalis) and resident (J.h. carolinensis) individuals. We predicted that compared to residents, migrants would have higher baseline CORT, higher stress-induced CORT, and weaker negative feedback. Juncos were sampled in western Virginia in early March, which was about 2-4wk before migratory departure for migrants and 4-5wk before first clutch initiation for residents. Contrary to our predictions, we found that migrants had lower baseline and stress-induced CORT and similar negative feedback efficacy compared with residents, which suggests that delayed breeding in migrants is influenced by other physiological mechanisms. Our findings also suggest that baseline CORT is not elevated during pre-migratory fattening, as migrants had lower baseline CORT and were fatter than residents. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Hypothalamic-pituitary-adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters.

    Science.gov (United States)

    Ambrus, Livia; Lindqvist, Daniel; Träskman-Bendz, Lil; Westrin, Åsa

    2016-11-01

    Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately. Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items 'Concentration difficulties' and 'Failing memory' were extracted. Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = -0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = -0.372, p = 0.020). The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.

  4. Sex differences in the behavioural and hypothalamic-pituitary-adrenal response to contextual fear conditioning in rats.

    Science.gov (United States)

    Daviu, Núria; Andero, Raül; Armario, Antonio; Nadal, Roser

    2014-11-01

    In recent years, special attention is being paid to sex differences in susceptibility to disease. In this regard, there is evidence that male rats present higher levels of both cued and contextual fear conditioning than females. However, little is known about the concomitant hypothalamic-pituitary-adrenal (HPA) axis response to those situations which are critical in emotional memories. Here, we studied the behavioural and HPA responses of male and female Wistar rats to context fear conditioning using electric footshock as the aversive stimulus. Fear-conditioned rats showed a much greater ACTH and corticosterone response than those merely exposed to the fear conditioning chamber without receiving shocks. Moreover, males presented higher levels of freezing whereas HPA axis response was greater in females. Accordingly, during the fear extinction tests, female rats consistently showed less freezing and higher extinction rate, but greater HPA activation than males. Exposure to an open-field resulted in lower activity/exploration in fear-conditioned males, but not in females, suggesting greater conditioned cognitive generalization in males than females. It can be concluded that important sex differences in fear conditioning are observed in both freezing and HPA activation, but the two sets of variables are affected in the opposite direction: enhanced behavioural impact in males, but enhanced HPA responsiveness in females. Thus, the role of sex differences on fear-related stimuli may depend on the variables chosen to evaluate it, the greater responsiveness of the HPA axis in females perhaps being an important factor to be further explored. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Shilajit attenuates behavioral symptoms of chronic fatigue syndrome by modulating the hypothalamic-pituitary-adrenal axis and mitochondrial bioenergetics in rats.

    Science.gov (United States)

    Surapaneni, Dinesh Kumar; Adapa, Sree Rama Shiva Shanker; Preeti, Kumari; Teja, Gangineni Ravi; Veeraragavan, Muruganandam; Krishnamurthy, Sairam

    2012-08-30

    Shilajit has been used as a rejuvenator for ages in Indian ancient traditional medicine and has been validated for a number of pharmacological activities. The effect of processed shilajit which was standardized to dibenzo-α-pyrones (DBPs;0.43% w/w), DBP-chromoproteins (DCPs; 20.45% w/w) and fulvic acids (56.75% w/w) was evaluated in a rat model of chronic fatigue syndrome (CFS). The mitochondrial bioenergetics and the activity of hypothalamus-pituitary-adrenal (HPA) axis were evaluated for the plausible mechanism of action of shilajit. CFS was induced by forcing the rats to swim for 15mins for 21 consecutive days. The rats were treated with shilajit (25, 50 and 100mg/kg) for 21 days before exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility and the climbing period. The post-CFS anxiety level was assessed by elevated plus maze (EPM) test. Plasma corticosterone and adrenal gland weight were estimated as indices of HPA axis activity. Analysis of mitochondrial complex chain enzymes (Complex I, II, IV and V) and mitochondrial membrane potential (MMP) in prefrontal cortex (PFC) were performed to evaluate the mitochondrial bioenergetics and integrity respectively. Shilajit reversed the CFS-induced increase in immobility period and decrease in climbing behavior as well as attenuated anxiety in the EPM test. Shilajit reversed CFS-induced decrease in plasma corticosterone level and loss of adrenal gland weight indicating modulation of HPA axis. Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing the complex enzyme activities and the loss of MMP. Shilajit reversed CFS-induced mitochondrial oxidative stress in terms of NO concentration and, LPO, SOD and catalase activities. The results indicate that shilajit mitigates the effects of CFS in this model possibly through the modulation of HPA axis and preservation of mitochondrial function and integrity. The reversal of CFS-induced behavioral symptoms and

  6. Essence of "Shen (Kidney) Controlling Bones": Conceptual Analysis Based on Hypothalamic-Pituitary-Adrenal-Osteo-Related Cells Axis.

    Science.gov (United States)

    Xu, Tao-Tao; Jin, Hong-Ting; Tong, Pei-Jian

    2018-04-12

    As a traditional concept of Chinese medicine (CM), the theory of "Shen (Kidney) controlling bones" has been gradually proven. And in modern allopathic medicine, the multiple mechanisms of bone growth, development and regeneration align with the theory. Shen defifi ciency as a pathological condition has a negative effect on the skeleton of body, specififi cally the disorder of bone homeostasis. Present studies indicate that Shen defifi ciency shares a common disorder characterized by dysfunction of hypothalamic-pituitary-adrenal (HPA) axis. HPA axis may be an important regulator of bone diseases with abnormal homeostasis. Therefore, we posit the existence of hypothalamic-pituitary-adrenal-osteo-related cells axis: cells that comprise bone tissue (osteo-related cells) are targets under the regulation of HPA axis in disorder of bone homeostasis. Chinese herbs for nourishing Shen have potential in the development of treatments for disorder of bone homeostasis.

  7. The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity

    OpenAIRE

    Lucassen, Eliane A.; Cizza, Giovanni

    2012-01-01

    Obesity, exposure to stress and inadequate sleep are prevalent phenomena in modern society. In this review we focus on their relationships and critically evaluate causality. In obese individuals, one of the main stress systems, the hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol are elevated in adipose tissue due to elevated local activity of 11β-hydroxysteroid dehydrogenase (HSD) type 1. Short sleep and decreased sleep quality are also associated with obesity....

  8. Effects of cytokines on the pituitary-adrenal axis in cancer patients.

    Science.gov (United States)

    Nolten, W E; Goldstein, D; Lindstrom, M; McKenna, M V; Carlson, I H; Trump, D L; Schiller, J; Borden, E C; Ehrlich, E N

    1993-10-01

    Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.

  9. Obesity and the hypothalamic-pituitary-adrenal axis in adolescent girls.

    Science.gov (United States)

    Hillman, Jennifer B; Dorn, Lorah D; Loucks, Tammy L; Berga, Sarah L

    2012-03-01

    Stress and stress-related concomitants, including hypothalamic-pituitary-adrenal (HPA) axis activation, are implicated in obesity and its attendant comorbidities. Little is known about this relationship in adolescents. To begin to address this important knowledge gap, we studied HPA axis activity in 262 healthy adolescent girls aged 11, 13, 15, and 17 years. We hypothesized that obesity would be correlated with increased HPA axis activity and reactivity. Measures of HPA axis activity included 3 blood samples obtained midday (between 1:00 and 2:00 pm) over the course of 40 minutes; overnight urine free cortisol; and cortisol levels 0, 20, and 40 minutes after venipuncture (cortisol reactivity). Measures of adiposity included body mass index (BMI), BMI z score (BMI-Z), percentage body fat, and fat distribution (central adiposity) assessed by dual-energy x-ray absorptiometry. Daytime levels of serum cortisol were inversely associated with BMI-Z and central adiposity (P cortisol excretion rate was positively correlated with BMI, BMI-Z, and central adiposity. There was blunting of cortisol response to venipuncture with increasing adiposity. Our results suggest that there may be reduced cortisol levels during the day and increased levels at night with increasing degree of adiposity. This study provides preliminary findings indicating an alteration of the circadian rhythm of cortisol with obesity. We conclude that obesity is associated with altered HPA activity in adolescent girls. The clinical implications of our findings require further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

    Science.gov (United States)

    Čupić, Željko; Marković, Vladimir M.; Maćešić, Stevan; Stanojević, Ana; Damjanović, Svetozar; Vukojević, Vladana; Kolar-Anić, Ljiljana

    2016-03-01

    Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamic-pituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.

  11. 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.

  12. Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker Correlates in Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Kelly Doolin

    2017-10-01

    Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis and inflammatory systems is a consistent finding in patients with Major Depressive Disorder (MDD. Cortisol is often assessed by measurement of the cortisol awakening response (CAR and/or diurnal cortisol levels. Some methods of cortisol measurement overestimate cortisol concentration due to detection of other glucocorticoids including the relatively inert cortisone, therefore this study aimed to assess the presence of both cortisol and cortisone, and the cortisol-cortisone catalyzing enzyme 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1, in depressed patients and controls. Because the HPA axis is known to regulate the body’s immune system, relationships between measures of cytokines and cortisol were also assessed. Saliva samples were collected from 57 MDD patients and 40 healthy controls at five post-wakening time points (0, +30, +60, +720 and +750 min. Glucocorticoid concentrations were measured by liquid chromatography mass spectrometry. Whole blood mRNA expression of several inflammatory markers was measured by quantitative polymerase chain reaction. This study replicated the common finding of elevated morning cortisol and reduced CAR reactivity in MDD and found no differences in cortisone or 11β-HSD1 mRNA measures. There was a negative association between interleukin 1-β (IL-1β mRNA and morning cortisol reactivity within the depressed group, indicating that dysregulation of the HPA axis and immune system may be interconnected.

  13. 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.

  14. Hypothalamic-pituitary-adrenal axis, childhood adversity and adolescent nonsuicidal self-injury.

    Science.gov (United States)

    Reichl, Corinna; Heyer, Anne; Brunner, Romuald; Parzer, Peter; Völker, Julia Madeleine; Resch, Franz; Kaess, Michael

    2016-12-01

    Whereas childhood adversity (CA) and the hypothalamus-pituitary-adrenal (HPA) axis have been suggested to play a major role in the etiology of non-suicidal self-injury (NSSI), no study has thus far investigated both its associations and interactions with adolescent NSSI. We investigated CA (antipathy, neglect, physical, psychological, and sexual abuse) and indices of HPA axis activity (salivary and hair cortisol) in a clinical sample of 26 adolescents engaging in NSSI and 26 age- and gender-matched healthy controls (HC). We used standardized interviews for the assessment of CA (CECA), NSSI (SITBI-G), and axis I diagnoses (MINI-KID). Salivary cortisol sampling was surveyed using a monitoring system and instructed via telephone calls. Adolescents engaging in NSSI exhibited significantly higher cortisol awakening responses compared to HC. No differences were found with respect to the diurnal slope or hair cortisol. In the presence of CA, healthy adolescents showed flatted diurnal cortisol slopes while those engaging in NSSI exhibited significantly steeper ones. Our findings indicate that adolescents engaging in NSSI may exhibit a stronger cortisol awakening response, potentially in expectation of strain. However, elevated cortisol levels may not be maintained throughout the day, especially among adolescents with a history of CA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder.

    Science.gov (United States)

    Geisel, Olga; Panneck, Patricia; Hellweg, Rainer; Wiedemann, Klaus; Müller, Christian A

    2015-03-30

    Alterations in secretion of stress hormones within the hypothalamic-pituitary-adrenal (HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might contribute to the development and maintenance of substance use disorders by facilitatory effects on behavioral responses to substances of abuse. The objective of this pilot study was to investigate HPA axis activity in patients with non-substance-related addictive disorders, i.e. pathological gambling and internet use disorder. We measured plasma levels of copeptin, a vasopressin surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with pathological gambling (n=14), internet use disorder (n=11) and matched healthy controls for pathological gambling (n=13) and internet use disorder (n=10). Plasma levels of copeptin, ACTH and cortisol in patients with pathological gambling or internet use disorder did not differ among groups. However, cortisol plasma levels correlated negatively with the severity of pathological gambling as measured by the PG-YBOCS. Together with our findings of increased serum levels of brain-derived neurotrophic factor (BDNF) in pathological gambling but not internet use disorder, these results suggest that the pathophysiology of pathological gambling shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in internet use disorder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

    Science.gov (United States)

    van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

    2018-01-01

    Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

  17. Stress-induced sensitization: the hypothalamic-pituitary-adrenal axis and beyond.

    Science.gov (United States)

    Belda, Xavier; Fuentes, Silvia; Daviu, Nuria; Nadal, Roser; Armario, Antonio

    2015-01-01

    Exposure to certain acute and chronic stressors results in an immediate behavioral and physiological response to the situation followed by a period of days when cross-sensitization to further novel stressors is observed. Cross-sensitization affects to different behavioral and physiological systems, more particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that the nature of the initial (triggering) stressor plays a major role, HPA cross-sensitization being more widely observed with systemic or high-intensity emotional stressors. Less important appears to be the nature of the novel (challenging) stressor, although HPA cross-sensitization is better observed with short duration (5-15 min) challenging stressors. In some studies with acute immune stressors, HPA sensitization appears to develop over time (incubation), but most results indicate a strong initial sensitization that progressively declines over the days. Sensitization can affect other physiological system (i.e. plasma catecholamines, brain monoamines), but it is not a general phenomenon. When studied concurrently, behavioral sensitization appears to persist longer than that of the HPA axis, a finding of interest regarding long-term consequences of traumatic stress. In many cases, behavioral and physiological consequences of prior stress can only be observed following imposition of a new stressor, suggesting long-term latent effects of the initial exposure.

  18. Effects of high fat diet on the Basal activity of the hypothalamus-pituitary-adrenal axis in mice: a systematic review.

    Science.gov (United States)

    Auvinen, H E; Romijn, J A; Biermasz, N R; Havekes, L M; Smit, J W A; Rensen, P C N; Pereira, A M

    2011-12-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the hypothalamus-pituitary-adrenal-axis activation. The aim of this review was to assess the effects of high fat feeding on the activity of the hypothalamus-pituitary-adrenal-axis in mice. PubMed, EMBASE, Web of Science, the Cochrane database, and Science Direct were electronically searched and reviewed by 2 individual researchers. We included only original mouse studies reporting parameters of the hypothalamus-pituitary-adrenal-axis after high fat feeding, and at least 1 basal corticosterone level with a proper control group. Studies with adrenalectomized mice, transgenic animals only, high fat diet for less than 2 weeks, or other interventions besides high fat diet, were excluded. 20 studies were included. The hypothalamus-pituitary-adrenal-axis evaluation was the primary research question in only 5 studies. Plasma corticosterone levels were unchanged in 40%, elevated in 30%, and decreased in 20% of the studies. The effects in the peripheral tissues and the central nervous system were also inconsistent. However, major differences were found between mouse strains, experimental conditions, and the content and duration of the diets. This systematic review demonstrates that the effects of high fat feeding on the basal activity of the hypothalamus-pituitary-adrenal-axis in mice are limited and inconclusive. Differences in experimental conditions hamper comparisons and accentuate the need for standardized evaluations to discern the effects of diet-induced obesity on the hypothalamus-pituitary-adrenal-axis. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Impact of maternal undernutrition on the hypothalamic-pituitary-adrenal axis responsiveness in sheep at different ages postnatal.

    Science.gov (United States)

    Chadio, S E; Kotsampasi, B; Papadomichelakis, G; Deligeorgis, S; Kalogiannis, D; Menegatos, I; Zervas, G

    2007-03-01

    Epidemiological and experimental data support the hypothesis of 'fetal programming', which proposes that alterations in fetal nutrition and endocrine status lead to permanent adaptations in fetal homeostatic mechanisms, producing long-term changes in physiology and determine susceptibility to later disease. Altered hypothalamic-pituitary-adrenal (HPA) axis function has been proposed to play an important role in programming of disease risk. The aim of the present study was to examine the effects of maternal nutrient restriction imposed during different periods of gestation on the HPA axis function in sheep, at different ages postnatal. Pregnant ewes were fed a 50% nutrient-restricted diet from days 0-30 (group R1, n = 7), or from days 31-100 of gestation (group R2, n = 7) or a control 100% diet throughout pregnancy, (Control, n = 8). Blood samples were collected at 10-day intervals from day 40 of gestation to term. Lambs were born naturally and fed to appetite throughout the study period. At 2, 5.5, and 10 months of age lambs were given an i.v. injection of corticotrophin-releasing hormone (CRH) and blood samples were collected at -15, 0, 15, 30, 60, 120, and 180 min postinjection. Maternal cortisol levels were significantly higher (P < 0.05) in group R1 compared with the other two groups, whereas maternal insulin levels were lower (P < 0.05) in group R2 compared with control. Birth weight of lambs was not affected by the maternal nutritional manipulation. The area under the curve for ACTH and cortisol response to CRH challenge was greater (P < 0.05) in lambs of group R1 at two months of age, whereas no difference was detected at the ages of 5.5 and 10 months. However, significantly higher (P < 0.01) basal cortisol levels were observed in lambs of R1 group at 5.5 months of age. There was no interaction between treatment and sex for both pituitary and adrenal responses to the challenge. A significant sex effect was evident with females responding with higher ACTH and

  20. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

    Science.gov (United States)

    Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

    2016-04-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

  1. The role of hypothalamus-pituitary-adrenal genes and childhood trauma in borderline personality disorder.

    Science.gov (United States)

    Martín-Blanco, Ana; Ferrer, Marc; Soler, Joaquim; Arranz, Maria Jesús; Vega, Daniel; Calvo, Natalia; Elices, Matilde; Sanchez-Mora, Cristina; García-Martinez, Iris; Salazar, Juliana; Carmona, Cristina; Bauzà, Joana; Prat, Mónica; Pérez, Víctor; Pascual, Juan C

    2016-06-01

    Current knowledge suggests that borderline personality disorder (BPD) results from the interaction between genetic and environmental factors. Research has mainly focused on monoaminergic genetic variants and their modulation by traumatic events, especially those occurring during childhood. However, to the best of our knowledge, there are no studies on the genetics of hypothalamus-pituitary-adrenal (HPA) axis, despite its vulnerability to early stress and its involvement in BPD pathogenesis. The aim of this study was to investigate the contribution of genetic variants in the HPA axis and to explore the modulating effect of childhood trauma in a large sample of BPD patients and controls. DNA was obtained from a sample of 481 subjects with BPD and 442 controls. Case-control differences in allelic frequencies of 47 polymorphisms in 10 HPA axis genes were analysed. Modulation of genetic associations by the presence of childhood trauma was also investigated by dividing the sample into three groups: BPD with trauma, BPD without trauma and controls. Two FKBP5 polymorphisms (rs4713902-C and rs9470079-A) showed significant associations with BPD. There were also associations between BPD and haplotype combinations of the genes FKBP5 and CRHR1. Two FKBP5 alleles (rs3798347-T and rs10947563-A) were more frequent in BPD subjects with history of physical abuse and emotional neglect and two CRHR2 variants (rs4722999-C and rs12701020-C) in BPD subjects with sexual and physical abuse. Our findings suggest a contribution of HPA axis genetic variants to BPD pathogenesis and reinforce the hypothesis of the modulating effect of childhood trauma in the development of this disorder.

  2. Orexin receptor expression in the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes of free-living European beavers (Castor fiber L.) in different periods of the reproductive cycle.

    Science.gov (United States)

    Czerwinska, Joanna; Chojnowska, Katarzyna; Kaminski, Tadeusz; Bogacka, Iwona; Smolinska, Nina; Kaminska, Barbara

    2017-01-01

    Orexins are hypothalamic neuropeptides acting via two G protein-coupled receptors in mammals: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). In European beavers, which are seasonally breeding animals, the presence and functions of orexins and their receptors remain unknown. Our study aimed to determine the expression of OXR mRNAs and the localization of OXR proteins in hypothalamic-pituitary-adrenal/gonadal (HPA/HPG) axes in free-living beavers. The expression of OXR genes (OX1R, OX2R) and proteins was found in all analysed tissues during three periods of beavers' reproductive cycle (April, July, November). The expression of OXR mRNAs in the beaver HPA axis varied seasonally (Ppituitary and adrenals, OX1R mRNA levels were relatively constant in females and peaked in July in males (P<0.05), whereas the OX2R was most highly expressed in males in November and in females in April (P<0.05). In gonads, OX1R expression did not fluctuate between seasons or sexes, but transcript levels were elevated in the testes in November and in the ovaries in July (P<0.05). In turn, OX2R mRNA levels varied between the sexes (P<0.05) and were higher in females (July and November) than in males (P<0.05). The circannual variations in OXR mRNA levels in HPA and HPG axes suggest that the expression of these receptors is associated with sex-specific changes in beavers' reproductive activity and their environmental adaptations. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Stability analysis of a hypothalamic-pituitary-adrenal axis model with inclusion of glucocorticoid receptor and memory

    Science.gov (United States)

    Kaslik, Eva; Navolan, Dan Bogdan; Neamţu, Mihaela

    2017-01-01

    This paper analyzes a four-dimensional model of the hypothalamic-pituitary-adrenal (HPA) axis that includes the influence of the glucocorticoid receptor in the pituitary. Due to the spatial separation between the hypothalamus, pituitary and adrenal glands, distributed time delays are introduced in the mathematical model. The existence of the positive equilibrium point is proved and a local stability and bifurcation analysis is provided, considering several types of delay kernels. The fractional-order model with discrete time delays is also taken into account. Numerical simulations are provided to illustrate the effectiveness of the theoretical findings.

  4. The stability of the extended model of hypothalamic-pituitary-adrenal axis examined by stoichiometric network analysis

    Science.gov (United States)

    Marković, V. M.; Čupić, Ž.; Ivanović, A.; Kolar-Anić, Lj.

    2011-12-01

    Stoichiometric network analysis (SNA) represents a powerful mathematical tool for stability analysis of complex stoichiometric networks. Recently, the important improvement of the method has been made, according to which instability relations can be entirely expressed via reaction rates, instead of thus far used, in general case undefined, current rates. Such an improved SNA methodology was applied to the determination of exact instability conditions of the extended model of the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrinological system, whose hormone concentrations exert complex oscillatory evolution. For emergence of oscillations, the Hopf bifurcation condition was utilized. Instability relations predicted by SNA showed good correlation with numerical simulation data of the HPA axis model.

  5. Effect of Local Vibration and Passive Exercise on the Hormones and Neurotransmitters of Hypothalamic-Pituitary-Adrenal Axis in Hindlimb Unloading Rats

    Science.gov (United States)

    Luan, Huiqin; Huang, Yunfei; Li, Jian; Sun, Lianwen; Fan, Yubo

    2018-04-01

    Astronauts are severely affected by spaceflight-induced bone loss. Mechanical stimulation through exercise inhibits bone resorption and improves bone formation. Exercise and vibration can prevent the degeneration of the musculoskeletal system in tail-suspended rats, and long-term exercise stress will affect endocrine and immune systems that are prone to fatigue. However, the mechanisms through which exercise and vibration affect the endocrine system remain unknown. This study mainly aimed to investigate the changes in the contents of endocrine axis-related hormones and the effects of local vibration and passive exercise on hypothalamic-pituitary-adrenal (HPA) axis-related hormones in tail-suspended rats. A total of 32 Sprague-Dawley rats were randomly distributed into four groups (n = 8 per group): tail suspension (TS), TS + 35Hz vibration, TS + passive exercise, and control. The rats were placed on a passive exercise and local vibration regimen for 21 days. On day 22 of the experiment, the contents of corticotrophin-releasing hormone, adrenocorticotropic hormone, cortisol, and 5-hydroxytryptamine in the rats were quantified with kits in accordance with the manufacturer's instructions. Histomorphometry was applied to evaluate histological changes in the hypothalamus. Results showed that 35Hz local vibration cannot cause rats to remain in a stressed state and that it might not inhibit the function of the HPA axis. Therefore, we speculate that this local vibration intensity can protect the function of the HPA axis and helps tail-suspended rats to transition from stressed to adaptive state.

  6. Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

    Science.gov (United States)

    Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

    2016-10-05

    A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Endocrine evaluation of reproductive function in girls during infancy, childhood and adolescence

    DEFF Research Database (Denmark)

    Juul, Anders; Hagen, Casper P; Aksglaede, Lise

    2012-01-01

    a spectrum of disorders such as premature thelarche, premature adrenarche, central and peripheral precocious puberty, adolescent polycystic ovarian syndrome, functional ovarian hyperandrogenism, late-onset congenital adrenal hyperplasia, primary and secondary amenorrhea, and premature ovarian insufficiency...... detailed knowledge on the normal maturational changes in the hypothalamic-pituitary-ovarian and hypothalamic-pituitary-adrenal axes. Changes in basal reproductive hormone levels in infancy, childhood and adolescence as well as the GnRH and ACTH test procedures in girls and adolescents are described...

  8. Exploration of the Hypothalamic-Pituitary-Adrenal Axis to Improve Animal Welfare by Means of Genetic Selection: Lessons from the South African Merino

    Directory of Open Access Journals (Sweden)

    Schalk Cloete

    2013-05-01

    Full Text Available It is a difficult task to improve animal production by means of genetic selection, if the environment does not allow full expression of the animal’s genetic potential. This concept may well be the future for animal welfare, because it highlights the need to incorporate traits related to production and robustness, simultaneously, to reach sustainable breeding goals. This review explores the identification of potential genetic markers for robustness within the hypothalamic-pituitary-adrenal axis (HPAA, since this axis plays a vital role in the stress response. If genetic selection for superior HPAA responses to stress is possible, then it ought to be possible to breed robust and easily managed genotypes that might be able to adapt to a wide range of environmental conditions whilst expressing a high production potential. This approach is explored in this review by means of lessons learnt from research on Merino sheep, which were divergently selected for their multiple rearing ability. These two selection lines have shown marked differences in reproduction, production and welfare, which makes this breeding programme ideal to investigate potential genetic markers of robustness. The HPAA function is explored in detail to elucidate where such genetic markers are likely to be found.

  9. Activity of the Hypothalamic-Pituitary-Adrenal System in Prenatally Stressed Male Rats on the Experimental Model of Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Pivina, S G; Rakitskaya, V V; Akulova, V K; Ordyan, N E

    2016-03-01

    Using the experimental model of post-traumatic stress disorder (stress-restress paradigm), we studied the dynamics of activity of the hypothalamic-pituitary-adrenal system (HPAS) in adult male rats, whose mothers were daily subjected to restraint stress on days 15-19 of pregnancy. Prenatally stressed males that were subjected to combined stress and subsequent restress exhibited not only increased sensitivity of HPAS to negative feedback signals (manifested under restress conditions), but also enhanced stress system reactivity. These changes persisted to the 30th day after restress. Under basal conditions, the number of cells in the hypothalamic paraventricular nucleus of these animals expressing corticotropin-releasing hormone and vasopressin was shown to decrease progressively on days 1-30. By contrast, combined stress and restress in control animals were followed by an increase in the count of CRH-immunopositive cells in the magnocellular and parvocellular parts of the paraventricular nucleus and number of vasopressin-immunopositive cells in the magnocellular part of the nucleus (to the 10th day after restress). Our results indicate a peculiar level of functional activity of HPAS in prenatally stressed males in the stress-restress paradigm: decreased activity under basal conditions and enhanced reactivity during stress.

  10. [Clinical study on the postburn change in the hypothalamus-pituitary-adrenal hormones in severely burned patients].

    Science.gov (United States)

    Li, Hong-mian; Liang, Zi-qian; Luo, Zuo-jie

    2003-06-01

    To investigate the postburn dynamic changes in the hypothalamus-pituitary-adrenal hormones in severely burned patients. Fifty burn patients were enrolled in the study. The plasma contents of total GC (cortisol), ACTH and aldosterone (ALDO) and urinary contents of 17-OHO and 17-KS were determined with radio-immunological assay (RIA) method after burn injury to compare with the normal values which were well established clinically. The postburn plasma and urinary contents of the above indices were increased evidently with two peak values in shock and infectious stages, whilst the majority of he indices were lower than the normal values after 6 postburn weeks (PBWs). The values of these hormones were the lowest in dying patients. On the other hand, the values approached normal levels in those patients whose burn wounds were healing. Increases of the plasma and urinary levels of hypothalamus-pituitary -adrenal hormones in severely burned patients were constantly seen. Burn shock and infection seemed to be the two major factors in inducing postburn stress reaction in burn victims. Abrupt decrease of the hormone levels in plasma and or urine indicated adrenal failure predicting a poor prognosis of the burn patients.

  11. The role of hypothalamic inflammation, the hypothalamic-pituitary-adrenal axis and serotonin in the cancer anorexia-cachexia syndrome.

    Science.gov (United States)

    van Norren, Klaske; Dwarkasing, Jvalini T; Witkamp, Renger F

    2017-09-01

    In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.

  12. Clinical correlates of hypothalamic-pituitary-adrenal axis measures in individuals at risk for psychosis and with first-episode psychosis.

    Science.gov (United States)

    Labad, Javier; Armario, Antonio; Nadal, Roser; Solé, Montse; Gutiérrez-Zotes, Alfonso; Montalvo, Itziar; Moreno-Samaniego, Lorena; Martorell, Lourdes; Sánchez-Gistau, Vanessa; Vilella, Elisabet

    2018-07-01

    Hypothalamic-pituitary-adrenal (HPA) axis alterations in at-risk mental states (ARMS) resemble those observed in established psychosis but are less consistent. We aimed to explore HPA axis abnormalities in both first-episode psychosis (FEP) and ARMS patients, while controlling for psychopathological symptoms. We studied 21 ARMS, 34 FEP patients and 34 healthy subjects. Clinical assessment included psychopathological symptoms (positive, negative, disorganized, excited and depressive symptoms) and stress measures. Saliva cortisol levels were determined at awakening, 30' and 60' post-awakening, 10:00 h, 23:00 h and 10:00 h on the day after the administration of 0.25 mg of dexamethasone, which occurred at 23:00 h. Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope and cortisol suppression ratio of the dexamethasone suppression test (DST). There were no significant differences between groups in HPA axis measures. However, when exploring the relationship between HPA axis measures and psychopathological symptoms, in ARMS subjects (but not FEP patients), a flatter cortisol slope was associated with more prominent negative symptoms, whereas a blunted CAR was associated with excited symptoms. Although no significant differences in HPA axis measures were found between diagnostic groups, subtle abnormalities in the CAR or circadian cortisol rhythmicity might be important for the phenotype of ARMS individuals. Copyright © 2018. Published by Elsevier B.V.

  13. Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.

    Science.gov (United States)

    Rompala, Gregory R; Finegersh, Andrey; Homanics, Gregg E

    2016-06-01

    A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol-drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse

    NARCIS (Netherlands)

    Rinne, Thomas; de Kloet, E. Ronald; Wouters, Luuk; Goekoop, Jaap G.; DeRijk, Roel H.; van den Brink, Wim

    2002-01-01

    Background: High coincidence of childhood abuse, major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) has been reported in patients with borderline personality disorder (BPD). Animals exposed to early trauma show increased stress-induced hypothalamic-pituitary-adrenal (HPA) axis

  15. Heavy alcohol use, rather than alcohol dependence, is associated with dysregulation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system

    NARCIS (Netherlands)

    Boschloo, Lynn; Vogelzangs, Nicole; Licht, Carmilla M. M.; Vreeburg, Sophie A.; Smit, Johannes H.; van den Brink, Wim; Veltman, Dick J.; de Geus, Eco J. C.; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.

    2011-01-01

    Heavy alcohol use as well as alcohol dependence (AD) have been associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA)-axis and the autonomic nervous system (ANS). However, the relative contribution of alcohol use and AD is unclear. Baseline data were derived from 2947 persons of

  16. Effects of high fat diet on the basal activity of the hypothalamus- pituitary-adrenal axis in mice: A systematic review

    NARCIS (Netherlands)

    Auvinen, H.E.; Romijn, J.A.; Biermasz, N.R.; Havekes, L.M.; Smit, J.W.A.; Rensen, P.C.N.; Pereira, A.M.

    2011-01-01

    Hypothalamus-pituitary-adrenal-axis activity is suggested to be involved in the pathophysiology of the metabolic syndrome. In diet-induced obesity mouse models, features of the metabolic syndrome are induced by feeding high fat diet. However, the models reveal conflicting results with respect to the

  17. The role of central melanocortin receptors in the activation of the hypothalamus pituitary adrenal axis and the induction of excessive grooming

    NARCIS (Netherlands)

    Gispen, W.H.; Frijtag, J.C. von; Croiset, G.; Adan, R.A.H.; Wiegant, V.M.

    1997-01-01

    In accord with previous studies intracerebroventricular (i.c.v.) injections of ACTH1-24 (1 g) induced a display of excessive grooming, and increased the plasma concentrations of ACTH and corticosterone. Pituitary-adrenal activation was blocked by pretreatment with dexamethasone, indicating that the

  18. Multi-level risk factors for suicidal ideation among at-risk adolescent females : The role of hypothalamic-pituitary-adrenal axis responses to stress

    NARCIS (Netherlands)

    Giletta, M.; Calhoun, C.D.; Hastings, P.D.; Rudolph, K.D.; Nock, M.K.; Prinstein, M.J.

    2015-01-01

    Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological,

  19. Responsiveness of the hypothalamic-pituitary-adrenal axis to different novel environments is a consistent individual trait in adult male outbred rats.

    Science.gov (United States)

    Márquez, Cristina; Nadal, Roser; Armario, Antonio

    2005-02-01

    Susceptibility to some stress-induced pathologies may be strongly related to individual differences in the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to stressors. However, there have been few attempts in rodents to study the reliability of the individual differences in the responsiveness of the HPA to stressors and the relationship to resting corticosterone levels. In the present work, we used a normal population of Sprague-Dawley rats, with a within-subject design. Our objectives were to study: (a) the reliability of the ACTH and corticosterone response to three different novel environments widely used in psychopharmacology and (b) the relationship between stress levels of HPA hormones and the daily pattern of corticosterone secretion (six samples over a 24-h-period). Animals were repeatedly sampled using tail-nick procedure. The novel environments were the elevated plus-maze, the hole-board and the circular corridor. Animals were sampled just after 15 min exposure to the tests and again at 15 and 30 min after the termination of exposure to them (post-tests). The hormonal levels just after the tests indicate that the hole-board seems to be more stressful than the circular corridor and the elevated plus-maze, the latter being characterized by the lowest defecation rate. Correlational analysis revealed that daily pattern of resting plasma corticosterone levels did not correlate to HPA responsiveness to the tests, suggesting no relationship between resting and stress levels of HPA hormones. In contrast, the present study demonstrates, for the first time, a good within-subject reliability of the ACTH and corticosterone responses to the three environments, suggesting that HPA responsiveness to these kind of stressors is a consistent individual trait in adult rats, despite differences in the physical characteristics of the novel environments.

  20. Frequent cellular phone use modifies hypothalamic-pituitary-adrenal axis response to a cellular phone call after mental stress in healthy children and adolescents: A pilot study.

    Science.gov (United States)

    Geronikolou, Styliani A; Chamakou, Aikaterini; Mantzou, Aimilia; Chrousos, George; KanakaGantenbein, Christina

    2015-12-01

    The hypothalamic-pituitary-adrenal (HPA) axis is the main "gate-keeper" of the organism's response to every somatic or mental stress. This prospective study aims to investigate the HPA-axis response to a cellular phone call exposure after mental stress in healthy children and adolescents and to assess the possible predictive role of baseline endocrine markers to this response. Two groups of healthy school-age children aged 11-14 (12.5±1.5) years were included in the study, the one comprising those who are occasional users of a cellular phone (Group A) while the second those who do regularly use one (Group B). Blood samples were obtained from all participants at 8.00 am after a 12-hour overnight fasting for thyroid hormone, glucose, insulin, and cortisol levels determination. The participants performed the Trier Social Stress Test for Children (TSST-C) (5 minoral task followed by 5 min arithmetic task). Salivary cortisol samples were obtained at baseline, 10' and 20' min after the TSST-C and 10' and 20' after a 5 minute cellular phone call. Significant changes in the salivary cortisol levels were noted between 10' and 20' mins after the cellular phone call with different responses between the two groups. Baseline thyroid hormone levels seem to predict the cortisol response to mental stress mainly in group A, while HOMA had no impact on salivary cortisol response at any phase of the test, in either group. HPA axis response to cellular phone after mental stress in children and adolescents follow a different pattern in frequent users than in occasional users that seems to be influenced by the baseline thyroid hormone levels. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. O eixo hipotálamo-pituitária-adrenal, a função dos receptores de glicocorticóides e sua importância na depressão The Hypothalamic Pituitary Adrenal axis, Glucocorticoid receptor function and relevance to depression

    Directory of Open Access Journals (Sweden)

    Mario F Juruena

    2004-09-01

    abordagem eficaz para maximizar os efeitos terapêuticos dos antidepressivos. Hipóteses referentes aos mecanismos destes receptores envolvem compostos não esteróides que regulam a função dos RGs via segundos mensageiros. A pesquisa nesta área trará novos entendimentos à fisiopatologia e ao tratamento dos transtornos afetivos, em especial na depressão.OBJECTIVES: Changes in the hypothalamic-pituitary-adrenocortical (HPA system are characteristic of depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR, several studies have examined the number and/or function of GRs in depressed patients. METHODS: Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of CRF in various brain regions postulated to be involved in the causality of depression. RESULTS: This article summarizes the literature on GR in depression and on the impact of antidepressants on the GR in clinical and preclinical studies, and supports the concept that impaired GR signalling is a key mechanism in the pathogenesis of depression, in the absence of clear evidence of decreased GR expression. The data also indicate that antidepressants have direct effects on the GR, leading to enhanced GR function and increased GR expression. Although the effects of antidepressants on glucocorticoid hormones and their receptors are relevant for the therapeutic action of these drugs, the molecular mechanisms underlying these effects are unclear. We propose that antidepressants in humans could inhibit steroid transporters localised on the blood-brain barrier and in neurones, like the multidrug resistance p-glycoprotein, and thus increase the access of cortisol to the brain and the glucocorticoid-mediated negative feedback on the HPA axis. CONCLUSION: Enhanced cortisol action

  2. A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

    Science.gov (United States)

    Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Influence of the hypothalamic-pituitary-adrenal axis dysregulation on the metabolic profile of patients affected by diabetes mellitus-associated late onset hypogonadism.

    Science.gov (United States)

    Tirabassi, G; Chelli, F M; Ciommi, M; Lenzi, A; Balercia, G

    2016-01-01

    Functional hypercortisolism (FH) is generated by clinical states able to chronically activate the hypothalamic-pituitary-adrenal (HPA) axis [e.g. diabetes mellitus (DM)]. No study has evaluated FH influence in worsening the metabolic profile of male patients affected by DM-associated hypogonadism. In this retrospective work, we assess the possible association between HPA axis-dysregulation and cardiovascular risk factors in men simultaneously affected by DM and late-onset hypogonadism (LOH). Fourteen DM and LOH subjects affected by FH (Hypercort-DM-LOH) and fourteen DM and LOH subjects who were not suffering from FH (Normocort-DM-LOH) were retrospectively considered. Clinical, hormonal and metabolic parameters were retrieved. All metabolic parameters, except for systolic blood pressure, were significantly worse in Hypercort-DM-LOH than in Normocort-DM-LOH. After adjustment for body mass index, waist and total testosterone, Hypercort-DM-LOH subjects showed significantly worse metabolic parameters than Normocort-DM-LOH ones. In Normocort-DM-LOH, no significant correlation between general/hormonal parameters and metabolic variables was present. In Hypercort-DM-LOH, positive and significant correlations of cortisol area under the curve (AUC) after corticotropin releasing hormone with glycemia, triglycerides and blood pressure were evident; on the other hand, negative and significant correlation was present between cortisol AUC and high density lipoprotein (HDL) cholesterol. The associations of AUC cortisol with glycemia, HDL cholesterol and diastolic blood pressure (DBP) were further confirmed at quantile regression after adjustment for therapy. FH may determine a worsening of the metabolic profile in DM-associated hypogonadism. Copyright © 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by

  4. Age-related differences in stress responsiveness of the hypothalamic-pituitary-adrenal axis of nonhuman primates with various types of adaptive behavior.

    Science.gov (United States)

    Goncharova, Nadezhda D; Oganyan, Tamara E

    2018-03-01

    Aging is characterized by disturbances in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, associated with disturbances in the adaptation processes and increase of the probability of the onset of post-stress syndrome. However, the individual features of age-related disorders stress reactivity of HPA axis have not been studied. The purpose was to study individual characteristics of the HPA axis responsiveness to acute psycho-emotional stress exposure (restraint, ASE) at different age periods on the model of the young adult and old physically healthy female rhesus monkeys that differ in their behavioral responses to stress, i.e., with depression-like and anxiety-like behavior (DAB) on the one hand and healthy standard (control) adaptive behavior (SB) on the other hand. No significant intergroup differences were observed in HPA axis responses to ASE in young animals. During aging the monkeys with SB showed reduced ACTH response to the ASE, whereas the monkeys with DAB demonstrated its increase. The old animals with DAB in response to ASE demonstrated the most pronounced HPA axis disorders, such as the highest levels of corticotrophin (ACTH), the lowest levels of dehydroepiandrosterone sulfate (DHEAS), reduced cortisol (F) levels and the highest values of the F/DHEAS molar ratio. The ratio F/DHEAS positively correlates with the malondialdehyde concentration in erythrocytes that is considered as the biomarker of oxidative stress. Thus, these data allow us to consider the old monkeys with DAB as individuals with higher vulnerability to the adverse effects of ASE. In addition, depression-like and anxiety-like behavior of aged primates under mild/moderate stress along with reduced DHEAS plasma concentration and increased values of F/DHEAS ratio can be used to identify individuals with increased vulnerability to ASE and accelerated aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Long-term effects of a single exposure to stress in adult rats on behavior and hypothalamic-pituitary-adrenal responsiveness: comparison of two outbred rat strains.

    Science.gov (United States)

    Belda, Xavier; Márquez, Cristina; Armario, Antonio

    2004-10-05

    We have previously observed that a single exposure to immobilization (IMO), a severe stressor, caused long-term (days to weeks) desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis to the homotypic stressor, with no changes in behavioral reactivity to novel environments. In contrast, other laboratories have reported that a single exposure to footshock induced a long-term sensitization of both HPA and behavioral responses to novel environments. To test whether these apparent discrepancies can be explained by the use of different stressors or different strains of rats, we studied in the present work the long-term effects of a single exposure to two different stressors (footshock or IMO) in two different strains of rats (Sprague-Dawley from Iffa-Credo and Wistar rats from Harlan). We found that both strains showed desensitization of the HPA response to the same (homotypic) stressor after a previous exposure to either shock or IMO. The long-term effects were higher after IMO than shock. No major changes in behavior in two novel environments (circular corridor, CC and elevated plus-maze, EPM) were observed after a single exposure to shock or IMO in neither strain, despite the fact that shocked rats showed a conditioned freezing response to the shock boxes. The present results demonstrate that long-term stress-induced desensitization of the HPA axis is a reliable phenomenon that can be observed with different stressors and strains. However, only behavioral changes related to shock-induced conditioned fear were found, which suggests that so far poorly characterized factors are determining the long-term behavioral consequences of a single exposure to stress.

  6. Hypothalamic-Pituitary-Adrenal Axis Function in Children with Attention-Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Kaneko, Motohisa; And Others

    1993-01-01

    This study with 30 children showing attention deficit hyperactivity disorder (ADHD) found a normal diurnal saliva cortisol rhythm in only 43.3 percent of the subjects and a dexamethasone suppression in 46.7 percent, with both these abnormalities more frequent in the severely than the mildly hyperactive group. Results suggest abnormalities in…

  7. The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms involved.

    Science.gov (United States)

    Bonfiglio, Juan José; Inda, Carolina; Refojo, Damián; Holsboer, Florian; Arzt, Eduardo; Silberstein, Susana

    2011-01-01

    Corticotropin-releasing hormone (CRH) plays a key role in adjusting the basal and stress-activated hypothalamic-pituitary-adrenal axis (HPA). CRH is also widely distributed in extrahypothalamic circuits, where it acts as a neuroregulator to integrate the complex neuroendocrine, autonomic, and behavioral adaptive response to stress. Hyperactive and/or dysregulated CRH circuits are involved in neuroendocrinological disturbances and stress-related mood disorders such as anxiety and depression. This review describes the main physiological features of the CRH network and summarizes recent relevant information concerning the molecular mechanism of CRH action obtained from signal transduction studies using cells and wild-type and transgenic mice lines. Special focus is placed on the MAPK signaling pathways triggered by CRH through the CRH receptor 1 that plays an essential role in CRH action in pituitary corticotrophs and in specific brain structures. Recent findings underpin the concept of specific CRH-signaling pathways restricted to specific anatomical areas. Understanding CRH action at molecular levels will not only provide insight into the precise CRH mechanism of action, but will also be instrumental in identifying novel targets for pharmacological intervention in neuroendocrine tissues and specific brain areas involved in CRH-related disorders. Copyright © 2011 S. Karger AG, Basel.

  8. Cranial electrotherapy stimulation affects mood state but not levels of peripheral neurotrophic factors or hypothalamic- pituitary-adrenal axis regulation.

    Science.gov (United States)

    Roh, Hee-Tae; So, Wi-Young

    2017-01-01

    Cranial electrotherapy stimulation (CES) is reported to aid in relieving symptoms of depression and anxiety, though the mechanism underlying this effect remains unclear. Therefore, the present study aimed to evaluate changes in the hypothalamic-pituitary-adrenal (HPA) axis response and levels of neurotrophic factors, as well as changes in mood state, in patients undergoing CES therapy. Fifty healthy postmenopausal women were randomly assigned to either a Sham CES group (n = 25) or an Active CES group (n = 25). CES treatment was conducted in 20-minute sessions, three times per week for 8 weeks, using a micro current cranial electrotherapy stimulator. Blood samples were collected prior to and following the 8-week treatment period for measurement of cortisol, adrenocorticotropic hormone (ACTH), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) levels. Changes in mood state were also examined at the time of blood collection using the Profile of Mood States (POMS). No significant differences in cortisol, ACTH, BDNF, or NGF were observed between the two participant groups (p > 0.05) following the treatment period. However, those in the Active CES group exhibited significantly decreased Tension-Anxiety and Depression-Dejection scores on the POMS relative to pre-treatment scores (p 0.05). These results suggest that 8 weeks of CES treatment does not induce changes in blood levels of neurotrophic factors or HPA-axis-related hormones, though such treatment may be effective in treating symptoms of anxiety and depression.

