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Sample records for analog induce cortisol

  1. Can the neural–cortisol association be moderated by experience-induced changes in awareness?

    PubMed Central

    Lau, Way K. W.; Leung, Mei-Kei; Chan, Chetwyn C. H.; Wong, Samuel S. Y.; Lee, Tatia M. C.

    2015-01-01

    Cortisol homeostasis is important for cognitive and affective functions that depend on cortisol-sensitive brain regions including the hippocampus and prefrontal cortex. Recent studies have shown that training induces changes in the brain. We report the findings of a longitudinal study that verified the moderation effect of experience-induced changes in awareness on the neural–cortisol association in cortisol-sensitive brain regions. These findings provide the first piece of evidence that planned behavioral experience can moderate the neural–cortisol association. A range of changes in awareness was achieved in a sample of 21 Chinese participants, divided into two groups: Awareness-based compassion meditation (ABCM) (n = 10) and relaxation (n = 11). We observed that changes in awareness were significant moderators of hippocampal–cortisol changes. Furthermore, a significant negative association between changes in plasma cortisol level and the resting-state synchrony of the right hippocampal and insular-frontal-operculum regions was observed. These novel findings shed light on the inter-relationships between changes in hippocampal–cortisol levels and changes in awareness and preliminarily identify the neural underpinnings of interventions for cortisol-related abnormal functioning for further study. PMID:26577539

  2. Condition dependent intra-individual repeatability of stress-induced cortisol in a freshwater fish.

    PubMed

    Cook, K V; O'Connor, C M; McConnachie, S H; Gilmour, K M; Cooke, S J

    2012-03-01

    The glucocorticoid (GC) stress response is thought to be an individual trait associated with behaviour and life history strategies. Studies exploring such relationships typically assume measured hormone values to be repeatable within an individual. However, repeatability of GCs has proven variable in wild animals and underlying reasons remain unknown. We assessed individual repeatability of circulating stress-induced cortisol, the primary GC in teleost fish, and glucose concentrations in a wild teleost fish held under consistent laboratory conditions. We also tested the hypothesis that the magnitude of intra-individual variability in stress-induced cortisol concentrations ("cortisol variability") is influenced by body condition. Wild-caught bluegill sunfish (Lepomis macrochirus) were subjected to repeated standardized stressors and blood sampled (3 times over 6 days) once cortisol concentrations peaked. Various indicators of fish condition, both whole body and physiological, were also measured. Overall, stress-induced circulating cortisol concentrations were repeatable but stress-induced glucose was not. Cortisol variability was related to Fulton's condition factor and size (eviscerated mass) where smaller fish in poor condition exhibited increased cortisol variability. The findings have implications for the interpretation of studies that examine correlates of GC concentrations as they suggest consistency in stress responsiveness is influenced by factors such as size and condition. PMID:22179071

  3. Psychological and cortisol reactivity to experimentally induced stress in adults with ADHD.

    PubMed

    Raz, Sivan; Leykin, Dmitry

    2015-10-01

    Individuals with ADHD suffer from increased vulnerability to environmental and mental stressors and may be at increased risk for chronic stress in everyday life. The Hypothalamic-Pituitary-Adrenal (HPA) axis is a critical physiological system that mediates responses to stress. The present study seeks to examine test performance, test anxiety, self-reported psychological stress and cortisol reactivity to mental-cognitive stress in adults with ADHD when compared with healthy controls. Stress was induced by an arithmetic ability test. Psychological stress was assessed repeatedly throughout the experimental session. Salivary cortisol, an indicator of the HPA axis function, was evaluated immediately upon arrival, as well as 1 min and 20 min post-test completion. Results revealed higher levels of test anxiety and poorer performance on the test in the ADHD group. The ADHD and control groups showed no difference in base-line levels of subjective stress and in subjective stress levels 20 min after the test. In contrast, individuals with ADHD reported significantly higher levels of stress at the test anticipation phase and 1 min post-test completion. Cortisol response to stress differed according to group: in the ADHD group, 20 min post-test cortisol levels were significantly higher than base-line cortisol levels. This was not evident in the control group. These results suggest greater activation of the HPA axis in response to stress in adults with ADHD when compared with healthy controls. Adults with ADHD do not differ from controls in basal levels of subjective stress and cortisol, but do have stronger psychophysiological reactions in response to stressful challenges. The present findings are among the first to demonstrate significant alterations in cortisol reactivity to stress in adults with ADHD. PMID:26107579

  4. Acute stress-induced cortisol elevations mediate reward system activity during subconscious processing of sexual stimuli.