  9. Chlorella vulgaris reduces the impact of stress on hypothalamic-pituitary-adrenal axis and brain c-fos expression.

    Science.gov (United States)

    Souza Queiroz, Julia; Marín Blasco, Ignacio; Gagliano, Humberto; Daviu, Nuria; Gómez Román, Almudena; Belda, Xavier; Carrasco, Javier; Rocha, Michelle C; Palermo Neto, João; Armario, Antonio

    2016-03-01

    Predominantly emotional stressors activate a wide range of brain areas, as revealed by the expression of immediate early genes, such as c-fos. Chlorella vulgaris (CV) is considered a biological response modifier, as demonstrated by its protective activities against infections, tumors and stress. We evaluated the effect of acute pretreatment with CV on the peripheral and central responses to forced swimming stress in adult male rats. Pretreatment with CV produced a significant reduction of stress-related hypothalamic-pituitary-adrenal activation, demonstrated by decreased corticotrophin releasing factor gene expression in the hypothalamic paraventricular nucleus (PVN) and lower ACTH response. Hyperglycemia induced by the stressor was similarly reduced. This attenuated neuroendocrine response to stress occurred in parallel with a diminished c-fos expression in most evaluated areas, including the PVN. The data presented in this study reinforce the usefulness of CV to diminish the impact of stressors, by reducing the HPA response. Although our results suggest a central effect of CV, further studies are necessary to understand the precise mechanisms underpinning this effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Critical features of acute stress-induced cross-sensitization identified through the hypothalamic-pituitary-adrenal axis output.

    Science.gov (United States)

    Belda, Xavier; Nadal, Roser; Armario, Antonio

    2016-08-11

    Stress-induced sensitization represents a process whereby prior exposure to severe stressors leaves animals or humans in a hyper-responsive state to further stressors. Indeed, this phenomenon is assumed to be the basis of certain stress-associated pathologies, including post-traumatic stress disorder and psychosis. One biological system particularly prone to sensitization is the hypothalamic-pituitary-adrenal (HPA) axis, the prototypic stress system. It is well established that under certain conditions, prior exposure of animals to acute and chronic (triggering) stressors enhances HPA responses to novel (heterotypic) stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels). However, such changes remain somewhat controversial and thus, the present study aimed to identify the critical characteristics of the triggering and challenging stressors that affect acute stress-induced HPA cross-sensitization in adult rats. We found that HPA cross-sensitization is markedly influenced by the intensity of the triggering stressor, whereas the length of exposure mainly affects its persistence. Importantly, HPA sensitization is more evident with mild than strong challenging stressors, and it may remain unnoticed if exposure to the challenging stressor is prolonged beyond 15 min. We speculate that heterotypic HPA sensitization might have developed to optimize biologically adaptive responses to further brief stressors.

  11. Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder.

    Science.gov (United States)

    Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia

    2017-04-01

    Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.

  12. Diabetes Mellitus-Associated Functional Hypercortisolism Impairs Sexual Function in Male Late-Onset Hypogonadism.

    Science.gov (United States)

    Tirabassi, G; Corona, G; Lamonica, G R; Lenzi, A; Maggi, M; Balercia, G

    2016-01-01

    Functional hypercortisolism is generated by conditions able to chronically activate hypothalamic-pituitary-adrenal axis and has been proven to have a negative role in several complications. However, no study has evaluated the possible influence of diabetes mellitus-associated functional hypercortisolism on male hypogonadism and sexual function. We aimed to identify any association of hypothalamic-pituitary-adrenal axis dysregulation measures with testosterone and sexual function in men simultaneously affected by diabetes mellitus and late-onset hypogonadism. Fifteen diabetes mellitus and late-onset hypogonadism subjects suffering from functional hypercortisolism and fifteen diabetes mellitus and late-onset hypogonadism subjects who were free of functional hypercortisolism were retrospectively reviewed. Clinical, hormonal, and sexual parameters were considered. Hypercortisolemic subjects showed higher values of body mass index, waist, and glycated hemoglobin and lower ones of testosterone compared to normocortisolemic ones. All sexual parameters, except for orgasmic function, were significantly worse in hypercortisolemic than in normocortisolemic subjects. Hypercortisolemic patients showed higher values of cortisol after dexamethasone and urinary free cortisol as well as a lesser ACTH response after corticotropin releasing hormone test (ACTH area under curve) compared to normocortisolemic ones. No significant association was found at Poisson regression analysis between hormonal and sexual variables in normocortisolemic patients. In hypercortisolemic subjects, negative and significant associations of cortisol response after corticotropin releasing hormone (cortisol area under curve) with erectile function (β: -0.0008; p: 0.015) and total international index of erectile function score (β: -0.0006; p: 0.001) were evident. This study suggests for the first time the impairing influence of the dysregulated hypothalamic-pituitary-adrenal axis on sexual function in

  13. Characterization of central and peripheral components of the hypothalamus-pituitary-adrenal axis in the inbred Roman rat strains.

    Science.gov (United States)

    Carrasco, Javier; Márquez, Cristina; Nadal, Roser; Tobeña, Adolfo; Fernández-Teruel, Albert; Armario, Antonio

    2008-05-01

    Several studies performed in outbred Roman high- and low-avoidance lines (RHA and RLA, respectively) have demonstrated that the more anxious line (RLA) is characterized by a higher hypothalamic-pituitary-adrenal (HPA) response to certain stressors than the less anxious one (RHA). However, inconsistent results have also been reported. Taking advantage of the generation of an inbred colony of RLA and RHA rats (RHA-I and RLA-I, respectively), we have characterized in the two strains not only resting and stress levels of peripheral HPA hormones but also central components of the HPA axis, including CRF gene expression in extra-hypothalamic areas. Whereas resting levels of ACTH and corticosterone did not differ between the strains, a greater response to a novel environment was found in RLA-I as compared to RHA-I rats. RLA-I rats showed enhanced CRF gene expression in the paraventricular nucleus (PVN) of the hypothalamus, with normal arginin-vasopressin gene expression in both parvocellular and magnocellular regions of the PVN. This enhanced CRF gene expression is not apparently related to altered negative corticosteroid feedback as similar levels of expression of brain glucorticoid and mineralocorticoid receptors were found in the two rat strains. CRF gene expression tended to be higher in the central amygdala and it was significantly higher in the dorsal region of the bed nucleus of stria terminalis (BNST) of RLA-I rats, while no differences appeared in the ventral region of BNST. Considering the involvement of CRF and the BNST in anxiety and stress-related behavioral alterations, the present data suggest that the CRF system may be a critical neurobiological substrate underlying differences between the two rat strains.

  14. Cat odor causes long-lasting contextual fear conditioning and increased pituitary-adrenal activation, without modifying anxiety.

    Science.gov (United States)

    Muñoz-Abellán, Cristina; Daviu, Nuria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

    2009-10-01

    A single exposure to a cat or cat odors has been reported by some groups to induce contextual and auditory fear conditioning and long-lasting changes in anxiety-like behaviour, but there is no evidence for parallel changes in biological stress markers. In the present study we demonstrated in male rats that exposure to a novel environment containing a cloth impregnated with cat fur odor resulted in avoidance of the odor, lower levels of activity and higher pituitary-adrenal (PA) response as compared to those exposed to the novel environment containing a clean cloth, suggesting increased levels of stress in the former animals. When re-exposed 9 days later to the same environment with a clean cloth, previously cat fur exposed rats again showed avoidance of the cloth area and lower levels of activity, suggesting development of contextual fear conditioning, which again was associated with a higher PA activation. In contrast, unaltered both anxiety-like behaviour and PA responsiveness to an elevated plus-maze were found 7 days after cat odor exposure. It is concluded that: (i) PA activation is able to reflect both the stressful properties of cat fur odor and odor-induced contextual fear conditioning; (ii) development of cat odor-induced contextual fear conditioning is independent of the induction of long-lasting changes in anxiety-like behaviour; and (iii) greater PA activation during exposure to the odor context is not explained by non-specific sensitization of the PA axis caused by previous exposure to cat fur odor.

  15. A single exposure to immobilization causes long-lasting pituitary-adrenal and behavioral sensitization to mild stressors.

    Science.gov (United States)

    Belda, Xavier; Fuentes, Silvia; Nadal, Roser; Armario, Antonio

    2008-11-01

    We have previously reported that a single exposure to immobilization (IMO) in rats causes a long-term desensitization of the hypothalamic-pituitary-adrenal (HPA) response to the same (homotypic) stressor. Since there are reports showing that a single exposure to other stressors causes sensitization of the HPA response to heterotypic stressors and increases anxiety-like behavior, we studied in the present work the long-term effects of IMO on behavioral and HPA response to mild superimposed stressors. In Experiments 1 and 2, adult male Sprague-Dawley rats were subjected to 2 h of IMO and then exposed for 5 min to the elevated plus-maze (EPM) at 1, 3 or 7 days after IMO. Blood samples were taken at 15 min after initial exposure to the EPM. Increases in anxiety-like behavior and HPA responsiveness to the EPM were found at all times post-IMO. Changes in the resting levels of HPA hormones did not explain the enhanced HPA responsiveness to the EPM (Experiment 3). In Experiments 4 and 5, we studied the effects of a single exposure to a shorter session of IMO (1 h) on behavioral and HPA responses to a brief and mild session of foot-shocks done 10 days after IMO. Neither previous IMO nor exposure to shocks in control rats modified behavior in the EPM. However, a brief session of shocks in previously IMO-exposed rats dramatically increased anxiety in the EPM. HPA and freezing responses to shocks were similar in control and previous IMO groups. Therefore, a single exposure to IMO appears to induce long-lasting HPA and behavioral sensitization to mild superimposed stressors, although the two responses are likely to be at least partially independent. Long-term effects of IMO on the susceptibility to stress-induced endocrine and emotional disturbances may be relevant to the characterization of animal models of post-traumatic stress.

  16. The effects of chronic food restriction on hypothalamic-pituitary-adrenal activity depend on morning versus evening availability of food.

    Science.gov (United States)

    Belda, Xavier; Ons, Sheila; Carrasco, Javier; Armario, Antonio

    2005-05-01

    Partial food restriction (FR) protocols have been used not only to study behavioral and physiological consequences of decrease food intake, but as a necessary treatment of the animals in some operant learning tasks. It is well-established in rodents that restricting food availability to a few hours in the morning causes an alteration of the daily rhythm of corticosterone, thus making it difficult to evaluate whether or not such treatments are stressful. In the present experiment adult male Sprague-Dawley rats were subjected to two different FR schedules: food availability after 1100 h (LFR) or after 1900 h (DFR). After 14 days, animals from both groups, together with corresponding controls, were killed under resting conditions, either in the morning or in the evening, just before daily access to food in FR rats. Both FR schedules reduced body weight gain to the same extent, but their impact on the hypothalamic-pituitary-adrenal (HPA) axis was different: DFR increased relative, but not absolute, adrenal weight and morning and evening levels of corticosterone, whereas LFR increased both absolute and relative adrenal weights and increased morning corticosterone levels to a greater extent than DFR rats. Neither serum ACTH nor corticotropin-releasing factor (CRF) mRNA levels in the paraventricular nucleus of the hypothalamus were altered by DFR or LFR protocols, suggesting that factors other than CRF and ACTH are involved in the control of adrenocortical secretion under FR. It appears that LFR caused more alterations in the HPA axis than DFR and, therefore, the latter FR schedule should be used in those protocols necessarily involving partial FR.

  17. Angiotensin type 1 receptors in the subfornical organ mediate the drinking and hypothalamic-pituitary-adrenal response to systemic isoproterenol.

    Science.gov (United States)

    Krause, Eric G; Melhorn, Susan J; Davis, Jon F; Scott, Karen A; Ma, Li Y; de Kloet, Annette D; Benoit, Stephen C; Woods, Stephen C; Sakai, Randall R

    2008-12-01

    Circulating angiotensin II (ANGII) elicits water intake and activates the hypothalamic-pituitary-adrenal (HPA) axis by stimulating angiotensin type 1 receptors (AT1Rs) within circumventricular organs. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT1Rs that bind blood-borne ANGII and stimulate integrative and effector regions of the brain. The goal of these studies was to determine the contribution of AT1Rs within the SFO and OVLT to the water intake and HPA response to increased circulating ANGII. Antisense oligonucleotides directed against the AT1R [AT1R antisense (AT1R AS)] were administered into the OVLT or SFO. Quantitative receptor autoradiography confirmed that AT1R AS decreased ANGII binding in the SFO and OVLT compared with the scrambled sequence control but did not affect AT1R binding in other nuclei. Subsequently, water intake, ACTH, and corticosterone (CORT) were assessed after administration of isoproterenol, a beta-adrenergic agonist that decreases blood pressure and elevates circulating ANGII. Delivery of AT1R AS into the SFO attenuated water intake, ACTH, and CORT after isoproterenol, whereas similar treatment in the OVLT had no effect. To determine the specificity of this blunted drinking and HPA response, the same parameters were measured after treatment with hypertonic saline, a stimulus that induces drinking independently of ANGII. Delivery of AT1R AS into the SFO or OVLT had no effect on water intake, ACTH, or CORT after hypertonic saline. The results imply that AT1R within the SFO mediate drinking and HPA responses to stimuli that increase circulating ANGII.

  18. Biological indicators of illness risk in offspring of bipolar parents: targeting the hypothalamic-pituitary-adrenal axis and immune system.

    Science.gov (United States)

    Duffy, Anne; Lewitzka, Ute; Doucette, Sarah; Andreazza, Ana; Grof, Paul

    2012-05-01

    The study aims to provide a selective review of the literature pertaining to the hypothalamic-pituitary-adrenal (HPA) axis and immune abnormalities as informative biological indicators of vulnerability in bipolar disorder (BD). We summarize key findings relating to HPA axis and immunological abnormalities in bipolar patients and their high-risk offspring. Findings derive from a review of selected original papers published in the literature, and supplemented by papers identified through bibliography review. Neurobiological findings are discussed in the context of emergent BD in those at genetic risk and synthesized into a neurodevelopmental model of illness onset and progression. BD is associated with a number of genetic and possibly epigenetic abnormalities associated with neurotransmitter, hormonal and immunologically mediated neurobiological pathways. Data from clinical and high-risk studies implicate HPA axis and immune system abnormalities, which may represent inherited vulnerabilities important for the transition to illness onset. Post-mortem and clinical studies implicate intracellular signal transduction processes and disturbance in energy metabolism associated with established BD. Specifically, long-standing maladaptive alterations such as changes in neuronal systems may be mediated through changes in intracellular signalling pathways, oxidative stress, cellular energy metabolism and apoptosis associated with substantial burden of illness. Prospective longitudinal studies of endophenotypes and biomarkers such as HPA axis and immune abnormalities in high-risk offspring will be helpful to understand genetically mediated biological pathways associated with illness onset and progression. A clinical staging model describing emergent illness in those at genetic risk should facilitate this line of investigation. © 2011 Blackwell Publishing Asia Pty Ltd.

  19. The role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

    Science.gov (United States)

    Harris, Breanna N; Carr, James A

    2016-05-01

    Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  1. Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Garcia-Leal, C; Del-Ben, C M; Leal, F M; Graeff, F G; Guimarães, F S

    2010-05-01

    Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.

  2. Expression of genes related to the hypothalamic-pituitary-adrenal axis in murine fetal lungs in late gestation

    Directory of Open Access Journals (Sweden)

    Côté Mélissa

    2010-11-01

    Full Text Available Abstract Background Lung maturation is modulated by several factors, including glucocorticoids. Expression of hypothalamic-pituitary-adrenal (HPA axis-related components, with proposed or described local regulatory systems analogous to the HPA axis, was reported in peripheral tissues. Here, HPA axis-related genes were studied in the mouse developing lung during a period overlapping the surge of surfactant production. Methods Expression of genes encoding for corticotropin-releasing hormone (CRH, CRH receptors (CRHR 1 and 2beta, CRH-binding protein, proopiomelanocortin (POMC, melanocortin receptor 2 (MC2R, and glucocorticoid receptor was quantified by real-time PCR and localized by in situ hydridization in fetal lungs at gestational days (GD 15.5, 16.5, and 17.5, and was also quantified in primary mesenchymal- and epithelial cell-enriched cultures. In addition, the capability of CRH and adrenocorticotropic hormone (ACTH to stimulate pulmonary expression of enzymes involved in the adrenal pathway of glucocorticoid synthesis was addressed, as well as the glucocorticoid production by fetal lung explants. Results We report that all the studied genes are expressed in fetal lungs according to different patterns. On GD 15.5, Mc2r showed peaks in expression in samples that have previously presented high mRNA levels for glucocorticoid synthesizing enzymes, including 11beta-hydroxylase (Cyp11b1. Crhr1 mRNA co-localized with Pomc mRNA in cells surrounding the proximal epithelium on GD 15.5 and 16.5. A transition in expression sites toward distal epithelial cells was observed between GD 15.5 and 17.5 for all the studied genes. CRH or ACTH stimulation of genes involved in the adrenal pathway of glucocorticoid synthesis was not observed in lung explants on GD 15.5, whereas CRH significantly increased expression of 21-hydroxylase (Cyp21a1 on GD 17.5. A deoxycorticosterone production by fetal lung explants was observed. Conclusions Temporal and spatial

  3. Hypothalamic-pituitary-adrenal and cardiac autonomic responses to transrectal examination differ with behavioral reactivity in dairy cows.

    Science.gov (United States)

    Kovács, L; Kézér, F L; Kulcsár-Huszenicza, M; Ruff, F; Szenci, O; Jurkovich, V

    2016-09-01

    Behavior, hypothalamic-pituitary-adrenal axis, and cardiac autonomic nervous system (ANS) activity were evaluated in response to transrectal examination in nonlactating Holstein-Friesian cows with different behavioral reactivity. According to behavioral reactions shown to the procedure of fixing the heart rate (HR) monitors, the 20 cows with the highest and the 20 cows with the lowest behavioral reactivity were involved in the study (high responder, n=20; and low responder, n=20, respectively). Activity of the ANS was assessed by HR and HR variability parameters. Blood and saliva were collected at 5 min before (baseline) and 0, 5 10, 15, 20, 30, 40, 60, and 120 min after the examination to determine cortisol concentrations. The examination lasted for 5 min. Cardiac parameters included HR, the root mean square of successive differences between the consecutive interbeat intervals, the high frequency (HF) component of heart rate variability, and the ratio between the low frequency (LF) and HF parameter (LF/HF). Following the examination, peak plasma and saliva cortisol levels and the amplitude of the plasma and saliva cortisol response were higher in high responder cows than in low responders. Areas under the plasma and saliva cortisol response curves were greater in high responder cows. Plasma and salivary cortisol levels correlated significantly at baseline (r=0.91), right after examination (r=0.98), and at peak levels (r=0.96). Area under the HR response curve was higher in low responder cows; however, maximum HR and the amplitude of the HR response showed no differences between groups. Minimum values of both parameters calculated for the examination were higher in high responders. Following the examination, response parameters of root mean square of successive differences and HF did not differ between groups. The maximum and the amplitude of LF/HF response and area under the LF/HF response curve were lower in low responder cows, suggesting a lower sympathetic

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

    Science.gov (United States)

    Haller, J; Barna, I; Kovács, J L

    1994-08-01

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

  5. Clinical study on the relationship between FENG syndrome and pituitary-adrenal axis hormones at the onset of acute cerebral infarction

    International Nuclear Information System (INIS)

    Guan Shaoxia; Chen Jianfei; Ma Yaling

    2002-01-01

    Objective: To find the relationship between FENG syndrome and pituitary-adrenal axis hormones (adrenocorticotropic hormone ACTH, corticosteroid CS) at the onset of acute cerebral infarction (ACI). Methods: Using the table of syndrome quantitative diagnosis formulated according to the experiences of apoplectic experts to score the patient at the onset for 151 cases, the patients were divided into two groups: those of FENG syndrome (score ≥ 7 n=77) and NON-FENG syndrome (score<7 n=74). Levels of plasma ACTH and CS in there two groups and 60 healthy subject were determined with RIA. Results: 1) The levels of plasma ACTH and CS in the FENG group were very significantly higher than those in the NON-FENG group (p<0.001); the same result existed between patients and healthy subjects (p<0.001). 2) Highly positive cor-relationship existed between the scores of 77 FENG syndrome cases and the levels of plasma ACTH (r=0.89, t=14.61); moderately positive cor-relationship existed between the scores of FENG syndrome cases and the levels of plasma CS (r=0.53, t=4.83). Conclusion: There is a positive cor-relationship between FENG syndrome and pituitary adrenal axis hormones (ACTH, CS), the levels of plasma ACTH and CS can be regarded as index to differentiate FENG syndrome from NON-FENG syndrome

  6. Enhancement of BDNF Concentration and Restoration of the Hypothalamic-Pituitary-Adrenal Axis Accompany Reduced Depressive-Like Behaviour in Stressed Ovariectomised Rats Treated with Either Tualang Honey or Estrogen

    Directory of Open Access Journals (Sweden)

    Badriya Al-Rahbi

    2014-01-01

    Full Text Available A possible interaction between glucocorticoids and estrogen-induced increases in brain-derived-neurotrophic factor (BDNF expression in enhancing depressive-like behaviour has been documented. Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17β-estradiol (E2 on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX rats. The animals were divided into six groups: (i nonstressed sham-operated control, (ii stressed sham-operated control, (iii nonstressed OVX, (iv stressed OVX, (v stressed OVX treated with E2 (20 μg daily, sc, and (vi stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally. Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration was significantly decreased compared to other experimental groups. These changes were notably reversed by both E2 and Tualang honey. In conclusion, both Tualang honey and E2 mediate antidepressive-like effects in stressed OVX rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis and enhancement of the BDNF concentration.

  7. Dexamethasone PONV prophylaxis alters the hypothalamic-pituitary-adrenal axis after transsphenoidal pituitary surgery.

    Science.gov (United States)

    Burkhardt, Till; Rotermund, Roman; Schmidt, Nils-Ole; Kiefmann, Rainer; Flitsch, Jörg

    2014-07-01

    Postoperative nausea and vomiting (PONV) is common after general anesthesia and are reported by approximately 20% to 25% of all patients and up to 39% of patients undergoing neurosurgical procedures. The most common standard prophylaxis is a single application of 4 mg of dexamethasone before initiating anesthesia. Dexamethasone is known to suppress adreno-corticotroph hormone and cortisol levels. The objective was to find out whether this prophylaxis has an effect on the postoperative levels of cortisol in patients undergoing transsphenoidal pituitary surgery, and therefore simulates pituitary deficiency. A retrospective analysis of the files of 136 consecutive patients who were operated during a course of 6 months were included. Nineteen patients with a known history of PONV received a standard dose of 4 mg of dexamethasone perioperatively. Blood tests were drawn at the first postoperative day and were compared with blood tests of patients who had no history of PONV and therefore received no prophylaxis. Patients who were treated with a dexamethasone PONV prophylaxis showed no significant changes in cortisol levels; preoperative median of 93 μg/L (range, 39 to 427) and a postoperative median of 87 μg/L (range, 10 to 733; P=0.798) opposed to patients who did not receive such treatment; preoperative cortisol 114 μg/L (range, 10 to 387) and postoperative levels of 273 μg/L (range, 10 to 1352; Ptranssphenoidal surgery, the probability that dexamethasone PONV prophylaxis suppresses postoperative cortisol levels should be considered.

  8. Effect of laparotomy on the pituitary-adrenal axis in dogs.

    Science.gov (United States)

    Skovira, Emily J; Behrend, Ellen N; Martin, Linda G; Palmer, Lee E; Kemppainen, Robert J; Lee, Hollie P

    2017-08-01

    OBJECTIVE To assess effects of major abdominal surgery on serum cortisol and aldosterone and plasma canine ACTH (cACTH) concentrations. ANIMALS 39 healthy dogs undergoing laparotomy during veterinary student surgical laboratories. PROCEDURES Blood samples were obtained before and at completion of surgery. Serum cortisol and aldosterone and plasma cACTH concentrations were measured by use of validated radioimmunoassays. Changes in concentrations (postoperative concentration minus preoperative concentration) were calculated. Data were analyzed by use of the Wilcoxon signed rank test, Pearson correlation analysis, and Mann-Whitney rank sum test. RESULTS Cortisol, aldosterone, and cACTH concentrations increased significantly from before to after surgery. Although cortisol and aldosterone concentrations increased in almost all dogs, cACTH concentrations decreased in 6 of 32 (19%) dogs. All dogs had preoperative cortisol concentrations within the reference range, but 24 of 39 (62%) dogs had postoperative concentrations above the reference range. A correlation between the change in cACTH concentration and the change in cortisol concentration was not detected. CONCLUSIONS AND CLINICAL RELEVANCE Laparotomy caused a significant increase in serum cortisol and aldosterone concentrations. In most dogs, but not all dogs, plasma cACTH concentrations increased. Lack of correlation between the change in cACTH concentration and the change in cortisol concentration suggested that increased postoperative cortisol concentrations may have been attributable to ACTH-independent mechanisms, an early ACTH increase that caused a sustained cortisol release, or decreased cortisol clearance. Further studies are indicated to evaluate the effects of various anesthetic protocols and minimally invasive surgical techniques on the stress response.

  9. Relative contributions of pituitary-adrenal hormones to the ontogeny of behavioral inhibition in the rat.

    Science.gov (United States)

    Takahashi, L K; Kim, H

    1995-04-01

    Recent investigations revealed that adrenalectomized (ADX) rat pups exhibit deficits in behavioral inhibition. Furthermore, administration of exogenous corticosterone (CORT) restores behavioral inhibition in ADX pups. Although these studies suggest that CORT has an important role in the development of behavioral inhibition, the relative behavioral effects of elevated pituitary hormone secretion induced by ADX are not known. Therefore, experiments were conducted to assess the potential behavioral effects of elevated adrenocorticotropin (ACTH) secretion induced by ADX and to further evaluate the contribution of endogenous CORT to the development of behavioral inhibition. In Experiment 1., we verified that 10-day-old ADX rats exhibit high levels of plasma ACTH throughout the preweaning period associated with the development of behavioral inhibition. In Experiment 2, 10-day-old pups were hypophysectomized (HYPOX) and ADX and were compared behaviorally to sham-operated controls on day 14. When tested in the presence of an anesthetized unfamiliar adult male rat, HYPOX + ADX pups exhibited low levels of freezing accompanied by ultrasonic vocalizations. These pups also had reduced concentrations of plasma ACTH and CORT. In Experiment 3, 10-day-old pups were HYPOX and tested for behavioral inhibition on day 14. In comparison to sham-operated controls, HYPOX rats exhibited significantly lower levels of freezing and had reduced plasma concentrations of ACTH and CORT. Results demonstrate clearly that deficits in freezing occur even in the presence of low plasma ACTH concentrations. Therefore, elevated secretion of pituitary hormones is not a major factor that contributes to the ADX-induced deficits in behavioral inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.

    LENUS (Irish Health Repository)

    O'Connor, T M

    2012-02-03

    Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)\\/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.

  11. Adaptation of the hypothalamus-pituitary-adrenal axis to daily repeated stress does not follow the rules of habituation: A new perspective.

    Science.gov (United States)

    Rabasa, Cristina; Gagliano, Humberto; Pastor-Ciurana, Jordi; Fuentes, Silvia; Belda, Xavier; Nadal, Roser; Armario, Antonio

    2015-09-01

    Repeated exposure to a wide range of stressors differing in nature and intensity results in a reduced response of prototypical stress markers (i.e. plasma levels of ACTH and adrenaline) after an acute challenge with the same (homotypic) stressor. This reduction has been considered to be a habituation-like phenomenon. However, direct experimental evidence for this assumption is scarce. In the present work we demonstrate in adult male rats that adaptation of the hypothalamus-pituitary-adrenal (HPA) axis to repeated stress does not follow some of the critical rules of habituation. Briefly, adaptation was stronger and faster with more severe stressors, maximally observed even with a single exposure to severe stressors, extremely long-lasting, negatively related to the interval between the exposures and positively related to the length of daily exposure. We offer a new theoretical view to explain adaptation to daily repeated stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Modelling of the Hypothalamic-Pituitary-Adrenal Axis Perturbations by Externally Induced Cholesterol Pulses of Finite Duration and with Asymmetrically Distributed Concentration Profile

    Science.gov (United States)

    Stanojević, A.; Marković, V. M.; Čupić, Ž.; Vukojević, V.; Kolar-Anić, L.

    2017-12-01

    A model was developed that can be used to study the effect of gradual cholesterol intake by food on the HPA axis dynamics. Namely, well defined oscillatory dynamics of vital neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis has proven to be necessary for maintaining regular basal physiology and formulating appropriate stress response to various types of perturbations. Cholesterol, as a precursor of all steroid HPA axis hormones, can alter the dynamics of HPA axis. To analyse its particular influence on the HPA axis dynamics we used stoichiometric model of HPA axis activity, and simulate cholesterol perturbations in the form of finite duration pulses, with asymmetrically distributed concentration profile. Our numerical simulations showed that there is a complex, nonlinear dependence between the HPA axis responsiveness and different forms of applied cholesterol concentration pulses, indicating the significance of kinetic modelling, and dynamical systems theory for the understanding of large-scale self-regulatory, and homeostatic processes within this neuroendocrine system.

  13. Diurnal and nocturnal differences in hypothalamic-pituitary-adrenal axis function in Galápagos marine iguanas.

    Science.gov (United States)

    Romero, L Michael; Wikelski, Martin

    2006-01-15

    Temporal modulation of the stress response is a ubiquitous characteristic of animals. Here, we investigate possible mechanisms underlying daily changes in corticosterone release in an ectotherm model system. Earlier work indicated that free-living Galápagos marine iguanas (Amblyrhynchus cristatus) have lower corticosterone concentrations during the night than during the day. This could result from: (i) a lower circadian secretion of adrenocorticotropic hormone (ACTH) as seen in mammals; (ii) from an increase in corticosterone negative feedback; or (iii) reflect lower metabolic activity during the night when core body temperature falls (from 35 degrees C during the day to as low as 21 degrees C during the night). To begin to distinguish between these three possibilities, exogenous ACTH was used to compare diel differences in adrenocortical tissue responsiveness, and dexamethasone was used to compare diel differences in the efficacy of corticosterone negative feedback. Low levels of exogenous ACTH (30 IU/kg body weight) potently stimulated both daytime and nighttime corticosterone release. Dexamethasone (1 mg/kg) inhibited only daytime, but not nighttime endogenous corticosterone release. Because the response to ACTH was similar between day and night we suggest that a simple lowering of core body temperature cannot explain the nighttime reduction in corticosterone release. However, the failure of negative feedback at night suggests that the response is not equivalent to the controlled downregulation seen in mammals.

  14. The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers.

    Science.gov (United States)

    Mohammadi, Ali Akbar; Jazayeri, Shima; Khosravi-Darani, Kianoush; Solati, Zahra; Mohammadpour, Nakisa; Asemi, Zatollah; Adab, Zohre; Djalali, Mahmoud; Tehrani-Doost, Mehdi; Hosseini, Mostafa; Eghtesadi, Shahryar

    2016-11-01

    The aim of this study was to determine effects of probiotic yogurt and multispecies probiotic capsule supplementation on mental health and hypothalamic-pituitary-adrenal axis in petrochemical workers. The present randomized double-blind, placebo-controlled trial was conducted on 70 petrochemical workers. Subjects were randomly divided into three groups to receive 100 g/day probiotic yogurt + one placebo capsule (n = 25) or one probiotic capsule daily + 100 g/day conventional yogurt (n = 25) or 100 g/day conventional yogurt + one placebo capsule (n = 20) for 6 weeks. Mental health parameters including general health questionnaire (GHQ) and depression anxiety and stress scale (DASS) scores were measured. Fasting blood samples were obtained at the beginning and 6 weeks after the intervention to quantify hypothalamic-pituitary-adrenal axis. After 6 weeks of intervention, a significant improvement of GHQ was observed in the probiotic yogurt (18.0 ± 1.5 vs. 13.5 ± 1.9, P = 0.007) and in the probiotic capsule group (16.9 ± 1.8 vs. 9.8 ± 1.9, P = 0.001), as well as a significant improvement in DASS scores in the probiotic yogurt (23.3 ± 3.7 vs. 13.0 ± 3.7, P = 0.02) and the probiotic capsule group (18.9 ± 3.2 vs. 9.4 ± 4.0, P = 0.006). However, there was no significant improvement in the conventional yogurt group (P = 0.05 for GHQ and P = 0.08 for DASS). The consumption of probiotic yogurt or a multispecies probiotic capsule had beneficial effects on mental health parameters in petrochemical workers.

  15. Distress calls of the greater short-nosed fruit bat Cynopterus sphinx activate hypothalamic-pituitary-adrenal (HPA) axis in conspecifics.

    Science.gov (United States)

    Mariappan, Subramanian; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

    2013-09-01

    In a stressful situation, greater short-nosed fruit bats (Cynopterus sphinx) emit audible vocalization either to warn or to inform conspecifics. We examined the effect of distress calls on bats emitting the call as well as the bats receiving the distress signal through analysis of the hypothalamic-pituitary-adrenal axis and catacholaminargic systems. We measured the levels of neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)] and stress hormones [(adrenocorticotropic hormone (ACTH) and corticosterone (CORT)]. Our results showed that distress call emission elevated the level of ACTH and CORT, as well as 5-HT, DA and NE in the amygdala, for both the call emitting bat and the responding bat. Subsequently, we observed increased activity of glucocorticoid receptor and its steroid receptor co-activator (SRC-1). An expression of SRC-1 was up-regulated in the distress call emitter only, whereas it was at a similar level in both the call responder and silent bats. These findings suggest that bats emitting distress calls and also bats responding to such calls have similar neurotransmitter expression patterns, and may react similarly in response to stress.

  16. Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

    Science.gov (United States)

    Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

    2016-09-01

    The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    Science.gov (United States)

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  18. Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL/6J mice during abstinence from chronic ethanol consumption

    Directory of Open Access Journals (Sweden)

    Terence Y Pang

    2013-07-01

    Full Text Available Depression is a commonly reported co-morbidity during rehabilitation from alcohol use disorders and its presence is associated with an increased likelihood of relapse. Interventions which impede the development of depression could be of potential benefit if incorporated into treatment programs. We previously demonstrated an ameliorative effect of physical exercise on depressive behaviours in a mouse model of alcohol abstinence. Here, we show that environmental enrichment (cognitive and social stimulation has a similar beneficial effect. The hypothalamic-pituitary-adrenal (HPA axis is a key physiological system regulating stress responses and its dysregulation has been separably implicated in the pathophysiology of depression and addiction disorders. We performed a series of dexamethasone challenges and found that mice undergoing 2 weeks of alcohol abstinence had significantly greater corticosterone and ACTH levels following a DEX-CRH challenge compared to water controls. Environmental enrichment during alcohol abstinence corrected the abnormal DEX-CRH corticosterone response despite a further elevation of ACTH levels. Examination of gene expression revealed abstinence-associated alterations in glucocorticoid receptor (Gr, corticotrophin releasing hormone (Crh and pro-opiomelanocortin (Pomc1 mRNA levels which were differentially modulated by environmental enrichment. Overall, our study demonstrates a benefit of environmental enrichment on alcohol abstinence-associated depressive behaviours and HPA axis dysregulation.

  19. Validation of the long-term assessment of hypothalamic-pituitary-adrenal activity in rats using hair corticosterone as a biomarker.

    Science.gov (United States)

    Scorrano, Fabrizio; Carrasco, Javier; Pastor-Ciurana, Jordi; Belda, Xavier; Rami-Bastante, Alicia; Bacci, Maria Laura; Armario, Antonio

    2015-03-01

    The evaluation of chronic activity of the hypothalamic-pituitary-adrenal (HPA) axis is critical for determining the impact of chronic stressful situations. However, current methods have important limitations. The potential use of hair glucocorticoids as a noninvasive retrospective biomarker of long-term HPA activity is gaining acceptance in humans and wild animals. However, there is no study examining hair corticosterone (HC) in laboratory animals. The present study validates a method for measuring HC in rats and demonstrates that it properly reflects chronic HPA activity. The HC concentration was similar in male and female rats, despite higher total plasma corticosterone levels in females, tentatively suggesting that it reflects free rather than total plasma corticosterone. Exposure of male rats to 2 different chronic stress protocols (chronic immobilization and chronic unpredictable stress) resulted in similarly higher HC levels compared to controls (1.8-fold). HC also increased after a mild chronic stressor (30 min daily restraint). Chronic administration of 2 different doses of a long-acting ACTH preparation dramatically increased HC (3.1- and 21.5-fold, respectively), demonstrating that a ceiling effect in HC accumulation is unlikely under other more natural conditions. Finally, adrenalectomy significantly reduced HC. In conclusion, HC measurement in rats appears appropriate to evaluate integrated chronic changes in circulating corticosterone. © FASEB.

  20. Comparison of the effects of single and daily repeated immobilization stress on resting activity and heterotypic sensitization of the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Daviu, Núria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

    2014-03-01

    Acute exposure to severe stressors causes marked activation of the hypothalamic-pituitary-adrenal (HPA) axis that is reflected on the day after higher resting levels of HPA hormones and sensitization of the HPA response to novel (heterotypic) stressors. However, whether a single exposure to a severe stressor or daily repeated exposure to the same (homotypic) stressor modifies these responses to the same extent has not been studied. In this experiment, we studied this issue in adult male Sprague-Dawley rats daily exposed for seven days to a severe stressor such as immobilization on boards (IMO). A first exposure to 1 h IMO resulted in a marked activation of the HPA axis as reflected in plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and such activation was significantly reduced after the seventh IMO. On the day after the first IMO, higher resting levels of ACTH and corticosterone and sensitization of their responses to a short exposure to an open-field (OF) were observed, together with a marked hypoactivity in this environment. Repeated exposure to IMO partially reduced hypoactivity, the increase in resting levels of HPA hormones and the ACTH responsiveness to the OF on the day after the last exposure to IMO. In contrast, corticosterone response was gradually increased, suggesting partial dissociation from ACTH. These results indicate that daily repeated exposure to the same stressor partially reduced the HPA response to the homotypic stressor as well as the sensitization of HPA axis activity observed the day after chronic stress cessation.

  1. Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis.

    Science.gov (United States)

    Belda, Xavier; Armario, Antonio

    2009-10-01

    Whereas the role of most biogenic amines in the control of the hypothalamus-pituitary-adrenal (HPA) response to stress has been extensively studied, the role of dopamine has not. We studied the effect of different dopamine receptor antagonists on HPA response to a severe stressor (immobilization, IMO) in adult male Sprague-Dawley rats. Haloperidol administration reduced adrenocorticotropin hormone and corticosterone responses to acute IMO, particularly during the post-IMO period. This effect cannot be explained by a role of dopamine to maintain a sustained activation of the HPA axis as haloperidol did not modify the response to prolonged (up to 6 h) IMO. Administration of more selective D1 and D2 receptor antagonists (SCH23390 and eticlopride, respectively) also resulted in lower and/or shorter lasting HPA response to IMO. Dopamine, acting through both D1 and D2 receptors, exerts a stimulatory role on the activation of the HPA axis in response to a severe stressor. The finding that dopamine is involved in the maintenance of post-stress activation of the HPA axis is potentially important because the actual pathological impact of HPA activation is likely to be related to the area under the curve of plasma glucocorticoid levels, which is critically dependent on how long after stress high levels of glucocorticoid are maintained.

  2. Adaptation of the hypothalamic-pituitary-adrenal axis and glucose to repeated immobilization or restraint stress is not influenced by associative signals.

    Science.gov (United States)

    Rabasa, Cristina; Delgado-Morales, Raúl; Muñoz-Abellán, Cristina; Nadal, Roser; Armario, Antonio

    2011-02-02

    Repeated exposure to the same stressor very often results in a reduction of some prototypical stress responses, namely those related to the hypothalamic-pituitary-adrenal (HPA) and sympatho-medullo-adrenal (SMA) axes. This reduced response to repeated exposure to the same (homotypic) stressor (adaptation) is usually considered as a habituation-like process, and therefore, a non-associative type of learning. However, there is some evidence that contextual cues and therefore associative processes could contribute to adaptation. In the present study we demonstrated in two experiments using adult male rats that repeated daily exposure to restraint (REST) or immobilization on boards (IMO) reduced the HPA (plasma levels of ACTH and corticosterone) and glucose responses to the homotypic stressor and such reduced responses remained intact when all putative cues associated to the procedure (experimenter, way of transporting to the stress room, stress boxes, stress room and colour of the restrainer in the case of REST) were modified on the next day. Therefore, the present results do not favour the view that adaptation after repeated exposure to a stressor may involve associative processes related to signals predicting the imminence of the stressors, but more studies are needed on this issue. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. The response of the pituitary-adrenal and pituitary-thyroidal axes to the plasma glucose perturbations in Babesia canis rossi babesiosis

    Directory of Open Access Journals (Sweden)

    J.P. Schoeman

    2007-06-01

    Full Text Available This prospective, cross-sectional, interventional study was designed to determine the association between the hormones of the pituitary-adrenal and pituitary-thyroid axes and other clinical parameters with the blood glucose perturbations in dogs with naturally occurring Babesia canis rossi babesiosis. Thirty-six dogs with canine babesiosis were studied. Blood samples were obtained from the jugular vein in each dog prior to treatment at admission to hospital and serum endogenous adrenocorticotrophic hormone(ACTH, pre-ACTH cortisol, thyroxine, free thyroxine and TSH concentrations were measured. Immediately thereafter each dog was injected intravenously with 5 µg/kg of ACTH (tetracosactrin. A 2nd blood sample was taken 1 hour later for serumpost-ACTHcortisol measurement. Three patient groups were recruited: hypoglycaemic dogs (glucose 5.5 mmol/ℓ, n = 12. Basal and post-ACTH serum cortisol concentrations were significantly higher in hypoglycaemic dogs, whereas body temperature, serum thyroxine and free thyroxine were significantly lower in hypoglycaemic dogs. Haematocrit was significantly lower in both hypo-and hyperglycaemic dogs compared with normoglycaemic dogs. Low blood glucose concentrations were significantly associated with high basal and post-ACTH cortisol concentrations and with low serum thyroxine and free thyroxine concentrations in dogs suffering from B. canis rossi babesiosis.

  4. Variation in the ovine cortisol response to systemic bacterial endotoxin challenge is predominantly determined by signalling within the hypothalamic-pituitary-adrenal axis

    International Nuclear Information System (INIS)

    You Qiumei; Karrow, Niel A.; Cao Honghe; Rodriguez, Alexander; Mallard, Bonnie A.; Boermans, Herman J.

    2008-01-01

    Bi-directional communication between the neuroendocrine and immune systems is designed, in part, to maintain or restore homeostasis during physiological stress. Exposure to endotoxin during Gram-negative bacterial infection for example, elicits the release of pro-inflammatory cytokines that activate the hypothalamic-pituitary-adrenal axis (HPAA). The secretion of adrenal glucocorticoids subsequently down regulates the host inflammatory response, minimizing potential tissue damage. Sequence and epigenetic variants in genes involved in regulating the neuroendocrine and immune systems are likely to contribute to individual differences in the HPAA response, and this may influence the host anti-inflammatory response to toxin exposure and susceptibility to inflammatory disease. In this study, high (HCR) and low (LCR) cortisol responders were selected from a normal population of 110 female sheep challenged iv with Escherichia coli endotoxin (400 ng/kg) to identify potential determinants that contribute to variation in the cortisol response phenotype. This phenotype was stable over several years in the HCR and LCR animals, and did not appear to be attributed to differences in expression of hepatic immune-related genes or systemic pro-inflammatory cytokine concentrations. Mechanistic studies using corticotrophin-releasing factor (0.5 μg/kg body weight), arginine vasopressin (0.5 μg/kg), and adrenocorticotropic hormone (0.5 μg/kg) administered iv demonstrated that variation in this phenotype is largely determined by signalling within the HPAA. Future studies will use this ovine HCR/LCR model to investigate potential genetic and epigenetic variants that may contribute to variation in cortisol responsiveness to bacterial endotoxin

  5. Influence of Regularity of Exposure to Chronic Stress on the Pattern of Habituation of Pituitary-Adrenal Hormones, Prolactin and Glucose.

    Science.gov (United States)

    Martí; Armario

    1997-05-01

    The effect of regularity of exposure to two different chronic stressors (noise or immobilization (IMO)) on the pattern of habituation of pituitary-adrenal (PA) hormones, prolactin and glucose was evaluated in adult male rats. Animals were chronically subjected to either regular or irregular time schedule of noise (30 min/day) or IMO (2 h/day) for two weeks. The day after the last stress session the rats were killed without stress or after having been subjected to 30 min of the homotypic stressor. Whereas regular noise did not affect food intake, body weight gain or adrenal weight, irregular noise decreased body weight gain and induced a moderate adrenal hypertrophy. In addition, previous daily exposure to regular but not to irregular noise reduced both prolactin and corticosterone responses to acute noise. In contrast, glucose response to acute noise was reduced after both regular and irregular exposure to chronic noise. Either regular or irregular exposure to chronic IMO decreased food intake and body weight and increased adrenal weight to the same extent. Likewise, no influence of regularity of exposure to chronic IMO on corticosterone and prolactin responses to acute IMO was observed. However, habituation of the ACTH response to acute IMO was observed in rats subjected to chronic regular IMO, but not in rats subjected to chronic irregular IMO. Finally, acute IMO-induced hyperglycemia diminished to the same extent after regular and irregular IMO. From these results we can conclude that: first, the process of habituation of the PA axis to chronic stress is greatly dependent upon factors such as regularity of exposure to the stressor and stressor intensity, and second, the influence of regularity on the pattern of habituation to a repeated stressor is dependent on the physiological variable we are dealing with.

  6. Modifications of glucocorticoid receptors mRNA expression in the hypothalamic-pituitary-adrenal axis in response to early-life stress in female Japanese quail.

    Science.gov (United States)

    Zimmer, C; Spencer, K A

    2014-12-01

    Stress exposure during early-life development can programme individual brain and physiology. The hypothalamic-pituitary-adrenal (HPA) axis is one of the primary targets of this programming, which is generally associated with a hyperactive HPA axis, indicative of a reduced negative-feedback. This reduced feedback efficiency usually results from a reduced level of the glucocorticoid receptor (GR) and/or the mineralocorticoid receptor (MR) within the HPA axis. However, a few studies have shown that early-life stress exposure results in an attenuated physiological stress response, suggesting an enhance feedback efficiency. In the present study, we aimed to determine whether early-life stress had long-term consequences on GR and MR levels in quail and whether the effects on the physiological response to acute stress observed in prenatally stressed individuals were underpinned by changes in GR and/or MR levels in one or more HPA axis components. We determined GR and MR mRNA expression in the hippocampus, hypothalamus and pituitary gland in quail exposed to elevated corticosterone during prenatal development, postnatal development, or both, and in control individuals exposed to none of the stressors. We showed that prenatal stress increased the GR:MR ratio in the hippocampus, GR and MR expression in the hypothalamus and GR expression in the pituitary gland. Postnatal stress resulted in a reduced MR expression in the hippocampus. Both early-life treatments permanently affected the expression of both receptor types in HPA axis regions. The effects of prenatal stress are in accordance with a more efficient negative-feedback within the HPA axis and thus can explain the attenuated stress response observed in these birds. Therefore, these changes in receptor density or number as a consequence of early-life stress exposure might be the mechanism that allows an adaptive response to later-life stressful conditions. © 2014 The Authors. Journal of Neuroendocrinology published by

  7. Featured Article: Community Crime Exposure and Risk for Obesity in Preschool Children: Moderation by the Hypothalamic-Pituitary-Adrenal-Axis Response.

    Science.gov (United States)

    Gartstein, Maria A; Seamon, Erich; Thompson, Stephanie F; Lengua, Liliana J

    2018-05-01

    Identification of early risk factors related to obesity is critical to preventative public health efforts. In this study, we investigated links between the Hypothalamic-Pituitary-Adrenal (HPA)-axis activity (diurnal cortisol pattern), geospatially operationalized exposure to neighborhood crime, and body mass index (BMI) for a sample of 5-year-old children. Greater community crime exposure and lower HPA-axis activity were hypothesized to contribute to higher BMI, with child HPA-axis moderating the association between crime exposure and BMI. Families residing within the boundaries of the City of Seattle (N = 114) provided information concerning demographic/psychosocial risk factors, used to calculate a Cumulative Risk Index, indicating the number of contextual adversities present. Child BMI and diurnal cortisol pattern (derived from assays of saliva samples) were examined, along with neighborhood crime indices computed with publically available information, based on participants' locations. Hierarchical multiple regression analyses, adjusted for covariates (cumulative risk, age, and sex), indicated that crime proximity made a unique contribution to child BMI, in the direction signaling an increase in the risk for obesity. Consistent with our hypothesis, a significant interaction was observed, indicative of moderation by diurnal cortisol pattern. Follow-up simple slope analyses demonstrated that crime exposure was significantly related to higher BMI for children with low-flat (blunted) diurnal cortisol patterns, where community crime and BMI were not significantly associated at higher levels of cortisol. Community crime exposure contributes to higher BMI as early as the preschool period, and blunted diurnal cortisol patterns may place children experiencing neighborhood adversity at greater risk for obesity.

  8. The Effects of a Korean Ginseng, GINST15, on Hypo-Pituitary-Adrenal and Oxidative Activity Induced by Intense Work Stress.

    Science.gov (United States)

    Flanagan, Shawn D; DuPont, William H; Caldwell, Lydia K; Hardesty, Vincent H; Barnhart, Emily C; Beeler, Matthew K; Post, Emily M; Volek, Jeff S; Kraemer, William J

    2018-01-01

    The effect of GINST15, an enzyme fermented ginseng supplement, on hormonal and inflammatory responses to physical stress in humans is unknown. The purpose of this investigation was to examine the constitutive and stress-induced effects of GINST15 supplement on hypo-pituitary-adrenal (HPA) and antioxidant activity in addition to muscle damage. Ten women (age: 38.7 ± 7.8 years; height: 163.81 ± 4.4 cm; body mass 76.0 ± 11.6 kg) and nine men (age: 41.2. ± 9.7 years; height: 177.4 ± 5.3 cm; body mass: 88.5 ± 5.0 kg) participated in a double-blinded, placebo-controlled, counterbalanced within-group study. Participants completed three 14-day treatment cycles with different doses (high: 960 mg; low: 160 mg; placebo: 0 mg) separated by a 1-week washout period. At the end of treatment, physical stress was imposed with intense resistance exercise work stress. Participants provided blood at rest and various time points after exercise (immediately [IP], 30 min [30], 60 min [60], 24 h [+24HR]). Cortisol (CORT), superoxide dismutase (SOD), total glutathione, nonspecific antioxidant activity, total antioxidant power (TAP), and creatine kinase were measured. GINST15 supplementation produced stress-inducible dose-dependent reductions in circulating cortisol and increased enzymatic and nonspecific antioxidant activity. Twenty-four hours after intense exercise, a high dose GINST15, a bioactive ginsenoside metabolite, significantly reduces muscle damage and HPA responses to physical stress in humans; these effects may result from increased antioxidant expression.

  9. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Reynolds, Anna R; Saunders, Meredith A; Brewton, Honoree' W; Winchester, Sydney R; Elgumati, Ibrahim S; Prendergast, Mark A

    2015-09-01

    The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

    Science.gov (United States)

    Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

    2015-08-01

    There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  11. Psychostimulants and forced swim stress interaction: how activation of the hypothalamic-pituitary-adrenal axis and stress-induced hyperglycemia are affected.

    Science.gov (United States)

    Gagliano, Humberto; Ortega-Sanchez, Juan Antonio; Nadal, Roser; Armario, Antonio

    2017-10-01

    We recently reported that simultaneous exposure to amphetamine and various stressors resulted in reduced hypothalamic-pituitary-adrenal (HPA) and glycemic responses to the stressors. Since this is a new and relevant phenomenon, we wanted to further explore this interaction. This study aims (i) to characterize the effect of various doses of amphetamine on the physiological response to a predominantly emotional stressor (forced swim) when the drug was given immediately before stress; (ii) to study if an interaction appears when the drug was given 30 min or 7 days before swim; and (iii) to know whether cocaine causes similar effects when given just before stress. Adult male rats were used and plasma levels of ACTH, corticosterone, and glucose were the outcomes. Amphetamine caused a dose-dependent activation of the HPA axis, but all doses reduced HPA and glycemic responses to swim when given just before the stressor. Importantly, during the post-swim period, the stressor potently inhibited the ACTH response to amphetamine, demonstrating mutual inhibition between the two stimuli. The highest dose of amphetamine also reduced the response to swim when given 30 min before stress, whereas it caused HPA sensitization when given 7 days before. Cocaine also reduced stress-induced HPA activation when given just before swim. The present results demonstrate a negative synergy between psychostimulants (amphetamine and cocaine) and stress regarding HPA and glucose responses when rats were exposed simultaneously to both stimuli. The inhibitory effect of amphetamine is also observed when given shortly before stress, but not some days before.

  12. Exposure to severe stressors causes long-lasting dysregulation of resting and stress-induced activation of the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Belda, Xavier; Rotllant, David; Fuentes, Silvia; Delgado, Raúl; Nadal, Roser; Armario, Antonio

    2008-12-01

    Exposure to some predominantly emotional (electric shock) and systemic (interleukin-1beta) stressors has been found to induce long-term sensitization of the hypothalamic-pituitary-adrenal (HPA) responsiveness to further superimposed stressors. Since exposure to immobilization on wooden boards (IMO) is a severe stressor and may have interest regarding putative animal models of post-traumatic stress disorders (PTSD), we have characterized long-lasting effects of a single exposure to IMO and other stressors on the HPA response to the same (homotypic) and to novel (heterotypic) stressors and the putative mechanisms involved. A single exposure to IMO caused a long-lasting reduction of peripheral and central responses of the HPA axis, likely to be mediated by some brain areas, such as the lateral septum and the medial amygdala. This desensitization is not explained by changes in negative glucocorticoid feedback, and, surprisingly, it is positively related to the intensity of the stressors. In contrast, the HPA response to heterotypic stressors (novel environments) was enhanced, with maximal sensitization on the day after IMO. Sensitization progressively vanished over the course of 1-2 weeks and was not modulated by IMO-induced corticosterone release. Moreover, it could not be explained by changes in the sensitivity of the HPA axis to fast or intermediate/delayed negative feedback, as evaluated 1 week after exposure to IMO, using shock as the heterotypic stressor. Long-lasting stress-induced behavioral changes reminiscent of enhanced anxiety and HPA sensitization are likely to be parallel but partially independent phenomena, the former being apparently not related to the intensity of stressors.

  13. Acute stress-induced sensitization of the pituitary-adrenal response to heterotypic stressors: independence of glucocorticoid release and activation of CRH1 receptors.

    Science.gov (United States)

    Belda, Xavier; Daviu, Núria; Nadal, Roser; Armario, Antonio

    2012-09-01

    A single exposure to some severe stressors causes sensitization of the hypothalamic-pituitary-adrenal (HPA) response to novel stressors. However, the putative factors involved in stress-induced sensitization are not known. In the present work we studied in adult male rats the possible role of glucocorticoids and CRH type 1 receptor (CRH-R1), using an inhibitor of glucocorticoid synthesis (metyrapone, MET), the glucocorticoid receptor (GR) antagonist RU38486 (mifepristone) and the non-peptide CRH-R1 antagonist R121919. In a first experiment we demonstrated with different doses of MET (40-150 mg/kg) that the highest dose acted as a pharmacological stressor greatly increasing ACTH release and altering the normal circadian pattern of HPA hormones, but no dose affected ACTH responsiveness to a novel environment as assessed 3 days after drug administration. In a second experiment, we found that MET, at a dose (75 mg/kg) that blocked the corticosterone response to immobilization (IMO), did not alter IMO-induced ACTH sensitization. Finally, neither the GR nor the CRH-R1 antagonists blocked IMO-induced ACTH sensitization on the day after IMO. Thus, a high dose of MET, in contrast to IMO, was unable to sensitize the HPA response to a novel environment despite the huge activation of the HPA axis caused by the drug. Neither a moderate dose of MET that markedly reduced corticosterone response to IMO, nor the blockade of GR or CRH-R1 receptors was able to alter stress-induced HPA sensitization. Therefore, stress-induced sensitization is not the mere consequence of a marked HPA activation and does not involve activation of glucocorticoid or CRH-R1 receptors. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Adaptation of the pituitary-adrenal axis to daily repeated forced swim exposure in rats is dependent on the temperature of water.

    Science.gov (United States)

    Rabasa, Cristina; Delgado-Morales, Raúl; Gómez-Román, Almudena; Nadal, Roser; Armario, Antonio

    2013-11-01

    Comparison of exposure to certain predominantly emotional stressors reveals a qualitatively similar neuroendocrine response profile as well as a reduction of physiological responses after daily repeated exposure (adaptation). However, particular physical components of the stressor may interfere with adaptation. As defective adaptation to stress can enhance the probability to develop pathologies, we studied in adult male rats (n = 10/group) swimming behavior (struggling, immobility and mild swim) and physiological responses (ACTH, corticosterone and rectal temperature) to daily repeated exposure to forced swim (20 min, 13 d) at 25 or 36 °C (swim25 or swim36). Rats were repeatedly blood-sampled by tail-nick and hormones measured by radioimmunoassay. Some differences were observed between the two swim temperature groups after the first exposure to forced swim: (a) active behaviors were greater in swim25 than swim36 groups; (b) swim25 but not swim36 caused hypothermia; and (c) swim36 elicited the same ACTH response as swim25, but plasma corticosterone concentration was lower for swim36 at 30 min post-swim. After daily repeated exposure, adaptation in ACTH secretion was observed with swim36 already on day 4, whereas with swim25 adaptation was not observed until day 13 and was of lower magnitude. Nevertheless, after repeated exposure to swim25 a partial protection from hypothermia was observed and the two swim conditions resulted in progressive reduction of active behaviors. Thus, daily repeated swim at 25 °C impairs adaptation of the hypothalamic-pituitary-adrenal axis as compared to swim at 36 °C, supporting the hypothesis that certain physical components of predominantly emotional stressors can interfere with the process of adaptation.

  15. Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment.

    Science.gov (United States)

    Zhang, W; Li, Q; Deyssenroth, M; Lambertini, L; Finik, J; Ham, J; Huang, Y; Tsuchiya, K J; Pehme, P; Buthmann, J; Yoshida, S; Chen, J; Nomura, Y

    2018-04-01

    Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood. © 2018 British Society for Neuroendocrinology.

  16. Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress

    Science.gov (United States)

    Calhoun, Casey D.; Hastings, Paul D.; Rudolph, Karen D.; Nock, Matthew K.; Prinstein, Mitchell J.

    2014-01-01

    Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological, interpersonal and biological). Participants were 138 adolescent females (Mage=14.13 years, SD=1.40) at risk for suicidal behaviors. At baseline, lifetime suicidal ideation and a number of risk factors were assessed (i.e., depressive symptoms, impulsiveness, pubertal status and peer stress). Participants were exposed to a psychosocial stress task and HPA-axis responses were assessed by measuring cortisol levels pre- and post-stressor. At 3 months post-baseline, suicidal ideation again was assessed. Using group-based trajectory modeling, three groups of cortisol stress-response patterns were identified (i.e., hyporesponsive, normative, and hyperresponsive). As compared to females in the normative and hyporesponsive group, females in the hyperresponsive group were more likely to report a lifetime history of suicidal ideation at baseline, above and beyond the effects of the other predictors. Moreover, as compared to females in the normative group, females in the hyperresponsive group were at increased risk for reporting suicidal ideation 3 months later, after controlling for prior ideation. No interactions between cortisol group and the other risk factors were significant, with the exception of a non-significant trend between impulsiveness and cortisol group on lifetime suicidal ideation. Findings highlight the importance of HPA-axis responses to acute stressors as a risk factor for suicidal ideation among adolescents. PMID:24958308

  17. Imidazoline2 (I2) receptor- and alpha2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats.

    Science.gov (United States)

    Finn, David P; Hudson, Alan L; Kinoshita, Hiroshi; Coventry, Toni L; Jessop, David S; Nutt, David J; Harbuz, Michael S

    2004-03-01

    Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. alpha2-adrenoceptors and imidazoline2 (I2) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of alpha2-adrenoceptors and I2 receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined alpha2-adrenoceptor antagonist and I2 receptor ligand idazoxan (10 mg/kg), the selective I2 receptor ligand BU224 (2.5 or 10 mg/kg) or the selective alpha2-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both alpha2-adrenoceptors and I2 receptors play a role in modulating basal HPA axis activity and that I2 receptors may play a more important role than alpha2-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.

  18. Antiglucocorticoid RU 38486 attenuates retention of a behaviour and disinhibits the hypothalamic-pituitary adrenal axis at different brain sites

    NARCIS (Netherlands)

    De Kloet, E R; De Kock, Susanne E.; Schild, V; Veldhuis, H D

    Adrenalectomized rats displayed a deficiency in retention of an immobility response acquired during an initial 15-min forced swimming procedure (Porsolt swimming test) and measured 24 h later in a 5-min retest session. The deficit could be restored dose dependently with the glucocorticoid

  19. The neuroimmune-endocrine axis: pathophysiological implications for the central nervous system cytokines and hypothalamus-pituitary-adrenal hormone dynamics

    Directory of Open Access Journals (Sweden)

    J. Licinio

    2000-10-01

    Full Text Available Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are expressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms by which cytokine signaling affects the function of stress-related neuroendocrine systems are reviewed in this article.

  20. Fish oil alleviates activation of the hypothalamic-pituitary-adrenal axis associated with inhibition of TLR4 and NOD signaling pathways in weaned piglets after a lipopolysaccharide challenge.

    Science.gov (United States)

    Liu, Yulan; Chen, Feng; Li, Quan; Odle, Jack; Lin, Xi; Zhu, Huiling; Pi, Dingan; Hou, Yongqing; Hong, Yu; Shi, Haifeng

    2013-11-01

    Long-chain n-3 (ω-3) polyunsaturated fatty acids exert beneficial effects in neuroendocrine dysfunctions in animal models and clinical trials. However, the mechanism(s) underlying the beneficial effects remains to be elucidated. We hypothesized that dietary treatment with fish oil (FO) could mitigate LPS-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis through inhibition of Toll-like receptor 4 and nucleotide-binding oligomerization domain protein signaling pathways. Twenty-four weaned pigs were used in a 2 × 2 factorial design, and the main factors consisted of diet (5% corn oil vs. 5% FO) and immunological challenge (saline vs. LPS). After 21 d of dietary treatment with 5% corn oil or FO diets, pigs were treated with saline or LPS. Blood samples were collected at 0 (preinjection), 2, and 4 h postinjection, and then pigs were humanely killed by intravenous injection of 40 mg/kg body weight sodium pentobarbital for tissue sample collection. FO led to enrichment of eicosapentaenoic acid and docosahexaenoic acid and total n-3 polyunsaturated fatty acids in hypothalamus, pituitary gland, adrenal gland, spleen, and thymus. FO decreased plasma adrenocorticotrophin and cortisol concentrations as well as mRNA expressions of hypothalamic corticotropin releasing hormone and pituitary proopiomelanocortin. FO also reduced mRNA expression of tumor necrosis factor-α in hypothalamus, adrenal gland, spleen, and thymus, and of cyclooxygenase 2 in hypothalamus. Moreover, FO downregulated the mRNA expressions of Toll-like receptor 4 (TLR4) and its downstream molecules, including cluster differentiation factor 14, myeloid differentiation factor 2, myeloid differentiation factor 88, interleukin-1 receptor-associated kinase 1, tumor necrosis factor-α receptor-associated factor 6, and nuclear factor kappa-light-chain-enhancer of activated B cells p65, and also decreased the mRNA expressions of nucleotide-binding oligomerization domain 1, nucleotide

  1. A desk evaluation review of project MYA/6/015 hormonal studies on pituitary adrenal disorders. Project desk evaluation

    International Nuclear Information System (INIS)

    1994-01-01

    Snake-bite is one of the high priority health problems in Myanmar, causing high mortality and mobility rates among the rural population. In 1982 the Department of Medical Research (DMR) of the Ministry of Health launched a research programme for the comprehensive studies of snake (Russell's viper) bites and since then various research divisions of the DMR have been actively engaged in both basic and clinical studies aimed at obtaining adequate knowledge of the biochemical, clinical and pathophysiological mechanisms to guide rational management of snake-bite cases. Also, a clinical research unit has been established in a particular area where the incidence of Russell's viper bite is quite high. Project MYA/6/015 was initiated in 1989 with the objective of determining the incidence, facilitating early diagnosis and assessing the value of therapy in hypopituitarism following snake bite, through the measurements of pituitary and adreno-cortical hormones in serum and their changes in response to dynamic tests. The project was completed in July 1993. The review was undertaken upon request by the Asia and Pacific Section, to assess the overall performance of the project

  2. A desk evaluation review of project MYA/6/015 hormonal studies on pituitary adrenal disorders. Project desk evaluation

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-03-09

    Snake-bite is one of the high priority health problems in Myanmar, causing high mortality and mobility rates among the rural population. In 1982 the Department of Medical Research (DMR) of the Ministry of Health launched a research programme for the comprehensive studies of snake (Russell`s viper) bites and since then various research divisions of the DMR have been actively engaged in both basic and clinical studies aimed at obtaining adequate knowledge of the biochemical, clinical and pathophysiological mechanisms to guide rational management of snake-bite cases. Also, a clinical research unit has been established in a particular area where the incidence of Russell`s viper bite is quite high. Project MYA/6/015 was initiated in 1989 with the objective of determining the incidence, facilitating early diagnosis and assessing the value of therapy in hypopituitarism following snake bite, through the measurements of pituitary and adreno-cortical hormones in serum and their changes in response to dynamic tests. The project was completed in July 1993. The review was undertaken upon request by the Asia and Pacific Section, to assess the overall performance of the project.

  3. Interrelationship of Cytokines, Hypothalamic-Pituitary-Adrenal Axis Hormones, and Psychosocial Variables in the Prediction of Preterm Birth

    Science.gov (United States)

    Pearce, B.D.; Grove, J.; Bonney, E.A.; Bliwise, N.; Dudley, D.J.; Schendel, D.E.; Thorsen, P.

    2010-01-01

    Background/Aims To examine the relationship of biological mediators (cytokines, stress hormones), psychosocial, obstetric history, and demographic factors in the early prediction of preterm birth (PTB) using a comprehensive logistic regression model incorporating diverse risk factors. Methods In this prospective case-control study, maternal serum biomarkers were quantified at 9–23 weeks’ gestation in 60 women delivering at order interactions. Results Among individual biomarkers, we found that macrophage migration inhibitory factor (MIF), interleukin-10, C-reactive protein (CRP), and tumor necrosis factor-α were statistically significant predictors of PTB at all cutoff levels tested (75th, 85th, and 90th percentiles). We fit multifactor models for PTB prediction at each biomarker cutoff. Our best models revealed that MIF, CRP, risk-taking behavior, and low educational attainment were consistent predictors of PTB at all biomarker cutoffs. The 75th percentile cutoff yielded the best predicting model with an area under the ROC curve of 0.808 (95% CI 0.743–0.874). Conclusion Our comprehensive models highlight the prominence of behavioral risk factors for PTB and point to MIF as a possible psychobiological mediator. PMID:20160447

  4. Pituitary function following megavoltage therapy for Cushings' disease; long term follow up

    International Nuclear Information System (INIS)

    Sharpe, G.F.; Kendall-Taylor, P.; Prescott, R.W.G.; Ross, W.M.; Davison, C.; Watson, M.J.; Cook, D.B.

    1985-01-01

    Eight patients who had received megavoltage therapy for Cushings' disease 5-12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic-pituitary function. One patient showed clear evidence of relapse of Cushings' disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary-adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic-pituitary function follow megavoltage therapy and these may progress to overt hypopituitarism. (author)

  5. Thyroid Function Tests

    Science.gov (United States)

    ... Home » Thyroid Function Tests Leer en Español Thyroid Function Tests FUNCTION HOW DOES THE THYROID GLAND FUNCTION? ... Cancer Thyroid Nodules in Children and Adolescents Thyroid Function Tests Resources Thyroid Function Tests Brochure PDF En ...

  6. Sex Differences in Salivary Cortisol, Alpha-Amylase, and Psychological Functioning Following Hurricane Katrina

    Science.gov (United States)

    Vigil, Jacob M.; Geary, David C.; Granger, Douglas A.; Flinn, Mark V.

    2010-01-01

    The study examines group and individual differences in psychological functioning and hypothalamic-pituitary-adrenal and sympathetic nervous system (SNS) activity among adolescents displaced by Hurricane Katrina and living in a U.S. government relocation camp (n = 62, ages 12-19 years) 2 months postdisaster. Levels of salivary cortisol, salivary…

  7. Common functional mineralocorticoid receptor polymorphisms modulate the cortisol awakening response : Interaction with SSRIs

    NARCIS (Netherlands)

    Klok, Melanie D.; Vreeburg, Sophie A.; Penninx, Brenda W. J. H.; Zitman, Frans G.; de Kloet, E. Ron; DeRijk, Roel H.

    Background: Cortisol controls the activity of the hypothalamic pituitary adrenal (HPA) axis during stress and during the circadian cycle through central mineralocorticoid (MR) and glucocorticoid receptors (GR). Changes in MR and GR functioning, therefore, may affect HPA axis activity. In this study

  8. Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test

    NARCIS (Netherlands)

    Maniaci, G.; Goudriaan, A. E.; Cannizzaro, C.; van Holst, R. J.

    2017-01-01

    Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST)

  9. Associations of salivary cortisol with cognitive function in the Baltimore memory study.

    Science.gov (United States)

    Lee, Brian K; Glass, Thomas A; McAtee, Matthew J; Wand, Gary S; Bandeen-Roche, Karen; Bolla, Karen I; Schwartz, Brian S

    2007-07-01

    The stress responses of the hypothalamic-pituitary-adrenal axis can produce adverse effects on the brain. Previous studies have concluded that an elevated level of cortisol is a risk factor for cognitive dysfunction and decline in aging but have been limited by sex exclusion, restricted cognitive batteries, and small sample sizes. To examine associations among salivary cortisol metrics and cognitive domain scores in an urban adult population. A cross-sectional analysis was conducted using data from a longitudinal study involving 1140 Baltimore, Maryland, residents aged 50 to 70 years. Four salivary cortisol samples were obtained from 967 participants across 1 study visit (before, during, and after cognitive testing as well as at the end of the visit) from which 7 cortisol metrics were created. We examined associations of cortisol metrics with cognitive performance using multiple linear regression. Performance on 20 standard cognitive tests was measured and combined to form summary measures in 7 domains (language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction). Higher levels of pretest and mean cortisol as well as the area under the curve of cortisol over the study visit were associated with worse performance (P executive functioning, verbal memory and learning, and visual memory). For instance, an interquartile range increase in the area under the curve was equivalent to a decrease in the language score expected from an increase in 5.6 (95% confidence interval, 4.2-7.1) years of age. Elevated cortisol was associated with poorer cognitive function across a range of domains in this large population-based study. We believe the findings are consistent with the hypothesis that hypothalamic-pituitary-adrenal axis dysregulation may be a risk factor for poorer cognitive performance in older persons.

  10. Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

    Science.gov (United States)

    Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

    2015-09-01

    Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary

  11. Increased cortisol in the cerebrospinal fluid of women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Brundu, Benedetta; Loucks, Tammy L; Adler, Lauri J; Cameron, Judy L; Berga, Sarah L

    2006-04-01

    The proximate cause of functional hypothalamic amenorrhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast doubt about the extent of hypothalamic-pituitary-adrenal activation in FHA and, therefore, we wondered whether central cortisol levels were elevated. We tested the null hypothesis that CSF cortisol levels would be comparable in FHA and eumenorrheic women (EW). The study is a cross-sectional comparison. The study was set in a general clinical research center at an academic medical center. Fifteen women with FHA who were of normal body weight and 14 EW participated. Blood samples were collected at 15-min intervals for 24 h, followed by procurement of 25 ml CSF. Cortisol, cortisol-binding globulin (CBG), and SHBG levels in blood and CSF were the main outcome measures. CSF cortisol concentrations were 30% greater when serum cortisol was 16% higher in FHA compared with EW. Circulating CBG, but not SHBG, was increased in FHA and, thus, the circulating free cortisol index was similar in FHA and EW. Because CBG and SHBG were nil in CSF, the increase in CSF cortisol in FHA was unbound. The hypothalamic-pituitary-adrenal axis is activated in FHA. The maintenance of CRH drive despite increased CSF cortisol indicates resistance to cortisol feedback inhibition. The mechanisms mediating feedback resistance likely involve altered hippocampal corticosteroid reception and serotonergic and GABAergic neuromodulation.

  12. Hair-Normalized Cortisol Waking Response as a Novel Biomarker of Hypothalamic-Pituitary-Adrenal Axis Activity following Acute Trauma: A Proof-of-Concept Study with Pilot Results

    Directory of Open Access Journals (Sweden)

    David M. Walton

    2013-01-01

    Full Text Available The mechanisms underlying the development of persistent posttraumatic pain and disability remain elusive. Recent evidence suggests that disordered stress-system pathway (hypothalamic-pituitary-adrenal axis activity may be responsible for the genesis and maintenance of long-term sensory and emotional problems. However, confidence in current evidence is limited by the necessarily retrospective collection of data. Hair cortisol can serve as a calendar of HPA axis activity going back several months prior to injury. The purposes of this pilot study were to determine the feasibility of using hair cortisol and hair-normalized salivary cortisol as biomarkers of distress following traumatic injuries of whiplash or distal radius fracture. Ten subjects provided complete data within 3 weeks of injury. Hair cortisol, cortisol waking response (CWR, and mean daily cortisol (MDC were captured at inception, as were self-report indicators of pain, disability, and pain catastrophizing. Pain and disability were also captured 3 months after injury. Results indicate that cortisol waking response may be a useful biomarker of current distress as measured using the pain catastrophizing scale, especially when normalized to 3-month hair cortisol (r=0.77 raw, 0.93 normalized. Hair-normalized CWR may also have predictive capacity, correlating with 3-month self-reported disability at r=0.70. While promising, the results must be viewed in light of the small sample.

  13. Extraocular muscle function testing

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003397.htm Extraocular muscle function testing To use the sharing features on this page, please enable JavaScript. Extraocular muscle function testing examines the function of the eye muscles. ...

  14. Platelet Function Tests

    Science.gov (United States)

    ... Patient Resources For Health Professionals Subscribe Search Platelet Function Tests Send Us Your Feedback Choose Topic At ... Also Known As Platelet Aggregation Studies PFT Platelet Function Assay PFA Formal Name Platelet Function Tests This ...

  15. Kidney function tests

    Science.gov (United States)

    Kidney function tests are common lab tests used to evaluate how well the kidneys are working. Such tests include: ... Oh MS, Briefel G. Evaluation of renal function, water, electrolytes ... and Management by Laboratory Methods . 23rd ed. Philadelphia, ...

  16. Liver Function Tests

    Science.gov (United States)

    ... digest food, store energy, and remove poisons. Liver function tests are blood tests that check to see ... as hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or ...

  17. Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

    Science.gov (United States)

    Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

    2000-03-01

    Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

  18. Effects of moderate treadmill exercise and fluoxetine on behavioural and cognitive deficits, hypothalamic-pituitary-adrenal axis dysfunction and alternations in hippocampal BDNF and mRNA expression of apoptosis - related proteins in a rat model of post-traumatic stress disorder.

    Science.gov (United States)

    Shafia, Sakineh; Vafaei, Abbas Ali; Samaei, Seyed Afshin; Bandegi, Ahmad Reza; Rafiei, Alireza; Valadan, Reza; Hosseini-Khah, Zahra; Mohammadkhani, Raziyeh; Rashidy-Pour, Ali

    2017-03-01

    Post-traumatic stress disorder (PTSD) is a condition that develops after an individual has experienced a major trauma. Currently, selective serotonin reuptake inhibitors (SSRIs) like fluoxetine are the first-line choice in PTSD drug treatment but their moderate response rates and side effects indicate an urgent need for the development of new treatment. Physical activity is known to improve symptoms of certain neuropsychiatric disorders. The present study investigated the effects of moderate treadmill exercise, the antidepressant fluoxetine and the combined treatment on behavioural deficits, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. We also examined alternations in hippocampal brain-derived neurotrophic factor (BDNF) and mRNA expression of apoptosis - related proteins in a rat model of PTSD: the single prolonged stress (SPS) model. Rats were exposed to SPS (restraint for 2h, forced swimming for 20min and ether anaesthesia) and were then kept undisturbed for 14days. After that, SPS rats were subjected to chronic treatment with fluoxetine (10mg/kg/day, for 4weeks), moderate treadmill running (4weeks, 5day per week) and the combined treatment (fluoxetine plus treadmill exercise), followed by behavioural, biochemical and apoptosis markers assessments. SPS rats exhibited increased anxiety levels in the elevated plus maze and light/dark box, impaired fear conditioning and extinction in inhibitory avoidance (IA) task, impaired spatial memory in a recognition location memory task and enhanced negative feedback on the HPA axis following a dexamethasone suppression test. SPS rats also showed reduced hippocampal BDNF and enhanced apoptosis. Moderate treadmill exercise, fluoxetine and the combined treatment alleviated the SPS-induced alterations in terms of anxiety levels, HPA axis inhibition, IA conditioning and extinction, hippocampal BDNF and apoptosis markers. Furthermore, the combined treatment was more effective than fluoxetine alone, but in most tests

  19. Pancreatic Exocrine Function Testing

    OpenAIRE

    Berk, J. Edward

    1982-01-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and par...

  20. The protective effects of social bonding on behavioral and pituitary-adrenal axis reactivity to chronic mild stress in prairie voles.

    Science.gov (United States)

    McNeal, Neal; Appleton, Katherine M; Johnson, Alan Kim; Scotti, Melissa-Ann L; Wardwell, Joshua; Murphy, Rachel; Bishop, Christina; Knecht, Alison; Grippo, Angela J

    2017-03-01

    Positive social interactions may protect against stress. This study investigated the beneficial effects of pairing with a social partner on behaviors and neuroendocrine function in response to chronic mild stress (CMS) in 13 prairie vole pairs. Following 5 days of social bonding, male and female prairie voles were exposed to 10 days of CMS (mild, unpredictable stressors of varying durations, for instance, strobe light, white noise, and damp bedding), housed with either the social partner (paired group) or individually (isolated group). Active and passive behavioral responses to the forced swim test (FST) and tail-suspension test (TST), and plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone, were measured in all prairie voles following the CMS period. Both female and male prairie voles housed with a social partner displayed lower durations of passive behavioral responses (immobility, a maladaptive behavioral response) in the FST (mean ± SEM; females: 17.3 ± 5.4 s; males: 9.3 ± 4.6 s) and TST (females: 56.8 ± 16.4 s; males: 40.2 ± 11.3 s), versus both sexes housed individually (females, FST: 98.6 ± 12.9 s; females, TST: 155.1 ± 19.3 s; males, FST: 92.4 ± 14.1 s; males, TST: 158.9 ± 22.0 s). Female (but not male) prairie voles displayed attenuated plasma stress hormones when housed with a male partner (ACTH: 945 ± 24.7 pg/ml; corticosterone: 624 ± 139.5 ng/ml), versus females housed individually (ACTH: 1100 ± 23.2 pg/ml; corticosterone: 1064 ± 121.7 ng/ml). These results may inform understanding of the benefits of social interactions on stress resilience. Lay Summary: Social stress can lead to depression. The study of social bonding and stress using an animal model will inform understanding of the protective effects of social bonds. This study showed that social bonding in a rodent model can protect against behavioral responses to stress, and may

  1. Age and Chronicity of Administration Dramatically Influenced the Impact of Low Dose Paraquat Exposure on Behavior and Hypothalamic-Pituitary-Adrenal Activity

    Directory of Open Access Journals (Sweden)

    Chris A. Rudyk

    2017-07-01

    Full Text Available Little is known of the age-dependent and long-term consequences of low exposure levels of the herbicide and dopaminergic toxicant, paraquat. Thus, we assessed the dose-dependent effects of paraquat using a typical short-term (3 week exposure procedure, followed by an assessment of the effects of chronic (16 weeks exposure to a very low dose (1/10th of what previously induced dopaminergic neuronal damage. Short term paraquat treatment dose-dependently induced deficits in locomotion, sucrose preference and Y-maze performance. Chronic low dose paraquat treatment had a very different pattern of effects that were also dependent upon the age of the animal: in direct contrast to the short-term effects, chronic low dose paraquat increased sucrose consumption and reduced forced swim test (FST immobility. Yet these effects were age-dependent, only emerging in mice older than 13 months. Likewise, Y-maze spontaneous alternations and home cage activity were dramatically altered as a function of age and paraquat chronicity. In both the short and long-term exposure studies, increased corticosterone and altered hippocampal glucocorticoid receptor (GR levels were induced by paraquat, but surprisingly these effects were blunted in the older mice. Thus, paraquat clearly acts as a systemic stressor in terms of corticoid signaling and behavioral outcomes, but that paradoxical effects may occur with: (a repeated exposure at; (b very low doses; and (c older age. Collectively, these data raise the possibility that repeated “hits” with low doses of paraquat in combination with aging processes might have promoted compensatory outcomes.

  2. Functional Task Test (FTT)

    Science.gov (United States)

    Bloomberg, Jacob J.; Mulavara, Ajitkumar; Peters, Brian T.; Rescheke, Millard F.; Wood, Scott; Lawrence, Emily; Koffman, Igor; Ploutz-Snyder, Lori; Spiering, Barry A.; Feeback, Daniel L.; hide

    2009-01-01

    This slide presentation reviews the Functional Task Test (FTT), an interdisciplinary testing regimen that has been developed to evaluate astronaut postflight functional performance and related physiological changes. The objectives of the project are: (1) to develop a set of functional tasks that represent critical mission tasks for the Constellation Program, (2) determine the ability to perform these tasks after space flight, (3) Identify the key physiological factors that contribute to functional decrements and (4) Use this information to develop targeted countermeasures.

  3. Pancreatic exocrine function testing

    International Nuclear Information System (INIS)

    Goff, J.S.

    1981-01-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each

  4. Des-Acyl Ghrelin and Ghrelin O-Acyltransferase Regulate Hypothalamic-Pituitary-Adrenal Axis Activation and Anxiety in Response to Acute Stress

    NARCIS (Netherlands)

    Stark, R.; Santos, V.V.; Geenen, B.; Cabral, A.; Dinan, T.; Bayliss, J.A.; Lockie, S.H.; Reichenbach, A.; Lemus, M.B.; Perello, M.; Spencer, S.J.; Kozicz, L.T.; Andrews, Z.B.

    2016-01-01

    Ghrelin exists in two forms in circulation, acyl ghrelin and des-acyl ghrelin, both of which have distinct and fundamental roles in a variety of physiological functions. Despite this fact, a large proportion of papers simply measure and refer to plasma ghrelin without specifying the acylation

  5. Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis

    NARCIS (Netherlands)

    Doelen, R.H.A. van der; Deschamps, W.; D'Annibale, C.; Peeters, D.; Wevers, R.A.; Zelena, D.; Homberg, J.R.; Kozicz, L.T.

    2014-01-01

    The short allelic variant of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) has been associated with the etiology of major depression by interaction with early life stress (ELS). Furthermore, 5-HTTLPR has been associated with abnormal functioning of the

  6. Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress.

    Science.gov (United States)

    Naert, Gaelle; Ixart, Guy; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

    2011-01-01

    Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3h/day for 3 weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. [Contributions of cortisol suppression tests to understanding of psychiatric disorders: a narrative review of literature].

    Science.gov (United States)

    Tajima-Pozo, Kazuhiro; Montes-Montero, Ana; Güemes, Itziar; González-Vives, Sara; Díaz-Marsá, Marina; Carrasco, José Luis

    2013-01-01

    Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for detecting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis. Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  8. Alarin-induced antidepressant-like effects and their relationship with hypothalamus-pituitary-adrenal axis activity and brain derived neurotrophic factor levels in mice.

    Science.gov (United States)

    Wang, Ming; Chen, Qian; Li, Mei; Zhou, Wei; Ma, Tengfei; Wang, Yun; Gu, Shuling

    2014-06-01

    Alarin is a newly identified member of the galanin family of peptides. Galanin has been shown to exert regulatory effects on depression. Similar to galanin in distribution, alarin is also expressed in the medial amygdala and hypothalamus, i.e., regions interrelated with depression. However, it remains a puzzle whether alarin is involved in depression. Accordingly, we established the depression-like mouse model using behavioral tests to ascertain the possible involvement of alarin, with fluoxetine as a positive control. With the positive antidepressant-like effects of alarin, we further examined its relationship to HPA axis activity and brain-derived neurotrophic factor (BDNF) levels in different brain areas in a chronic unpredictable mild stress (CUMS) paradigm. In the acute studies, alarin produced a dose-related reduction in the immobility duration in tail suspension test (TST) in mice. In the open-field test, intracerebroventricular (i.c.v.) injection of alarin (1.0 nmol) did not impair locomotion or motor coordination in the treated mice. In the CUMS paradigm, alarin administration (1.0 nmol, i.c.v.) significantly improved murine behaviors (FST and locomotor activity), which was associated with a decrease in corticotropin-releasing hormone (CRH) mRNA levels in the hypothalamus, as well as a decline in serum levels of CRH, adrenocorticotropic hormone (ACTH) and corticosterone (CORT), all of which are key hormones of the HPA axis. Furthermore, alarin upregulated BDNF mRNA levels in the prefrontal cortex and hippocampus. These findings suggest that alarin may potentiate the development of new antidepressants, which would be further secured with the identification of its receptor(s). Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Liver Function Tests

    Science.gov (United States)

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  10. Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level.

    Science.gov (United States)

    Jindal, Ankur; Mahesh, Radhakrishnan; Bhatt, Shvetank

    2013-11-01

    Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (pBDNF level and inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any

  11. Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis Due to Dysfunction of the Hypothalamic Glucocorticoid Receptor in Sigma-1 Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    Tingting Di

    2017-09-01

    Full Text Available Sigma-1 receptor knockout (σ1R-KO mice exhibit a depressive-like phenotype. Because σ1R is highly expressed in the neuronal cells of hypothalamic paraventricular nuclei (PVN, this study investigated the influence of σ1R deficiency on the regulation of the hypothalamic-pituitary-adrenocortical (HPA axis. Here, we show that the levels of basal serum corticosterone (CORT, adrenocorticotropic hormone (ACTH and corticotrophin releasing factor (CRF as well as the level of CRF mRNA in PVN did not significantly differ between adult male σ1R-KO mice and wild-type (WT mice. Acute mild restraint stress (AMRS induced a higher and more sustainable increase in activity of HPA axis and CRF expression in σ1R-KO mice. Percentage of dexamethasone (Dex-induced reduction in level of CORT was markedly attenuated in σ1R−/− mice. The levels of glucocorticoid receptor (GR and protein kinase C (PKC phosphorylation were reduced in the PVN of σ1R-KO mice and σ1R antagonist NE100-treated WT mice. The exposure to AMRS in σ1R-KO mice induced a stronger phosphorylation of cAMP-response element binding protein (CREB in PVN than that in WT mice. Intracerebroventricular (i.c.v. injection of PKC activator PMA for 3 days in σ1R-KO mice not only recovered the GR phosphorylation and the percentage of Dex-reduced CORT but also corrected the AMRS-induced hyperactivity of HPA axis and enhancement of CRF mRNA and CREB phosphorylation. Furthermore, the injection (i.c.v. of PMA in σ1R-KO mice corrected the prolongation of immobility time in forced swim test (FST and tail suspension test (TST. These results indicate that σ1R deficiency causes down-regulation of GR by reducing PKC phosphorylation, which attenuates GR-mediated feedback inhibition of HPA axis and facilitates the stress response of HPA axis leading to the production of depressive-like behaviors.

  12. Automate functional testing

    Directory of Open Access Journals (Sweden)

    Ramesh Kalindri

    2014-06-01

    Full Text Available Currently, software engineers are increasingly turning to the option of automating functional tests, but not always have successful in this endeavor. Reasons range from low planning until over cost in the process. Some principles that can guide teams in automating these tests are described in this article.

  13. Hypothalamic-pituitary-adrenal axis reactivity to psychological stress and memory in middle-aged women: high responders exhibit enhanced declarative memory performance.

    Science.gov (United States)

    Domes, G; Heinrichs, M; Reichwald, U; Hautzinger, M

    2002-10-01

    According to recent studies, elevated cortisol levels are associated with impaired declarative memory performance. This specific effect of cortisol has been shown in several studies using pharmacological doses of cortisol. The present study was designed to determine the effects of endogenously stimulated cortisol secretion on memory performance in healthy middle-aged women. For psychological stress challenging, we employed the Trier Social Stress Test (TSST). Subjects were assigned to either the TSST or a non-stressful control condition. Declarative and non-declarative memory performance was measured by a combined priming-free-recall-task. No significant group differences were found for memory performance. Post hoc analyses of variance indicated that regardless of experimental condition the subjects with remarkably high cortisol increase in response to the experimental procedure (high responders) showed increased memory performance in the declarative task compared to subjects with low cortisol response (low responders). The results suggest that stress-induced cortisol failed to impair memory performance. The results are discussed with respect to gender-specific effects and modulatory effects of the sympathetic nervous system and psychological variables. Copyright 2002 Elsevier Science Ltd.

  14. Effects of prenatal dexamethasone treatment on physical growth, pituitary-adrenal hormones, and performance of motor, motivational, and cognitive tasks in juvenile and adolescent common marmoset monkeys.

    Science.gov (United States)

    Hauser, Jonas; Knapman, Alana; Zürcher, Nicole R; Pilloud, Sonia; Maier, Claudia; Diaz-Heijtz, Rochellys; Forssberg, Hans; Dettling, Andrea; Feldon, Joram; Pryce, Christopher R

    2008-12-01

    Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to prevent respiratory distress syndrome in preterm infants, but there is emerging evidence of subsequent neurobehavioral abnormalities (e.g. problems with inattention/hyperactivity). In the present study, we exposed pregnant common marmosets (Callithrix jacchus, primates) to daily repeated DEX (5 mg/kg by mouth) during either early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 days). Relative to control, and with a longitudinal design, we investigated DEX effects in offspring in terms of physical growth, plasma ACTH and cortisol titers, social and maintenance behaviors, skilled motor reaching, motivation for palatable reward, and learning between infancy and adolescence. Early DEX resulted in reduced sociability in infants and increased motivation for palatable reward in adolescents. Late DEX resulted in a mild transient increase in knee-heel length in infants and enhanced reversal learning of stimulus-reward association in adolescents. There was no effect of either early or late DEX on basal plasma ACTH or cortisol titers. Both treatments resulted in impaired skilled motor reaching in juveniles, which attenuated in early DEX but persisted in late DEX across test sessions. The increased palatable-reward motivation and decreased social motivation observed in early DEX subjects provide experimental support for the clinical reports that prenatal glucocorticoid treatment impairs social development and predisposes to metabolic syndrome. These novel primate findings indicate that fetal glucocorticoid overexposure can lead to abnormal development of motor, affective, and cognitive behaviors. Importantly, the outcome is highly dependent upon the timing of glucocorticoid overexposure.

  15. Evidence that metyrapone can act as a stressor: effect on pituitary-adrenal hormones, plasma glucose and brain c-fos induction.

    Science.gov (United States)

    Rotllant, David; Ons, Sheila; Carrasco, Javier; Armario, Antonio

    2002-08-01

    Metyrapone, a 11-beta steroid hydroxylase inhibitor that blocks stress-induced glucocorticoid release, is extensively used to study the physiological and behavioural roles of glucocorticoids. However, there is circumstantial evidence suggesting that metyrapone could act as a pharmacological stressor. Thus, the effects of various doses of metyrapone on two well-characterized stress markers (ACTH and glucose) were studied in male rats. Metyrapone administration, while exerting a modest effect on plasma corticosterone levels, dose-dependently increased plasma ACTH and glucose levels. Using the highest doses previously tested (200 mg/kg) we further observed, as evaluated by fos-like immunoreactivity (FLI), a strong activation of a wide range of brain areas, including the parvocellular region of the hypothalamic paraventricular nucleus (PVNp), the origin of the main ACTH secretagogues. Metyrapone-induced FLI was observed in neocortical and allocortical areas, in several limbic, thalamic and hypothalamic nuclei and, to a lesser extent, in the brainstem. In a final experiment, a dose-response study of metyrapone-induced FLI was carried out focusing on selected brain areas. The study revealed that the paraventricular thalamic nucleus and central amygdala were the areas most sensitive to metyrapone as they responded even to the lowest dose of the drug. Most areas, among them the PVNp, only showed enhanced FLI with the two highest doses, i.e. when it was associated with ACTH and glucose responses. These data suggest that some of the effects of metyrapone could be due to its stressful properties rather than its ability to inhibit glucocorticoid synthesis. The exact mechanisms involved remain to be established.