    PubMed

    Oei, Nicole Y L; Both, Stephanie; van Heemst, Diana; van der Grond, Jeroen

    2014-01-01

    Stress is thought to alter motivational processes by increasing dopamine (DA) secretion in the brain's "reward system", and its key region, the nucleus accumbens (NAcc). However, stress studies using functional magnetic resonance imaging (fMRI), mainly found evidence for stress-induced decreases in NAcc responsiveness toward reward cues. Results from both animal and human PET studies indicate that the stress hormone cortisol may be crucial in the interaction between stress and dopaminergic actions. In the present study we therefore investigated whether cortisol mediated the effect of stress on DA-related responses to -subliminal-presentation of reward cues using the Trier Social Stress Test (TSST), which is known to reliably enhance cortisol levels. Young healthy males (n = 37) were randomly assigned to the TSST or control condition. After stress induction, brain activation was assessed using fMRI during a backward-masking paradigm in which potentially rewarding (sexual), emotionally negative and neutral stimuli were presented subliminally, masked by pictures of inanimate objects. A region of interest analysis showed that stress decreased activation in the NAcc in response to masked sexual cues (voxel-corrected, p<05). Furthermore, with mediation analysis it was found that high cortisol levels were related to stronger NAcc activation, showing that cortisol acted as a suppressor variable in the negative relation between stress and NAcc activation. The present findings indicate that cortisol is crucially involved in the relation between stress and the responsiveness of the reward system. Although generally stress decreases activation in the NAcc in response to rewarding stimuli, high stress-induced cortisol levels suppress this relation, and are associated with stronger NAcc activation. Individuals with a high cortisol response to stress might on one hand be protected against reductions in reward sensitivity, which has been linked to anhedonia and depression, but

  5. Socioeconomic deprivation, perceived neighborhood factors, and cortisol responses to induced stress among healthy adults

    PubMed Central

    Barrington, Wendy E.; Stafford, Mai; Hamer, Mark; Beresford, Shirley A.A.; Koepsell, Thomas; Steptoe, Andrew

    2014-01-01

    Associations between measures of neighborhood socioeconomic deprivation and health have been identified, yet work is needed to uncover explanatory mechanisms. One hypothesized pathway is through stress, yet the few studies that have evaluated associations between characteristics of deprived neighborhoods and biomarkers of stress are mixed. This study evaluated whether objectively measured neighborhood socioeconomic deprivation and individual perceived neighborhood characteristics (i.e. social control and fear of crime) impacted cortisol responses to an induced stressor among older healthy adults. Data from Heart Scan, a sub-study of the Whitehall II cohort, were used to generate multilevel piecewise growth-curve models of cortisol trajectories after a laboratory stressor accounting for neighborhood and demographic characteristics. Neighborhood socioeconomic deprivation was significantly associated with individual perceptions of social control and fear of crime in the neighborhood while an association with blunted cortisol reactivity was only evidence among women. Social control was significantly associated with greater cortisol reactivity and mediation between neighborhood deprivation and cortisol reactivity was suggested among women. These findings support a gender-dependent role of neighborhood in stress process models of health. PMID:24603009

  6. Neighborhood socioeconomic deprivation, perceived neighborhood factors, and cortisol responses to induced stress among healthy adults.

    PubMed

    Barrington, Wendy E; Stafford, Mai; Hamer, Mark; Beresford, Shirley A A; Koepsell, Thomas; Steptoe, Andrew

    2014-05-01

    Associations between measures of neighborhood socioeconomic deprivation and health have been identified, yet work is needed to uncover explanatory mechanisms. One hypothesized pathway is through stress, yet the few studies that have evaluated associations between characteristics of deprived neighborhoods and biomarkers of stress are mixed. This study evaluated whether objectively measured neighborhood socioeconomic deprivation and individual perceived neighborhood characteristics (i.e. social control and fear of crime) impacted cortisol responses to an induced stressor among older healthy adults. Data from Heart Scan, a sub-study of the Whitehall II cohort, were used to generate multilevel piecewise growth-curve models of cortisol trajectories after a laboratory stressor accounting for neighborhood and demographic characteristics. Neighborhood socioeconomic deprivation was significantly associated with individual perceptions of social control and fear of crime in the neighborhood while an association with blunted cortisol reactivity was only evidence among women. Social control was significantly associated with greater cortisol reactivity and mediation between neighborhood socioeconomic deprivation and cortisol reactivity was suggested among women. These findings support a gender-dependent role of neighborhood in stress process models of health. PMID:24603009