  16. Vestibular function testing.

    LENUS (Irish Health Repository)

    Lang, E E

    2010-06-01

    Vestibular symptoms of vertigo, dizziness and dysequilibrium are common complaints which can be disabling both physically and psychologically. Routine examination of the ear nose and throat and neurological system are often normal in these patients. An accurate history and thorough clinical examination can provide a diagnosis in the majority of patients. However, in a subgroup of patients, vestibular function testing may be invaluable in arriving at a correct diagnosis and ultimately in the optimal treatment of these patients.

  17. Functional Testing Airborne Radars

    Science.gov (United States)

    1981-03-27

    recorded, and presented in accordance with this TOP? Yes No Comment : 2. Were the facilities, test equipment, instrumentation, and support accommo- dations...adequate to accomplish the test objectives? Yes No Comment : 3. Have all data collected been reviewed for correctness and completeness? Yes No ... Comment : 4. Were the test results compromised in any way due to insufficient test planning? Yes No . Comment : 5. Were the test results compromised in any

  18. Testing properties of generic functions

    NARCIS (Netherlands)

    Jansson, P.; Jeuring, J.T.; Cabenda, L.; Engels, G.; Kleerekoper, J.; Mak, S.; Overeem, M.; Visser, Kees

    2006-01-01

    Software testing is an important part of the software devel- opment process. Testing comes in many flavours: unit testing, property testing, regression testing, contract checking, etc. QuickCheck is proba- bly one of the most advanced tools for testing properties of functional programs. It

  19. Testing properties of generic functions

    NARCIS (Netherlands)

    Jansson, P.; Jeuring, J.T.; Cabenda, L.; Engels, G.; Kleerekoper, J.; Mak, S.; Overeem, M.; Visser, Kees

    2007-01-01

    A datatype-generic function is a family of functions indexed by (the structure of) a type. Examples include equality tests, maps and pretty printers. Property based testing tools like QuickCheck and Gast support the de¯nition of properties and test-data generators, and they check if a

  20. Biological and psychological markers of stress in humans: focus on the Trier Social Stress Test.

    Science.gov (United States)

    Allen, Andrew P; Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2014-01-01

    Validated biological and psychological markers of acute stress in humans are an important tool in translational research. The Trier Social Stress Test (TSST), involving public interview and mental arithmetic performance, is among the most popular methods of inducing acute stress in experimental settings, and reliably increases hypothalamic-pituitary-adrenal axis activation. However, although much research has focused on HPA axis activity, the TSST also affects the sympathetic-adrenal-medullary system, the immune system, cardiovascular outputs, gastric function and cognition. We critically assess the utility of different biological and psychological markers, with guidance for future research, and discuss factors which can moderate TSST effects. We outline the effects of the TSST in stress-related disorders, and if these responses can be abrogated by pharmacological and psychological treatments. Modified TSST protocols are discussed, and the TSST is compared to alternative methods of inducing acute stress. Our analysis suggests that multiple readouts are necessary to derive maximum information; this strategy will enhance our understanding of the psychobiology of stress and provide the means to assess novel therapeutic agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. LUNG FUNCTION TESTING IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Matjaž Fležar

    2004-03-01

    Full Text Available Background. Lung function testing in children above five years old is standardised similarly as is in adult population (1. Nevertheless bronchial provocation testing can be more hazardous since the calibre and reactivity of childhood airway is different. We analysed the frequency of different lung function testing procedures and addressed the safety issues of bronchial provocation testing in children.Methods. We analysed lung function testing results in 517 children, older than 5 years, tested in our laboratory in threeyear period. Spirometry was done in every patient, metacholine provocation test was used as a part of diagnostic work-up in suspected asthma. In case of airway obstruction, bronchodilator test with salbutamol was used instead of a metacholine provocation test.Results. The most common procedure in children was spirometry with bronchial provocation test as a part of diagnostic work-up of obstructive syndrome (mostly asthma. 291 children required metacholine test and 153 tests were interpreted as positive. The decline in expiratory flows (forced expiratory flow in first second – FEV1 in positive tests was greater than in adult population as was the dose of metacholine, needed to induce bronchoconstriction. The compliance of children was better than in adults.Conclusions. Lung function testing in children is reliable and safe and can be done in a well-standardised laboratory that follows the regulations of such testing in adults.

  2. Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: associations with clinical symptoms.

    Science.gov (United States)

    Bruce, Kenneth R; Steiger, Howard; Israël, Mimi; Groleau, Patricia; Ng Ying Kin, N M K; Ouellette, Anne-Sophie; Sycz, Lindsay; Badawi, Ghislaine

    2012-08-07

    Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Effects of childhood trauma exposure and cortisol levels on cognitive functioning among breast cancer survivors.

    Science.gov (United States)

    Kamen, Charles; Scheiber, Caroline; Janelsins, Michelle; Jo, Booil; Shen, Hanyang; Palesh, Oxana

    2017-10-01

    Cognitive functioning difficultiesin breast cancer patients receiving chemotherapy are common, but not all women experience these impairments. Exposure to childhood trauma may impair cognitive functioning following chemotherapy, and these impairments may be mediated by dysregulation of hypothalamic-pituitary-adrenal (HPA) axis function and cortisol slope. This study evaluated the association between childhood trauma exposure, cortisol, and cognition in a sample of breast cancer survivors. 56 women completed measures of trauma exposure (the Traumatic Events Survey), salivary cortisol, and self-reported cognitive functioning (the Functional Assessment of Cancer Therapy - Cognitive). We examined correlations between childhood trauma exposure and cognitive functioning, then used linear regression to control for factors associated with cognition (age, education, time since chemotherapy, depression, anxiety, and insomnia), and the MacArthur approach to test whether cortisol levels mediated the relationship between trauma and cognitive functioning. 57.1% of the sample had experienced at least one traumatic event in childhood, with 19.6% of the sample witnessing a serious injury, 17.9% experiencing physical abuse, and 14.3% experiencing sexual abuse. Childhood trauma exposure and cognitive functioning were moderately associated (r=-0.29). This association remained even when controlling for other factors associated with cognition; the final model explained 47% of the variance in cognitive functioning. The association between childhood trauma and cognitive functioning was mediated by steeper cortisol slope (partial r=0.35, p=0.02). Childhood trauma exposure is associated with self-reported cognitive functioning among breast cancer survivors and is mediated by cortisol dysregulation. Trauma should be considered, among other factors, in programs aiming to address cognition in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Functional tests for myocardial ischemia

    International Nuclear Information System (INIS)

    Levinson, J.R.; Guiney, T.E.; Boucher, C.A.

    1991-01-01

    Functional tests for myocardial ischemia are numerous. Most depend upon a combination of either exercise or pharmacologic intervention with analysis of the electrocardiogram, of regional perfusion with radionuclide imaging, or of regional wall motion with radionuclide imaging or echocardiography. While each test has unique features, especially at the research level, they are generally quite similar in clinical practice, so the clinician is advised to concentrate on one or two in which local expertise is high.22 references

  5. Safety of pulmonary function testing

    DEFF Research Database (Denmark)

    Roberts, Cara; Ward, Simon; Walsted, Emil

    2017-01-01

    BACKGROUND: Pulmonary function testing (PFT) is a key investigation in the evaluation of individuals with respiratory symptoms; however, the safety of routine and specialised PFT testing has not been reported in a large data set. Using patient safety incident (PSI) records, we aimed to assess risk...... was rated using the NHS National Patient Safety Agency and any hospital admission reported. RESULTS: There were 119 PSIs reported from 186 000 PFT; that is, 0.6 PSIs per 1000 tests. Cardiopulmonary PSIs were 3.3 times more likely to occur than non-cardiopulmonary (95% CI 2.17 to 5.12). Syncope was the most...

  6. Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Cooper, Odelia; Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

    2017-06-01

    Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Prospective controlled study in an outpatient clinic. Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm 3 [standard deviation (SD), 227.3 mm 3 ] in PTSD subjects vs 835.2 mm 3 (SD, 302.8 mm 3 ) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects ( P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches.

  7. Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

    Science.gov (United States)

    Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

    2017-01-01

    Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

  8. Cortisol and cognitive function in midlife: the role of childhood cognition and educational attainment.

    Science.gov (United States)

    Gaysina, Darya; Gardner, Michael P; Richards, Marcus; Ben-Shlomo, Yoav

    2014-09-01

    Adult cognition and age-related cognitive decline can be influenced by dysregulation of the hypothalamic pituitary adrenal axis with concomitant changes in cortisol levels. However, very little is known about the role of childhood cognition and educational attainment in this relationship. Using data from the British 1946 birth cohort, the present study investigated: (1) associations between cortisol levels and patterns and cognitive function in midlife; (2) direct and interactive effects of childhood cognition, educational attainment and cortisol on cognitive function in midlife. Verbal memory, letter search speed and reaction time were assessed at age 60-64 years. Salivary cortisol samples (wakening, 30 min after wakening and evening) were collected at the same age. Childhood cognitive ability was measured at ages 8, 11, and 15, and educational level was reported at age 26. Associations between cortisol, childhood cognition, educational attainment and cognitive function in midlife were tested using linear regression and structural equation modelling approaches. Higher evening cortisol level was associated with slower reaction time and lower verbal memory. These associations were independent of childhood cognition and education as well as a range of other potential confounders. Childhood cognition and education were not directly associated with evening cortisol. However, there was a significant interaction effect between childhood cognition and evening cortisol on reaction time (p=.002): higher evening cortisol was associated with slower reaction time only among those with low childhood cognitive ability. There was little evidence of associations between the other cortisol measures and cognitive function. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.

    Science.gov (United States)

    Elias, E; Benrick, A; Behre, C J; Ekman, R; Zetterberg, H; Stenlöf, K; Wallenius, V

    2011-06-01

    Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ = 0.695, P fat distribution and central HPA axis mediators. The importance of these findings is unclear but could suggest a role for CSF L-PGDS in the regulation of visceral obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

  10. Repetitive stress leads to impaired cognitive function that is associated with DNA hypomethylation, reduced BDNF and a dysregulated HPA axis.

    Science.gov (United States)

    Makhathini, Khayelihle B; Abboussi, Oualid; Stein, Dan J; Mabandla, Musa V; Daniels, William M U

    2017-08-01

    Exposure to repetitive stress has a negative influence on cognitive-affective functioning, with growing evidence that these effects may be mediated by a dysregulated hypothalamic-pituitary-adrenal (HPA) axis, abnormal neurotrophic factor levels and its subsequent impact on hippocampal function. However, there are few data about the effect of repetitive stressors on epigenetic changes in the hippocampus. In the present study, we examine how repetitive restrain stress (RRS) affects cognitive-affective functioning, HPA axis regulation, brain-derived neurotrophic factor (BDNF) levels, and global hippocampal DNA methylation. RRS was induced in rats by restraining the animals for 6h per day for 28 days. The novel object recognition test (NORT) was used to assess cognitive functioning and the open field test (OFT) was performed to assess anxiety-like behavior during the last week of stress. Hippocampal BDNF levels, glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA were assessed using real-time PCR and confirmed with Western blot, while ELISAs were used to determine plasma corticosterone levels and the global methylation status of the hippocampus. Animals exposed to repetitive stress demonstrated significant alterations in the NORT and OFT, had significantly increased plasma corticosterone and significantly decreased hippocampal BDNF concentrations. The expression levels of GR and MR mRNA and protein levels of these genes were significantly decreased in the stressed group compared to control animals. The global DNA methylation of the hippocampal genome of stressed animals was also significantly decreased compared to controls. The data here are consistent with previous work emphasizing the role of the HPA axis and neurotrophic factors in mediating cognitive-affective changes after exposure to repetitive stressors. Our findings, however, extend the literature by indicating that epigenetic alterations in the hippocampal genome may also play an important role in the

  11. 14 CFR 35.40 - Functional test.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Functional test. 35.40 Section 35.40... STANDARDS: PROPELLERS Tests and Inspections § 35.40 Functional test. The variable-pitch propeller system must be subjected to the applicable functional tests of this section. The same propeller system used in...

  12. Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults.

    Science.gov (United States)

    Sasayama, Daimei; Hori, Hiroaki; Iijima, Yoshimi; Teraishi, Toshiya; Hattori, Kotaro; Ota, Miho; Fujii, Takashi; Higuchi, Teruhiko; Amano, Naoji; Kunugi, Hiroshi

    2011-07-05

    Recently, hypothalamus-pituitary-adrenal (HPA) axis function assessed with the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944) in the interleukin-1beta (IL-1β) gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between IL-1β gene polymorphisms and HPA axis function assessed with the DEX/CRH test. DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 ± 15.8 years; 134 females: mean age 47.1 ± 13.2 years). Five tagging single nucleotide polymorphisms (SNPs) of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were selected at an r2 threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA) was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, P values rs16944 (P = 0.00049) and rs1143633 (P = 0.0060), with no significant gender effect or genotype × gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol) were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype × gender interaction. Our results suggest that genetic variations in the IL-1β gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the IL-1β gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into the communication between the immune system and the HPA axis.

  13. Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis

    NARCIS (Netherlands)

    Kalsbeek, A.; van der Spek, R.; Lei, J.; Endert, E.; Buijs, R. M.; Fliers, E.

    2012-01-01

    The pronounced daily variation in the release of adrenal hormones has been at the heart of the deciphering and understanding of the circadian timing system. Indeed, the first demonstration of an endocrine day/night rhythm was provided by Pincus (1943), by showing a daily pattern of 17-keto-steroid

  14. The Minimal Model of the Hypothalamic-Pituitary-Adrenal Axis

    DEFF Research Database (Denmark)

    Vinther, Frank; Andersen, Morten; Ottesen, Johnny T.

    2011-01-01

    -physiological values of the parameters are needed in order to achieve local instability of the fixed point. Small changes inphysiologically relevant parameters cause the system to be globally stable using the analytical criteria. All simulations show a globally stable fixed point, ruling out periodic solutions even...... are modeled as a system of three coupled, nonlinear differential equations. Experimental data shows the circadian as well as the ultradian rhythm. This paper focuses on the ultradian rhythm. The ultradian rhythm can mathematically be explained by oscillating solutions. Oscillating solutions to an ODE emerges...... from an unstable fixed point with complex eigenvalues with a positive real parts and a non-zero imaginary parts. The first part of the paper describes the general considerations to be obeyed for a mathematical model of the HPA axis. In this paper we only include the most widely accepted mechanisms...

  15. Pulmonary Function Testing in Children

    Science.gov (United States)

    ... breathing test. About 15 minutes after taking the medicine, your child will repeat the breathing test. The results from ... the first test to find out if the medicine has improved your child’s breathing. Why shouldn’t I give my child ...

  16. Increased cortisol responsivity to adrenocorticotropic hormone and low plasma levels of interleukin-1 receptor antagonist in women with functional hypothalamic amenorrhea.

    Science.gov (United States)

    Lindahl, Magnus S; Olovsson, Matts; Nyberg, Sigrid; Thorsen, Kim; Olsson, Tommy; Sundström Poromaa, Inger

    2007-01-01

    To assess the hypothalamic-pituitary-adrenal (HPA) axis at all levels, to determine the origin of the previously reported hypercortisolism in patients with functional hypothalamic amenorrhea. A secondary aim was to evaluate factors outside the central nervous system which are known to affect the HPA axis, i.e., circulating levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and fat mass-adjusted leptin levels, in patients with functional hypothalamic amenorrhea and healthy controls. Cross-sectional study. Umeå University Hospital, Umeå, Sweden. Fifteen subjects with hypothalamic amenorrhea, and 14 age- and weight-matched controls. None. We collected blood samples four times during a 24-hour interval for analysis of cortisol, leptin, IL-1Ra, and IL-6 levels. We performed a low-dose oral dexamethasone test and a low-dose ACTH test. We measured body-fat percentage using a dual-energy X-ray absorptiometer. Patients with hypothalamic amenorrhea had increased diurnal cortisol levels (P<.001). The cortisol response to intravenous low-dose ACTH was increased in functional hypothalamic amenorrhea patients compared to control subjects (P<.01), but they had similar rates of dexamethasone suppression. Patients with hypothalamic amenorrhea also had decreased diurnal leptin (P<.05), and decreased diurnal IL-1Ra levels (P<.05), compared to controls. Body-fat percentage was the main predictor of leptin levels. The present study suggests novel links for the development of functional hypothalamic amenorrhea, including increased adrenal responsiveness and impairments in proinflammatory cytokine pathways.

  17. Sex-specific association between functional neuropeptide S receptor gene (NPSR1) variants and cortisol and central stress responses.

    Science.gov (United States)

    Streit, Fabian; Akdeniz, Ceren; Haddad, Leila; Kumsta, Robert; Entringer, Sonja; Frank, Josef; Yim, Ilona S; Zänkert, Sandra; Witt, Stephanie H; Kirsch, Peter; Rietschel, Marcella; Wüst, Stefan

    2017-02-01

    The brain neuropeptide S (NPS) system has recently generated substantial interest and may be of major relevance for central stress regulation. The NPS receptor (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated. In humans, associations between NPSR1 variants and anxiety and panic disorder, as well as amygdala responsiveness to fear- relevant faces and prefrontal cortex activity in a fear conditioning paradigm have been reported. Moreover, a NPSR1 sequence variant was found to be associated with cortisol stress responses in males. Here, we performed a haplotype-based analysis covering three functional NPSR1 single nucleotide polymorphisms in the promoter (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects who were exposed to the Trier Social Stress Test (TSST). A significant sex-specific association with salivary cortisol responses to acute psychosocial stress was detected for the common TTC haplotype 2 (frequency of about 20%). In an additional study using an imaging genetics approach, 65 healthy subjects were exposed to a stress paradigm for scanner environments (“ScanSTRESS”). We found a significant and, again, sex-specific interaction between rs324981 (whose minor T-allele is harbored by haplotype 2) and the neural stress response in a cluster close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the TSST sample, NPSR1 variation was associated with salivary cortisol responses (on a trend level) in a sex-specific way. In summary, our preliminary findings in two independent cohorts exposed to different stress paradigms suggest that the NPS system significantly influences acute stress responses and that sequence variation in NPSR1 may contribute to sex differences in stress regulation. Copyright © 2016

  18. How to interpret liver function tests

    Directory of Open Access Journals (Sweden)

    Christina Levick

    2017-05-01

    Full Text Available Careful interpretation of liver function tests within the clinical context can help elucidate the cause and severity of the underlying pathology. Predominantly raised alkaline phosphatase represents the cholestatic pattern of biliary pathology, whilst predominantly raised alanine aminotransferase and aspartate aminotransferase represent the hepatocellular pattern of hepatocellular pathology. The severity of liver dysfunction or biliary obstruction is reflected in the bilirubin level and the degree of liver synthetic function can also be indicated by the albumin level. Beyond the liver function tests, prothrombin time provides another marker of liver synthetic function and a low platelet count suggests portal hypertension.

  19. Test bank for precalculus functions & graphs

    CERN Document Server

    Kolman, Bernard; Levitan, Michael L

    1984-01-01

    Test Bank for Precalculus: Functions & Graphs is a supplementary material for the text, Precalculus: Functions & Graphs. The book is intended for use by mathematics teachers.The book contains standard tests for each chapter in the textbook. Each set of test focuses on gauging the level of knowledge the student has achieved during the course. The answers for each chapter test and the final exam are found at the end of the book.Mathematics teachers teaching calculus will find the book extremely useful.

  20. Nonparametric tests for equality of psychometric functions.

    Science.gov (United States)

    García-Pérez, Miguel A; Núñez-Antón, Vicente

    2017-12-07

    Many empirical studies measure psychometric functions (curves describing how observers' performance varies with stimulus magnitude) because these functions capture the effects of experimental conditions. To assess these effects, parametric curves are often fitted to the data and comparisons are carried out by testing for equality of mean parameter estimates across conditions. This approach is parametric and, thus, vulnerable to violations of the implied assumptions. Furthermore, testing for equality of means of parameters may be misleading: Psychometric functions may vary meaningfully across conditions on an observer-by-observer basis with no effect on the mean values of the estimated parameters. Alternative approaches to assess equality of psychometric functions per se are thus needed. This paper compares three nonparametric tests that are applicable in all situations of interest: The existing generalized Mantel-Haenszel test, a generalization of the Berry-Mielke test that was developed here, and a split variant of the generalized Mantel-Haenszel test also developed here. Their statistical properties (accuracy and power) are studied via simulation and the results show that all tests are indistinguishable as to accuracy but they differ non-uniformly as to power. Empirical use of the tests is illustrated via analyses of published data sets and practical recommendations are given. The computer code in MATLAB and R to conduct these tests is available as Electronic Supplemental Material.

  1. Summary of functional and performance test procedures

    DEFF Research Database (Denmark)

    Mitzel, Jens; Gülzow, Erich; Friedrich, K. Andreas

    Different Test Modules (TM) are defined for the functional and performance characterization of a PEMFC stack. The master document TM2.00 defines requirements and methodology for parameter variation, stability and data acquisition.......Different Test Modules (TM) are defined for the functional and performance characterization of a PEMFC stack. The master document TM2.00 defines requirements and methodology for parameter variation, stability and data acquisition....

  2. Functional and nonfunctional testing of ATM networks

    Science.gov (United States)

    Ricardo, Manuel; Ferreira, M. E. P.; Guimaraes, Francisco E.; Mamede, J.; Henriques, M.; da Silva, Jorge A.; Carrapatoso, E.

    1995-02-01

    ATM network will support new multimedia services that will require new protocols, those services and protocols will need different test strategies and tools. In this paper, the concepts of functional and non-functional testers of ATM networks are discussed, a multimedia service and its requirements are presented and finally, a summary description of an ATM network and of the test tool that will be used to validate it are presented.

  3. Indications and interpretation of esophageal function testing.

    Science.gov (United States)

    Gyawali, C Prakash; de Bortoli, Nicola; Clarke, John; Marinelli, Carla; Tolone, Salvatore; Roman, Sabine; Savarino, Edoardo

    2018-05-12

    Esophageal symptoms are common, and can arise from mucosal, motor, functional, and neoplastic processes, among others. Judicious use of diagnostic testing can help define the etiology of symptoms and can direct management. Endoscopy, esophageal high-resolution manometry (HRM), ambulatory pH or pH-impedance manometry, and barium radiography are commonly used for esophageal function testing; functional lumen imaging probe is an emerging option. Recent consensus guidelines have provided direction in using test findings toward defining mechanisms of esophageal symptoms. The Chicago Classification describes hierarchical steps in diagnosing esophageal motility disorders. The Lyon Consensus characterizes conclusive evidence on esophageal testing for a diagnosis of gastroesophageal reflux disease (GERD), and establishes a motor classification of GERD. Taking these recent advances into consideration, our discussion focuses primarily on the indications, technique, equipment, and interpretation of esophageal HRM and ambulatory reflux monitoring in the evaluation of esophageal symptoms, and describes indications for alternative esophageal tests. © 2018 New York Academy of Sciences.

  4. Platelet function testing in pediatric patients

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Favaloro, Emmanuel J

    2017-01-01

    Introduction: Platelets play a key role in primary hemostasis and are also intricately linked to secondary hemostasis. Investigation of platelet function in children, especially in neonates, is seriously challenged by the volumes required to perform the majority of platelet function tests and due...

  5. Liver Function Tests in Tuberculoid Leprosy

    Directory of Open Access Journals (Sweden)

    R V Korane

    1979-01-01

    Full Text Available A total of 24 patients with untreated tuberculoid leprosy were taken up for study, They were the same group of patients in whom the authors have earlier reported involvement of liver in 85 % cases. Five healthy controls, studied also belonged to the same series. Liver function tests included prothrombin time, serum bilirubin, zinc sulphate turbidity, serum proteins and serum transaminases. No significant alterations in the liver function were observed. This is because the changes in the liver were so minimal and focal that they were not reflected in the various liver function tests.

  6. ELEFUNT, Testing of Elementary Function Subroutines

    International Nuclear Information System (INIS)

    Cody, W.J.

    1981-01-01

    1 - Description of problem or function: ELEFUNT is a FORTRAN test package for the elementary functions. Each program is an aggressive test of one or more of the elementary function subroutines generally supplied with the support library accompanying a FORTRAN compiler. Functions tested are ALOG/ALOG10, ASIN/ACOS, ATAN, EXP, POWER, SIN/ COS, SINH/COSH, SQRT, TAN/COTAN, and TANH. 2 - Method of solution: The programs check the accuracy of the functions by using purified random arguments from appropriate intervals in carefully selected identities. They also check special properties of each function, test for the handling of special arguments, and exercise the error returns. 3 - Restrictions on the complexity of the problem: The package contains one subroutine (MACHAR) for dynamic determination of parameters describing the floating-point arithmetic system of the host machine, the test programs must be modified to insert the necessary machine- dependent parameters in DATA statements, or otherwise make them available. This computing environment inquiry routine is known to malfunction when the arithmetic registers are wider than the storage registers

  7. Quantum algorithms for testing Boolean functions

    Directory of Open Access Journals (Sweden)

    Erika Andersson

    2010-06-01

    Full Text Available We discuss quantum algorithms, based on the Bernstein-Vazirani algorithm, for finding which variables a Boolean function depends on. There are 2^n possible linear Boolean functions of n variables; given a linear Boolean function, the Bernstein-Vazirani quantum algorithm can deterministically identify which one of these Boolean functions we are given using just one single function query. The same quantum algorithm can also be used to learn which input variables other types of Boolean functions depend on, with a success probability that depends on the form of the Boolean function that is tested, but does not depend on the total number of input variables. We also outline a procedure to futher amplify the success probability, based on another quantum algorithm, the Grover search.

  8. Semen analysis and sperm function tests: How much to test?

    Directory of Open Access Journals (Sweden)

    S S Vasan

    2011-01-01

    Full Text Available Semen analysis as an integral part of infertility investigations is taken as a surrogate measure for male fecundity in clinical andrology, male fertility, and pregnancy risk assessments. Clearly, laboratory seminology is still very much in its infancy. In as much as the creation of a conventional semen profile will always represent the foundations of male fertility evaluation, the 5th edition of the World Health Organization (WHO manual is a definitive statement on how such assessments should be carried out and how the quality should be controlled. A major advance in this new edition of the WHO manual, resolving the most salient critique of previous editions, is the development of the first well-defined reference ranges for semen analysis based on the analysis of over 1900 recent fathers. The methodology used in the assessment of the usual variables in semen analysis is described, as are many of the less common, but very valuable, sperm function tests. Sperm function testing is used to determine if the sperm have the biologic capacity to perform the tasks necessary to reach and fertilize ova and ultimately result in live births. A variety of tests are available to evaluate different aspects of these functions. To accurately use these functional assays, the clinician must understand what the tests measure, what the indications are for the assays, and how to interpret the results to direct further testing or patient management.

  9. CIT photoheliograph functional verification unit test program

    Science.gov (United States)

    1973-01-01

    Tests of the 2/3-meter photoheliograph functional verification unit FVU were performed with the FVU installed in its Big Bear Solar Observatory vacuum chamber. Interferometric tests were run both in Newtonian (f/3.85) and Gregorian (f/50) configurations. Tests were run in both configurations with optical axis horizontal, vertical, and at 45 deg to attempt to determine any gravity effects on the system. Gravity effects, if present, were masked by scatter in the data associated with the system wavefront error of 0.16 lambda rms ( = 6328A) apparently due to problems in the primary mirror. Tests showed that the redesigned secondary mirror assembly works well.

  10. Functional Testing of Wireless Sensor Node Designs

    DEFF Research Database (Denmark)

    Virk, Kashif M.; Madsen, Jan

    2007-01-01

    Wireless sensor networks are networked embedded computer systems with stringent power, performance, cost and form-factor requirements along with numerous other constraints related to their pervasiveness and ubiquitousness. Therefore, only a systematic design methdology coupled with an efficient...... test approach can enable their conformance to design and deployment specifications. We discuss off-line, hierarchical, functional testing of complete wireless sensor nodes containing configurable logic through a combination of FPGA-based board test and Software-Based Self-Test (SBST) techniques...

  11. Esophageal function testing: Billing and coding update.

    Science.gov (United States)

    Khan, A; Massey, B; Rao, S; Pandolfino, J

    2018-01-01

    Esophageal function testing is being increasingly utilized in diagnosis and management of esophageal disorders. There have been several recent technological advances in the field to allow practitioners the ability to more accurately assess and treat such conditions, but there has been a relative lack of education in the literature regarding the associated Common Procedural Terminology (CPT) codes and methods of reimbursement. This review, commissioned and supported by the American Neurogastroenterology and Motility Society Council, aims to summarize each of the CPT codes for esophageal function testing and show the trends of associated reimbursement, as well as recommend coding methods in a practical context. We also aim to encourage many of these codes to be reviewed on a gastrointestinal (GI) societal level, by providing evidence of both discrepancies in coding definitions and inadequate reimbursement in this new era of esophageal function testing. © 2017 John Wiley & Sons Ltd.

  12. An automated system for pulmonary function testing

    Science.gov (United States)

    Mauldin, D. G.

    1974-01-01

    An experiment to quantitate pulmonary function was accepted for the space shuttle concept verification test. The single breath maneuver and the nitrogen washout are combined to reduce the test time. Parameters are defined from the forced vital capacity maneuvers. A spirometer measures the breath volume and a magnetic section mass spectrometer provides definition of gas composition. Mass spectrometer and spirometer data are analyzed by a PDP-81 digital computer.

  13. Daily family stress and HPA axis functioning during adolescence: The moderating role of sleep

    Science.gov (United States)

    Chiang, Jessica J.; Tsai, Kim M.; Park, Heejung; Bower, Julienne E.; Almeida, David M.; Dahl, Ronald E.; Irwin, Michael R.; Seeman, Teresa E.; Fuligni, Andrew J.

    2017-01-01

    The present study examined the moderating role of sleep in the association between family demands and conflict and hypothalamic-pituitary-adrenal (HPA) axis functioning in a sample of ethnically diverse adolescents (n = 316). Adolescents completed daily diary reports of family demands and conflict for 15 days, and wore actigraph watches during the first 8 nights to assess sleep. Participants also provided five saliva samples for 3 consecutive days to assess diurnal cortisol rhythms. Regression analyses indicated that sleep latency and efficiency moderated the link between family demands and the cortisol awakening response. Specifically, family demands were related to a smaller cortisol awakening response only among adolescents with longer sleep latency and lower sleep efficiency. These results suggest that certain aspects of HPA axis functioning may be sensitive to family demands primarily in the context of longer sleep latency and lower sleep efficiency. PMID:27235639

  14. Gestational cortisol and social play shape development of marmosets' HPA functioning and behavioral responses to stressors.

    Science.gov (United States)

    Mustoe, Aaryn C; Taylor, Jack H; Birnie, Andrew K; Huffman, Michelle C; French, Jeffrey A

    2014-09-01

    Both gestational cortisol exposure (GCE) and variability in postnatal environments can shape the later-life behavioral and endocrine outcomes of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the influence of GCE and social play on HPA functioning in developing marmosets. Maternal urinary cortisol samples were collected across pregnancy to determine GCE for 28 marmoset offspring (19 litters). We administered a social separation stressor to offspring at 6, 12, and 18 months of age, during which we collected urinary cortisol samples and behavioral observations. Increased GCE was associated with increased basal cortisol levels and cortisol reactivity, but the strength of this relationship decreased across age. Increased social play was associated with decreased basal cortisol levels and a marginally greater reduction in cortisol reactivity as offspring aged, regardless of offspring GCE. Thus, GCE is associated with HPA functioning, but socially enriching postnatal environments can alter the effects associated with increased fetal exposure to glucocorticoids. © 2014 Wiley Periodicals, Inc.

  15. Pulmonary function testing in children and infants

    International Nuclear Information System (INIS)

    Vogt, B; Weiler, N; Frerichs, I; Falkenberg, C

    2014-01-01

    Pulmonary function testing is performed in children and infants with the aim of documenting lung development with age and making diagnoses of lung diseases. In children and infants with an established lung disease, pulmonary function is tested to assess the disease progression and the efficacy of therapy. It is difficult to carry out the measurements in this age group without disturbances, so obtaining results of good quality and reproducibility is challenging. Young children are often uncooperative during the examinations. This is partly related to their young age but also due to the long testing duration and the unpopular equipment. We address a variety of examination techniques for lung function assessment in children and infants in this review. We describe the measuring principles, examination procedures, clinical findings and their interpretation, as well as advantages and limitations of these methods. The comparability between devices and centres as well as the availability of reference values are still considered a challenge in many of these techniques. In recent years, new technologies have emerged allowing the assessment of lung function not only on the global level but also on the regional level. This opens new possibilities for detecting regional lung function heterogeneity that might lead to a better understanding of respiratory pathophysiology in children. (topical review)

  16. Gas Test Loop Functional and Technical Requirements

    International Nuclear Information System (INIS)

    Glen R. Longhurst; Soli T. Khericha; James L. Jones

    2004-01-01

    This document defines the technical and functional requirements for a gas test loop (GTL) to be constructed for the purpose of providing a high intensity fast-flux irradiation environment for developers of advanced concept nuclear reactors. This capability is needed to meet fuels and materials testing requirements of the designers of Generation IV (GEN IV) reactors and other programs within the purview of the Advanced Fuel Cycle Initiative (AFCI). Space nuclear power development programs may also benefit by the services the GTL will offer. The overall GTL technical objective is to provide developers with the means for investigating and qualifying fuels and materials needed for advanced reactor concepts. The testing environment includes a fast-flux neutron spectrum of sufficient intensity to perform accelerated irradiation testing. Appropriate irradiation temperature, gaseous environment, test volume, diagnostics, and access and handling features are also needed. This document serves to identify those requirements as well as generic requirements applicable to any system of this kind

  17. Gas Test Loop Functional and Technical Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Glen R. Longhurst; Soli T. Khericha; James L. Jones

    2004-09-01

    This document defines the technical and functional requirements for a gas test loop (GTL) to be constructed for the purpose of providing a high intensity fast-flux irradiation environment for developers of advanced concept nuclear reactors. This capability is needed to meet fuels and materials testing requirements of the designers of Generation IV (GEN IV) reactors and other programs within the purview of the Advanced Fuel Cycle Initiative (AFCI). Space nuclear power development programs may also benefit by the services the GTL will offer. The overall GTL technical objective is to provide developers with the means for investigating and qualifying fuels and materials needed for advanced reactor concepts. The testing environment includes a fast-flux neutron spectrum of sufficient intensity to perform accelerated irradiation testing. Appropriate irradiation temperature, gaseous environment, test volume, diagnostics, and access and handling features are also needed. This document serves to identify those requirements as well as generic requirements applicable to any system of this kind.

  18. Do functional tests predict low back pain?

    Science.gov (United States)

    Takala, E P; Viikari-Juntura, E

    2000-08-15

    A cohort of 307 nonsymptomatic workers and another cohort of 123 workers with previous episodes of low back pain were followed up for 2 years. The outcomes were measured by symptoms, medical consultations, and sick leaves due to low back disorders. To study the predictive value of a set of tests measuring the physical performance of the back in a working population. The hypothesis was that subjects with poor functional capacity are liable to back disorders. Reduced functional performance has been associated with back pain. There are few data to show whether reduced functional capacity is a cause or a consequence of pain. Mobility of the trunk in forward and side bending, maximal isokinetic trunk extension, flexion and lifting strength, and static endurance of back extension were measured. Standing balance and foot reaction time were recorded with a force plate. Clinical tests for the provocation of back or leg pain were performed. Gender, workload, age, and anthropometrics were managed as potential confounders in the analysis. Marked overlapping was seen in the measures of the subjects with different outcomes. Among the nonsymptomatic subjects, low performance in tests of mobility and standing balance was associated with future back disorders. Among workers with previous episodes of back pain, low isokinetic extension strength, poor standing balance, and positive clinical signs predicted future pain. Some associations were found between the functional tests and future low back pain. The wide variation in the results questions the value of the tests in health examinations (e.g., in screening or surveillance of low back disorders).

  19. Radioimmunoassay for estimation of 11-deoxycortisol in plasma. Application for metopirone-test

    International Nuclear Information System (INIS)

    Hubl, W.; Buechner, M.; Haussig, K.; Rohde, W.; Stahl, F.

    1978-01-01

    A radioimmunoassay for the measurement of 11-deoxycortisol in plasma is described. Antiserum against 11-deoxycortisol was produced by immunizing rabbits with the 21-hemisuccinate of 11-deoxycortisol coupled to bovine serum albumin. The method does not require chromatography but instead makes use of a simple extraction procedure which, in combination with the antibody characteristics, is relatively specific for the 11-deoxycortisol determination. The smallest amount measurable is 5 pg. The intra-assay coefficient of variation was 6.3% before metopirone and 7.2% after metopirone. The inter-assay coefficient of variation was 12.5% before metopirone and 10.3% after metopirone. Pituitary-adrenal reserve was evaluted in control and hypopituitary subjects by a simple midnight metopirone test. (author)

  20. The EORTC emotional functioning computerized adaptive test

    DEFF Research Database (Denmark)

    Gamper, Eva-Maria; Grønvold, Mogens; Petersen, Morten Aa

    2014-01-01

    The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group is currently developing computerized adaptive testing measures for the Quality of Life Questionnaire Core-30 (QLQ-C30) scales. The work presented here describes the development of an EORTC item bank for e...... for emotional functioning (EF), which is one of the core domains of the QLQ-C30....

  1. Update on endoscopic pancreatic function testing

    Institute of Scientific and Technical Information of China (English)

    Tyler Stevens; Mansour A Parsi

    2011-01-01

    Hormone-stimulated pancreatic function tests (PFTs) are considered the gold standard for measuring pancreatic exocrine function. PFTs involve the administration of intravenous secretin or cholecystokinin, followed by collection and analysis of pancreatic secretions. Because exocrine function may decline in the earliest phase of pancreatic fibrosis, PFTs are considered accurate for diagnosing chronic pancreatitis. Unfortunately, these potentially valuable tests are infrequently performed except at specialized centers, because they are time consuming and complicated. To overcome these limitations, endoscopic PFT methods have been developed which include aspiration of pancreatic secretions through the suction channel of the endoscope. The secretin endoscopic pancreatic function test (ePFT) involves collection of duodenal aspirates at 15, 30, 45 and 60 min after secretin stimulation. A bicarbonate concentration greater than 80 mmol/L in any of the samples is considered a normal result. The secretin ePFT has demonstrated good sensitivity and specificity compared with various reference standards, including the "Dreiling tube" secretin PFT, endoscopic ultrasound, and surgical histology. Furthermore, a standard autoanalyzer can be used for bicarbonate analysis, which allows the secretin ePFT to be performed at any hospital. The secretin ePFT may complement imaging tests like endoscopic ultrasound (EUS) in the diagnosis of early chronic pancreatitis.This paper will review the literature validating the use of ePFT in the diagnosis of exocrine insufficiency and chronic pancreatitis. Newer developments will also be discussed, including the feasibility of combined EUS/ePFT, the use of cholecystokinin alone or in combination with secretin, and the discovery of new protein and lipid pancreatic juice biomarkers which may complement traditionalfluid analysis.

  2. Functional hypothalamic amenorrhea due to increased CRH tone in melanocortin receptor 2-deficient mice.

    Science.gov (United States)

    Matsuwaki, Takashi; Nishihara, Masugi; Sato, Tsuyoshi; Yoda, Tetsuya; Iwakura, Yoichiro; Chida, Dai

    2010-11-01

    Exposure to chronic stressors results in dysregulation of the hypothalamic-pituitary-adrenal axis and a disruption in reproduction. CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis induces the secretion of ACTH from the pituitary, which stimulates adrenal steroidogenesis via the specific cell-surface melanocortin 2 receptor (MC2R). Previously, we demonstrated that MC2R(-/-) mice had undetectable levels of corticosterone despite high ACTH levels. Here, we evaluated the reproductive functions of female MC2R(-/-) mice and analyzed the mechanism of the disrupted cyclicity of these mice. The expression of CRH in the paraventricular nucleus was significantly increased in MC2R(-/-) mice under nonstressed conditions. Although MC2R(-/-) females were fertile, they showed a prolonged estrous cycle. After hormonal stimulation, MC2R(-/-) females produced nearly-normal numbers of eggs, but slightly less than MC2R(+/-) females, and showed near-normal ovarian histology. During diestrus, the number of GnRH-positive cells in the medial preoptic area was significantly reduced in MC2R(-/-) females. CRH type 1 receptor antagonist restored estrous cyclicity in MC2R(-/-) females. Kisspeptin-positive areas in the arcuate nucleus were comparable, whereas kisspeptin-positive areas in the anteroventral periventricular nucleus in MC2R(-/-) females were significantly reduced compared with MC2R(+/-) females, suggesting that arcuate nucleus kisspeptin is not involved, but anteroventral periventricular nucleus kisspeptin may be involved, in the maintenance of estrous cyclicity. Our findings show that high levels of hypothalamic CRH disturb estrous cyclicity in the female animals and that the MC2R(-/-) female is a unique animal model of functional hypothalamic amenorrhea.

  3. The intramuscular glucagon stimulation test does not provide good discrimination between normal and inadequate ACTH reserve when used in the investigation of short healthy children.

    Science.gov (United States)

    Tenenbaum, Ariel; Phillip, Moshe; de Vries, Liat

    2014-01-01

    Few studies have addressed the role of the glucagon stimulation test (GST) in evaluating the hypothalamic-pituitary-adrenal axis in children. We investigated the diagnostic value of the GST in evaluating the adrenocortical response in short healthy children. The GST was performed in 190 children investigated for short stature. A peak cortisol >500 nmol/l was considered a normal response. In the 45 (23.7%) with subnormal response, a 250-μg ACTH test was done. The rate of subnormal adrenal response to GST was higher among boys (33.9 vs. 8.9%, p 500 nmol/l in all the patients undergoing an ACTH stimulation test. Since adrenal response to GST is age- and gender-related and the false-positive rate is high, its routine performance in healthy children warrants reconsideration. © 2014 S. Karger AG, Basel.

  4. A test for measuring gustatory function.

    Science.gov (United States)

    Smutzer, Gregory; Lam, Si; Hastings, Lloyd; Desai, Hetvi; Abarintos, Ray A; Sobel, Marc; Sayed, Nabil

    2008-08-01

    The purpose of this study was to determine the usefulness of edible taste strips for measuring human gustatory function. The physical properties of edible taste strips were examined to determine their potential for delivering threshold and suprathreshold amounts of taste stimuli to the oral cavity. Taste strips were then assayed by fluorescence to analyze the uniformity and distribution of bitter tastant in the strips. Finally, taste recognition thresholds for sweet taste were examined to determine whether or not taste strips could detect recognition thresholds that were equal to or better than those obtained from aqueous tests. Edible strips were prepared from pullulan-hydroxypropyl methylcellulose solutions that were dried to a thin film. The maximal amount of a tastant that could be incorporated in a 2.54 cm2 taste strip was identified by including representative taste stimuli for each class of tastant (sweet, sour, salty, bitter, and umami) during strip formation. Distribution of the bitter tastant quinine hydrochloride in taste strips was assayed by fluorescence emission spectroscopy. The efficacy of taste strips for evaluating human gustatory function was examined by using a single series ascending method of limits protocol. Sucrose taste recognition threshold data from edible strips was then compared with results that were obtained from a standard "sip and spit" recognition threshold test. Edible films that formed from a pullulan-hydroxypropyl methylcellulose polymer mixture can be used to prepare clear, thin strips that have essentially no background taste and leave no physical presence after release of tastant. Edible taste strips could uniformly incorporate up to 5% of their composition as tastant. Taste recognition thresholds for sweet taste were over one order of magnitude lower with edible taste strips when compared with an aqueous taste test. Edible taste strips are a highly sensitive method for examining taste recognition thresholds in humans. This

  5. Water chemistry management during hot functional test

    International Nuclear Information System (INIS)

    Yokoyama, Jiro; Kanda, Tomio; Kagawa, Masaru

    1988-01-01

    To reduce radiation exposure in light water reactor, it is important decrease radioactive corrosion product which is a radiation source. One of the countermeasures is to improve water quality during plant trial operation to form a stable oxide film and to minimize metal release to the coolant at the beginning of commercial operation. This study reviews the optimum water quality conditions to form a chromium rich oxide film during hot functional test (HFT) that is thought to be stable under the PWR condition and reduce the release of Ni that is the source of Co-58, the main radiation source of exposure. (author)

  6. Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test.

    Science.gov (United States)

    Maniaci, G; Goudriaan, A E; Cannizzaro, C; van Holst, R J

    2018-03-01

    Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress response was measured during and after the TSST by salivary cortisol and cardiac interbeat intervals; impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Exposure to the TSST produced a significant increase in salivary cortisol and interbeat intervals in both groups, without differences between groups. We found a negative correlation between baseline cortisol and duration of pathological gambling indicating that the longer the duration of the disorder the lower the baseline cortisol levels. Additionally, we found a main effect of impulsivity across groups on interbeat interval during the TSST, indicating an association between impulsivity and the intensity of the neurovegetative stress response during the TSST. Involvement of the hypothalamic-pituitary-adrenal axis in pathological gambling was confirmed together with evidence of a correlation between length of the disorder and diminished baseline cortisol levels. Impulsivity emerged as a personality trait expressed by pathological gamblers; however the neurovegetative response to the TSST, although associated with impulsivity, appeared to be independent of the presence of pathological gambling.

  7. Validity of an Interactive Functional Reach Test.

    Science.gov (United States)

    Galen, Sujay S; Pardo, Vicky; Wyatt, Douglas; Diamond, Andrew; Brodith, Victor; Pavlov, Alex

    2015-08-01

    Videogaming platforms such as the Microsoft (Redmond, WA) Kinect(®) are increasingly being used in rehabilitation to improve balance performance and mobility. These gaming platforms do not have built-in clinical measures that offer clinically meaningful data. We have now developed software that will enable the Kinect sensor to assess a patient's balance using an interactive functional reach test (I-FRT). The aim of the study was to test the concurrent validity of the I-FRT and to establish the feasibility of implementing the I-FRT in a clinical setting. The concurrent validity of the I-FRT was tested among 20 healthy adults (mean age, 25.8±3.4 years; 14 women). The Functional Reach Test (FRT) was measured simultaneously by both the Kinect sensor using the I-FRT software and the Optotrak Certus(®) 3D motion-capture system (Northern Digital Inc., Waterloo, ON, Canada). The feasibility of implementing the I-FRT in a clinical setting was assessed by performing the I-FRT in 10 participants with mild balance impairments recruited from the outpatient physical therapy clinic (mean age, 55.8±13.5 years; four women) and obtaining their feedback using a NASA Task Load Index (NASA-TLX) questionnaire. There was moderate to good agreement between FRT measures made by the two measurement systems. The greatest agreement between the two measurement system was found with the Kinect sensor placed at a distance of 2.5 m [intraclass correlation coefficient (2,k)=0.786; PNASA/TLX questionnaire. FRT measures made using the Kinect sensor I-FRT software provides a valid clinical measure that can be used with the gaming platforms.

  8. Integrated Locomotor Function Tests for Countermeasure Evaluation

    Science.gov (United States)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Landsness, E. C.; Black, F. O.

    2005-01-01

    Following spaceflight crewmembers experience locomotor dysfunction due to inflight adaptive alterations in sensorimotor function. Countermeasures designed to mitigate these postflight gait alterations need to be assessed with a new generation of tests that evaluate the interaction of various sensorimotor sub-systems central to locomotor control. The goal of the present study was to develop new functional tests of locomotor control that could be used to test the efficacy of countermeasures. These tests were designed to simultaneously examine the function of multiple sensorimotor systems underlying the control of locomotion and be operationally relevant to the astronaut population. Traditionally, gaze stabilization has been studied almost exclusively in seated subjects performing target acquisition tasks requiring only the involvement of coordinated eye-head movements. However, activities like walking involve full-body movement and require coordination between lower limbs and the eye-head-trunk complex to achieve stabilized gaze during locomotion. Therefore the first goal of this study was to determine how the multiple, interdependent, full-body sensorimotor gaze stabilization subsystems are functionally coordinated during locomotion. In an earlier study we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects walked on a treadmill and either focused on a central point target or read numeral characters. We measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. In comparison to the point target fixation condition, the results of the number reading task showed that compensatory head pitch movements increased, peak head acceleration was reduced and knee flexion at heel-strike was increased. In a more recent study we investigated the

  9. Hot functional test chemistry - long term experience

    International Nuclear Information System (INIS)

    Vonkova, K.; Kysela, J.; Marcinsky, M.; Martykan, M.

    2010-01-01

    Primary circuit materials undergo general corrosion in high temperature, deoxygenated, neutral or mildly alkaline solutions to form thin oxide films. These oxide layers (films) serve as protective film and mitigate the further corrosion of primary materials. Inner chromium-rich oxide layer has low cation diffusion coefficients and thus control iron and nickel transport from the metal surface to the outer layer and their dissolution into the coolant. Much less corrosion products are generated by the compact, integral and stable oxide (passivation) layer. For the latest Czech and Slovak stations commissioned (Temelin and Mochovce) a modified Hot Functional Test (HFT) chemistry was developed in the NRI Rez. Chromium rich surface layer formatted due to modified HTF chemistry ensures lower corrosion rates and radiation field formation and thus also mitigates crud formation during operation. This procedure was also designed to prepare the commissioned unit for the further proper water chemistry practise. Mochovce 1 (SK) was the first station commissioned using these recommendations in 1998. Mochovce 2 (1999) and Temelin 1 and 2 (CZ - 2000 and 2002) were subsequently commissioned using these guidelines too. The main principles of the controlled primary water chemistry applied during the hot functional tests are reviewed and importance of the water chemistry, technological and other relevant parameters is stressed regarding to the quality of the passive layer formed on the primary system surfaces. Samples from Mochovce indicated that duplex oxide layers up to 20 μm thick were produced, which were mainly magnetite substituted with nickel and chromium (e.g. 60-65% Fe, 18-28% Cr, 9-12% Ni, <1% Mn and 1-2% Si on a stainless steel primary circuit sample). Long term operation experience from both nuclear power plants are discussed in this paper. Radiation field, occupational radiation exposure and corrosion layers evolution during the first c. ten years of operation are

  10. Functional testing of the ATLAS SCT barrels

    International Nuclear Information System (INIS)

    Phillips, Peter W.

    2007-01-01

    The ATLAS SCT (semiconductor tracker) comprises 2112 barrel modules mounted on four concentric barrels of length 1.6m and up to 1m diameter, and 1976 endcap modules supported by a series of nine wheels at each end of the barrel region, giving a total silicon area of 60m 2 . The assembly of modules onto each of the four barrel structures has recently been completed. In addition to functional tests made during the assembly process, each completed barrel was operated in its entirety. In the case of the largest barrel, with an active silicon area of approximately 10m 2 , this corresponds to more than one million instrumented channels. This paper documents the electrical performance of the four individual SCT barrels. An overview of the readout chain is also given

  11. Basic pulmonary function tests in pig farmers

    Directory of Open Access Journals (Sweden)

    Đuričić Slaviša M.

    2004-01-01

    Full Text Available INTRODUCTION Many epidemiological and clinical studies have demonstrated an increased risk for the symptoms of respiratory disorders consistent with chronic bronchitis and asthma and alterations of pulmonary function tests in pig farmers. AIM The aim of this study was to determine basic pulmonary function values in workers in swine confinement buildings and to compare them with the same values in the control group of unexposed persons. The next aim was to examine the association between these values with duration of professional exposure, cigarette smoking, age, and sex of the examined persons. METHODS We randomly selected for examination 145 workers of both sex who had worked for at least 2 previous years in pig farms and spent at least 3 hours per day, 6 days per week in a swine confinement building. The farmers worked at 6 different farms with 12,383 pigs on average on each farms. The subject was eligible for the study if he had had no history of atopic disease nor any serious chronic disease, and no acute respiratory infection within 3 previous months. As control group we examined 156 subjects who had lived and/or worked in the same areas and had had no history of exposure to farming environment or any other known occupational air pollutants. In both groups the study comprised cigarette smokers and persons who had never smoked. Pulmonary function data were collected according to the standard protocol with a Micro Spirometer, (Micro Medical Ltd, England, UK. The registered parameters were FEV1 and FVC At least three satisfactory forced maximal expirations were performed by each subject and the best value was accepted for analyses. The results were also expressed as a percentage of predicted values and FEV1/FVCxlOO was calculated. RESULTS There were no differences in the main demographic characteristics between two examined groups (Table1. Mean duration of work in pig farming was 11.6 years (SD=8.5; range 2-40. The average values of examined

  12. Fort St. Vrain hot functional test results

    International Nuclear Information System (INIS)

    Phelps, R.D.

    1974-01-01

    A description is given of Fort St. Vrain hot functional tests performed to evaluate the initial nonnuclear performance of the primary coolant system and the associated effects on the various internal components of the reactor vessel and primary coolant system. The components included the twelve steam generator modules, the four helium circulators, the PCRV thermal barrier and liner coolant system, the helium purification system, and the primary and secondary closures at each of the PCRV penetrations. Additional objectives included analysis of the parallel operation of the four helium circulators and the performance of several circulator start/stop transients under various conditions of primary coolant temperature and pressure. Vibration and acoustical phenomena within the vessel were measured, recorded, and compared to theoretical analyses; a verification of reverse flow in the shutdown loop steam generator during one loop operation was performed; the PCRV was again observed for its structural response to internal pressure; and comparisons were made relative to data recorded during the initial pressure test completed in July 1971. (U.S.)

  13. Modulation of cortisol responses to the DEX/CRH test by polymorphisms of the interleukin-1beta gene in healthy adults

    Directory of Open Access Journals (Sweden)

    Ota Miho

    2011-07-01

    Full Text Available Abstract Background Recently, hypothalamus-pituitary-adrenal (HPA axis function assessed with the combined dexamethasone (DEX/corticotropin releasing hormone (CRH test has been shown to be associated with response to antidepressant treatment. A polymorphism (rs16944 in the interleukin-1beta (IL-1β gene has also been reported to be associated with the medication response in depression. These findings prompted us to examine the possible association between IL-1β gene polymorphisms and HPA axis function assessed with the DEX/CRH test. Methods DEX/CRH test was performed in 179 healthy volunteers (45 males: mean age 40.5 ± 15.8 years; 134 females: mean age 47.1 ± 13.2 years. Five tagging single nucleotide polymorphisms (SNPs of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944 were selected at an r2 threshold of 0.80 with a minor allele frequency > 0.1. Genotyping was performed by the TaqMan allelic discrimination assay. A two-way factorial analysis of variance (ANOVA was performed with the DEX/CRH test results as the dependent variable and genotype and gender as independent variables. To account for multiple testing, P values Results The cortisol levels after DEX administration (DST-Cortisol showed significant associations with the genotypes of rs16944 (P = 0.00049 and rs1143633 (P = 0.0060, with no significant gender effect or genotype × gender interaction. On the other hand, cortisol levels after CRH administration (DEX/CRH-Cortisol were affected by gender but were not significantly influenced by the genotype of the examined SNPs, with no significant genotype × gender interaction. Conclusions Our results suggest that genetic variations in the IL-1β gene contribute to the HPA axis alteration assessed by DST-Cortisol in healthy subjects. On the other hand, no significant associations of the IL-1β gene polymorphisms with the DEX/CRH-Cortisol were observed. Confirmation of our findings in futures studies may add new insight into

  14. Kinetic test of pancreatic exocrine function

    International Nuclear Information System (INIS)

    Sawabu, Norio; Hirose, Shoichiro; Nakazima, Shin; Yoneda, Masao; Nishimura, Keigo

    1975-01-01

    In order to improve the diagnostic evaluation of pancreatic exocrine function, 75 Se-activity in the duodenal aspirate of twenty control subjects and 131 subjects with pancertic and/or gastrointestinal disease was measured following intravenous injection of 75 Se-selenomethionine. Radioactivity in the duodenal aspirate of the control subjects remained low until 80 min. It then rose rapidly and reached a plateau at 115 min. In contrast, radioactivity in the subjects with pancreatic diseases remained low, or rose only slowly throughout the period of collection. Radioactivity of the protein fraction (TCA-precipitable) in the 80 to 130 min. duodenal aspirates showed good separation between controls and subjects with pancreatic disease. The incidence of abnormalities of TCA-precipitable radioactivity in the 80 to 130 min. duodenal aspirates was significantly higher than that of the conventional PS-test parameters in groups with various pancreatic diseases. All of the subjects having an abnormal maximal ratio of TCA-precipitable radioactivity to protein (representing pancreatic enzyme synthesis) showed an abnormal distribution in output of TCA-precipitable radioactivity in 80 to 130 min. collection (representing both enzyme synthesis and excretion). On the other hand, subjects with an abnormal output of TCA-precipitable radioactivity in 80 to 130 min. could be separated into those with normal and abnormal ratios of TCA-precipitable radioactivity, suggesting the presence of two types of disturbance in pancreatic function. In the latter group both synthesis and secretion of enzyme were impaired. In the former group, secretion of enzyme was depressed, although enzyme synthesis was fairly well preserved. (author)

  15. Kinetic test of pancreatic exocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Sawabu, N; Hirose, S; Nakazima, S; Yoneda, M; Nishimura, K [Kanazawa Univ. (Japan). School of Medicine

    1975-01-01

    In order to improve the diagnostic evaluation of pancreatic exocrine function, /sup 75/Se-activity in the duodenal aspirate of twenty control subjects and 131 subjects with pancertic and/or gastrointestinal disease was measured following intravenous injection of /sup 75/Se-selenomethionine. Radioactivity in the duodenal aspirate of the control subjects remained low until 80 min. It then rose rapidly and reached a plateau at 115 min. In contrast, radioactivity in the subjects with pancreatic diseases remained low, or rose only slowly throughout the period of collection. Radioactivity of the protein fraction (TCA-precipitable) in the 80 to 130 min. duodenal aspirates showed good separation between controls and subjects with pancreatic disease. The incidence of abnormalities of TCA-precipitable radioactivity in the 80 to 130 min. duodenal aspirates was significantly higher than that of the conventional PS-test parameters in groups with various pancreatic diseases. All of the subjects having an abnormal maximal ratio of TCA-precipitable radioactivity to protein (representing pancreatic enzyme synthesis) showed an abnormal distribution in output of TCA-precipitable radioactivity in 80 to 130 min. collection (representing both enzyme synthesis and excretion). On the other hand, subjects with an abnormal output of TCA-precipitable radioactivity in 80 to 130 min. could be separated into those with normal and abnormal ratios of TCA-precipitable radioactivity, suggesting the presence of two types of disturbance in pancreatic function. In the latter group both synthesis and secretion of enzyme were impaired. In the former group, secretion of enzyme was depressed, although enzyme synthesis was fairly well preserved.

  16. Gall bladder function test with Ceruletid

    International Nuclear Information System (INIS)

    Schindler, G.

    1981-01-01

    Compared with the stimulating food given orally in the gall bladder function test the administration of the decapeptide Ceruletid which is related with Cholecystokinin has the advantage of avoiding resorption disturbances in the upper gastrointestinal tract. To 100 patients with positive peroral cholecystography, Ceruletid was injected i.m. in a dose of 0.4 μg/kg body weight. The contrasting of the main bile duct was thus increased from 10% to 86%. The oral stimulating food brings an increase to appr. 20%. A special importance is assigned to the frequent diagnosis of adenomyomatoses which, with 6%, lies significantly above the 0.8% achieved by means of the oral stimulating food. More contractile segments of the gall bladder wall can cause pain symptoms which are typical for the biliary tract. Adenomyomatoses in the region of the infundibulum of the gall bladder cause colicky pains and are, as generally accepted, an absolute indication for a surgical intervention. The finding of small gall bladder conrements is often connected with a strong diminution of the gall bladder in order to prevent the small concrements from being overlapped by the non-contrasting bladder bile. Therefore, the application of Ceruletid should be considered also within the frame of the intravenous cholegraphy, thinking of the large number of normal gall bladder findings which were obtained with the oral stimulating food as the only diagnostical help. (orig./MG) [de

  17. Diurnal Cortisol Patterns and Dexamethasone Suppression Test Responses in Healthy Young Adults Born Preterm at Very Low Birth Weight.

    Directory of Open Access Journals (Sweden)

    Nina Kaseva

    Full Text Available Early life stress, such as painful and stressful procedures during neonatal intensive care after preterm birth, can permanently affect physiological, hormonal and neurobiological systems. This may contribute to altered programming of the hypothalamic-pituitary-adrenal axis (HPAA and provoke changes in HPAA function with long-term health impacts. Previous studies suggest a lower HPAA response to stress in young adults born preterm compared with controls born at term. We assessed whether these differences in HPAA stress responsiveness are reflected in everyday life HPAA functioning, i.e. in diurnal salivary cortisol patterns, and reactivity to a low-dose dexamethasone suppression test (DST, in unimpaired young adults born preterm at very low birth weight (VLBW; <1500 g.The participants were recruited from the Helsinki Study of Very Low Birth Weight Adults cohort study. At mean age 23.3 years (2.1 SD, 49 VLBW and 36 controls born at term participated in the study. For cortisol analyzes, saliva samples were collected on two consecutive days at 0, 15, 30 and 60 min after wake-up, at 12:00 h, 17:00 h and 22:00 h. After the last salivary sample of the first study day the participants were instructed to take a 0.5 mg dexamethasone tablet.With mixed-effects model no difference was seen in overall diurnal salivary cortisol between VLBW and control groups [13.9% (95% CI: -11.6, 47.0, P = 0.31]. Salivary cortisol increased similarly after awakening in both VLBW and control participants [mean difference -2.9% (29.2, 33.0, P = 0.85]. Also reactivity to the low-dose DST (awakening cortisol ratio day2/day1 was similar between VLBW and control groups [-1.1% (-53.5, 103.8, P = 0.97].Diurnal cortisol patterns and reactivity to a low-dose DST in young adulthood were not associated with preterm birth.

  18. Significance tests for functional data with complex dependence structure

    KAUST Repository

    Staicu, Ana-Maria; Lahiri, Soumen N.; Carroll, Raymond J.

    2015-01-01

    We propose an L (2)-norm based global testing procedure for the null hypothesis that multiple group mean functions are equal, for functional data with complex dependence structure. Specifically, we consider the setting of functional data with a

  19. Quality of Liver and Kideny Function Test

    African Journals Online (AJOL)

    GB

    results for kidney functions and liver functions in. HIV diagnostic and monitoring laboratory are extremely important for decision making with patients under ART programs, and the consequences of erroneous results are huge (8, 9). 1University of Bahir Dar, Biological Inorganic Chemistry, P.O.Box-79, Bahir Dar, Ethiopia.

  20. 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.

  1. Platelet Function Tests: Preanalytical Variables, Clinical Utility, Advantages, and Disadvantages.

    Science.gov (United States)

    Hvas, Anne-Mette; Grove, Erik Lerkevang

    2017-01-01

    Platelet function tests are mainly used in the diagnostic work-up of platelet disorders. During the last decade, the additional use of platelet function tests to evaluate the effect of antiplatelet therapy has also emerged in an attempt to identify patients with an increased risk of arterial thrombosis. Furthermore, platelet function tests are increasingly used to measure residual effect of antiplatelet therapy prior to surgery with the aim of reducing the risk of bleeding. To a limited extend, platelet function tests are also used to evaluate hyperaggregability as a potential marker of a prothrombotic state outside the setting of antiplatelet therapy. This multifaceted use of platelet function tests and the development of simpler point-of-care tests with narrower application have increased the use of platelet function testing and also facilitated the use of platelet function tests outside the highly specialized laboratories. The present chapter describes the preanalytical variables, which should be taken into account when planning platelet function testing. Also, the most widely used platelet function tests are introduced, and their clinical utility and their relative advantages and disadvantages are discussed.

  2. Axial force measurement for esophageal function testing

    DEFF Research Database (Denmark)

    Gravesen, Flemming Holbæk; Funch-Jensen, Peter; Gregersen, Hans

    2009-01-01

    force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external...... force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been...... documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe...

  3. [Syncope: electrocardiogram and autonomic function tests].

    Science.gov (United States)

    Uribe, William; Baranchuk, Adrián; Botero, Federico

    2016-12-23

    Syncope represents one of the most frequent reasons for consultation in the emergency department. A proper identification will allow a precise etiologic approach and the optimization of delivery of health resources.
Once knowing the classification of syncope; it is the clinical interrogatory what enables to discriminate which of these patients present with a neurogenic mediated syncope or a cardiac mediated syncope. The use of diagnostic methods such as the tilt test, will clarify what type of neurally mediated syncope predominates in the patient.
The electrocardiogram is the cornerstone in the identification of those patients who had a true episode of self-limited or aborted sudden death as the first manifestation of their syncope, a fact which provides prognostic and therapeutic information that will impact the morbidity and mortality.

  4. Executive Functioning Profiles and Test Anxiety in College Students

    Science.gov (United States)

    O'Donnell, Patrick S.

    2017-01-01

    The current study attempted to answer whether a specific executive functioning profile for individuals with test anxiety exists and whether deficits in working memory are associated with an earlier onset of test anxiety. Two hundred eighty-four undergraduate students completed a survey on test anxiety and self-report measures of test anxiety and…

  5. Visceral pain hypersensitivity in functional gastrointestinal disorders.

    Science.gov (United States)

    Farmer, A D; Aziz, Q

    2009-01-01

    Functional gastrointestinal disorders (FGIDs) are a highly prevalent group of heterogeneous disorders whose diagnostic criteria are symptom based in the absence of a demonstrable structural or biochemical abnormality. Chronic abdominal pain or discomfort is a defining characteristic of these disorders and a proportion of patients may display heightened pain sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity (VPH). We examined the most recent literature in order to concisely review the evidence for some of the most important recent advances in the putative mechanisms concerned in the pathophysiology of VPH. VPH may occur due to anomalies at any level of the visceral nociceptive neuraxis. Important peripheral and central mechanisms of sensitization that have been postulated include a wide range of ion channels, neurotransmitter receptors and trophic factors. Data from functional brain imaging studies have also provided evidence for aberrant central pain processing in cortical and subcortical regions. In addition, descending modulation of visceral nociceptive pathways by the autonomic nervous system, hypothalamo-pituitary-adrenal axis and psychological factors have all been implicated in the generation of VPH. Particular areas of controversy have included the development of efficacious treatment of VPH. Therapies have been slow to emerge, mainly due to concerns regarding safety. The burgeoning field of genome wide association studies may provide further evidence for the pleiotropic genetic basis of VPH development. Tangible progress will only be made in the treatment of VPH when we begin to individually characterize patients with FGIDs based on their clinical phenotype, genetics and visceral nociceptive physiology.

  6. IMPORTANCE OF THYROID FUNCTION TEST IN DIABETES

    Directory of Open Access Journals (Sweden)

    Mohd.

    2015-05-01

    Full Text Available BACKGROUND : Thyroid disorder and Diabetes are both hormone and endocrine and problems. When thyroid disease occurs in someone with diabetes, it can make blood glucose control more difficult. The incidence and occurrence of thyroid diseases in general population is increasing more and more day by day . As the prevalence of diabetes and thyroid both is more in India, correlation of these two diseases was studied in this study. MATERIAL AND METHOD: this study was conducted on 105 diabetic (both type I and II patients attending Outpatient Department. Thyroid tests including TSH, and T4 were measured using enzyme immune assay. RESULTS: We have enrolled 105 patients which are Prediabetes, and Type 2 Diabetes Mellitus. Out of these 55 are male and 50 patients are females. 68 patients are on oral hypoglycemic drugs and 28 patients are on insulin with oral hypoglycemic agents, 09 patients were only on Diabetic D iet. We have observed that patient with diabetes predominantly females were having abnormal thyroid levels than compared to control group. Hypothyroidism was seen to be more common in females than in males in both the control and study group. Similarly hyp erthyroidism also seems to be common in females compared to males in both diabetic and non - diabetic groups (Perros P 1995. DISCUSSION: Abnormal thyroid hormone levels were observed more commonly in study group than in control group. Hypothyroidism was see n to be more common in females than in males in both the control and study group. Similarly hyperthyroidism also seems to be common in females compared to males in both diabetic and non - diabetic groups

  7. 15N liver function tests - concept, validity, clinical use

    International Nuclear Information System (INIS)

    Faust, H.; Jung, K.; Krumbiegel, P.; Hirschberg, K.; Reinhardt, R.; Junghans, P.

    1987-01-01

    Several liver function tests using the oral application of a nitrogen compound labelled with 15 N and the subsequent determination of 15 N in a certain fraction of urine by emission spectrometry are described. Because of the key position of the liver in the metabolism of nitrogen compounds the results of these tests allow conclusions concerning disturbances of special liver functions. Instructions for the clinical use of the '[ 15 N]Ammonium Test', '[ 15 N]Hippurate Test' the '[ 15 N]Methacetin Test', and the '[ 15 N]Glycine Test' are given. (author)

  8. Experimental fast reactor JOYO MK-III functional test. Primary auxiliary cooling system test

    International Nuclear Information System (INIS)

    Karube, Koji; Akagi, Shinji; Terano, Toshihiro; Onuki, Osamu; Ito, Hideaki; Aoki, Hiroshi; Odo, Toshihiro

    2004-03-01

    This paper describes the results of primary auxiliary cooling system, which were done as a part of JOYO MK-III function test. The aim of the tests was to confirm the operational performance of primary auxiliary EMP and the protection system including siphon breaker of primary auxiliary cooling system. The items of the tests were: (Test No.): (Test item). 1) SKS-117: EMP start up test. 2) SKS-118-1: EMP start up test when pony motor running. 3) SKS-121: Function test of siphon breaker. The results of the tests satisfied the required performance, and demonstrated successful operation of primary auxiliary cooling system. (author)

  9. 33 CFR 157.12f - Workshop functional test requirements.

    Science.gov (United States)

    2010-07-01

    ... CARRYING OIL IN BULK Design, Equipment, and Installation § 157.12f Workshop functional test requirements... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Workshop functional test requirements. 157.12f Section 157.12f Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND...

  10. Significance tests for functional data with complex dependence structure.

    Science.gov (United States)

    Staicu, Ana-Maria; Lahiri, Soumen N; Carroll, Raymond J

    2015-01-01

    We propose an L 2 -norm based global testing procedure for the null hypothesis that multiple group mean functions are equal, for functional data with complex dependence structure. Specifically, we consider the setting of functional data with a multilevel structure of the form groups-clusters or subjects-units, where the unit-level profiles are spatially correlated within the cluster, and the cluster-level data are independent. Orthogonal series expansions are used to approximate the group mean functions and the test statistic is estimated using the basis coefficients. The asymptotic null distribution of the test statistic is developed, under mild regularity conditions. To our knowledge this is the first work that studies hypothesis testing, when data have such complex multilevel functional and spatial structure. Two small-sample alternatives, including a novel block bootstrap for functional data, are proposed, and their performance is examined in simulation studies. The paper concludes with an illustration of a motivating experiment.

  11. Significance tests for functional data with complex dependence structure

    KAUST Repository

    Staicu, Ana-Maria

    2015-01-01

    We propose an L (2)-norm based global testing procedure for the null hypothesis that multiple group mean functions are equal, for functional data with complex dependence structure. Specifically, we consider the setting of functional data with a multilevel structure of the form groups-clusters or subjects-units, where the unit-level profiles are spatially correlated within the cluster, and the cluster-level data are independent. Orthogonal series expansions are used to approximate the group mean functions and the test statistic is estimated using the basis coefficients. The asymptotic null distribution of the test statistic is developed, under mild regularity conditions. To our knowledge this is the first work that studies hypothesis testing, when data have such complex multilevel functional and spatial structure. Two small-sample alternatives, including a novel block bootstrap for functional data, are proposed, and their performance is examined in simulation studies. The paper concludes with an illustration of a motivating experiment.

  12. A New Nonlinear Unit Root Test with Fourier Function

    OpenAIRE

    Güriş, Burak

    2017-01-01

    Traditional unit root tests display a tendency to be nonstationary in the case of structural breaks and nonlinearity. To eliminate this problem this paper proposes a new flexible Fourier form nonlinear unit root test. This test eliminates this problem to add structural breaks and nonlinearity together to the test procedure. In this test procedure, structural breaks are modeled by means of a Fourier function and nonlinear adjustment is modeled by means of an Exponential Smooth Threshold Autore...

  13. A test of conformal invariance: Correlation functions on a disk

    International Nuclear Information System (INIS)

    Badke, R.; Rittenberg, V.; Ruegg, H.

    1985-06-01

    Using conformal invariance one can derive the correlation functions of a disk from those in the half-plane. The correlation function in the half-plane is determined by the 'small' conformal invariance up to an unknown function of one variable. By measuring through the Monte Carlo method the correlation function for two different configurations, the unknown function can be eliminated and one obtains a test of conformal invariance. It is shown that the Ising and the three state Potts model pass the test for very small lattices. (orig.)

  14. Liver function tests using the stable istope 15N

    International Nuclear Information System (INIS)

    Faust, H.; Jung, K.; Hirschberg, K.; Krumbiegel, P.; Junghans, P.; Reinhardt, R.; Teichmann, B.

    1988-01-01

    Several liver function tests using oral application of a nitrogen compound labelled with 15 N and the subsequent determination of 15 N in a certain fraction of urine or in the total urine by emission spectrometry are described. Because of the key function of the liver in the metabolism of nitrogen compounds, the results of these tests allow conclusions concerning some disturbances of liver functions. (author)

  15. Liver function tests using the stable isotope /sup 15/N

    Energy Technology Data Exchange (ETDEWEB)

    Faust, H; Jung, K; Hirschberg, K; Krumbiegel, P; Junghans, P; Reinhardt, R; Matkowitz, R; Teichmann, B

    1988-01-01

    Several liver function tests using oral application of a nitrogen compound labelled with /sup 15/N and the subsequent determination of /sup 15/N in a certain fraction of urine or in the total urine by emission spectrometry are described. Because of the key function of the liver in the metabolism of nitrogen compounds, the results of these tests allow conclusions concerning some disturbances of liver functions.

  16. Functions and Design Scheme of Tibet High Altitude Test Base

    Institute of Scientific and Technical Information of China (English)

    Yu Yongqing; Guo Jian; Yin Yu; Mao Yan; Li Guangfan; Fan Jianbin; Lu Jiayu; Su Zhiyi; Li Peng; Li Qingfeng; Liao Weiming; Zhou Jun

    2010-01-01

    @@ The functional orientation of the Tibet High Altitude Test Base, subordinated to the State Grid Corporation of China (SGCC), is to serve power transmission projects in high altitude areas, especially to provide technical support for southwestern hydropower delivery projects by UHVDC transmission and Qinghai-Tibet grid interconnection project. This paper presents the matters concerned during siting and planning, functions,design scheme, the main performances and parameters of the test facilities, as well as the tests and research tasks already carried out.

  17. Bandwidth Analysis of Functional Interconnects Used as Test Access Mechanism

    NARCIS (Netherlands)

    Van den Berg, A.; Ren, P.; Marinissen, E.J.; Gaydadjiev, G.; Goossens, K.

    2010-01-01

    Test data travels through a System on Chip (SOC) from the chip pins to the Core-Under-Test (CUT) and vice versa via a Test Access Mechanism (TAM). Conventionally, a TAM is implemented using dedicated communication infrastructure. However, also existing functional interconnect, such as a bus or

  18. Bandwidth analysis of functional interconnects used as test access mechanism

    NARCIS (Netherlands)

    Berg, van den Ardy; Ren, P.; Marinissen, Erik Jan; Gaydadjiev, G.N.; Goossens, K.G.W.

    2010-01-01

    Test data travels through a System on Chip (SOC) from the chip pins to the Core-Under-Test (CUT) and vice versa via a Test Access Mechanism (TAM). Conventionally, a TAM is implemented using dedicated communication infrastructure. However, also existing functional interconnect, such as a bus or

  19. Detection of differential item functioning using Lagrange multiplier tests

    NARCIS (Netherlands)

    Glas, Cornelis A.W.

    1998-01-01

    Abstract: In the present paper it is shown that differential item functioning can be evaluated using the Lagrange multiplier test or Rao’s efficient score test. The test is presented in the framework of a number of IRT models such as the Rasch model, the OPLM, the 2-parameter logistic model, the

  20. Detection of differential item functioning using Lagrange multiplier tests

    NARCIS (Netherlands)

    Glas, Cornelis A.W.

    1996-01-01

    In this paper it is shown that differential item functioning can be evaluated using the Lagrange multiplier test or C. R. Rao's efficient score test. The test is presented in the framework of a number of item response theory (IRT) models such as the Rasch model, the one-parameter logistic model, the

  1. Sensitivity and Specificity of Clinical and Laboratory Otolith Function Tests.

    Science.gov (United States)

    Kumar, Lokesh; Thakar, Alok; Thakur, Bhaskar; Sikka, Kapil

    2017-10-01

    To evaluate clinic based and laboratory tests of otolith function for their sensitivity and specificity in demarcating unilateral compensated complete vestibular deficit from normal. Prospective cross-sectional study. Tertiary care hospital vestibular physiology laboratory. Control group-30 healthy adults, 20-45 years age; Case group-15 subjects post vestibular shwannoma excision or post-labyrinthectomy with compensated unilateral complete audio-vestibular loss. Otolith function evaluation by precise clinical testing (head tilt test-HTT; subjective visual vertical-SVV) and laboratory testing (headroll-eye counterroll-HR-ECR; vesibular evoked myogenic potentials-cVEMP). Sensitivity and specificity of clinical and laboratory tests in differentiating case and control subjects. Measurable test results were universally obtained with clinical otolith tests (SVV; HTT) but not with laboratory tests. The HR-ECR test did not indicate any definitive wave forms in 10% controls and 26% cases. cVEMP responses were absent in 10% controls.HTT test with normative cutoff at 2 degrees deviations from vertical noted as 93.33% sensitive and 100% specific. SVV test with normative cutoff at 1.3 degrees noted as 100% sensitive and 100% specific. Laboratory tests demonstrated poorer specificities owing primarily to significant unresponsiveness in normal controls. Clinical otolith function tests, if conducted with precision, demonstrate greater ability than laboratory testing in discriminating normal controls from cases with unilateral complete compensated vestibular dysfunction.

  2. Power functional theory for the dynamic test particle limit

    International Nuclear Information System (INIS)

    Brader, Joseph M; Schmidt, Matthias

    2015-01-01

    For classical Brownian systems both in and out of equilibrium we extend the power functional formalism of Schmidt and Brader (2013 J. Chem. Phys. 138 214101) to mixtures of different types of particles. We apply the framework to develop an exact dynamical test particle theory for the self and distinct parts of the van Hove function, which characterize tagged and collective particle motion. The memory functions that induce non-Markovian dynamics are related to functional derivatives of the excess (over ideal) free power dissipation functional. The method offers an alternative to the recently found nonequilibrium Ornstein–Zernike relation for dynamic pair correlation functions. (paper)

  3. Usng subjective percentiles and test data for estimating fragility functions

    International Nuclear Information System (INIS)

    George, L.L.; Mensing, R.W.

    1981-01-01

    Fragility functions are cumulative distribution functions (cdfs) of strengths at failure. They are needed for reliability analyses of systems such as power generation and transmission systems. Subjective opinions supplement sparse test data for estimating fragility functions. Often the opinions are opinions on the percentiles of the fragility function. Subjective percentiles are likely to be less biased than opinions on parameters of cdfs. Solutions to several problems in the estimation of fragility functions are found for subjective percentiles and test data. How subjective percentiles should be used to estimate subjective fragility functions, how subjective percentiles should be combined with test data, how fragility functions for several failure modes should be combined into a composite fragility function, and how inherent randomness and uncertainty due to lack of knowledge should be represented are considered. Subjective percentiles are treated as independent estimates of percentiles. The following are derived: least-squares parameter estimators for normal and lognormal cdfs, based on subjective percentiles (the method is applicable to any invertible cdf); a composite fragility function for combining several failure modes; estimators of variation within and between groups of experts for nonidentically distributed subjective percentiles; weighted least-squares estimators when subjective percentiles have higher variation at higher percents; and weighted least-squares and Bayes parameter estimators based on combining subjective percentiles and test data. 4 figures, 2 tables

  4. Pulmonary function tests in patients with Parkinson's disease: A ...

    African Journals Online (AJOL)

    Methods: Pulmonary function test (PFT) was conducted using the Spirolab Spirometry kit, and results of forced vital capacity ... [3] Though the effects of PD on respiration are still a .... patient becomes sedentary, and exercise training as a part.

  5. Platelet function testing: methods of assessment and clinical utility.

    LENUS (Irish Health Repository)

    Mylotte, Darren

    2012-02-01

    Platelets play a central role in the regulation of both thrombosis and haemostasis yet tests of platelet function have, until recently, been exclusively used in the diagnosis and management of bleeding disorders. Recent advances have demonstrated the clinical utility of platelet function testing in patients with cardiovascular disease. The ex vivo measurement of response to antiplatelet therapies (aspirin and clopidogrel), by an ever-increasing array of platelet function tests, is with some assays, predictive of adverse clinical events and thus, represents an emerging area of interest for both the clinician and basic scientist. This review article will describe the advantages and disadvantages of the currently available methods of measuring platelet function and discuss both the limitations and emerging data supporting the role of platelet function studies in clinical practice.

  6. Platelet function testing: methods of assessment and clinical utility.

    LENUS (Irish Health Repository)

    Mylotte, Darren

    2011-01-01

    Platelets play a central role in the regulation of both thrombosis and haemostasis yet tests of platelet function have, until recently, been exclusively used in the diagnosis and management of bleeding disorders. Recent advances have demonstrated the clinical utility of platelet function testing in patients with cardiovascular disease. The ex vivo measurement of response to antiplatelet therapies (aspirin and clopidogrel), by an ever-increasing array of platelet function tests, is with some assays, predictive of adverse clinical events and thus, represents an emerging area of interest for both the clinician and basic scientist. This review article will describe the advantages and disadvantages of the currently available methods of measuring platelet function and discuss both the limitations and emerging data supporting the role of platelet function studies in clinical practice.

  7. Evaluation of snubber functional test methods: Tier 1

    International Nuclear Information System (INIS)

    Brown, D.P.

    1993-07-01

    The objective of the research is to establish technical bases in support of efforts on the part of the Snubber Utility Group (SNUG) and the Subsection ISTD Working Group of the ASME O ampersand M Code in developing guidelines and methodologies for snubber functional testing to ensure that snubbers are tested in a manner that ensures reliable and meaningful test results. The methodology used in this research includes both a review of available industry information as well as the testing of different snubber models using various test machines. Information is provided pertaining to current industry practices in regard to snubber testing including recommended test procedures, technical description of various test machines, and the number and types of snubbers used in the nuclear power industry. A review of previous test methodology research conducted by the Snubber Utility Group is also included. The effects of variations in controllable test parameters on snubber test results are discussed. Also included are the results of confirmatory tests in which various snubber models were tested using various test machines. Recommendations are provided for standard test methods to be included in Subsection ISTD of the ASME O ampersand M Code [4]. General information and recommendations are provided that may be used by utility personnel in specifying snubber test equipment that is most suited for plant-specific needs as well as information that may be effectively used in the review and interpretation of test results

  8. MAVL wastes containers functional demonstration and associated tests program

    International Nuclear Information System (INIS)

    Templier, J.C.

    2002-01-01

    In the framework of studies on the MAVL wastes, the CEA develops containers for middle time wastes storage. This program aims to realize a ''B wastes containers'' demonstrator. A demonstrator is a container, parts of a container or samples which must validate the tests. This document presents the state of the study in the following three chapters: functions description, base data and design choices; presentation of the functional demonstrators; demonstration tests description. (A.L.B.)

  9. Formal Functional Test Designs: Bridging the Gap Between Test Requirements and Test Specifications

    Science.gov (United States)

    Hops, Jonathan

    1993-01-01

    This presentation describes the testing life cycle, the purpose of the test design phase, and test design methods and gives an example application. Also included is a description of Test Representation Language (TRL), a summary of the language, and an example of an application of TRL. A sample test requirement and sample test design are included.

  10. Safety and Function Test Report for the SWIFT Wind Turbine

    Energy Technology Data Exchange (ETDEWEB)

    Mendoza, I.; Hur, J.

    2013-01-01

    This test was conducted as part of the U.S. Department of Energy's (DOE) Independent Testing project. This project was established to help reduce the barriers of wind energy expansion by providing independent testing results for small turbines. Three turbines where selected for testing at the National Wind Technology Center (NWTC) as a part of round two of the Small Wind Turbine Independent Testing project. Safety and Function testing is one of up to 5 tests that may be performed on the turbines. Other tests include power performance, duration, noise, and power quality. The results of the testing will provide the manufacturers with reports that may be used for small wind turbine certification.

  11. Thyroid function testing in women who had a stillbirth

    NARCIS (Netherlands)

    Nijkamp, Janna W.; Korteweg, Fleurisca J.; Groen, Henk; Timmer, Albertus; Van den Berg, Gerrit; Bossuyt, Patrick M.; Mol, Ben Willem J.; Erwich, Jan Jaap H. M.

    ContextThyroid dysfunction is thought to be associated with stillbirth. Therefore, thyroid function is often recommended in the diagnostic investigations for stillbirth. ObjectiveWe aimed to evaluate the added value of thyroid function testing in the diagnostic investigations for stillbirth. Design

  12. Polynomial regression analysis and significance test of the regression function

    International Nuclear Information System (INIS)

    Gao Zhengming; Zhao Juan; He Shengping

    2012-01-01

    In order to analyze the decay heating power of a certain radioactive isotope per kilogram with polynomial regression method, the paper firstly demonstrated the broad usage of polynomial function and deduced its parameters with ordinary least squares estimate. Then significance test method of polynomial regression function is derived considering the similarity between the polynomial regression model and the multivariable linear regression model. Finally, polynomial regression analysis and significance test of the polynomial function are done to the decay heating power of the iso tope per kilogram in accord with the authors' real work. (authors)

  13. Correlation with liver scintigram, reticuloendothelial function test, plasma endotoxin level and liver function tests in chronic liver diseases. Multivariate analysis

    Energy Technology Data Exchange (ETDEWEB)

    Ohmoto, Kenji; Yamamoto, Shinichi; Ideguchi, Seiji and others

    1989-02-01

    Liver scintigrams with Tc-99m phytate were reviewed in a total of 64 consecutive patients, comprising 28 with chronic hepatitis and 36 with liver cirrhosis. Reticuloendothelial (RES) function, plasma endotoxin (Et) levels and findings of general liver function tests were used as reference parameters to determine the diagnostic ability of liver scintigraphy. Multivariate analyses revealed that liver scintigrams had a strong correlation with RES function and Et levels in terms of morphology of the liver and hepatic and bone marrow Tc-99m uptake. General liver function tests revealed gamma globulin to be correlated with hepatic uptake and the degree of splenogemaly on liver scintigrams; and ICG levels at 15 min to be correlated with bone marrow and splenic uptake. Accuracy of liver scintigraphy was 73% for chronic hepatitis, which was inferior to general liver function tests (83%). When both modalities were combined, diangostic accuracy increased to 95%. Liver scintigraphy seems to be useful as a complementary approach. (Namekawa, K).

  14. Correlation between HRCT and pulmonary functional tests in cystic fibrosis

    International Nuclear Information System (INIS)

    Mastellari, Paola; Biggi, Simona; Lombardi, Alfonsa; Zompatori, Maurizio; Grzincich, Gianluigi; Pisi, Giovanna; Spaggiari, Cinzia

    2005-01-01

    Purpose. To compare the HRCT score by Oikonottlou and air trapping in expiratory scans with pulmonary functional tests and evaluate which radiological criteria are more useful to predict clinical impairment. Materials and methods. From January to September 2003, pulmonary HRCT study was performed in 37 patients (23 males), aged between 7 and 41 years, with cystic fibrosis. In the same day of CT examination they also received a complete functional evaluation. HRCT studies were evaluated by three radiologists blinded to the clinical data and were correlated with the lung function tests. Results. We obtained a high correlation (p=0.01) for two of the HRCT signs: extent of mucus plugging and mosaic perfusion pattern and all function tests. Discussion. Previous studies have demonstrated good correlation between lung function tests, in particular with FEV1 and HRCT signs. Our study differed from previous ones in that we analysed the correlation between lung function tests and with both single and combined CT criteria. Conclusion. Our results suggest that a simplified HRCT store could be useful to evaluate patients with cystic fibrosis [it

  15. The psyche and gastric functions.

    Science.gov (United States)

    Nardone, Gerardo; Compare, Debora

    2014-01-01

    Although the idea that gastric problems are in some way related to mental activity dates back to the beginning of the last century, until now it has received scant attention by physiologists, general practitioners and gastroenterologists. The major breakthrough in understanding the interactions between the central nervous system and the gut was the discovery of the enteric nervous system (ENS) in the 19th century. ENS (also called 'little brain') plays a crucial role in the regulation of the physiological gut functions. Furthermore, the identification of corticotropin-releasing factor (CRF) and the development of specific CRF receptor antagonists have permitted to characterize the neurochemical basis of the stress response. The neurobiological response to stress in mammals involves three key mechanisms: (1) stress is perceived and processed by higher brain centers; (2) the brain mounts a neuroendocrine response by way of the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS), and (3) the brain triggers feedback mechanisms by HPA and ANS stimulation to restore homeostasis. Various stressors such as anger, fear, painful stimuli, as well as life or social learning experiences affect both the individual's physiologic and gastric function, revealing a two-way interaction between brain and stomach. There is overwhelming experimental and clinical evidence that stress influences gastric function, thereby outlining the pathogenesis of gastric diseases such as functional dyspepsia, gastroesophageal reflux disease and peptic ulcer disease. A better understanding of the role of pathological stressors in the modulation of disease activity may have important pathogenetic and therapeutic implications. © 2014 S. Karger AG, Basel.

  16. Dynamic behavior and functional integrity tests on RC shear walls

    International Nuclear Information System (INIS)

    Akino, Kinji; Nasuda, Toshiaki; Shibata, Akenori.

    1991-01-01

    A project consisting of seven subprojects has been conducted to study the dynamic behavior and functional integrity of reinforced concrete (RC) shear walls in reactor buildings. The objective of this project is to obtain the data to improve and prepare the seismic analysis code regarding the nonlinear structural behavior and integrity of reactor buildings during and after earthquakes. The project started in April, 1986, and will end in March, 1994. Seven subprojects are strain rate test, damping characteristic test, ultimate state response test and the verification test for the test of restoring force characteristics regarding dynamic restoring force characteristics and damping performance; the restoring force characteristic test on the shear walls with openings; and pull-out strength test and the test on air leakage through concrete cracks regarding the functional integrity. The objectives of respective subprojects, the test models and the interim results are reported. Three subprojects have been completed by March, 1990. The results of these projects will be used for the overall evaluation. The strain rate test showed that the ultimate strength of shear walls increased with strain rate. A formula for estimating air flow through the cracks in walls was given by the leakage test. (K.I.)

  17. Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

    2012-01-01

    It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is gr......It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since....... Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point...

  18. Ingesting alcohol prior to food can alter the activity of the hypothalamic-pituitary-adrenal axis.

    Science.gov (United States)

    Kokavec, Anna; Lindner, Amy J; Ryan, Jaymee E; Crowe, Simon F

    2009-08-01

    There is an increasing evidence that long-term alcohol intake can promote damage to most of the body's major organs. However, regular consumption of a small-moderate amount of alcohol is often recommended as being beneficial to health and of concern is that the effect of ingesting commercially available alcohol products on steroid hormone synthesis under variable nutritional conditions has not been thoroughly investigated. Many individuals consume alcohol alone prior to a meal and the aim of the present study was to assess the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary cortisol and salivary dehydroepiandrosterone sulfate (DHEAS) before and after a meal. A total of 24 males aged 19-22 years participated in the current investigation. The experimental procedure required participants to fast for 6 h before being asked to ingest either 40 g alcohol in the form of red wine (n=8), low alcohol and high beer (n=8), white wine (n=8) or the equivalent amount of placebo over a 135-min period before consuming food for 45-min. The level of blood alcohol, salivary cortisol and salivary DHEAS was assessed upon arrival and then at regular 45-min intervals during the 180-min experimental period. The results showed that the consumption of alcohol and placebo can significantly lower the level of salivary cortisol. However, the effect of consuming a small-moderate amount of commercially available alcohol on the level of salivary DHEAS was dependent on the nutritional content of the beverage with red wine promoting no change, white wine promoting a significant decrease, and beer having a variable effect on salivary DHEAS concentration when compared to placebo. It was concluded that the effect of commercially available alcohol on the HPA axis is not the same for all alcohol products and both the nutritional status of participants and the nutritional content of the alcoholic beverage being administered should be taken into consideration when investigating the effect of alcohol on the HPA axis.

  19. Role of the pituitary-adrenal hormones in the acquisition of schedule-induced polydipsia.

    Science.gov (United States)

    Levine, R; Levine, S

    1989-06-01

    Adrenalectomized female rats failed to develop schedule-induced polydipsia (SIP). Dexamethasone (DEX) injections failed to reinstate SIP in adrenalectomized rats. They did not prevent intact rats from acquiring SIP but interfered with subsequent expression of this behavior. In contrast, corticosterone, the rats' normally occurring glucocorticoid, fully restored the acquisition and subsequent expression of SIP in adrenalectomized rats. This strongly suggests that corticosterone plays an essential role in the normal acquisition and development of this behavior. Data are interpreted in the context of current information concerning adrenal hormone receptors. It is hypothesized SIP acquisition is at least partly regulated by the Type I (mineralocorticoid) receptor.

  20. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  1. Maternal Influences on Epigenetic Programming of the Developing Hypothalamic-Pituitary-Adrenal Axis

    Science.gov (United States)

    Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing risk of disease later in life. Underlying mechanisms are beginning to be elucidated, and effects on a number of organ...

  2. Alteration of hypothalamus-pituitary-adrenal gland axis in colorectal cancer patients. Preliminary report.

    Science.gov (United States)

    Crippa, S; Mussi, C; Angelini, C; Caprotti, R; Bonardi, C; Muselli, P; Scotti, M; Piacentini, G; Uggeri, F

    2003-08-01

    In advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period, is often found and is associated with poor prognosis. Cortisol is strictly involved in the response to major surgical stress, is an immunosuppressor and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. In 21 patients with colorectal cancer undergoing surgery we evaluated the assessment of total lymphocytes, CD4+, cortisolemia, circadian rhythm of cortisol (11 p.m. and 8 a.m.) at baseline and in 3(rd) and 7(th) postoperative days. Increase of cortisolemia, as decrease of total and CD4+ lymphocytes in the postoperative period versus baseline was statistically significant. Patients with an altered circadian rhythm were 47% and 36% at 3rd and 7th postoperative days, respectively. At baseline 19% of patients had an altered cortisol circadian rhythm and it was more frequent in patients with nodal involvement (pcancer patients seems not to be associated with cortisol level and circadian rhythm alteration, either at baseline or after surgical stress. An impairment of circadian rhythm of cortisol was found at baseline in 19% of patients. It was significantly associated with the presence of metastatic disease.

  3. Increased Hair Cortisol Concentrations and BMI in Patients With Pituitary-Adrenal Disease on Hydrocortisone Replacement.

    Science.gov (United States)

    Staufenbiel, Sabine M; Andela, Cornelie D; Manenschijn, Laura; Pereira, Alberto M; van Rossum, Elisabeth F C; Biermasz, Nienke R

    2015-06-01

    Intrinsic imperfections and lack of reliable biomarkers preclude optimal individual dosing of hydrocortisone replacement in adrenal insufficiency (AI). However, the clinical relevance of optimal dosing is exemplified by frequently occurring side effects of overreplacement and the dangers of underreplacement. Cortisol in scalp hair has been identified as a retrospective biomarker for long-term cortisol exposure. We compared hair cortisol concentrations (CORT(hair)) of patients with primary or secondary AI on replacement therapy with those of patient controls with a pituitary disease without AI (PCs) and of healthy controls (HCs). In this cross-sectional study, hair samples and anthropometric data were collected in 132 AI patients (52 males), 42 PCs (11 males), and 195 HCs (90 males). The proximal 3 cm of hair were used. CORT(hair) were measured using an ELISA. CORT(hair) were higher in AI patients than in HCs and PCs (P AI patients demonstrated higher CORT(hair) than female patients (P AI patients had higher body mass index (BMI) than HCs (P AI.

  4. Hypothalamic-Pituitary-Adrenal Suppression and Iatrogenic Cushing's Syndrome as a Complication of Epidural Steroid Injections

    Directory of Open Access Journals (Sweden)

    Joyce Leary

    2013-01-01

    Full Text Available Epidural steroid injections are well accepted as a treatment for radicular back pain in appropriate candidates. While overall incidence of systemic side effects has not been well established, at least five biochemically proven cases of iatrogenic Cushing's Syndrome have been reported as complications of epidural steroid treatment. We present an additional case of iatrogenic Cushing's Syndrome and adrenal suppression in a middle-aged woman who received three epidural steroid injections over a four-month period. We review this case in the context of previous cases and discuss diagnostic and management issues.

  5. Fatigue in Multiple Sclerosis: Is it related to cytokines and hypothalamic-pituitary-adrenal axis?

    Science.gov (United States)

    Akcali, Aylin; Zengin, Fatma; Aksoy, Sefika Nur; Zengin, Orhan

    2017-07-01

    Fatigue is a common symptom of Multiple Sclerosis (MS) that diminishes the quality of life of patients, but its exact mechanism remains poorly understood. There is not a generally adopted scale to determine MS fatigue. Studies that investigated physiopathology of fatigue symptom have shown dysregulation of hypothalamic-pituitaryadrenal (HPA) axis. In the current study, we aimed to compare the results obtained with two separate scales, namely the Fatigue Severity Scale (FSS) and the Neurological Fatigue Index-Multiple Sclerosis (NFI-MS), and assess the relationship between fatigue and serum IL-1β, TNF-α, IL-35, IL-2, IL-10, ACTH, cortisol, α-MSH, β-MSH, γ-MSH and CLIP (Corticotropinlike intermediate lobe peptide) in MS patients categorized as fatigued and non-fatigued on the basis of FSS scores. For the study, a total of 54 (29 females, 25 males) patients diagnosed with RRMS including 26 with fatigue symptom (48.1%), and 26 healthy controls (13 females, 13 males) were enrolled. A FSS score ≥36 was considered as cut-off score to separate fatigued patients from nonfatigued patients. A significant positive correlation was determined between FSS score and NFI-MS scale, NFI-MS 1, NFI-MS 2, NFI-MS 3 and NFI-MS 4 scores. IL-1β, IL-10 and TNF-α levels did not differ between patient and control groups. IL-35 and IL-2 levels were significantly higher among MS patients (pfatigued and nonfatigued patients in the cytokines and HPA parameters studied. ACTH, cortisol and α-MSH were significantly higher in MS group (p=0.02, pfatigue; thus, it may also be widely used to evaluate that symptom. Generally HPA axis is hyperactive in MS patients, but it is not correlated with fatigue in our study. For the first time, levels of CLIP (a type of melanocortin) are studied, and determined to be lower among MS patients. Elevated levels of IL-35 and IL-2 suggest that these cytokines may have a prominent role in MS pathophysiology and can be investigated as potential targets for development of novel therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Hypothalamic-Pituitary-Adrenal and Sympathetic Nervous System Activity and Children's Behavioral Regulation

    Science.gov (United States)

    Lisonbee, Jared A.; Pendry, Patricia; Mize, Jacquelyn; Gwynn, Eugenia Parrett

    2010-01-01

    Self-regulation ability is an important component of children's academic success. Physiological reactivity may relate to brain activity governing attention and behavioral regulation. Saliva samples collected from 186 preschool children (101 boys, mean age = 53 months, 34% minority) before and after a series of mildly challenging games and again 30…

  7. Does the panic attack activate the hypothalamic-pituitary-adrenal axis?

    Directory of Open Access Journals (Sweden)

    Frederico G. Graeff

    2005-09-01

    Full Text Available A bibliographic search has been performed in MEDLINE using cortisol and panic as key-words, occurring in the title and/or in the abstract. Human studies were selected, with no time limit. The following publications were excluded: reviewarticles, case reports, panic attacks in disorders other than panic disorder, and studies on changes that occurred in-between panic attacks. The results showed that real-life panic attacks as well as those induced by selective panicogenic agents such as lactate and carbon dioxide do not activate the hypothalamicpituitary- adrenal (HPA axis. Agonists of the colecystokinin receptor B, such as the colecystokinin-4 peptide and pentagastrin, increase stress hormones regardless of the occurrence of a panic attack and thus, seem to activate the HPA axis directly. The benzodiazepine antagonist flumazenil does not increase stress hormones, but this agent does not reliably induce panic attacks. Pharmacological agents that increased anxiety in both normal subjects and panic patients raised stress hormone levels; among them are the alpha2-adrenergic antagonist yohimbine, the serotonergic agents 1-(m-chlorophenyl piperazine (mCPP and fenfluramine, as well as the psychostimulant agent caffeine. Therefore, the panic attack does not seem to activate the HPAaxis, in contrast to anticipatory anxiety.Realizou-se levantamento bibliográfico no indexadorMEDLINE, através das palavras-chave "cortisol" e "panic", sem limite de tempo, restringindo-se a sereshumanos e à localização das palavras-chave no título e no resumo. Foram excluídos artigos de revisão e relatos de caso, estudos sobre alterações ocorridas entre dois ataques, e os que tratavam de outras doenças psiquiátricas ou de sujeitos sadios, quando não comparados com pacientes de pânico. Os resultados mostraram que ataques de pânico naturais ou provocados pelos agentes panicogênicos seletivos, lactato de sódio e dióxido de carbono, não ativam o eixo hipotálamo-pituitária-adrenal (HPA. Agonistas do receptor de colecistocinina B elevam os hormônios de estresse, quer haja ataque de pânico ou não, parecendo ativar diretamente o eixo HPA. O antagonista benzodiazepínico flumazenil não eleva o nível dos hormônios de estresse, porém não induz ataques de pânico de modo consistente. Agentes farmacológicos que produzem ansiedade em pacientes de pânico e em voluntários saudáveis elevam o nível dos hormônios de estresse, entre estes o antagonista alfa2-adrenérgico ioimbina, os agentes serotonérgicos 1-(m-clorofenil piperazina (mCPP e fenfluramina, bem como o agente psicostimulante cafeína. Portanto, o ataque de pânico não parece ativar o eixo HPA, ao contrário da ansiedade antecipatória.

  8. Hypothalamic-Pituitary-Adrenal Axis Physiology and Cognitive Control of Behavior in Stress Inoculated Monkeys

    Science.gov (United States)

    Parker, Karen J.; Buckmaster, Christine L.; Lindley, Steven E.; Schatzberg, Alan F.; Lyons, David M.

    2012-01-01

    Monkeys exposed to stress inoculation protocols early in life subsequently exhibit diminished neurobiological responses to moderate psychological stressors and enhanced cognitive control of behavior during juvenile development compared to non-inoculated monkeys. The present experiments extended these findings and revealed that stress inoculated…

  9. Development of a battery of functional tests for low vision.

    Science.gov (United States)

    Dougherty, Bradley E; Martin, Scott R; Kelly, Corey B; Jones, Lisa A; Raasch, Thomas W; Bullimore, Mark A

    2009-08-01

    We describe the development and evaluation of a battery of tests of functional visual performance of everyday tasks intended to be suitable for assessment of low vision patients. The functional test battery comprises-Reading rate: reading aloud 20 unrelated words for each of four print sizes (8, 4, 2, & 1 M); Telephone book: finding a name and reading the telephone number; Medicine bottle label: reading the name and dosing; Utility bill: reading the due date and amount due; Cooking instructions: reading cooking time on a food package; Coin sorting: making a specified amount from coins placed on a table; Playing card recognition: identifying denomination and suit; and Face recognition: identifying expressions of printed, life-size faces at 1 and 3 m. All tests were timed except face and playing card recognition. Fourteen normally sighted and 24 low vision subjects were assessed with the functional test battery. Visual acuity, contrast sensitivity, and quality of life (National Eye Institute Visual Function Questionnaire 25 [NEI-VFQ 25]) were measured and the functional tests repeated. Subsequently, 23 low vision patients participated in a pilot randomized clinical trial with half receiving low vision rehabilitation and half a delayed intervention. The functional tests were administered at enrollment and 3 months later. Normally sighted subjects could perform all tasks but the proportion of trials performed correctly by the low vision subjects ranged from 35% for face recognition at 3 m, to 95% for the playing card identification. On average, low vision subjects performed three times slower than the normally sighted subjects. Timed tasks with a visual search component showed poorer repeatability. In the pilot clinical trial, low vision rehabilitation produced the greatest improvement for the medicine bottle and cooking instruction tasks. Performance of patients on these functional tests has been assessed. Some appear responsive to low vision rehabilitation.

  10. RELATIONSHIPS BETWEEN FUNCTIONAL MOVEMENT TESTS AND PERFORMANCE TESTS IN YOUNG ELITE MALE BASKETBALL PLAYERS.

    Science.gov (United States)

    Gonzalo-Skok, Oliver; Serna, Jorge; Rhea, Matthew R; Marín, Pedro J

    2015-10-01

    Sprinting and jumping are two common and important components of high-level sport performance. The weight-bearing dorsiflexion test (WB-DF) and Star Excursion Balance Test (SEBT) are tools developed to identify athletes at risk for lower extremity injury and may be related to running and jumping performance among athletes. The purposes of the present study were: 1) to identify any relationships between functional movement tests (WB-DF and SEBT) and performance tests (jumping, sprinting and changing direction); 2) to examine any relationships between asymmetries in functional movements and performance tests. Descriptive cohort study. Fifteen elite male basketball players (age: 15.4 ± 0.9 years) were assessed during a three-week period to determine the reliability of functional screening tools and performance tests and to examine the relationships between these tests. Relative (intraclass correlation coefficient) and absolute (coefficient of variation) reliability were used to assess the reproducibility of the tests. Significant correlations were detected between certain functional movement tests and performance tests. Both left and right excursion composite scores related to slower performance times in sprint testing, demonstrating that greater dynamic reach relates to decreased quickness and acceleration among these elite basketball athletes. The various relationships between dynamic functional movement testing, speed, and jump performance provide guidance for the strength and conditioning professional when conducting and evaluating data in an effort to improve performance and reduce risk of injury. The results of the present study suggest that these functional and performance tests do not measure the same components of human movement, and could be paired as outcome measures for the clinical and sport assessment of lower extremity function. 2b.

  11. Reference Values of Pulmonary Function Tests for Canadian Caucasians

    Directory of Open Access Journals (Sweden)

    Carlos Gutierrez

    2004-01-01

    Full Text Available A multicentre, cross-sectional study was carried out in six centres across Canada to establish a national standard for pulmonary function tests using healthy, lifetime nonsmokers, with each centre aiming to test 10 men and 10 women from each decade from 20 to 80 years of age. Data from each centre were used to derive prediction equations for each centre, and pooled data from all centres (total: 327 women and 300 men were used to derive Canadian predicted equations. The predictive models were compared with three widely used published models for selected tests. It was found that, in general, the equations modelled for each centre could be replaced by the models obtained when pooling all data (Canadian model. Comparisons with the published references showed good agreement and similar slopes for most tests. The results suggest that pulmonary function test results obtained from different centres in Canada were comparable and that standards currently used remain valid for Canadian Caucasians.

  12. Automated Functional Testing based on the Navigation of Web Applications

    Directory of Open Access Journals (Sweden)

    Boni García

    2011-08-01

    Full Text Available Web applications are becoming more and more complex. Testing such applications is an intricate hard and time-consuming activity. Therefore, testing is often poorly performed or skipped by practitioners. Test automation can help to avoid this situation. Hence, this paper presents a novel approach to perform automated software testing for web applications based on its navigation. On the one hand, web navigation is the process of traversing a web application using a browser. On the other hand, functional requirements are actions that an application must do. Therefore, the evaluation of the correct navigation of web applications results in the assessment of the specified functional requirements. The proposed method to perform the automation is done in four levels: test case generation, test data derivation, test case execution, and test case reporting. This method is driven by three kinds of inputs: i UML models; ii Selenium scripts; iii XML files. We have implemented our approach in an open-source testing framework named Automatic Testing Platform. The validation of this work has been carried out by means of a case study, in which the target is a real invoice management system developed using a model-driven approach.

  13. Computer Forensic Function Testing: Media Preparation, Write Protection And Verification

    Directory of Open Access Journals (Sweden)

    Yinghua (David Guo

    2010-06-01

    Full Text Available Normal 0 false false false EN-US JA AR-SA The growth in the computer forensic field has created a demand for new software (or increased functionality to existing software and a means to verify that this software is truly forensic i.e. capable of meeting the requirements of the trier of fact. In this work, we review our previous work---a function oriented testing framework for validation and verification of computer forensic tools. This framework consists of three parts: function mapping, requirements specification and reference set development. Through function mapping, we give a scientific and systemical description of the fundamentals of computer forensic discipline, i.e. what functions are needed in the computer forensic investigation process. We focus this paper on the functions of media preparation, write protection and verification. Specifically, we complete the function mapping of these functions and specify their requirements. Based on this work, future work can be conducted to develop corresponding reference sets to test any tools that possess these functions.

  14. Evaluation of thyroid function tests in non-thyroidal illness

    International Nuclear Information System (INIS)

    Schutte, D.P.

    1988-01-01

    Normal thyroid physiology and pathophysiology with reference to non-thyroidal illness (NTI) is reviewed including specific disease states and drugs and their effect on thyroid function tests. The diagnostic utility of two new highly sensitive thyrotrophin (TSH) assays as screening tests for thyroid dysfunction are evaluated and compared with conventional thyroid function assays. A group of 40 patients with NTI was studied. This group was compared to a group of normal controls and a group of thyrotoxic patients. Conventional thyroid function tests yielded many values outside the reference range in the NTI group. The general pattern that emerged was decreased total triiodothyronine levels in 70% of NTI patients, normal to low thyroxine values, increased mean free thyroxine values (dialysis), low mean values for the free thyroxine index and varying results for newer commercial assays for free thyroxine according to methodology. The TSH response to intravenous thyroliberin (TRH) was found to be blunted compared to controls. Basal TSH levels were measured with two ultasensitive TSH assays. The immunoradiometric assays yielded fewer values outside the reference range in the NTI group than conventional thyroid function tests. This assay yielded undetectable basal TSH levels in all thyrotoxic patients and could reliably separate thyrotoxic patients from the NTI group. Basal TSH levels with ultrasensitive TSH assays correlated well with the TSH response to TRH (TSH) and could obviate the need for TRH tests. Ultrasensitive TSH assays are promising first line screening tests in NTI. 120 refs., 13 figs., 7 tabs

  15. SP-100 nuclear assembly test: Test assembly functional requirements and system arrangement

    International Nuclear Information System (INIS)

    Fallas, T.T.; Gluck, R.; Motwani, K.; Clay, H.; O'Neill, G.

    1991-01-01

    This paper describes the functional requirements and the system that will be tested to validate the reactor, flight shield, and flight controller of the SP-100 Generic Flight System (GFS). The Nuclear Assembly Test (NAT) consists of the test article (SP-100 reactor with control devices and the flight shield) and its supporting systems. The NAT test assembly is being designed by GE. Westinghouse Hanford Company (WHC) is designing the test cell and vacuum vessel system that will contain the NAT test assembly (Renkey et al. 1989). Preliminary design reviews have been completed and the final design is under way

  16. Reliability of a functional test battery evaluating functionality, proprioception, and strength in recreational athletes with functional ankle instability.

    Science.gov (United States)

    Sekir, U; Yildiz, Y; Hazneci, B; Ors, F; Saka, T; Aydin, T

    2008-12-01

    In contrast to the single evaluation methods used in the past, the combination of multiple tests allows one to obtain a global assessment of the ankle joint. The aim of this study was to determine the reliability of the different tests in a functional test battery. Twenty-four male recreational athletes with unilateral functional ankle instability (FAI) were recruited for this study. One component of the test battery included five different functional ability tests. These tests included a single limb hopping course, single-legged and triple-legged hop for distance, and six and cross six meter hop for time. The ankle joint position sense and one leg standing test were used for evaluation of proprioception and sensorimotor control. The isokinetic strengths of the ankle invertor and evertor muscles were evaluated at a velocity of 120 degrees /s. The reliability of the test battery was assessed by calculating the intraclass correlation coefficient (ICC). Each subject was tested two times, with an interval of 3-5 days between the test sessions. The ICCs for ankle functional and proprioceptive ability showed high reliability (ICCs ranging from 0.94 to 0.98). Additionally, isokinetic ankle joint inversion and eversion strength measurements represented good to high reliability (ICCs between 0.82 and 0.98). The functional test battery investigated in this study proved to be a reliable tool for the assessment of athletes with functional ankle instability. Therefore, clinicians may obtain reliable information from the functional test battery during the assessment of ankle joint performance in patients with functional ankle instability.

  17. Outcomes of anatomical versus functional testing for coronary artery disease.

    Science.gov (United States)

    Douglas, Pamela S; Hoffmann, Udo; Patel, Manesh R; Mark, Daniel B; Al-Khalidi, Hussein R; Cavanaugh, Brendan; Cole, Jason; Dolor, Rowena J; Fordyce, Christopher B; Huang, Megan; Khan, Muhammad Akram; Kosinski, Andrzej S; Krucoff, Mitchell W; Malhotra, Vinay; Picard, Michael H; Udelson, James E; Velazquez, Eric J; Yow, Eric; Cooper, Lawton S; Lee, Kerry L

    2015-04-02

    Many patients have symptoms suggestive of coronary artery disease (CAD) and are often evaluated with the use of diagnostic testing, although there are limited data from randomized trials to guide care. We randomly assigned 10,003 symptomatic patients to a strategy of initial anatomical testing with the use of coronary computed tomographic angiography (CTA) or to functional testing (exercise electrocardiography, nuclear stress testing, or stress echocardiography). The composite primary end point was death, myocardial infarction, hospitalization for unstable angina, or major procedural complication. Secondary end points included invasive cardiac catheterization that did not show obstructive CAD and radiation exposure. The mean age of the patients was 60.8±8.3 years, 52.7% were women, and 87.7% had chest pain or dyspnea on exertion. The mean pretest likelihood of obstructive CAD was 53.3±21.4%. Over a median follow-up period of 25 months, a primary end-point event occurred in 164 of 4996 patients in the CTA group (3.3%) and in 151 of 5007 (3.0%) in the functional-testing group (adjusted hazard ratio, 1.04; 95% confidence interval, 0.83 to 1.29; P=0.75). CTA was associated with fewer catheterizations showing no obstructive CAD than was functional testing (3.4% vs. 4.3%, P=0.02), although more patients in the CTA group underwent catheterization within 90 days after randomization (12.2% vs. 8.1%). The median cumulative radiation exposure per patient was lower in the CTA group than in the functional-testing group (10.0 mSv vs. 11.3 mSv), but 32.6% of the patients in the functional-testing group had no exposure, so the overall exposure was higher in the CTA group (mean, 12.0 mSv vs. 10.1 mSv; P<0.001). In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute

  18. Request of thyroid function tests from Primary Care in Spain.

    Science.gov (United States)

    Salinas, Maria; López-Garrigós, Maite; Pomares, Francisco J; Flores, Emilio; Uris, Joaquín; Leiva-Salinas, Carlos

    2016-01-01

    Laboratory tests are crucial for diagnosis and monitoring of thyroid disorders. It is therefore necessary to study the pattern and variability in requests of thyroid function tests. The study objectives were to compare the inter-regional variability in the request of laboratory thyroid tests by general practitioners (GPs) in Spain, and to investigate the potential economic savings if the goals set for some suitability indicators were reached. Test requests per 1,000 inhabitants and test ratios (free thyroxine (FT4)/thyrotropin (TSH), free triiodothyronine (FT3)/TSH, thyroglobulin antibody (TgAb)/peroxidase antibody (TPOAb)) were compared between the different areas, according to their setting, location, and management. The resulting savings if each department achieved the goals for indicator (0.25 for FT4/TSH, 0.1 for FT3/TSH) were estimated. Seventy-six laboratories covering a population of 17,679,195 inhabitants participated in the study. TSH was requested significantly less in urban-rural areas, and the requests for FT3/1,000 inhabitants, FT3/TSH, and TgAb/TPOAb were higher in departments with private management. The savings generated if specifications for the ratios of related tests were met would be 937,260.5 €. The high variability reported in requests for thyroid function and autoimmunity tests in Spain suggests the need for implementing strategies to improve use of such tests. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  19. Pathophysiology of recent advances in current thyroid function testing

    International Nuclear Information System (INIS)

    Hesch, R.D.

    1977-01-01

    In the first chapter I have discussed thyroid function and thyroid status which is determined by thyroid gland function in secreting T4 and peripheral biotransformation of T4. The accuracy of a current in-vitro diagnostic strategy allows high reliability in clinical routine. More recent test procedures for iodothyronines and immunological phenomena need further evaluation. In another chapter the biotransformation of T4 to bioactive and regulatory iodothyronines with respect to possible clinical implications is discussed. Finally, the role of TBG for interpration of T4 and T3 concentrations is determined and more attention directed to its functional heterogeneity. (orig.) [de

  20. Semipalatinsk nuclear test site: History of building and function

    International Nuclear Information System (INIS)

    Sergazina, G.M.; Balmukhanov, S.B.

    1999-01-01

    A vast materials on history of Semipalatinsk nuclear test site creation and it building and function are presented. Authors with big reliability report one page of Kazakhstan's history. In steppe on naked place thousands of soldiers and officers, construct and military specialists have built the nuclear site on which during 40 years were conducting nuclear tests . Prolonged chronic radiation on population living near by site results to tragedy which is confessed by General Assembly of United Nations. In the book aspects of test site conversion and rehabilitation of injured population are considered. The book consists of introduction, three chapters and conclusion. The book is intended to wide circle of readers. (author)

  1. The Functional Task Test (FTT): An Interdisciplinary Testing Protocol to Investigate the Factors Underlying Changes in Astronaut Functional Performance

    Science.gov (United States)

    Bloomberg, J. J.; Lawrence, E. L.; Arzeno, N. M.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Mulavara, A. P.; Peters, B. T.; Platts. S. H.; hide

    2011-01-01

    Exposure to space flight causes adaptations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. To achieve this goal we developed an interdisciplinary testing protocol (Functional Task Test, FTT) that evaluates both astronaut functional performance and related physiological changes. Functional tests include ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall and object translation tasks. Physiological measures include assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, orthostatic intolerance, upper- and lower-body muscle strength, power, endurance, control, and neuromuscular drive. Crewmembers perform this integrated test protocol before and after short (Shuttle) and long-duration (ISS) space flight. Data are collected on two sessions before flight, on landing day (Shuttle only) and 1, 6 and 30 days after landing. Preliminary results from both Shuttle and ISS crewmembers indicate decrement in performance of the functional tasks after both short and long-duration space flight. On-going data collection continues to improve the statistical power required to map changes in functional task performance to alterations in physiological systems. The information obtained from this study will be used to design and implement countermeasures that specifically target the physiological systems most responsible for the altered functional performance associated with space flight.

  2. [Eosin Y-water test for sperm function examination].

    Science.gov (United States)

    Zha, Shu-wei; Lü, Nian-qing; Xu, Hao-qin

    2015-06-01

    Based on the principles of the in vitro staining technique, hypotonic swelling test, and water test, the Eosin Y-water test method was developed to simultaneously detect the integrity of the sperm head and tail and sperm membrane structure and function. As a widely used method in clinical laboratories in China, the Eosin Y-water test is methodologically characterized by three advantages. Firstly, both the sperm head and tail can be detected at the same time, which allows easy and comprehensive assessment of membrane damage in different parts of sperm. Secondly, distilled water is used instead of the usual formula solution to simplify and standardize the test by eliminating any potential effects on the water molecules through the sperm membrane due to different osmotic pressure or different sugar proportions and electrolyte solutions. Thirdly, the test takes less time and thus can be repeated before and after treatment. This article focuses on the fundamental principles and modification of the Eosin Y-water test and its application in sperm function examination and routine semen analysis for male infertility, assessment of the quality of sperm retrieved by testicular fine needle aspiration, semen cryopreservation program development, and evaluation of sperm membrane integrity after microwave radiation.

  3. Use of functional tests in radioimmune diagnosis of endocrine diseases

    International Nuclear Information System (INIS)

    Slavnov, V.N.

    1988-01-01

    Radioimmunoassay for determining corticotropin (ACTH), somatotropin (STH), prolactin (LTH) and thyrotropin (TTH) concentration in blood for endocrine disease diagnosis are described. Reactions of earlier mentioned functional tests to specific stimulators and inhibitors for differential diagnosis of such diseases as Icenko-Cushing one, pituitary body and hypothalamus diseases, galactorrhea and amenorrhea syndrome are considered. The diagnosis reliability is underlined

  4. Obtaining reliable Likelihood Ratio tests from simulated likelihood functions

    DEFF Research Database (Denmark)

    Andersen, Laura Mørch

    It is standard practice by researchers and the default option in many statistical programs to base test statistics for mixed models on simulations using asymmetric draws (e.g. Halton draws). This paper shows that when the estimated likelihood functions depend on standard deviations of mixed param...

  5. Numerical distribution functions of fractional unit root and cointegration tests

    DEFF Research Database (Denmark)

    MacKinnon, James G.; Nielsen, Morten Ørregaard

    We calculate numerically the asymptotic distribution functions of likelihood ratio tests for fractional unit roots and cointegration rank. Because these distributions depend on a real-valued parameter, b, which must be estimated, simple tabulation is not feasible. Partly due to the presence...

  6. 20 CFR 718.103 - Pulmonary function tests.

    Science.gov (United States)

    2010-04-01

    ... of the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC). The report... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Pulmonary function tests. 718.103 Section 718... DEATH DUE TO PNEUMOCONIOSIS Criteria for the Development of Medical Evidence § 718.103 Pulmonary...

  7. Effect of Differential Item Functioning on Test Equating

    Science.gov (United States)

    Kabasakal, Kübra Atalay; Kelecioglu, Hülya

    2015-01-01

    This study examines the effect of differential item functioning (DIF) items on test equating through multilevel item response models (MIRMs) and traditional IRMs. The performances of three different equating models were investigated under 24 different simulation conditions, and the variables whose effects were examined included sample size, test…

  8. Prevalence of abnormal liver function tests in rheumatoid arthritis ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence of Abnormal Liver Function Tests (LFTs) in patients with rheumatoid arthritis at the rheumatology out-patient clinic, Kenyatta National Hospital (KNH). Design: Cross-sectional descriptive study. Setting: Rheumatology out-patient clinic at KNH. Participants: One hundred and seven RA ...

  9. Quality of Liver and Kidney Function Tests among Public Medical ...

    African Journals Online (AJOL)

    The aim of this study is to assess the accuracy and precision of clinical chemistry laboratories in western region of Amhara national regional state of Ethiopia in testing liver and kidney functions. Methods: Eight laboratories in hospitals and a Regional Health Research Laboratory Center participated in this study from ...

  10. Effect of drugs on the thyroid function tests

    International Nuclear Information System (INIS)

    Cardoso, G.P.; Faria, A.C.S. de; Carvalho, M.C. de; Guimaraes, M.M.; Cordeiro, J.G.H.; Santa Casa do Rio de Janeiro

    1984-01-01

    The effects of drugs in the results of thyroid function tests, which could lead to misinterpretation of the real clinical state of the patients, are reviewed. The aspects of the metabolism of the thyreoidean hormones which could be related to these alterations are presented. (Author) [pt

  11. Lung Function Test in Asthmatics Patients in UBTH: Medical ...

    African Journals Online (AJOL)

    2004-06-30

    This report describes the result of a study on lung function tests on 75 asthmatics seen within a 6-month period (January 1 to June 30, 2004) at the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria. There was a preponderance of females (60%) to males (40%); The result also showed that a large proportion ...

  12. Making sense of thyroid function tests | Gezawa | Nigerian Journal of ...

    African Journals Online (AJOL)

    Background: Thyroid disorders are second only to diabetes mellitus among endocrine problems encountered in practice. Many patients with thyroid disorders tend to present with nonspecific symptoms to clinicians in different specialties, who are often quick to request for a thyroid function test. Although interpretation of the ...

  13. Functional Literacy Tests: A Case of Anticipatory Validity?

    Science.gov (United States)

    Anderson, Lorin W.; Anderson, Jo Craig

    1981-01-01

    Development of the mathematics functional literacy test (MFLT) is described, issues of predictive and content validity are discussed, and implications for educational policy are presented. Ten basic skill areas identified by the National Council of Supervisors of Mathematics were used as the basis for the development of the MFLT. (RL)

  14. The emerging role of transport systems in liver function tests

    NARCIS (Netherlands)

    Stieger, Bruno; Heger, Michal; de Graaf, Wilmar; Paumgartner, Gustav; van Gulik, Thomas

    2012-01-01

    Liver function tests are of critical importance for the management of patients with severe or terminal liver disease. They are also used as prognostic tools for planning liver resections. In recent years many transport systems have been identified that also transport substances employed in liver

  15. Plasma cortisol levels in response to a cold pressor test did not predict appetite or ad libitum test meal intake in obese women.

    Science.gov (United States)

    Geliebter, Allan; Gibson, Charlisa D; Hernandez, Dominica B; Atalayer, Deniz; Kwon, Anne; Lee, Michelle I; Mehta, Nandini; Phair, Donna; Gluck, Marci E

    2012-12-01

    Heightened cortisol response to stress due to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as appetite ratings and subsequent test meal intake (TMI) in obese women. Following an overnight fast on two counterbalanced days, 20 obese women immersed their non-dominant hand for 2min in ice water (CPT) or warm water (WW) as a control. Plasma cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress, pain, and appetite, were serially acquired. An ad libitum liquid meal was offered at 45min and intake measured covertly. Fasting cortisol was higher at 15min (mean peak cortisol) following the CPT compared to WW. Higher stress was reported at 2 and 15min for the CPT compared to WW. Pain, an indirect marker of the acute stress, systolic and diastolic blood pressure increased following the CPT at 2min compared to WW. Hunger decreased after the CPT at 2 and 15min, and desire to eat ratings were lower following CPT compared to WW. Subjects did not have greater test meal intake (TMI) following CPT compared to WW. There was also no significant relationship between cortisol levels following stress and TMI, indicating that cortisol did not predict subsequent intake in obese women. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Antidepressant-like activity of resveratrol treatment in the forced swim test and tail suspension test in mice: the HPA axis, BDNF expression and phosphorylation of ERK.

    Science.gov (United States)

    Wang, Zhen; Gu, Jianhua; Wang, Xueer; Xie, Kai; Luan, Qinsong; Wan, Nianqing; Zhang, Qun; Jiang, Hong; Liu, Dexiang

    2013-11-01

    Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities. There is only limited information about the antidepressant-like effect of resveratrol. The present study assessed whether resveratrol treatment (20, 40 and 80mg/kg, i.p., 21days) has an antidepressant-like effect on the forced swim test (FST) and tail suspension test (TST) in mice and examined what its molecular targets might be. The results showed that resveratrol administration produced antidepressant-like effects in mice, evidenced by the reduced immobility time in the FST and TST, while it had no effect on the locomotor activity in the open field test. Resveratrol treatment significantly reduced serum corticosterone levels, which had been elevated by the FST and TST. Moreover, resveratrol increased brain-derived neurotrophic factor (BDNF) protein and extracellular signal-regulated kinase (ERK) phosphorylation levels in the prefrontal cortex and hippocampus. All of these antidepressant-like effects of resveratrol were essentially similar to those observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of resveratrol in the FST and TST are mediated, at least in part, by modulating hypothalamic-pituitary-adrenal axis, BDNF and ERK phosphorylation expression in the brain region of mice. © 2013.

  17. Using Operational Analysis to Improve Access to Pulmonary Function Testing

    Directory of Open Access Journals (Sweden)

    Ada Ip

    2016-01-01

    Full Text Available Background. Timely pulmonary function testing is crucial to improving diagnosis and treatment of pulmonary diseases. Perceptions of poor access at an academic pulmonary function laboratory prompted analysis of system demand and capacity to identify factors contributing to poor access. Methods. Surveys and interviews identified stakeholder perspectives on operational processes and access challenges. Retrospective data on testing demand and resource capacity was analyzed to understand utilization of testing resources. Results. Qualitative analysis demonstrated that stakeholder groups had discrepant views on access and capacity in the laboratory. Mean daily resource utilization was 0.64 (SD 0.15, with monthly average utilization consistently less than 0.75. Reserved testing slots for subspecialty clinics were poorly utilized, leaving many testing slots unfilled. When subspecialty demand exceeded number of reserved slots, there was sufficient capacity in the pulmonary function schedule to accommodate added demand. Findings were shared with stakeholders and influenced scheduling process improvements. Conclusion. This study highlights the importance of operational data to identify causes of poor access, guide system decision-making, and determine effects of improvement initiatives in a variety of healthcare settings. Importantly, simple operational analysis can help to improve efficiency of health systems with little or no added financial investment.

  18. Advanced Grid Support Functionality Testing for Florida Power and Light

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, Austin [National Renewable Energy Lab. (NREL), Golden, CO (United States); Martin, Gregory [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hurtt, James [Florida Power and Light, Juno Beach, FL (United States)

    2017-03-21

    This report describes the results of laboratory testing of advanced photovoltaic (PV) inverter testing undertaken by the National Renewable Energy Laboratory (NREL) on behalf of the Florida Power and Light Company (FPL). FPL recently commissioned a 1.1 MW-AC PV installation on a solar carport at the Daytona International Speedway in Daytona Beach, Florida. In addition to providing a source of clean energy production, the site serves as a live test bed with 36 different PV inverters from eight different manufacturers. Each inverter type has varied support for advanced grid support functions (GSFs) that are becoming increasingly commonplace, and are being required through revised interconnection standards such as UL1741, IEEE1547, and California (CA) Rule 21. FPL is interested in evaluating the trade-offs between different GSFs, their compliance to emerging standards, and their effects on efficiency and reliability. NREL has provided a controlled laboratory environment to undertake such a study. This work covered nine different classes of tests to compare inverter capabilities and performance for four different inverters that were selected by FPL. The test inverters were all three-phase models rated between 24-36 kW, and containing multiple PV input power point trackers. Advanced grid support functions were tested for functional behavior, and included fixed power factor operation, voltage-ride through, frequency ride-through, volt-var control, and frequency-Watt control. Response to abnormal grid conditions with GSFs enabled was studied through anti-islanding, fault, and load rejection overvoltage tests. Finally, efficiency was evaluated across a range of operating conditions that included power factor, output power, and input voltage variations. Test procedures were derived from requirements of a draft revision of UL741, CA Rule 21, and/or previous studies at NREL. This reports summarizes the results of each test case, providing a comparative performance analysis

  19. I and C functional test facility user guide

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Ki Chun [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1996-07-01

    The objective of I and C functional test facility (FTF) is to validate newly developed digital control and protection algorithm, alarm reduction algorithm and the function of operator support system and so on. Test facility is divided into three major parts; software, hardware and graphic user interface. Software consists of mathematical modeling which simulates 3 loop pressurizer water reactor, 993 MWe Westinghouse plant and supervisory module which interpret user instructions and data interface program. FTF is implemented in HP747I workstation using FORTRAN77 and ``C`` language under UNIX operating system. This User Guide provides file structure, instructions and program modification method and provides initial data, malfunction list, process variables list and simulation diagram as an appendix to test developed prototype. 12 figs. (Author).

  20. I and C functional test facility user guide

    International Nuclear Information System (INIS)

    Kwon, Ki Chun

    1996-07-01

    The objective of I and C functional test facility (FTF) is to validate newly developed digital control and protection algorithm, alarm reduction algorithm and the function of operator support system and so on. Test facility is divided into three major parts; software, hardware and graphic user interface. Software consists of mathematical modeling which simulates 3 loop pressurizer water reactor, 993 MWe Westinghouse plant and supervisory module which interpret user instructions and data interface program. FTF is implemented in HP747I workstation using FORTRAN77 and ''C'' language under UNIX operating system. This User Guide provides file structure, instructions and program modification method and provides initial data, malfunction list, process variables list and simulation diagram as an appendix to test developed prototype. 12 figs. (Author)

  1. Survey of clinical infant lung function testing practices.

    Science.gov (United States)

    Peterson-Carmichael, Stacey L; Rosenfeld, Margaret; Ascher, Simon B; Hornik, Christoph P; Arets, H G M; Davis, Stephanie D; Hall, Graham L

    2014-02-01

    Data supporting the clinical use of infant lung function (ILF) tests are limited making the interpretation of clinical ILF measures difficult. To evaluate current ILF testing practices and to survey users regarding the indications, limitations and perceived clinical benefits of ILF testing. We created a 26-item survey hosted on the European Respiratory Society (ERS) website between January and May 2010. Notifications were sent to members of the ERS, American Thoracic Society and the Asian Pacific Society of Respirology. Responses were sought from ILF laboratory directors and pediatric respirologists. The survey assessed the clinical indications, patient populations, equipment and reference data used, and perceived limitations of ILF testing. We received 148 responses with 98 respondents having ILF equipment and performing testing in a clinical capacity. Centers in North America were less likely to perform ≥50 studies/year than centers in Europe or other continents (13% vs. 41%). Most respondents used ILF data to either "start a new therapy" (78%) or "help decide about initiation of further diagnostic workup such as bronchoscopy, chest CT or serological testing" (69%). Factors reported as limiting clinical ILF testing were need for sedation, uncertainty regarding clinical impact of study results and time intensive nature of the study. Clinical practices associated with ILF testing vary significantly; centers that perform more studies are more likely to use the results for clinical purposes and decision making. The future of ILF testing is uncertain in the face of the limitations perceived by the survey respondents. © 2013 Wiley Periodicals, Inc.

  2. Occlusion and brain function: mastication as a prevention of cognitive dysfunction.

    Science.gov (United States)

    Ono, Y; Yamamoto, T; Kubo, K-ya; Onozuka, M

    2010-08-01

    Research in animals and humans has shown that mastication maintains cognitive function in the hippocampus, a brain area important for learning and memory. Reduced mastication, an epidemiological risk factor for the development of dementia in humans, attenuates spatial memory and causes hippocampal neurons to deteriorate morphologically and functionally, especially in aged animals. Active mastication rescues the stress-attenuated hippocampal memory process in animals and attenuates the perception of stress in humans by suppressing endocrinological and autonomic stress responses. Active mastication further improves the performance of sustained cognitive tasks by increasing the activation of the hippocampus and the prefrontal cortex, the brain regions that are essential for cognitive processing. Abnormal mastication caused by experimental occlusal disharmony in animals produces chronic stress, which in turn suppresses spatial learning ability. The negative correlation between mastication and corticosteroids has raised the hypothesis that the suppression of the hypothalamic-pituitary-adrenal (HPA) axis by masticatory stimulation contributes, in part, to preserving cognitive functions associated with mastication. In the present review, we examine research pertaining to the mastication-induced amelioration of deficits in cognitive function, its possible relationship with the HPA axis, and the neuronal mechanisms that may be involved in this process in the hippocampus.

  3. Low basal serum cortisol in patients with severe atopic dermatitis : potent topical corticosteroids wrongfully accused

    NARCIS (Netherlands)

    Haeck, I.M.; Timmer-de Mik, L.; Lentjes, E.G.; Buskens, E.; Hijnen, D.J.; Guikers, C.; Bruijnzeel-Koomen, C.A.; de Bruin-Weller, M.S.

    2007-01-01

    BACKGROUND: Topical corticosteroids are used extensively to treat inflammatory skin disorders including atopic dermatitis (AD). Several studies have described temporary reversible suppression of hypothalamic-pituitary-adrenal function. However, sound evidence of permanent disturbance of adrenal

  4. I and C functional test facility malfunction cause and effect

    International Nuclear Information System (INIS)

    Kwon, Kee Choon.

    1997-06-01

    The objective of I and C function test facility (FTF) is to validate newly developed digital control and protection algorithm, alarm reduction algorithm and the function of operator support system and so on. To realize transient and accident situation in the FTF, the result of the activation of malfunction should be similar to the situation of real nuclear power plants. In this technical report, describe the Group, Malfunction No., Description, Option, Recommendations, Considered in Subroutine, Limitations, Cause, and Effect of the malfunctions implemented in FTF. (author)

  5. Human performance in nondestructive inspections and functional tests: Final report

    International Nuclear Information System (INIS)

    Harris, D.H.

    1988-10-01

    Human performance plays a vital role in the inspections and tests conducted to assure the physical integrity of nuclear power plants. Even when technically-sophisticated equipment is employed, the outcome is highly dependent on human control actions, calibrations, observations, analyses, and interpretations. The principal consequences of inadequate performance are missed or falsely-reported defects. However, the cost-avoidance that stems from addressing potential risks promptly, and the increasing costs likely with aging plants, emphasize that timeliness and efficiency are important inspection-performance considerations also. Human performance issues were studied in a sample of inspections and tests regularly conducted in nuclear power plants. These tasks, selected by an industry advisory panel, were: eddy-current inspection of steam-generator tubes; ultrasonic inspection of pipe welds; inservice testing of pumps and valves; and functional testing of shock suppressors. Information was obtained for the study from industry and plant procedural documents; training materials; research reports and related documents; interviews with training specialists, inspectors, supervisory personnel, and equipment designers; and first-hand observations of task performance. Eleven recommendations are developed for improving human performance on nondestructive inspections and functional tests. Two recommendations were for the more-effective application of existing knowledge; nine recommendations were for research projects that should be undertaken to assure continuing improvements in human performance on these tasks. 25 refs., 9 figs., 1 tab

  6. A Powerful Test for Comparing Multiple Regression Functions.

    Science.gov (United States)

    Maity, Arnab

    2012-09-01

    In this article, we address the important problem of comparison of two or more population regression functions. Recently, Pardo-Fernández, Van Keilegom and González-Manteiga (2007) developed test statistics for simple nonparametric regression models: Y(ij) = θ(j)(Z(ij)) + σ(j)(Z(ij))∊(ij), based on empirical distributions of the errors in each population j = 1, … , J. In this paper, we propose a test for equality of the θ(j)(·) based on the concept of generalized likelihood ratio type statistics. We also generalize our test for other nonparametric regression setups, e.g, nonparametric logistic regression, where the loglikelihood for population j is any general smooth function [Formula: see text]. We describe a resampling procedure to obtain the critical values of the test. In addition, we present a simulation study to evaluate the performance of the proposed test and compare our results to those in Pardo-Fernández et al. (2007).

  7. Prenatal cocaine exposure and its impact on cognitive functions of offspring: a pathophysiological insight.

    Science.gov (United States)

    Gkioka, Eleana; Korou, Laskarina Maria; Daskalopoulou, Afrodite; Misitzi, Angelica; Batsidis, Eleni; Bakoyiannis, Ioannis; Pergialiotis, Vasilios

    2016-07-01

    It is estimated that approximately 0.5%-3% of fetuses are prenatally exposed to cocaine (COC). The neurodevelopmental implications of this exposure are numerous and include motor skill impairments, alterations of social function, predisposition to anxiety, and memory function and attention deficits; these implications are commonly observed in experimental studies and ultimately affect both learning and IQ. According to previous studies, the clinical manifestations of prenatal COC exposure seem to persist at least until adolescence. The pathophysiological cellular processes that underlie these impairments include dysfunctional myelination, disrupted dendritic architecture, and synaptic alterations. On a molecular level, various neurotransmitters such as serotonin, dopamine, catecholamines, and γ-aminobutyric acid seem to participate in this process. Finally, prenatal COC abuse has been also associated with functional changes in the hormones of the hypothalamic-pituitary-adrenal axis that mediate neuroendocrine responses. The purpose of this review is to summarize the neurodevelopmental consequences of prenatal COC abuse, to describe the pathophysiological pathways that underlie these consequences, and to provide implications for future research in the field.

  8. Test Protocols for Advanced Inverter Interoperability Functions - Appendices

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jay Dean [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gonzalez, Sigifredo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ralph, Mark E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ellis, Abraham [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Broderick, Robert Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2013-11-01

    Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated on grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not now required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are already apparent as

  9. Test Protocols for Advanced Inverter Interoperability Functions – Main Document

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jay Dean [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gonzalez, Sigifredo [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ralph, Mark E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Ellis, Abraham [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Broderick, Robert Joseph [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2013-11-01

    Distributed energy resources (DER) such as photovoltaic (PV) systems, when deployed in a large scale, are capable of influencing significantly the operation of power systems. Looking to the future, stakeholders are working on standards to make it possible to manage the potentially complex interactions between DER and the power system. In 2009, the Electric Power Research Institute (EPRI), Sandia National Laboratories (SNL) with the U.S. Department of Energy (DOE), and the Solar Electric Power Association (SEPA) initiated a large industry collaborative to identify and standardize definitions for a set of DER grid support functions. While the initial effort concentrated on grid-tied PV inverters and energy storage systems, the concepts have applicability to all DER. A partial product of this on-going effort is a reference definitions document (IEC TR 61850-90-7, Object models for power converters in distributed energy resources (DER) systems) that has become a basis for expansion of related International Electrotechnical Commission (IEC) standards, and is supported by US National Institute of Standards and Technology (NIST) Smart Grid Interoperability Panel (SGIP). Some industry-led organizations advancing communications protocols have also embraced this work. As standards continue to evolve, it is necessary to develop test protocols to independently verify that the inverters are properly executing the advanced functions. Interoperability is assured by establishing common definitions for the functions and a method to test compliance with operational requirements. This document describes test protocols developed by SNL to evaluate the electrical performance and operational capabilities of PV inverters and energy storage, as described in IEC TR 61850-90-7. While many of these functions are not currently required by existing grid codes or may not be widely available commercially, the industry is rapidly moving in that direction. Interoperability issues are already

  10. 131I-BSP liver function test by BSP tolerance

    International Nuclear Information System (INIS)

    Kanda, Koichi

    1974-01-01

    131 I-BSP liver function test after BSP intravenous tolerance was discussed, assuming that the reason why measurements of 131 I-BSP retention rate at 30 minutes and 131 I-BSP disappearance rate in blood showed respectable overlapping between normal group and group with slight liver disorders as compared with BSP test and the reason why differential diagnosis was difficult were due to underestimate of tolerance volume of 131 I-BSP. 131 I-BSP was observed with time as to 70 persons with normal liver function and 257 cases of liver diseases, using 5, 3 and 2 mg of non-radioactive BSP tolerance volume per kilogram of body weight. 131 I-BSP retention rate at 30 minutes and 131 I-BSP disappearance rate in blood are possible to separate overlapping over control in each measurement value at 3-5 mg/kg of tolerance, and in comparison of 3 mg and 5 mg, the latter showed a little excellent result. So, it was decided that tolerance of 3 mg/kg was a proper dose, considering tolerance to liver cells. 131 I-BSP retention rate at 30 minutes was a little excellent in accuracy and disappearance rate in blood after BSP tolerance is simple and profitable for practical use because collection of blood was only one time and measurement could be made with whole blood. As mentioned above, this method is seemed to be useful to practice of liver function test. (Kanao, N.)

  11. The partial coherence modulation transfer function in testing lithography lens

    Science.gov (United States)

    Huang, Jiun-Woei

    2018-03-01

    Due to the lithography demanding high performance in projection of semiconductor mask to wafer, the lens has to be almost free in spherical and coma aberration, thus, in situ optical testing for diagnosis of lens performance has to be established to verify the performance and to provide the suggesting for further improvement of the lens, before the lens has been build and integrated with light source. The measurement of modulation transfer function of critical dimension (CD) is main performance parameter to evaluate the line width of semiconductor platform fabricating ability for the smallest line width of producing tiny integrated circuits. Although the modulation transfer function (MTF) has been popularly used to evaluation the optical system, but in lithography, the contrast of each line-pair is in one dimension or two dimensions, analytically, while the lens stand along in the test bench integrated with the light source coherent or near coherent for the small dimension near the optical diffraction limit, the MTF is not only contributed by the lens, also by illumination of platform. In the study, the partial coherence modulation transfer function (PCMTF) for testing a lithography lens is suggested by measuring MTF in the high spatial frequency of in situ lithography lens, blended with the illumination of partial and in coherent light source. PCMTF can be one of measurement to evaluate the imperfect lens of lithography lens for further improvement in lens performance.

  12. Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

    Directory of Open Access Journals (Sweden)

    Chai Ryoung Eun

    2014-03-01

    Full Text Available Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication.

  13. The development of functional requirement for integrated test facility

    International Nuclear Information System (INIS)

    Sim, B.S.; Oh, I.S.; Cha, K.H.; Lee, H.C.

    1994-01-01

    An Integrated Test Facility (ITF) is a human factors experimental environment comprised of a nuclear power plant function simulator, man-machine interfaces (MMI), human performance recording systems, and signal control and data analysis systems. In this study, we are going to describe how the functional requirements are developed by identification of both the characteristics of generic advanced control rooms and the research topics of world-wide research interest in human factors community. The functional requirements of user interface developed in this paper together with those of the other elements will be used for the design and implementation of the ITF which will serve as the basis for experimental research on a line of human factors topics. (author). 15 refs, 1 fig

  14. Measurement of Function Post Hip Fracture: Testing a Comprehensive Measurement Model of Physical Function.

    Science.gov (United States)

    Resnick, Barbara; Gruber-Baldini, Ann L; Hicks, Gregory; Ostir, Glen; Klinedinst, N Jennifer; Orwig, Denise; Magaziner, Jay

    2016-07-01

    Measurement of physical function post hip fracture has been conceptualized using multiple different measures. This study tested a comprehensive measurement model of physical function. This was a descriptive secondary data analysis including 168 men and 171 women post hip fracture. Using structural equation modeling, a measurement model of physical function which included grip strength, activities of daily living, instrumental activities of daily living, and performance was tested for fit at 2 and 12 months post hip fracture, and among male and female participants. Validity of the measurement model of physical function was evaluated based on how well the model explained physical activity, exercise, and social activities post hip fracture. The measurement model of physical function fit the data. The amount of variance the model or individual factors of the model explained varied depending on the activity. Decisions about the ideal way in which to measure physical function should be based on outcomes considered and participants. The measurement model of physical function is a reliable and valid method to comprehensively measure physical function across the hip fracture recovery trajectory. © 2015 Association of Rehabilitation Nurses.

  15. Reference values for paediatric pulmonary function testing: The Utrecht dataset.

    Science.gov (United States)

    Koopman, Marije; Zanen, Pieter; Kruitwagen, Cas L J J; van der Ent, Cornelis K; Arets, Hubertus G M

    2011-01-01

    Since populations evolve, measurement protocols and equipment improve and analysis techniques progress, there is an ongoing need to reassess reference data for pulmonary function tests. Furthermore, reference values for total lung capacity and carbon monoxide diffusion capacity are scarcely available in children. We aimed to provide updated reference equations for most commonly used pulmonary function indices in Caucasian children. In the 'Utrecht Pulmonary Function Reference Data Study' we collected data in Caucasian children aged 2-18 years. We analyzed them using the 'Generalized Additive Models for Location Scale and Shape' (GAMLSS) statistical method. Measurements of interrupter resistance (R(int)) (n = 877), spirometry (n = 1042), body plethysmography (n = 723) and carbon monoxide diffusion/helium dilution (n = 543) were obtained in healthy children. Height (or the natural logarithm of height) and age (or the natural logarithm of age) were both significantly related to most outcome measures. Also sex was a significant determinant, except for RV, RV/TLC, FRC(pleth), Raw(0,5), Raw(tot), R(int) and FEF values. The application of previously published reference equations on the study population resulted in misinterpretation of pulmonary function. These new paediatric reference equations provide accurate estimates of the range of normality for most commonly used pulmonary function indices, resulting in less underdiagnosis and overdiagnosis of pulmonary diseases. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Effects of therapy with [177Lu-DOTA0,Tyr3]octreotate on endocrine function

    International Nuclear Information System (INIS)

    Teunissen, Jaap J.M.; Kwekkeboom, Dik J.; Krenning, Eric P.; Jong, Frank H. de; Feelders, Richard A.; Aken, Maarten O. van; Herder, Wouter W. de; Rijke, Yolanda B. de

    2009-01-01

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 ± 16 to 25 ± 4 ng/l, p 4 ) levels decreased (17.7 ± 0.4 to 15.6 ± 0.6 pmol/l, p 3 ) levels did not change. Reverse triiodothyronine (rT 3 ) levels decreased (0.38 ± 0.03 to 0.30 ± 0.01 nmol/l, p 550 nmol/l, n = 18). Five patients developed elevated HbA 1c levels (> 6.5%). In men 177 Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non-SHBG-bound T levels remained unaffected. In the long term, gonadotropin levels decreased significantly in postmenopausal women. Only a few patients developed hypothyroidism or elevated levels of HbA 1c . Therefore, PRRT with 177 Lu-octreotate can be regarded as a safe treatment modality with respect to short- and long-term endocrine function. (orig.)

  17. Thyroid function testing in neonates born to women with hypothyroidism.

    Science.gov (United States)

    McGovern, Matthew; Reyani, Zahra; O'Connor, Pamela; White, Martin; Miletin, Jan

    2016-12-01

    Our aim was to assess the utility of serum thyroxine and thyroid stimulating hormone performed at 10-14 days of life in diagnosing congenital hypothyroidism (CH) in babies born to mothers with hypothyroidism. This was a retrospective study of all babies born in a tertiary referral centre for neonatology over a 12-month period. Infants who had thyroid function testing (TFT) checked at 10-14 days of life because of maternal hypothyroidism during the period of study were included. The results of the newborn bloodspot and day 10-14 TFT were recorded along with whether or not patients were subsequently treated. Of the 319 patients included in the study, only two patients were found to have CH and in both cases the newborn blood spot had been abnormal. No extra cases of CH were detected from the thyroid test at 10-14 days and this practice should be discontinued due to the robust nature of existing newborn screening programmes. What is Known: • Congenital hypothyroidism(CH) is the commonest preventable cause of childhood intellectual impairment. • Family history of hypothyroidism has been implicated as a risk factor for CH. • CH has formed part of newborn screening since the 1970s. What is New: • There is no research recommending thyroid function testing at 10-14 days of life to detect CH in neonates born to mothers with hypothyroidism. • Thyroid function testing at 10-14 days of life does not improve diagnostic yield for CH in babies born to mothers with hypothyroidism. • Newborn blood spot remains the mainstay for accurate and timely diagnosis of CH.

  18. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

    2015-11-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

  19. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

    2015-01-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

  20. The Abnormal Functional Connectivity between the Hypothalamus and the Temporal Gyrus Underlying Depression in Alzheimer's Disease Patients.

    Science.gov (United States)

    Liu, Xiaozheng; Chen, Wei; Tu, Yunhai; Hou, Hongtao; Huang, Xiaoyan; Chen, Xingli; Guo, Zhongwei; Bai, Guanghui; Chen, Wei

    2018-01-01

    Hypothalamic communication with the rest of the brain is critical for accomplishing a wide variety of physiological and psychological functions, including the maintenance of neuroendocrine circadian rhythms and the management of affective processes. Evidence has shown that major depressive disorder (MDD) patients exhibit increased functioning of the hypothalamic-pituitary-adrenal (HPA) axis. Neurofibrillary tangles are also found in the hypothalamus of Alzheimer's disease (AD) patients, and AD patients exhibit abnormal changes in the HPA. However, little is known of how the hypothalamus interacts with other brain regions in AD patients with depression (D-AD). Functional connectivity (FC) analysis explores the connectivity between brain regions that share functional properties. Here, we used resting-state (rs) magnetic resonance imaging (MRI) technology and the FC method to measure hypothalamic connectivity across the whole brain in 22 D-AD patients and 21 non-depressed AD patients (nD-AD). Our results showed that D-AD patients had reduced FC among the hypothalamus, the right middle temporal gyrus (MTG) and the right superior temporal gyrus (STG) compared with the FC of nD-AD patients, suggesting that the abnormal FC between the hypothalamus and the temporal lobe may play a key role in the pathophysiology of depression in AD patients.

  1. Effects of Differential Item Functioning on Examinees' Test Performance and Reliability of Test

    Science.gov (United States)

    Lee, Yi-Hsuan; Zhang, Jinming

    2017-01-01

    Simulations were conducted to examine the effect of differential item functioning (DIF) on measurement consequences such as total scores, item response theory (IRT) ability estimates, and test reliability in terms of the ratio of true-score variance to observed-score variance and the standard error of estimation for the IRT ability parameter. The…

  2. Structure of four executive functioning tests in healthy older adults.

    Science.gov (United States)

    de Frias, Cindy M; Dixon, Roger A; Strauss, Esther

    2006-03-01

    The authors examined the factor structure of 4 indicators of executive functioning derived from 2 new (i.e., Hayling and Brixton) and 2 traditional (i.e., Stroop and Color Trails) tests. Data were from a cross-sectional sample of 55- to 85-year-old healthy adults (N=427) from the Victoria Longitudinal Study. Confirmatory factor analysis (LISREL 8.52) tested both a 2-factor model of Inhibition (Hayling, Stroop) and Shifting (Brixton, Color Trails) and a single-factor model. The 2-factor model did not fit the data because the covariance matrix of the factors was not positive definite. The single-factor model fit the data well, chi(2)(2, N=427)=0.32, p=.85, root-mean-square error of approximation (RMSEA)=.00, comparative fit index (CFI)=1.00, goodness-of-fit index (GFI)=1.00. Moreover, the single-factor structure of executive functioning was invariant (configural and metric) across gender, and invariant (configural with limited metric) across age. Structural relations showed that poorer executive functioning performance was related to older age and lower fluid intelligence, chi(2)(11, N=418)=23.04, p=.02, RMSEA=.05, CFI=.97, GFI=.98.

  3. Staging chronic pancreatitis with exocrine function tests: Are we better?

    Science.gov (United States)

    Sperti, Cosimo; Moletta, Lucia

    2017-10-14

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas evolving in progressive fibrotic disruption of the gland with exocrine and endocrine pancreatic insufficiency. Although imaging features of CP are well known, their correlation with exocrine pancreatic function tests are not obvious, particularly in the early stage of the disease. There are many clinical classification of CP, all suggested for better distinguish and manage different forms based on etiological and clinical factors, and severity of the disease. Recently, a new classification of CP has been suggested: the M-ANNHEIM multiple risk factor classification that includes etiology, stage classification and degree of clinical severity. However, more accurate determination of clinical severity of CP requires a correct determination of exocrine function of the pancreas and fecal fat excretion. Recently, Kamath et al demonstrated that the evaluation of exocrine pancreatic function by acid steatocrit and fecal elastase-1 (EF-1) was helpful, but EF-1 was able to detect exocrine pancreatic insufficiency in more patients, upgrading some patients in higher stage of disease according to M-ANNHEIM classification. So, EF-1 is a more accurate test to determine exocrine pancreatic insufficiency and to stage chronic pancreatitis in the M-ANNHEIM classification. On the contrary, EF-1 determination shows low sensitivity in detecting exocrine pancreatic insufficiency in early stage of the disease.

  4. Validation of Cardiovascular Parameters during NASA's Functional Task Test

    Science.gov (United States)

    Arzeno, N. M.; Stenger, M. B.; Bloomberg, J. J.; Platts, S. H.

    2009-01-01

    Microgravity exposure causes physiological deconditioning and impairs crewmember task performance. The Functional Task Test (FTT) is designed to correlate these physiological changes to performance in a series of operationally-relevant tasks. One of these, the Recovery from Fall/Stand Test (RFST), tests both the ability to recover from a prone position and cardiovascular responses to orthostasis. PURPOSE: Three minutes were chosen for the duration of this test, yet it is unknown if this is long enough to induce cardiovascular responses similar to the operational 5 min stand test. The purpose of this study was to determine the validity and reliability of heart rate variability (HRV) analysis of a 3 min stand and to examine the effect of spaceflight on these measures. METHODS: To determine the validity of using 3 vs. 5 min of standing to assess HRV, ECG was collected from 7 healthy subjects who participated in a 6 min RFST. Mean R-R interval (RR) and spectral HRV were measured in minutes 0-3 and 0-5 following the heart rate transient due to standing. Significant differences between the segments were determined by a paired t-test. To determine the reliability of the 3-min stand test, 13 healthy subjects completed 3 trials of the FTT on separate days, including the RFST with a 3 min stand. Analysis of variance (ANOVA) was performed on the HRV measures. One crewmember completed the FTT before a 14-day mission, on landing day (R+0) and one (R+1) day after returning to Earth. RESULTS VALIDITY: HRV measures reflecting autonomic activity were not significantly different during the 0-3 and 0-5 min segments. RELIABILITY: The average coefficient of variation for RR, systolic (SBP) and diastolic blood pressures during the RFST were less than 8% for the 3 sessions. ANOVA results yielded a greater inter-subject variability (p0.05) for HRV in the RFST. SPACEFLIGHT: Lower RR and higher SBP were observed on R+0 in rest and stand. On R+1, both RR and SBP trended towards preflight

  5. A computer vision based candidate for functional balance test.

    Science.gov (United States)

    Nalci, Alican; Khodamoradi, Alireza; Balkan, Ozgur; Nahab, Fatta; Garudadri, Harinath

    2015-08-01

    Balance in humans is a motor skill based on complex multimodal sensing, processing and control. Ability to maintain balance in activities of daily living (ADL) is compromised due to aging, diseases, injuries and environmental factors. Center for Disease Control and Prevention (CDC) estimate of the costs of falls among older adults was $34 billion in 2013 and is expected to reach $54.9 billion in 2020. In this paper, we present a brief review of balance impairments followed by subjective and objective tools currently used in clinical settings for human balance assessment. We propose a novel computer vision (CV) based approach as a candidate for functional balance test. The test will take less than a minute to administer and expected to be objective, repeatable and highly discriminative in quantifying ability to maintain posture and balance. We present an informal study with preliminary data from 10 healthy volunteers, and compare performance with a balance assessment system called BTrackS Balance Assessment Board. Our results show high degree of correlation with BTrackS. The proposed system promises to be a good candidate for objective functional balance tests and warrants further investigations to assess validity in clinical settings, including acute care, long term care and assisted living care facilities. Our long term goals include non-intrusive approaches to assess balance competence during ADL in independent living environments.

  6. The Reliability of a Functional Agility Test for Water Polo

    Directory of Open Access Journals (Sweden)

    Tucher Guilherme

    2014-07-01

    Full Text Available Few functional agility tests for water polo take into consideration its specific characteristics. The preliminary objective of this study was to evaluate the reliability of an agility test for water polo players. Fifteen players (16.3 ± 1.8 years old with a minimum of two years of competitive experience were evaluated. A Functional Test for Agility Performance (FTAP was designed to represent the context of this sport. Several trials were performed to familiarize the athlete with the movement. Two experienced coaches measured three repetitions of the FTAP. Descriptive statistics, repeated measures analysis of variance (ANOVA, 95% limit of agreement (LOA, intraclass correlation coefficient (ICC and standard error of measurements (SEM were used for data analysis. It was considered that certain criteria of reliability measures were met. There was no significant difference between the repetitions, which may be explained by an effect of the evaluator, the ability of the players or fatigue (p > 0.05. The ICC average from evaluators was high (0.88. The SEM varied between 0.13 s and 0.49 s. The CV average considering each individual was near 6-7%. These values depended on the condition of measurement. As the FTAP contains some characteristics that create a degree of unpredictability, the same athlete may reach different performance results, increasing variability. An adjustment in the sample, familiarization and careful selection of subjects help to improve this situation and enhance the reliability of the indicators.

  7. Reliability of a Functional Test Battery Evaluating Functionality, Proprioception and Strength of the Ankle Joint

    OpenAIRE

    YILDIZ, Yavuz; ŞEKİR, Ufuk; HAZNECİ, Bülent

    2009-01-01

    Aim: In contrast to the one-sided evaluation methods used in the past, combining multiple tests allows one to obtain a global assessment of the ankle joint. Materials and Methods: Twenty healthy male volunteers participated in this study. One component of the test battery included five different functional ability tests, which included: single limb hopping course, one-legged and triple-legged hop for distance, and six-meter (6-m) and cross 6-m hop for time. Ankle joint position sense and on...

  8. Testing intermolecular potential functions using transport property data

    International Nuclear Information System (INIS)

    Clifford, A.A.; Dickinson, E.; Gray, P.; Scott, A.C.

    1975-01-01

    The viscosity of hydrogen has been measured at eight temperatures from 273 to 1060K, using a capillary-flow viscometer. The results have been used to test the repulsive part of a recently formulated H 2 /H 2 intermolecular potential function, obtained from molecular-beam measurements. Agreement between the experimental and predicted values for viscosity is within 3.5%, which corresponds approximately to the combined quoted uncertainties in the two sets of data. However, if the value of the distance parameter of the potential is reduced by about 1.5%, the agreement obtained is within 0.75% over the whole temperature range. This modified potential function gives better agreement with the available higher temperature viscosities and second virial coefficients. (author)

  9. Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells

    Directory of Open Access Journals (Sweden)

    Gerard Ruiz-Babot

    2018-01-01

    Full Text Available Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies.

  10. Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells.

    Science.gov (United States)

    Ruiz-Babot, Gerard; Balyura, Mariya; Hadjidemetriou, Irene; Ajodha, Sharon J; Taylor, David R; Ghataore, Lea; Taylor, Norman F; Schubert, Undine; Ziegler, Christian G; Storr, Helen L; Druce, Maralyn R; Gevers, Evelien F; Drake, William M; Srirangalingam, Umasuthan; Conway, Gerard S; King, Peter J; Metherell, Louise A; Bornstein, Stefan R; Guasti, Leonardo

    2018-01-30

    Adrenal insufficiency is managed by hormone replacement therapy, which is far from optimal; the ability to generate functional steroidogenic cells would offer a unique opportunity for a curative approach to restoring the complex feedback regulation of the hypothalamic-pituitary-adrenal axis. Here, we generated human induced steroidogenic cells (hiSCs) from fibroblasts, blood-, and urine-derived cells through forced expression of steroidogenic factor-1 and activation of the PKA and LHRH pathways. hiSCs had ultrastructural features resembling steroid-secreting cells, expressed steroidogenic enzymes, and secreted steroid hormones in response to stimuli. hiSCs were viable when transplanted into the mouse kidney capsule and intra-adrenal. Importantly, the hypocortisolism of hiSCs derived from patients with adrenal insufficiency due to congenital adrenal hyperplasia was rescued by expressing the wild-type version of the defective disease-causing enzymes. Our study provides an effective tool with many potential applications for studying adrenal pathobiology in a personalized manner and opens venues for the development of precision therapies. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Assessing Differential Item Functioning on the Test of Relational Reasoning

    Directory of Open Access Journals (Sweden)

    Denis Dumas

    2018-03-01

    Full Text Available The test of relational reasoning (TORR is designed to assess the ability to identify complex patterns within visuospatial stimuli. The TORR is designed for use in school and university settings, and therefore, its measurement invariance across diverse groups is critical. In this investigation, a large sample, representative of a major university on key demographic variables, was collected, and the resulting data were analyzed using a multi-group, multidimensional item-response theory model-comparison procedure. No significant differential item functioning was found on any of the TORR items across any of the demographic groups of interest. This finding is interpreted as evidence of the cultural fairness of the TORR, and potential test-development choices that may have contributed to that cultural fairness are discussed.

  12. A virtual shopping test for realistic assessment of cognitive function.

    Science.gov (United States)

    Okahashi, Sayaka; Seki, Keiko; Nagano, Akinori; Luo, Zhiwei; Kojima, Maki; Futaki, Toshiko

    2013-06-18

    Cognitive dysfunction caused by brain injury often prevents a patient from achieving a healthy and high quality of life. By now, each cognitive function is assessed precisely by neuropsychological tests. However, it is also important to provide an overall assessment of the patients' ability in their everyday life. We have developed a Virtual Shopping Test (VST) using virtual reality technology. The objective of this study was to clarify 1) the significance of VST by comparing VST with other conventional tests, 2) the applicability of VST to brain-damaged patients, and 3) the performance of VST in relation to age differences. The participants included 10 patients with brain damage, 10 age-matched healthy subjects for controls, 10 old healthy subjects, and 10 young healthy subjects. VST and neuropsychological tests/questionnaires about attention, memory and executive function were conducted on the patients, while VST and the Mini-Mental State Examination (MMSE) were conducted on the controls and healthy subjects. Within the VST, the participants were asked to buy four items in the virtual shopping mall quickly in a rational way. The score for evaluation included the number of items bought correctly, the number of times to refer to hints, the number of movements between shops, and the total time spent to complete the shopping. Some variables on VST correlated with the scores of conventional assessment about attention and everyday memory. The mean number of times referring to hints and the mean number of movements were significantly larger for the patients with brain damage, and the mean total time was significantly longer for the patients than for the controls. In addition, the mean total time was significantly longer for the old than for the young. The results suggest that VST is able to evaluate the ability of attention and everyday memory in patients with brain damage. The time of VST is increased by age.

  13. Mediators of compassionate goal intervention effects on human neuroendocrine responses to the Trier Social Stress Test.

    Science.gov (United States)

    Erickson, Thane M; Mayer, Stefanie E; Lopez-Duran, Nestor L; Scarsella, Gina M; McGuire, Adam P; Crocker, Jennifer; Abelson, James L

    2017-11-01

    The hypothalamic-pituitary-adrenal (HPA) axis is thought to mediate the effects of stress on illness. Research has identified a limited number of psychological variables that modulate human HPA responses to stressors (e.g. perceived control and social support). Prosocial goals can reduce subjective stress, but have not been carefully examined in experimental settings where pathways of impact on biological stress markers may be traced. Recent work demonstrated that coaching individuals to strive to help others reduced HPA responses to the Trier Social Stress Test (TSST) relative to other cognitive interventions. However, identification of mediational pathways, which were not examined in the original study, is necessary to determine whether the HPA buffering effects were due to helping motivations (compassionate goals; CGs) rather than via previously identified variables such as control or support. In this new analysis, we combined the original cortisol data with novel observer ratings of interpersonal behavior and psychological variables during the stress task, and conducted new, theory-driven analyses to determine psychological mediators for the intervention's effect on cortisol responses (N = 54; 21 females, 33 males; 486 cortisol samples). Control, support, and task ego-threat failed to account for the effects of the intervention. As hypothesized, self and observer-rated CGs, as well as observer-rated perceptions of participants' interpersonal behavior as morally desirable (but not as dominant or affiliative) were significant mediators of neuroendocrine responses. The findings suggest that stress-reduction interventions based on prosocial behavior should target particular motivational and interpersonal features.

  14. Dynamic changes of central thyroid functions in the management of Cushing's syndrome.

    Science.gov (United States)

    Dogansen, Sema Ciftci; Yalin, Gulsah Yenidunya; Canbaz, Bulent; Tanrikulu, Seher; Yarman, Sema

    2018-01-01

    The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

  15. Stress reactivity in childhood functional abdominal pain or irritable bowel syndrome.

    Science.gov (United States)

    Gulewitsch, M D; Weimer, K; Enck, P; Schwille-Kiuntke, J; Hautzinger, M; Schlarb, A A

    2017-01-01

    Frequent abdominal pain (AP) in childhood has been shown to be associated with elevated experience of stress and with deficits in stress coping, but psychophysiological stress reactivity has been studied rarely. We examined whether children with frequent AP show altered reactions of the parasympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis during and following an afternoon laboratory social stress task in comparison to healthy children and children with anxiety disorders. Twenty-four children with frequent AP (18 with functional AP and six with irritable bowel syndrome; M = 9.9 years), and 24 healthy controls underwent stressful free speech and arithmetic tasks. Twelve children with anxiety disorders served as second comparison sample. Groups were compared regarding parasympathetic reaction and saliva cortisol concentration. We found no differences in parasympathetic withdrawal between the groups. Concerning the HPA axis, we detected an attenuated cortisol reactivity in children with AP compared to both other groups. This study provides preliminary evidence that childhood AP is not associated with altered parasympathetic withdrawal during stress. It seems to be related to a down-regulated reactivity of the HPA axis. This pattern was ascertained in comparison to healthy children and also in comparison to children with anxiety disorders. Childhood abdominal pain could be related to down-regulated HPA axis reactivity to stress but not to altered parasympathetic reaction. Children with abdominal pain and children with anxiety disorders exhibit a divergent stress-related HPA axis reaction. © 2016 European Pain Federation - EFIC®.

  16. Diurnal Variation of Plasma Brain-Derived Neurotrophic Factor Levels in Women with Functional Hypothalamic Amenorrhea.

    Science.gov (United States)

    Drakopoulos, Panagiotis; Casarosa, Elena; Bucci, Fiorella; Piccinino, Manuela; Wenger, Jean-Marie; Nappi, Rossella Elena; Polyzos, Nicholas; Genazzani, Andrea Riccardo; Pluchino, Nicola

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is strongly related to hormonal networks and is modulated by hypothalamic activity. To evaluate plasma BDNF concentration in patients with functional hypothalamic amenorrhea (FHA), with reference to the BDNF circadian rhythm and its relation with the cortisol (F) rhythm, and to assess whether the duration of amenorrhea might influence the BDNF:F ratio in FHA. This was an observational study evaluating 36 amenorrheic and 30 eumenorrheic women. Basal values of BDNF and hormones were examined in blood samples collected from 7:00 to 9:00 h in all the women. Basal BDNF and F levels were determined in blood samples collected in 12 subjects from each group at 8:00, 12:00, 16:00, 20:00, and 24:00 h. BDNF plasma levels are significantly lower in amenorrheic women (p 0.05), sex steroids, and F in FHA. Low plasma BDNF levels in FHA are not significantly correlated with duration of amenorrhea. The 24-hour variation of BDNF in amenorrheic women is significantly lower when compared to the control group, and normal daily variations of BDNF disappeared in FHA patients. F preserved its circadian rhythm in both groups. Interactions between BDNF, the hypothalamus-pituitary-adrenal axis, and sex steroids might be critical in clinical conditions of modified homeostasis/adaptation, such as FHA. © 2015 S. Karger AG, Basel.

  17. Tests of pancreatic function using /sup 75/Se--Selenomethionine

    Energy Technology Data Exchange (ETDEWEB)

    Krasner, N; Brodie, M J; Sumner, D J; Thomson, T J

    1976-04-01

    Pancreatic function was investigated in 43 patients using a combination of conventional and subtraction scans of the pancreas and duodenal aspiration of the /sup 75/Se-Selenomethionine injected, in the time periods 60 to 150 minutes, 90 to 120 minutes and 105 to 150 minutes after injection. Patients with chronic alcoholism, chronic pancreatitis, pancreatic carcinoma, extrahepatic biliary obstruction and liver disease were included. Seven patients with no evidence of gastro-intestinal disease served as controls. Pancreatic scanning provided eight false positive and two false negative results (23.3 percent) and with /sup 75/Se-Selenomethionine excretion at 105 to 150 minutes, six false results were obtained (14 percent). In only one patient was a false positive result obtained with both scans and the /sup 75/Se-Selenomethionine test. The performance of conventional and subtraction scans of the pancreas with measurement of /sup 75/Se-Selenomethionine activity in the duodenal aspirate collected from 105 to 150 minutes after injection provides a convenient means of testing pancreatic exocrine function in a single three hour session.

  18. Exercise and the Regulation of Immune Functions.

    Science.gov (United States)

    Simpson, Richard J; Kunz, Hawley; Agha, Nadia; Graff, Rachel

    2015-01-01

    Exercise has a profound effect on the normal functioning of the immune system. It is generally accepted that prolonged periods of intensive exercise training can depress immunity, while regular moderate intensity exercise is beneficial. Single bouts of exercise evoke a striking leukocytosis and a redistribution of effector cells between the blood compartment and the lymphoid and peripheral tissues, a response that is mediated by increased hemodynamics and the release of catecholamines and glucocorticoids following the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Single bouts of prolonged exercise may impair T-cell, NK-cell, and neutrophil function, alter the Type I and Type II cytokine balance, and blunt immune responses to primary and recall antigens in vivo. Elite athletes frequently report symptoms associated with upper respiratory tract infections (URTI) during periods of heavy training and competition that may be due to alterations in mucosal immunity, particularly reductions in secretory immunoglobulin A. In contrast, single bouts of moderate intensity exercise are "immuno-enhancing" and have been used to effectively increase vaccine responses in "at-risk" patients. Improvements in immunity due to regular exercise of moderate intensity may be due to reductions in inflammation, maintenance of thymic mass, alterations in the composition of "older" and "younger" immune cells, enhanced immunosurveillance, and/or the amelioration of psychological stress. Indeed, exercise is a powerful behavioral intervention that has the potential to improve immune and health outcomes in the elderly, the obese, and patients living with cancer and chronic viral infections such as HIV. © 2015 Elsevier Inc. All rights reserved.

  19. [TCD functional test for vertigo induced by ischemic cerebrovascular disorders].

    Science.gov (United States)

    Li, Q; Zhong, N; Xue, X

    1999-04-01

    To diagnose differentially the vetigo induced by some ischemic cerebrovascular disorder. Patients with vertebrobasilar artery transient ischemic vertigo (group A), migraine (group B), hyperventilation syndrome (group C), hypertension (group D) are measured by using TCD functional examination which included blood peak velocity of systolic (Vs) and diastolic (Vd) end-period of vertibrobasilar artery of routine TCD (TCD-R), one minute hyperventilation TCD (TCD-HV) and one minute voluntary apnea TCD (TCD-B) respectively. It showed that the Vs, Vd are decreased under the three conditions in A, B and D groups. The most apparent decrease are obversed in D group. The values of the decrease are similar between group A and B. No changes are found in C group. The abnormal Vs incidences of TCD-B measurement in group A are higher than those in group B and C, but significant lower than those in group D; and in TCD-HV test lower than group D and C, higher than group B; in TCD-R test, lower than group D, and no difference with group B and C. The abnormal incidences of Vd in group A are lower than group D and higher than group B in TCD-B test. In TCD-HV test, the group A abnormol incidences are lower than group D but higher than group B and C. In TCD-R test, the abnormal incidences are lower than group D and no difference between group B and C. The TCD measuremen is useful for differential diagnosis of vertigo induced by ischemic cerebrovascular disorders.

  20. Functional toxicology: tools to advance the future of toxicity testing

    Science.gov (United States)

    Gaytán, Brandon D.; Vulpe, Chris D.

    2014-01-01

    The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

  1. Grammar tests increase the ability to lateralize language function in the Wada test.

    Science.gov (United States)

    Połczyńska, Monika; Curtiss, Susan; Walshaw, Particia; Siddarth, Prabha; Benjamin, Chris; Moseley, Brian D; Vigil, Celia; Jones, Michael; Eliashiv, Dawn; Bookheimer, Susan

    2014-12-01

    Grammar is a core component of the language system, yet it is rarely assessed during the Wada (intracarotid amobarbital) test. It is hypothesized that adding grammar tests to the recovery phase of the Wada test will increase our ability to lateralize language function. Sixteen individuals (nine females, fifteen right-handed, mean age 38.4 years, SD=10.7) with medically refractory temporal lobe epilepsy participated in the study. On EEG ten patients had seizures originating in the left hemisphere (LH), five in the right hemisphere (RH), and one was insufficiently lateralized. We included only patients who were LH-dominant on the standard test in the encoding phase of the Wada test. In the recovery phase of Wada testing the participants underwent evaluation with a standard language and a new test of grammar, the CYCLE-N. Ten patients underwent bilateral injections, six unilateral (one RH, five LH). As expected, injection in the LH decreased language performance to a greater extent than injection to the RH on both tests. However, the CYCLE-N produced more profound language deficits in the injected LH compared to the RH (p=0.01), whereas the standard tests did not cause such pronounced differences (p=0.2). The results suggest that the standard tests did not significantly differentiate the effects of the injections and the CYCLE-N, for the most part, did. Our results are of particular relevance to patients who are too obtunded to speak in the encoding phase. In sum, the CYCLE-N may be helpful in assessing hemispheric dominance for language. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Functional Task Test: 1. Sensorimotor changes Associated with Postflight Alterations in Astronaut Functional Task Performance

    Science.gov (United States)

    Bloomberg, J. J.; Arzeno, N. H.; Buxton, R. E.; Feiveson, A. H.; Kofman, I. S.; Lee, S. M. C.; Miller, C. A.; Mulavara, A. P.; Platts, S. H.; Peters, B. T.; hide

    2011-01-01

    Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These changes may affect a crewmember s ability to perform critical mission tasks immediately after landing on a planetary surface. The overall goal of this project is to determine the effects of space flight on functional tests that are representative of high priority exploration mission tasks and to identify the key underlying physiological factors that contribute to decrements in performance. This presentation will focus on the sensorimotor contributions to postflight functional performance.

  3. A NEW CLINICAL MUSCLE FUNCTION TEST FOR ASSESSMENT OF HIP EXTERNAL ROTATION STRENGTH: AUGUSTSSON STRENGTH TEST.

    Science.gov (United States)

    Augustsson, Jesper

    2016-08-01

    Dynamic clinical tests of hip strength applicable on patients, non-athletes and athletes alike, are lacking. The aim of this study was therefore to develop and evaluate the reliability of a dynamic muscle function test of hip external rotation strength, using a novel device. A second aim was to determine if gender differences exist in absolute and relative hip strength using the new test. Fifty-three healthy sport science students (34 women and 19 men) were tested for hip external rotation strength using a device that consisted of a strap connected in series with an elastic resistance band loop, and a measuring tape connected in parallel with the elastic resistance band. The test was carried out with the subject side lying, positioned in 45 ° of hip flexion and the knees flexed to 90 ° with the device firmly fastened proximally across the knees. The subject then exerted maximal concentric hip external rotation force against the device thereby extending the elastic resistance band. The displacement achieved by the subject was documented by the tape measure and the corresponding force production was calculated. Both right and left hip strength was measured. Fifteen of the subjects were tested on repeated occasions to evaluate test-retest reliability. No significant test-retest differences were observed. Intra-class correlation coefficients ranged 0.93-0.94 and coefficients of variation 2.76-4.60%. In absolute values, men were significantly stronger in hip external rotation than women (right side 13.2 vs 11.0 kg, p = 0.001, left side 13.2 vs 11.5 kg, p = 0.002). There were no significant differences in hip external rotation strength normalized for body weight (BW) between men and women (right side 0.17 kg/BW vs 0.17 kg/BW, p = 0.675, left side 0.17 kg/BW vs 0.18 kg/BW, p = 0.156). The new muscle function test showed high reliability and thus could be useful for measuring dynamic hip external rotation strength in patients, non-athletes and athletes

  4. Quality and Timing of Stressors Differentially Impact on Brain Plasticity and Neuroendocrine-Immune Function in Mice

    Directory of Open Access Journals (Sweden)

    Sara Capoccia

    2013-01-01

    Full Text Available A growing body of evidence suggests that psychological stress is a major risk factor for psychiatric disorders. The basic mechanisms are still under investigation but involve changes in neuroendocrine-immune interactions, ultimately affecting brain plasticity. In this study we characterized central and peripheral effects of different stressors, applied for different time lengths, in adult male C57BL/6J mice. We compared the effects of repeated (7 versus 21 days restraint stress (RS and chronic disruption of social hierarchy (SS on neuroendocrine (corticosterone and immune function (cytokines and splenic apoptosis and on a marker of brain plasticity (brain-derived neurotrophic factor, BDNF . Neuroendocrine activation did not differ between SS and control subjects; by contrast, the RS group showed a strong neuroendocrine response characterized by a specific time-dependent profile. Immune function and hippocampal BDNF levels were inversely related to hypothalamic-pituitary-adrenal axis activation. These data show a fine modulation of the crosstalk between central and peripheral pathways of adaptation and plasticity and suggest that the length of stress exposure is crucial to determine its final outcome on health or disease.

  5. Pain on Functional Movement Screen Tests and Injury Risk.

    Science.gov (United States)

    Bushman, Timothy T; Grier, Tyson L; Canham-Chervak, Michelle C; Anderson, Morgan K; North, William J; Jones, Bruce H

    2015-11-01

    The Functional Movement Screen (FMS) is a tool intended to evaluate limitations or asymmetries of movement to detect individuals at risk for exercise- and sports-related injury. The purpose was to determine the association and predictive value of specific FMS tests with injury risk in physically active men. Soldiers aged 18-57 years completed the FMS (n = 2,476). Demographic and fitness data were collected by survey. Medical record data for any, overuse, and traumatic injury 6 months after the assessment were obtained. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated along with receiver operator characteristics to determine area under the curve (AUC). Risks, risk ratios, odds ratios (ORs), and 95% confidence intervals were calculated to assess injury risks. Multivariate logistic regression identified that pain on 5 of the 7 tests was associated with greater risk for any injury (OR = 1.50-3.51): deep squat, hurdle step, in-line lunge, trunk stability push-up, and rotary stability. However, FMS registered low sensitivity, PPV, and AUC for all 7 tests for the 3 injury types (2-24% sensitivity, 16-74% PPV, and 50-58% AUC). Although the presence of pain was associated with a higher risk of injury on 5 tests, a low sensitivity, PPV, and AUC were displayed. Therefore, caution is advised when implementing the FMS as a screening tool in an Army or similarly active population as it could lead to prevention and treatment resources being directed toward individuals who are not at greater risk for injury.

  6. Tuboimpedance: A New Test of Eustachian Tube Function.

    Science.gov (United States)

    Smith, Matthew E; Zou, Charlie C; Blythe, Andrew J C; Tysome, James R

    2017-04-01

    Objective Eustachian tube (ET) dysfunction is most frequently caused by a failure of the ET to adequately open; however, there is currently no reliable method of assessing this. Tubomanometry has recently shown good interindividual repeatability as a measure of ET function by measuring middle ear pressure after the application of regulated nasopharyngeal pressures during swallowing. We present the first reports of a novel test: middle ear impedance measurements during standard nasopharyngeal pressure application (tuboimpedance). We assess repeatability in healthy ears and any advantages over tubomanometry. Study Design Exploratory cohort diagnosis study. Setting Tertiary referral center. Subjects Twenty screened, healthy ears (10 volunteers). Methods Tubomanometry and tuboimpedance tests were performed while individuals swallowed with applied nasopharyngeal pressures of 20, 30, 40, and 50 mbar. Eustachian tube opening detection rate and test repeatability (measured by intraclass correlation coefficient [ICC]) for immediate and delayed repeats at each pressure were compared. Results ET opening was detected more frequently using tuboimpedance, with a 100% detection rate using a nasopharyngeal pressure of 30 mbar or more, compared to 88% to 96% with tubomanometry. Detection of ET opening at 20 mbar was possible with tuboimpedance. Repeatability of both tests was mostly strong (ICC >0.7) for both immediate and delayed repeats. Repeatability for the tubomanometry R value was only fair to moderate. Conclusion Tuboimpedance may provide a repeatable measure of ET opening that is easier to perform due to lower nasopharyngeal pressures required and fewer issues with poor ear-probe sealing. Further assessment in patients with different forms of ET dysfunction is required.

  7. Functionally graded bioactive coatings: From fabrication to testing

    Science.gov (United States)

    Foppiano, Silvia

    Every year about half a million Americans undergo total joint replacement surgery of some kind. This number is expected to steadily increase in the future. About 20% of these patients will need a revision surgery because of implant failure, with a significant increase in health care cost. Current implant materials for load bearing applications must be strong enough to support the loads involved in daily activities, and bioinert, to limit reactivity in the body that may cause inflammatory and other adverse reactions. Metal alloys are typically used as materials for load bearing implants and rely on mechanical interlocking to achieve fixation which can be improved by using bone cements. To improve implant osteointegration, metal implants have been coated with a bone-like mineral: hydroxyapatite (HA). The plasma spray technique is commonly used to apply the HA coating. Such implants do not require the use of bone cement. Plasma sprayed HA coated implants are FDA approved and currently on the market, but their properties are not reproducible or reliable. Thus, coating delamination can occur. Our research group developed a novel family of bioactive glasses which were enameled onto titanium alloy using a functionally graded approach. We stratified the coating with different glass compositions to fulfill different functions. We coupled a first glass layer, with a good CTE match to the alloy, with a second layer of bioactive glass obtaining a functionally graded bioactive coating (FGC). In this thesis for the first time the cytocompatibility of novel bioactive glasses, and their functionally graded coatings on Ti6Al4V, was studied with an in vitro bone model (MC3T3-E1.4 mouse preosteblast cells). The novel bioactive glasses are cytocompatible and no compositional change is required. The fabrication process is reproducible, introduces a small (average 6 vol%) amount of crystallization, which does not significantly affect bioactivity in SBF as tested. The coatings are

  8. Pulmonary function tests in obese people candidate to bariatric surgery

    Directory of Open Access Journals (Sweden)

    C. Guimarães

    2012-05-01

    Full Text Available Obesity is considered one of the most serious public health problems of the modern world. Because it alters the relationship between the lungs, chest wall and diaphragm, it is to be expected that it impacts on the respiratory function. In Portugal, there is not much data about the relationship between obesity and pulmonary function.The aim of this study was to characterize respiratory function in morbidly obese patients and to evaluate whether weight loss in patients submitted to bariatric surgery affects pulmonary function tests (PFT.We conducted a retrospective study with 36 morbidly obese patients submitted to bariatric surgery, with a mean age of 40.6 years, 64% female and with a mean body mass index (BMI of 49.7 kg/m2. All patients were clinical and functionally evaluated before surgery and after their weight had stabilized following surgery. They underwent a complete pulmonary function testing with spirometry, lung volumes, carbon monoxide diffusing capacity (DLCO, maximum respiratory pressures and arterial blood gases analysis. Prior to surgery almost all the patients had functional respiratory changes, 34 had a decrease in functional residual capacity (FRC 6 of whom a restrictive syndrome. Only 2 patients did not show any functional or arterial blood gas change. After bariatric surgery, BMI decreased to 34 kg/m2 and there was a significant improvement in almost all functional parameters with resolution of restrictive disorders. Nevertheless, in 13 patients the FRC remained decreased.After weight loss, the only correlation found was between reduction of BMI and increased FRC (r = −0.371; p = 0.028. This study suggests a relationship between obesity and pulmonary restriction and a positive impact of bariatric surgery in PFT. Resumo: A obesidade é considerada um problema de saúde pública da atualidade. Devido ao facto de alterar a relação entre pulmões, parede torácica e diafragma, a obesidade tem

  9. Radioselenium pancreozymin-secretin test as a clinical test for pancreatic exocrine function

    International Nuclear Information System (INIS)

    Shichiri, M.; Etani, N.; Yoshida, M.; Harano, Y.; Hoshi, M.; Shigeta, Y.; Abe, H.

    1975-01-01

    The appearance of radioselenium in the protein fraction of duodenal aspirates has been studied after an intravenous injection of 75 Se-selenomethionine. The continuous flow of pancreatic juice was stimulated by pancreozymin at 120 minutes and by secretin at 140 minutes. A good distinction between normal subjects and patients with pancreatic disease was obtained by measuring 75 Se-radioactivity in the protein fraction of duodenal aspirates; either cumulative radioactivity during the combined 80-minute post-pancreozymin-secretin period, or maximum 75 Se-specific activity during the postsecretin period was used as an index. The test presented here might be a useful and sufficiently reliable method for detecting abnormal pancreatic exocrine function. This test can be performed along with the conventional pancreozymin-secretin test, serum enzyme response to pancreozymin and secretin, and pancreatic scintiscanning

  10. Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

    Science.gov (United States)

    Berga, Sarah L; Loucks, Tammy L

    2006-12-01

    Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that

  11. Cochlear function tests in estimation of speech dynamic range.

    Science.gov (United States)

    Han, Jung Ju; Park, So Young; Park, Shi Nae; Na, Mi Sun; Lee, Philip; Han, Jae Sang

    2016-10-01

    The loss of active cochlear mechanics causes elevated thresholds, loudness recruitment, and reduced frequency selectivity. The problems faced by hearing-impaired listeners are largely related with reduced dynamic range (DR). The aim of this study was to determine which index of the cochlear function tests correlates best with the DR to speech stimuli. Audiological data on 516 ears with pure tone average (PTA) of ≤55 dB and word recognition score of ≥70% were analyzed. PTA, speech recognition threshold (SRT), uncomfortable loudness (UCL), and distortion product otoacoustic emission (DPOAE) were explored as the indices of cochlear function. Audiometric configurations were classified. Correlation between each index and the DR was assessed and multiple regression analysis was done. PTA and SRT demonstrated strong negative correlations with the DR (r = -0.788 and -0.860, respectively), while DPOAE sum was moderately correlated (r = 0.587). UCLs remained quite constant for the total range of the DR. The regression equation was Y (DR) = 75.238 - 0.719 × SRT (R(2 )=( )0.721, p equation.

  12. Occupational health surveillance: Pulmonary function testing in emergency responders

    Directory of Open Access Journals (Sweden)

    James D McCluskey

    2014-01-01

    Full Text Available Emergency responders may be exposed to a variety of fumes, gases, and particulates during the course of their job that can affect pulmonary function (PF and require the use of respiratory protection. This investigation used occupational health monitoring examination data to characterize PF in a population currently employed as emergency responders. PF tests for workers who required health examinations to ensure fitness for continued respirator use were compared to the National Health and Nutrition Examination Survey (NHANES III Raw Spirometry database to determine if decreased PF was associated with employment as an emergency responder. The results of this research indicated that the emergency responders experienced a modest, but statistically significant, increase in forced expiratory volume in 1 second (FEV1 and forced vital capacity (FVC mean values over the NHANES III population in both total and stratified analyses, including stratification by age, gender, height, and smoking history. Results are likely due to a combination of effectively controlled exposures in the workplace, and the healthy worker effect among long-term workers. PF testing required by the Occupational and Safety Health Administration (OSHA has substantial utility for conducting occupational surveillance at the population level. In this investigation, we were able to quickly evaluate if abnormal PF existed in an industrial sector known to have exposures that, when uncontrolled, can lead to PF impairment.

  13. Multiloop Integral System Test (MIST): MIST Facility Functional Specification

    International Nuclear Information System (INIS)

    Habib, T.F.; Koksal, C.G.; Moskal, T.E.; Rush, G.C.; Gloudemans, J.R.

    1991-04-01

    The Multiloop Integral System Test (MIST) is part of a multiphase program started in 1983 to address small-break loss-of-coolant accidents (SBLOCAs) specific to Babcock and Wilcox designed plants. MIST is sponsored by the US Nuclear Regulatory Commission, the Babcock ampersand Wilcox Owners Group, the Electric Power Research Institute, and Babcock and Wilcox. The unique features of the Babcock and Wilcox design, specifically the hot leg U-bends and steam generators, prevented the use of existing integral system data or existing integral facilities to address the thermal-hydraulic SBLOCA questions. MIST was specifically designed and constructed for this program, and an existing facility -- the Once Through Integral System (OTIS) -- was also used. Data from MIST and OTIS are used to benchmark the adequacy of system codes, such as RELAP5 and TRAC, for predicting abnormal plant transients. The MIST Functional Specification documents as-built design features, dimensions, instrumentation, and test approach. It also presents the scaling basis for the facility and serves to define the scope of work for the facility design and construction. 13 refs., 112 figs., 38 tabs

  14. Above-Level Test Item Functioning across Examinee Age Groups

    Science.gov (United States)

    Warne, Russell T.; Doty, Kristine J.; Malbica, Anne Marie; Angeles, Victor R.; Innes, Scott; Hall, Jared; Masterson-Nixon, Kelli

    2016-01-01

    "Above-level testing" (also called "above-grade testing," "out-of-level testing," and "off-level testing") is the practice of administering to a child a test that is designed for an examinee population that is older or in a more advanced grade. Above-level testing is frequently used to help educators design…

  15. Bradykinesia-akinesia incoordination test: validating an online keyboard test of upper limb function.

    Science.gov (United States)

    Noyce, Alastair J; Nagy, Anna; Acharya, Shami; Hadavi, Shahrzad; Bestwick, Jonathan P; Fearnley, Julian; Lees, Andrew J; Giovannoni, Gavin

    2014-01-01

    The Bradykinesia Akinesia Incoordination (BRAIN) test is a computer keyboard-tapping task that was developed for use in assessing the effect of symptomatic treatment on motor function in Parkinson's disease (PD). An online version has now been designed for use in a wider clinical context and the research setting. Validation of the online BRAIN test was undertaken in 58 patients with Parkinson's disease (PD) and 93 age-matched, non-neurological controls. Kinesia scores (KS30, number of key taps in 30 seconds), akinesia times (AT30, mean dwell time on each key in milliseconds), incoordination scores (IS30, variance of travelling time between key presses) and dysmetria scores (DS30, accuracy of key presses) were compared between groups. These parameters were correlated against total motor scores and sub-scores from the Unified Parkinson's Disease Rating Scale (UPDRS). Mean KS30, AT30 and IS30 were significantly different between PD patients and controls (p≤0.0001). Sensitivity for 85% specificity was 50% for KS30, 40% for AT30 and 29% for IS30. KS30, AT30 and IS30 correlated significantly with UPDRS total motor scores (r = -0.53, r = 0.27 and r = 0.28 respectively) and motor UPDRS sub-scores. The reliability of KS30, AT30 and DS30 was good on repeated testing. The BRAIN test is a reliable, convenient test of upper limb motor function that can be used routinely in the outpatient clinic, at home and in clinical trials. In addition, it can be used as an objective longitudinal measurement of emerging motor dysfunction for the prediction of PD in at-risk cohorts.

  16. Bradykinesia-akinesia incoordination test: validating an online keyboard test of upper limb function.

    Directory of Open Access Journals (Sweden)

    Alastair J Noyce

    Full Text Available The Bradykinesia Akinesia Incoordination (BRAIN test is a computer keyboard-tapping task that was developed for use in assessing the effect of symptomatic treatment on motor function in Parkinson's disease (PD. An online version has now been designed for use in a wider clinical context and the research setting.Validation of the online BRAIN test was undertaken in 58 patients with Parkinson's disease (PD and 93 age-matched, non-neurological controls. Kinesia scores (KS30, number of key taps in 30 seconds, akinesia times (AT30, mean dwell time on each key in milliseconds, incoordination scores (IS30, variance of travelling time between key presses and dysmetria scores (DS30, accuracy of key presses were compared between groups. These parameters were correlated against total motor scores and sub-scores from the Unified Parkinson's Disease Rating Scale (UPDRS.Mean KS30, AT30 and IS30 were significantly different between PD patients and controls (p≤0.0001. Sensitivity for 85% specificity was 50% for KS30, 40% for AT30 and 29% for IS30. KS30, AT30 and IS30 correlated significantly with UPDRS total motor scores (r = -0.53, r = 0.27 and r = 0.28 respectively and motor UPDRS sub-scores. The reliability of KS30, AT30 and DS30 was good on repeated testing.The BRAIN test is a reliable, convenient test of upper limb motor function that can be used routinely in the outpatient clinic, at home and in clinical trials. In addition, it can be used as an objective longitudinal measurement of emerging motor dysfunction for the prediction of PD in at-risk cohorts.

  17. Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test

    Directory of Open Access Journals (Sweden)

    Dong Wook Lim

    2016-02-01

    Full Text Available Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o. significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR. Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression.

  18. Correlation Between Haematological Parameters, Kidney Function Tests and Liver Function Tests in Plasmodium Falciparum and Vivax Malaria

    Directory of Open Access Journals (Sweden)

    Mitul Chhatriwala

    2017-12-01

    Full Text Available Abstract: Malaria remains a major cause of morbidity and mortality in India. Plasmodium falciparum remains the main culprit although cases with vivax malaria are on the rise. Severe malaria as defined by the WHO criteria has high rate of complications and mortality. In our study we recruited microscopy positive falciparum and vivax malaria patients. Haematological and biochemical laboratory investigations were carried out in recruited patients. Both parameters were found to be significantly derailed in falciparum cases as compared to vivax. A direct correlation has been observed between kidney function tests (serum creatinine,serum urea and direct bilirubin levels across all cases of malaria. Hence these parameters can be used to identify and monitor the progress of cases of severe malaria as significant proportion of patients fulfilled the criteria of severe malaria in the cohort.

  19. Developmental and contextual considerations for adrenal and gonadal hormone functioning during adolescence: Implications for adolescent mental health.

    Science.gov (United States)

    Marceau, Kristine; Ruttle, Paula L; Shirtcliff, Elizabeth A; Essex, Marilyn J; Susman, Elizabeth J

    2015-09-01

    Substantial research has implicated the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes independently in adolescent mental health problems, though this literature remains largely inconclusive. Given the cross-talk between the HPA and HPG axes and their increased activation in adolescence, a dual-axis approach that examines both axes simultaneously is proposed to predict the emergence and persistence of adolescent mental health problems. After briefly orienting readers to HPA and HPG axis functioning, we review the literature examining associations between hormone levels and changes with behavior during adolescence. Then, we provide a review of the literature supporting examination of both axes simultaneously and present the limited research that has taken a dual-axis approach. We propose future directions including consideration of between-person and within-person approaches to address questions of correlated changes in HPA and HPG hormones. Potential moderators are considered to increase understanding of the nuanced hormone-behavior associations during key developmental transitions. © 2014 Wiley Periodicals, Inc.

  20. Forward lunge as a functional performance test in ACL deficient subjects: test-retest reliability

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Henriksen, Marius; Dyhre-Poulsen, Poul

    2009-01-01

    The forward lunge movement may be used as a functional performance test of anterior cruciate ligament (ACL) deficient and reconstructed subjects. The purposes were 1) to determine the test-retest reliability of a forward lunge in healthy subjects and 2) to determine the required numbers...... of repetitions necessary to yield satisfactory reliability. Nineteen healthy subjects performed four trials of a forward lunge on two different days. The movement time, impulses of the ground reaction forces (IFz, IFy), knee joint kinematics and dynamics during the forward lunge were calculated. The relative...... reliability was determined by calculation of Intraclass Correlation Coefficients (ICC). The IFz, IFy and the positive work of the knee extensors showed excellent reliability (ICC >0.75). All other variables demonstrated acceptable reliability (0.4>ICCreliability increased when more than...

  1. Safety system function trend indicator: Theory and test application

    International Nuclear Information System (INIS)

    Azarm, M.A.; Carbonaro, J.F.; Boccio, J.L.; Vesely, W.E.

    1989-01-01

    The purpose of this paper is to summarize research conducted on the development and validation of quantitative indicators of safety performance. This work, performed under the Risk-Based Performance Indicator (RBPI) Project, FIN A-3295, for the Office of Research (RES), is considered part of NRC's Performance Indicator Program which is being coordinated through the Office for the Analysis and Evaluation of Operational Data (AEOD). The program originally focused on risk-based indicators at high levels of safety indices (e.g., core-damage frequency, functional unavailabilities, and sequence monitoring). The program was then redirected towards a more amenable goal, safety system unavailability indicators, mainly due to the lack of PRA models and plant data. In that regard, BNL published a technical report that introduced the concept of cycle-based indicators and also described various alternatives of monitoring safety system unavailabilities. Further simplification of these indicators was requested by NRC to facilitate their applications to all plants in a timely manner. This resulted in the development of Safety System Function Trend (SSFT) indicators which minimize the need for detailed system model as well as component history. The theoretical bases for these indicators were developed through various simulation studies to determine the ease of detecting a trend and/or unacceptable performance. These indicators, along with several other indicators, were then generated and compared using plant data as a part of a test application. The SSFT indicators, specifically, were constructed for a total of eight plants, consisting of two systems per plant. Emphasis was placed on examining relative changes, as well as the indicator's actual level. Both the trend and actual indicator level were found to be important in identifying plants with potential problems

  2. Characterization of thyroid function and antithyroid antibody tests among Saudis

    Science.gov (United States)

    Jammah, Anwar A.; Alshehri, Anwar S.; Alrakhis, Afaf A.; Alhedaithy, Asma S.; Almadhi, Asma M.; Alkwai, Hala M.; Alhamad, Maram M.; Alzahrani, Saad H.

    2015-01-01

    Objective: To determine the reference intervals for thyroid function tests and the prevalence of thyroid autoimmunity in the Saudi population. Methods: A cross-sectional prospective study was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies were measured using enzyme-linked immunosorbent-assay. Subjects with previous or a family history of thyroid disorders, those taking medications affecting thyroid function, pregnant or lactating women, and those with goiter were excluded. Individuals with positive antibodies were excluded from the final analysis of the TSH reference range, but were used to determine the prevalence of thyroid autoimmunity. Results: Out of 337 Saudi subjects initially screened, 132 (aged 13-60 years) were candidates for reference calculation, the mean±standard deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96±0.9 (0.59-4.37), for FT4 (pmol/L) was 15.47±1.83 (12.04-19.13), and for FT3 (pmol/L) was 5.22±0.7 (4.07-6.76). The TSH was higher in the antibodies positive group (2.5±1.17 mIU/L) compared with the negative one (1.96±0.9 mIU/L) (pantithyroid antibodies. Conclusion: The TSH reference range was similar to laboratory references. Thyroid antibodies were prevalent in Saudis, necessitating further work in larger scale studies. PMID:25987111

  3. Assessment of platelet function in healthy sedated cats using three whole blood platelet function tests.

    Science.gov (United States)

    Ho, Kimberly K; Abrams-Ogg, Anthony C G; Wood, R Darren; O'Sullivan, M Lynne; Kirby, Gordon M; Blois, Shauna L

    2015-05-01

    The objectives of this study were to establish feline references intervals for 3 commercial whole blood platelet function test analyzer systems: Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), Platelet Function Analyzer-100 (PF: Siemens Canada, Mississauga, Ontario, Canada), and Plateletworks Combo-25 kit (PW; Helena Laboratories, Beaumont, TX). Venipuncture was performed on 55 healthy sedated cats, and platelet aggregation in response to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA; MP only) was assessed using citrated blood. For the MP analyzer, median (95% confidence intervals [CIs]) area under curve (Units) for ADP, COL, and AA agonists were 87 (11-176), 81 (32-129), and 91 (59-129), respectively. For the PF analyzer, median (95% CIs) closure time, using COL-ADP cartridges, was 69 (46-89) sec. For the PW assay, median (95% CIs) percent aggregations for ADP and COL agonists were 71 (18-92) and 49 (9-96), respectively, using impedance hematology analyzer platelet counts, and 94 (25-98) and 68 (14-119), respectively, using flow cytometry hematology analyzer platelet counts. There were low correlations between the PF analyzer (COL-ADP cartridge) and MP analyzer (COL agonist; ρ = 0.11), and between the PF analyzer (COL-ADP cartridge) and PW assay (COL agonist using impedance platelet counts; ρ = 0.14). The PW assay percent aggregations using impedance and flow cytometric platelet counts were correlated for both ADP (ρ = 0.64) and COL (ρ = 0.64) agonists. Platelet function testing using these tests are feasible in cats, but 95% CIs are wide, so single results may be difficult to interpret. Platelet counting by impedance or flow cytometry may be used for the PW assay but are not interchangeable. © 2015 The Author(s).

  4. Potential Functional Embedding Theory at the Correlated Wave Function Level. 2. Error Sources and Performance Tests.

    Science.gov (United States)

    Cheng, Jin; Yu, Kuang; Libisch, Florian; Dieterich, Johannes M; Carter, Emily A

    2017-03-14

    Quantum mechanical embedding theories partition a complex system into multiple spatial regions that can use different electronic structure methods within each, to optimize trade-offs between accuracy and cost. The present work incorporates accurate but expensive correlated wave function (CW) methods for a subsystem containing the phenomenon or feature of greatest interest, while self-consistently capturing quantum effects of the surroundings using fast but less accurate density functional theory (DFT) approximations. We recently proposed two embedding methods [for a review, see: Acc. Chem. Res. 2014 , 47 , 2768 ]: density functional embedding theory (DFET) and potential functional embedding theory (PFET). DFET provides a fast but non-self-consistent density-based embedding scheme, whereas PFET offers a more rigorous theoretical framework to perform fully self-consistent, variational CW/DFT calculations [as defined in part 1, CW/DFT means subsystem 1(2) is treated with CW(DFT) methods]. When originally presented, PFET was only tested at the DFT/DFT level of theory as a proof of principle within a planewave (PW) basis. Part 1 of this two-part series demonstrated that PFET can be made to work well with mixed Gaussian type orbital (GTO)/PW bases, as long as optimized GTO bases and consistent electron-ion potentials are employed throughout. Here in part 2 we conduct the first PFET calculations at the CW/DFT level and compare them to DFET and full CW benchmarks. We test the performance of PFET at the CW/DFT level for a variety of types of interactions (hydrogen bonding, metallic, and ionic). By introducing an intermediate CW/DFT embedding scheme denoted DFET/PFET, we show how PFET remedies different types of errors in DFET, serving as a more robust type of embedding theory.

  5. Newton force from wave function collapse: speculation and test

    International Nuclear Information System (INIS)

    Diósi, Lajos

    2014-01-01

    The Diosi-Penrose model of quantum-classical boundary postulates gravity-related spontaneous wave function collapse of massive degrees of freedom. The decoherence effects of the collapses are in principle detectable if not masked by the overwhelming environmental decoherence. But the DP (or any other, like GRW, CSL) spontaneous collapses are not detectable themselves, they are merely the redundant formalism of spontaneous decoherence. To let DP collapses become testable physics, recently we extended the DP model and proposed that DP collapses are responsible for the emergence of the Newton gravitational force between massive objects. We identified the collapse rate, possibly of the order of 1/ms, with the rate of emergence of the Newton force. A simple heuristic emergence (delay) time was added to the Newton law of gravity. This non-relativistic delay is in peaceful coexistence with Einstein's relativistic theory of gravitation, at least no experimental evidence has so far surfaced against it. We derive new predictions of such a 'lazy' Newton law that will enable decisive laboratory tests with available technologies. The simple equation of 'lazy' Newton law deserves theoretical and experimental studies in itself, independently of the underlying quantum foundational considerations.

  6. Pulmonary Function Tests In Young Healthy Subjects Of North India

    Directory of Open Access Journals (Sweden)

    Parag Rastogi

    2004-06-01

    Full Text Available Study Objectives : The diagnosis of disease done by skiagram can be substantiated by pulmonary function tests. Substantial data of Indians on PFTs is not available. The present study therefore has been planned on young healthy north Indians.Setting : 119 males and 49 female medical students of North India.Measurements : PFT's, T.V. FEV1, FVC, FER and PEFR were measured. P<0.05 was considered as significant.Results : In North Indian males, mean T. V was 437.56 ± 65.83 ml, FEV1 3.26 ±041 L, FVC 3.82 ± 0.48 L, FER 85.09 ± 2.42% and PEFR was 495.42 ± 101.82 L / min. In North Indian females, average T. V was 386.12 ± 37.90 ml, FEV1 2.39 ± 0.38 L, FVC 2.79 ± 0.43 L, FER 85.38 ± 257% and PEFR was 307.12 ± 75.74 L / min.Conclusions: Males in comparison to females had more value of PFTs. All the PFTs showed positive correlation with Height, Weight and Surface area except Tidal Volume and FER.

  7. Assessment of Dengue Fever Severity Through Liver Function Tests

    International Nuclear Information System (INIS)

    Ahmed, A.; Alvi, A. H.; Nawaz, A. A.; Butt, A.; Hanif, A.

    2014-01-01

    Objective: To assess the utility of liver function tests (LFTs) for early recognition and prediction of severity of Dengue fever in hospitalized patients. Study Design: An analytical study. Place and Duration of Study: Services Institute of Medical Science and Fatima Memorial Hospital, Lahore, from September - December 2010. Methodology: Admitted cases of Dengue fever were divided into 3 groups; mild, moderate and severe increases in aminotransferases. Elevation in LFTs was co-related with good or bad outcome i.e. (survival or complication free stay) or (death or complications). Results were analyzed in SPSS version 18. Results: Out of the 353 patients with mean age of 37.12 +- 15.45 years, 245 (69.4%) were males and 108 (30.6%) were females. Seventy five patients (21.2%) had mild elevation of aminotransferases (2 fold increases), 265 patients (75.1%) had moderate increases (3 to 4 fold) and 13 (3.7%) had severe (> 4 fold increase). ALT was statistically higher in patients with septicemia, hepatic and renal failure (p-value 0.05). AST was higher in almost all complications. Prolonged hospital stay was associated with raised LFTs and greater complications and mortality. AST was found to be twice as much raised as ALT. Conclusion: AST and ALT were statistically higher in patients with worse outcome thus can lead to early recognition of high risk cases. (author)

  8. Design and functional tests of the Euclid grism mount

    Science.gov (United States)

    Rossin, Ch.; Grange, R.; Caillat, A.; Costille, A.; Sanchez, P.; Ceria, W.

    2017-11-01

    The Euclid mission selected by ESA in the Cosmic Vision program is dedicated to understand dark energy and dark matter. One of the probes based on detection of Baryonic Acoustic Oscillations required the redshift of millions of galaxies. This massive spectroscopic survey relies on the Near Infrared SpectroPhotometer (NISP) using grism in slitless mode. In this Euclid NISP context, we designed a cryogenic mount for the four grisms of the spectroscopic channel. This mount has to maintain optical performances and alignment at the cryogenic temperature of 120K and to survive launch vibrations. Due to a very small mass and volume budget allowed in the Grism Wheel Assembly our design relies on a weight relief Invar ring glued to the grism by tangential flexures. Tangential flexures have the advantage of small height but the drawback of less decoupling capabilities than bipods. We will present the design of the mount and the integration and functional tests to stay within the 60 nm RMS transmitted wavefront error budget allowed to the grism.

  9. Effects of therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate on endocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Teunissen, Jaap J.M.; Kwekkeboom, Dik J. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Jong, Frank H. de; Feelders, Richard A.; Aken, Maarten O. van; Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2009-11-15

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 {+-} 16 to 25 {+-} 4 ng/l, p < 0.05) and follicle-stimulating hormone (FSH) levels increased (5.9 {+-} 0.5 to 22.7 {+-} 1.4 IU/l, p < 0.05). These levels returned to near baseline levels. Total testosterone and sex hormone binding globulin (SHBG) levels decreased (15.0 {+-} 0.9 to 10.6 {+-} 1.0 nmol/l, p < 0.05 and 61.8 {+-} 8.7 to 33.2 {+-} 3.7 nmol, p < 0.05), respectively, whereas non-SHBG-bound T did not change. An increase (5.2 {+-} 0.6 to 7.7 {+-} 0.7 IU/l, p < 0.05) of luteinizing hormone (LH) levels was found at 3 months of follow-up returning to baseline levels thereafter. In 21 postmenopausal women, a decrease in levels of FSH (74.4 {+-} 5.6 to 62.4 {+-} 7.7 IU/l, p < 0.05) and LH (26.8 {+-} 2.1 to 21.1 {+-} 3.0 IU/l, p < 0.05) was found. Of 66 patients, 2 developed persistent primary hypothyroidism. Free thyroxine (FT{sub 4}) levels decreased (17.7 {+-} 0.4 to 15.6 {+-} 0.6 pmol/l, p < 0.05), whereas thyroid-stimulating hormone (TSH) and triiodothyronine (T{sub 3}) levels did not change. Reverse triiodothyronine (rT{sub 3}) levels decreased (0.38 {+-} 0.03 to 0.30 {+-} 0.01 nmol/l, p < 0.05). Before and after therapy adrenocorticotropic hormone (ACTH) stimulation tests showed an adequate response of serum cortisol (> 550 nmol/l, n = 18). Five patients developed elevated HbA{sub 1c} levels (> 6.5%). In men {sup 177}Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non

  10. Pulmonary Function Testing After Stereotactic Body Radiotherapy to the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Bishawi, Muath [Division of Cardiothoracic Surgery, Stony Brook University Medical Center, Stony Brook, NY (United States); Kim, Bong [Division of Radiology, Stony Brook University Medical Center, Stony Brook, NY (United States); Moore, William H. [Division of Radiation Oncology, Stony Brook University, Stony Brook, NY (United States); Bilfinger, Thomas V., E-mail: Thomas.bilfinger@stonybrook.edu [Division of Cardiothoracic Surgery, Stony Brook University Medical Center, Stony Brook, NY (United States)

    2012-01-01

    Purpose: Surgical resection remains the standard of care for operable early-stage non-small-cell lung cancer (NSCLC). However, some patients are not fit for surgery because of comorbidites such as chronic obstructive pulmonary disease (COPD) and other medical conditions. We aimed to evaluate pulmonary function and tumor volume before and after stereotactic body radiotherapy (SBRT) for patients with and without COPD in early-stage lung cancer. Methods and Materials: A review of prospectively collected data of Stage I and II lung cancers, all treated with SBRT, was performed. The total SBRT treatment was 60 Gy administered in three 20 Gy fractions. The patients were analyzed based on their COPD status, using their pretreatment pulmonary function test cutoffs as established by the American Thoracic Society guidelines (forced expiratory volume [FEV]% {<=}50% predicted, FEV%/forced vital capacity [FVC]% {<=}70%). Changes in tumor volume were also assessed by computed tomography. Results: Of a total of 30 patients with Stage I and II lung cancer, there were 7 patients in the COPD group (4 men, 3 women), and 23 in t he No-COPD group (9 men, 14 women). At a mean follow-up time of 4 months, for the COPD and No-COPD patients, pretreatment and posttreatment FEV% was similar: 39 {+-} 5 vs. 40 {+-} 9 (p = 0.4) and 77 {+-} 0.5 vs. 73 {+-} 24 (p = 0.9), respectively. The diffusing capacity of the lungs for carbon monoxide (DL{sub CO}) did significantly increase for the No-COPD group after SBRT treatment: 60 {+-} 24 vs. 69 {+-} 22 (p = 0.022); however, DL{sub CO} was unchanged for the COPD group: 49 {+-} 13 vs. 50 {+-} 14 (p = 0.8). Although pretreatment tumor volume was comparable for both groups, tumor volume significantly shrank in the No-COPD group from 19 {+-} 24 to 9 {+-} 16 (p < 0.001), and there was a trend in the COPD patients from 12 {+-} 9 to 6 {+-} 5 (p = 0.06). Conclusion: SBRT did not seem to have an effect on FEV{sub 1} and FVC, but it shrank tumor volume and

  11. Pulmonary Function Testing After Stereotactic Body Radiotherapy to the Lung

    International Nuclear Information System (INIS)

    Bishawi, Muath; Kim, Bong; Moore, William H.; Bilfinger, Thomas V.

    2012-01-01

    Purpose: Surgical resection remains the standard of care for operable early-stage non–small-cell lung cancer (NSCLC). However, some patients are not fit for surgery because of comorbidites such as chronic obstructive pulmonary disease (COPD) and other medical conditions. We aimed to evaluate pulmonary function and tumor volume before and after stereotactic body radiotherapy (SBRT) for patients with and without COPD in early-stage lung cancer. Methods and Materials: A review of prospectively collected data of Stage I and II lung cancers, all treated with SBRT, was performed. The total SBRT treatment was 60 Gy administered in three 20 Gy fractions. The patients were analyzed based on their COPD status, using their pretreatment pulmonary function test cutoffs as established by the American Thoracic Society guidelines (forced expiratory volume [FEV]% ≤50% predicted, FEV%/forced vital capacity [FVC]% ≤70%). Changes in tumor volume were also assessed by computed tomography. Results: Of a total of 30 patients with Stage I and II lung cancer, there were 7 patients in the COPD group (4 men, 3 women), and 23 in t he No-COPD group (9 men, 14 women). At a mean follow-up time of 4 months, for the COPD and No-COPD patients, pretreatment and posttreatment FEV% was similar: 39 ± 5 vs. 40 ± 9 (p = 0.4) and 77 ± 0.5 vs. 73 ± 24 (p = 0.9), respectively. The diffusing capacity of the lungs for carbon monoxide (DL CO ) did significantly increase for the No-COPD group after SBRT treatment: 60 ± 24 vs. 69 ± 22 (p = 0.022); however, DL CO was unchanged for the COPD group: 49 ± 13 vs. 50 ± 14 (p = 0.8). Although pretreatment tumor volume was comparable for both groups, tumor volume significantly shrank in the No-COPD group from 19 ± 24 to 9 ± 16 (p 1 and FVC, but it shrank tumor volume and improved DL CO for patients without COPD.

  12. Investigations of HPA Function and the Enduring Consequences of Stressors in Adolescence in Animal Models

    Science.gov (United States)

    McCormick, Cheryl M.; Mathews, Iva Z.; Thomas, Catherine; Waters, Patti

    2010-01-01

    Developmental differences in hypothalamic-pituitary-adrenal (HPA) axis responsiveness to stressors and ongoing development of glucocorticoid-sensitive brain regions in adolescence suggest that similar to the neonatal period of ontogeny, adolescence may also be a sensitive period for programming effects of stressors on the central nervous system.…

  13. Influence of fetal growth velocity and smallness at birth on adrenal function in adolescence

    DEFF Research Database (Denmark)

    Beck Jensen, Rikke; vielwerth, Signe; Larsen, Torben

    2011-01-01

    The hypothalamic-pituitary-adrenal axis is susceptible to programming during fetal development and may be linked to risk of disease later in life. In a former prospective study the cohort was divided into those born appropriate for gestational age (AGA) or small for gestational age (SGA; birth...

  14. PWR primary system chemistry control during hot functional testing

    International Nuclear Information System (INIS)

    Reid, Richard D.; Little, Michael J.

    2014-01-01

    Hot Functional Testing (HFT) involves a number of pre-operational exercises performed to confirm the operability of plant systems at conditions expected during both normal and off-normal operation of a pressurized water reactor (PWR), including operability of safety systems. While the primary purposes of HFT are to demonstrate operability of plant systems and satisfy regulatory requirements, chemistry control during HFT is important to long-term integrity and performance of plant systems. Specifically, HFT is the first time plant equipment is exposed to high temperature water and the chemistry maintained during HFT can impact the passivation layers that form on wetted surfaces and long-term release of metals from these surfaces. Metals released from the inner surfaces of steam generator tubing and reactor coolant loop piping become activated in the core and can redeposit on ex-core surfaces. Because HFT is performed before fuel is loaded in the core, HFT provides an opportunity to produce a passive layer on primary surfaces that is free of activated corrosion products, resistant to metals release during subsequent plant operation, and also resistant to incorporation of activated corrosion products (once fuel is loaded in the core). Thus, maintaining desirable primary chemistry control during HFT is important for source term management, minimization of future shutdown activity releases, minimization of dose rates, and asset preservation. This paper presents an overview of passive film formation in the austenitic stainless steel and high nickel alloys that make up the majority of the primary circuit in advanced PWR designs. Based on this information, a summary is provided of the effects on passive film formation of key chemistry parameters that may be controlled during HFT. (author)

  15. Modifications in adrenal hormones response to ethanol by prior ethanol dependence.

    Science.gov (United States)

    Guaza, C; Borrell, S

    1985-03-01

    Ethanol was administered to rats by means of a liquid diet for 16 days; after an ethanol-free interval of four weeks, animals received a test (IP) dose of ethanol (2 g/kg), and the adrenocortical and adrenomedullary responses were evaluated. Chronically ethanol-exposed animals showed tolerance to the stimulatory effect of ethanol in the pituitary-adrenal axis. Likewise, previously dependent rats showed tolerance to the increase in the activity of the adrenomedullary function induced by acute administration of the drug. Our results indicate that chronic ethanol ingestion can induce persistent changes after complete alcohol abstinence.

  16. Highly adaptive tests for group differences in brain functional connectivity

    Directory of Open Access Journals (Sweden)

    Junghi Kim

    2015-01-01

    The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only easy to use, but also high-powered robustly across various scenarios. The usage and advantages of these novel tests are demonstrated on an Alzheimer's disease dataset and simulated data.

  17. The Unilateral Below Elbow Test: a function test for children with unilateral congenital below elbow deficiency.

    Science.gov (United States)

    Bagley, Anita M; Molitor, Fred; Wagner, Lisa V; Tomhave, Wendy; James, Michelle A

    2006-07-01

    The Unilateral Below Elbow Test (UBET) was developed to evaluate function in bimanual activities for both the prosthesis wearer and non-wearer. Nine tasks were chosen for each of four age-specific categories defined by development stages of hand function (2-4y, 5-7y, 8-10y, and 11-21y). Two scales, Completion of Task and Method of Use, were designed to rate performance. To measure reliability, four occupational therapists scored samples of videotaped UBET performances. For Completion of Task, an interval scale, agreement in scoring was measured with interclass correlation coefficients (ICC; n=9; five females, four males). For Method of Use, a nominal scale, chance-adjusted association was calculated with Cohen's kappa coefficients (interobserver n=198; 111 females, 87 males; intraobserver n=93; 56 females, 37 males). For Completion of Task, the average ICC was 0.87 for the prosthesis-on condition, and 0.85 for the prosthesis-off condition. ICCs exceeded 0.80 for eight out of nine tasks for the two older age groups, but for only five out of nine tasks in the younger age groups. Higher inter- and intraobserver kappa coefficients for Method of Use resulted when scoring children with their prostheses on versus off. The oldest age group had lower kappa values than the other three groups. The UBET is recommended for the functional evaluation of Completion of Task in children with unilateral congenital below elbow deficiency with and without their prostheses. Method of Use scoring can evaluate individuals for directed therapy interventions or prosthetic training.

  18. A Comparison of Salivary Steroid Levels during Diagnostic Tests for Adrenal Insufficiency

    Directory of Open Access Journals (Sweden)

    Michaela Dušková

    2016-01-01

    Full Text Available Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis. The gold standard is still considered the insulin tolerance test (ITT, but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD ±4.8 years, and mean/median BMI (body mass index 25.38/24.82 (SD ±3.2 kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.

  19. Antidepressant-like effects of the ethyl acetate soluble fraction of the root bark of Morus alba on the immobility behavior of rats in the forced swim test.

    Science.gov (United States)

    Lim, Dong Wook; Kim, Yun Tai; Park, Ji-Hae; Baek, Nam-In; Han, Daeseok

    2014-06-12

    In this study, the antidepressant-like effects of Morus alba fractions in rats were investigated in the forced swim test (FST). Male Wistar rats (9-week-old) were administered orally the M. alba ethyl acetate (EtOAc 30 and 100 mg/kg) and M. alba n-butanol fractions (n-BuOH 30 and 100 mg/kg) every day for 7 consecutive days. On day 7, 1 h after the final administration of the fractions, the rats were exposed to the FST. M. alba EtOAc fraction at the dose of 100 mg/kg induced a decrease in immobility behavior (p alba EtOAc fraction at the dose of 100 mg/kg decreased the hypothalamic-pituitary-adrenal (HPA) axis response to the stress, as indicated by an attenuated corticosterone response and decreased c-fos immunoreactivity in the hippocampal and hypothalamic paraventricular nucleus (PVN) region. These findings demonstrated that M. alba EtOAc fraction have beneficial effects on depressive behaviors and restore both altered c-fos expression and HPA activity.

  20. Test Review: Barkley Deficits in Executive Functioning Scale (BDEFS)

    Science.gov (United States)

    Allee-Smith, Paula J.; Winters, Rebecca R.; Drake, Amanda; Joslin, Amanda K.

    2013-01-01

    The Barkley Deficits in Executive Functioning Scale (BDEFS), authored by Russell A. Barkley and published by Guilford in 2011, is an individually administered assessment tool that may be used to evaluate adults ages 18 to 81. The purpose of this measure is to screen those who may be experiencing executive functioning (EF) deficits in…

  1. 75 FR 50853 - Special Conditions: Cirrus Design Corporation Model SF50 Airplane; Function and Reliability Testing

    Science.gov (United States)

    2010-08-18

    ... airplanes. 1. Function and Reliability Testing. Flight tests: In place of 14 CFR 21.35(b)(2), the following...; Function and Reliability Testing AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final special... to CAR part 3 became effective January 15, 1951, and deleted the service test requirements in Section...

  2. Comparison of Esophageal Function Tests in Chinese Patients with Functional Heartburn and Reflux Hypersensitivity

    Directory of Open Access Journals (Sweden)

    Feng Gao

    2017-01-01

    Full Text Available Objective. To investigate the differences in the results of esophageal function tests for functional heartburn (FH and reflux hypersensitivity (RH. Methods. Patients with FH and RH and healthy volunteers (HVs from the Department of Gastroenterology, Beijing Anzhen Hospital and Beijing Chao-Yang hospital, who underwent high-resolution manometry and impedance (HRIM, and 24-hour multichannel intraluminal impedance and pH recording (MII/pH between 2014 and 2016, were enrolled in this study. Results. 36 HV, 147 FH patients, and 91 RH patients were enrolled. The postreflux swallow-induced peristaltic wave index (PSPW index and mean nocturnal baseline impedance (MNBI values were significantly lower in RH than in FH and HV. The ineffective esophageal motility (IEM, fragmented peristalsis rates, total bolus exposure, proximal total reflux events, and distal total reflux events were significantly greater in RH than in FH and HV. Conclusions. Compared to HV and FH patients, RH patients exhibited greater IEM and fragmented peristalsis rates, a greater total bolus exposure, more proximal total and distal total reflux events, and reduced chemical clearance and mucosal integrity. By using the above described parameters, HRIM and MII/pH assays could be used to correctly classify RH and FH and hence allow physicians to provide adequate relief from associated symptoms.

  3. Design of New Test Function Model Based on Multi-objective Optimization Method

    Directory of Open Access Journals (Sweden)

    Zhaoxia Shang

    2017-01-01

    Full Text Available Space partitioning method, as a new algorism, has been applied to planning and decision-making of investment portfolio more and more often. But currently there are so few testing function for this algorism, which has greatly restrained its further development and application. An innovative test function model is designed in this paper and is used to test the algorism. It is proved that for evaluation of space partitioning method in certain applications, this test function has fairly obvious advantage.

  4. Functional Testing Protocols for Commercial Building Efficiency Baseline Modeling Software

    Energy Technology Data Exchange (ETDEWEB)

    Jump, David; Price, Phillip N.; Granderson, Jessica; Sohn, Michael

    2013-09-06

    This document describes procedures for testing and validating proprietary baseline energy modeling software accuracy in predicting energy use over the period of interest, such as a month or a year. The procedures are designed according to the methodology used for public domain baselining software in another LBNL report that was (like the present report) prepared for Pacific Gas and Electric Company: ?Commercial Building Energy Baseline Modeling Software: Performance Metrics and Method Testing with Open Source Models and Implications for Proprietary Software Testing Protocols? (referred to here as the ?Model Analysis Report?). The test procedure focuses on the quality of the software?s predictions rather than on the specific algorithms used to predict energy use. In this way the software vendor is not required to divulge or share proprietary information about how their software works, while enabling stakeholders to assess its performance.

  5. Evaluating rodent motor functions: Which tests to choose?

    Science.gov (United States)

    Schönfeld, Lisa-Maria; Dooley, Dearbhaile; Jahanshahi, Ali; Temel, Yasin; Hendrix, Sven

    2017-12-01

    Damage to the motor cortex induced by stroke or traumatic brain injury (TBI) can result in chronic motor deficits. For the development and improvement of therapies, animal models which possess symptoms comparable to the clinical population are used. However, the use of experimental animals raises valid ethical and methodological concerns. To decrease discomfort by experimental procedures and to increase the quality of results, non-invasive and sensitive rodent motor tests are needed. A broad variety of rodent motor tests are available to determine deficits after stroke or TBI. The current review describes and evaluates motor tests that fall into three categories: Tests to evaluate fine motor skills and grip strength, tests for gait and inter-limb coordination and neurological deficit scores. In this review, we share our thoughts on standardized data presentation to increase data comparability between studies. We also critically evaluate current methods and provide recommendations for choosing the best behavioral test for a new research line. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The Functional Test for Agility Performance is a Reliable Quick Decision-Making Test for Skilled Water Polo Players

    Directory of Open Access Journals (Sweden)

    Tucher Guilherme

    2015-06-01

    Full Text Available The reliability of the Functional Test for Agility Performance has only been evaluated in water polo players in a small group of novice athletes. Thus, the aim of this study was to evaluate the reliability of the Functional Test for Agility Performance in skilled water polo players. Forty-two athletes (17.81 ± 3.24 years old with a minimum of 5 years of competitive experience (7.05 ± 2.84 years and playing at the national or international level were evaluated. The Functional Test for Agility Performance is characterized as a specific open decision-making test where a tested player moves as quickly as possible in accordance to a pass made by another player. The time spent in the test was measured by two experienced coaches. Descriptive statistics, repeated measures analysis of variance (ANOVA, 95% limit of agreement (LOA, intraclass correlation coefficient (ICC and standard error of measurements (SEM were used for data analysis. Athletes completed the Functional Test for Agility Performance in 4.15 0.47 s. The ICC value was 0.87 (95% IC = 0.80-0.92. The SEM varied between 0.24 and 0.38 s. The LOA was 1.20 s and the CV average considering each individual trial was 6%. The Functional Test for Agility Performance was shown to be a reliable quick decision-making test for skilled water polo players.

  7. Wada test for evaluation of language and memory function in medically intractable epilepsy

    International Nuclear Information System (INIS)

    Hong, Yong Kook; Chung, Tae Sub; Suh, Jung Ho; Kim, Dong Ik; Kim, Eun Kyung; Lee, Byung In; Huh, Kyun

    1992-01-01

    The Wada test was performed for lateralization of language and memory function, using intracarotid injection of Sodium Amytal. But the internal carotid artery (ICA) Wada test has some limitations for testing memory function. The posterior cerebral artery (PCA) Wada test has been designed to modify the ICA Wada test for testing memory function selectively. In our study, 10 patients out of 12 patients with intractable seizure underwent only the ICA Wada test and the other 2 patients underwent both the ICA and the selective PCA Wada test. In all 12 patients undergoing the ICA Wada test, we successfully localized speech and language dominance. Four of 12 patients who underwent the ICA Wada test for evaluation of memory function displayed superior memory functions in one hemisphere, but the other hemisphere also significantly contributed to memory. The selective PCA Wada test, performed in 2 patients, showed successful results of memory function test in both patients. Four of 12 patients underwent temporal lobectomy and there was no major post-operative language or memory deficits. We concluded that the ICA and PCA Wada tests are useful for preoperative evaluation of medically intractable epilepsy, and the PCA Wada test is valuable in memory evaluation in some patients who have high risk of postoperative global amnesia after temporal lobectomy following equivocal results of memory function by the ICA Wada test

  8. Wada test for evaluation of language and memory function in medically intractable epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Yong Kook; Chung, Tae Sub; Suh, Jung Ho; Kim, Dong Ik; Kim, Eun Kyung; Lee, Byung In; Huh, Kyun [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    1992-05-15

    The Wada test was performed for lateralization of language and memory function, using intracarotid injection of Sodium Amytal. But the internal carotid artery (ICA) Wada test has some limitations for testing memory function. The posterior cerebral artery (PCA) Wada test has been designed to modify the ICA Wada test for testing memory function selectively. In our study, 10 patients out of 12 patients with intractable seizure underwent only the ICA Wada test and the other 2 patients underwent both the ICA and the selective PCA Wada test. In all 12 patients undergoing the ICA Wada test, we successfully localized speech and language dominance. Four of 12 patients who underwent the ICA Wada test for evaluation of memory function displayed superior memory functions in one hemisphere, but the other hemisphere also significantly contributed to memory. The selective PCA Wada test, performed in 2 patients, showed successful results of memory function test in both patients. Four of 12 patients underwent temporal lobectomy and there was no major post-operative language or memory deficits. We concluded that the ICA and PCA Wada tests are useful for preoperative evaluation of medically intractable epilepsy, and the PCA Wada test is valuable in memory evaluation in some patients who have high risk of postoperative global amnesia after temporal lobectomy following equivocal results of memory function by the ICA Wada test.

  9. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

    NARCIS (Netherlands)

    Dieleman, G.C.; Huizink, A.C.; Tulen, J.H.M.; Utens, E.M.W.J.; Creemers, H.E.; van der Ende, J.; Verhulst, F.C.

    2015-01-01

    Background: It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different

  10. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

    NARCIS (Netherlands)

    Dieleman, Gwendolyn C.; Huizink, Anja C.; Tulen, Joke H. M.; Utens, Elisabeth M. W. J.; Creemers, Hanneke E.; van der Ende, Jan; Verhulst, Frank C.

    2015-01-01

    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. T