  7. Environmental stress-induced testis differentiation: androgen as a by-product of cortisol inactivation.

    PubMed

    Fernandino, Juan I; Hattori, Ricardo S; Moreno Acosta, Omar D; Strüssmann, Carlos A; Somoza, Gustavo M

    2013-10-01

    This review deals with the gonadal masculinization induced by thermal stress in fish with focus on the action of 11β-hydroxysteroid dehydrogenase (11β-HSD) as this mechanism key transducer. High temperatures have been reported to produce male-skewed sex ratios in several species with TSD (temperature-dependent sex determination), and in some of them, this process was reported to be associated with high levels of cortisol, the hormone-related stress in vertebrates, during early gonad development. In addition, in pejerrey larvae reared at high-masculinizing temperatures, 11-ketotestosterone (11-KT), the main and most potent androgen in fish, was also detected at high levels. In testicular explants, cortisol induced the synthesis of 11-KT, suggesting that its synthesis could be under the control of the stress axis at the time of gonadal fate determination. 11β-HSD is one of the enzymes shared by the glucocorticoid and androgen pathways; this enzyme converts cortisol to cortisone and also participates in the finals steps of the synthesis of the 11-oxigenated androgens. Based on these data and literature information, here we propose that the masculinization induced by thermal stress can be considered as a consequence of cortisol inactivation and the concomitant synthesis of 11-KT and discussing this as a possible mechanism of masculinization induced by different types of environmental stressors. PMID:23770022

  8. The influence of temperament on lipopolysaccharide (LPS) induced secretion of epinephrine and cortisol in bulls.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The host's complex reaction to a pathogenic stressor involves interaction of the neural, endocrine, and immune systems. For example, exposure to bacteria stimulates secretion of the stress-related hormones, cortisol (CS) and epinephrine (Epi; 1). Innate and induced secretion of CS and Epi are influe...

  9. The role of cortisol in chronic binge alcohol-induced cerebellar injury: Ovine model.

    PubMed

    Washburn, Shannon E; Tress, Ursula; Lunde, Emilie R; Chen, Wei-Jung A; Cudd, Timothy A

    2013-02-01

    Women who drink alcohol during pregnancy are at high risk of giving birth to children with neurodevelopmental disorders. Previous reports from our laboratory have shown that third trimester equivalent binge alcohol exposure at a dose of 1.75 g/kg/day results in significant fetal cerebellar Purkinje cell loss in fetal sheep and that both maternal and fetal adrenocorticotropin (ACTH) and cortisol levels are elevated in response to alcohol treatment. In this study, we hypothesized that repeated elevations in cortisol from chronic binge alcohol are responsible at least in part for fetal neuronal deficits. Animals were divided into four treatment groups: normal control, pair-fed saline control, alcohol and cortisol. The magnitude of elevation in cortisol in response to alcohol was mimicked in the cortisol group by infusing pregnant ewes with hydrocortisone for 6 h on each day of the experiment, and administering saline during the first hour in lieu of alcohol. The experiment was conducted on three consecutive days followed by four days without treatment beginning on gestational day (GD) 109 until GD 132. Peak maternal blood alcohol concentration in the alcohol group was 239 ± 7 mg/dl. The fetal brains were collected and processed for stereological cell counting on GD 133. The estimated total number of fetal cerebellar Purkinje cells, the reference volume and the Purkinje cell density were not altered in response to glucocorticoid infusion in the absence of alcohol. These results suggest that glucocorticoids independently during the third trimester equivalent may not produce fetal cerebellar Purkinje cell loss. However, the elevations in cortisol along with other changes induced by alcohol could together lead to brain injury seen in the fetal alcohol spectrum disorders. PMID:23218665

  10. Classical analogs of double electromagnetically induced transparency

    NASA Astrophysics Data System (ADS)

    Bai, Zhengyang; Hang, Chao; Huang, Guoxiang

    2013-03-01

    Double electromagnetically induced transparency (DEIT) in a four-level atomic system with tripod-type energy-level configuration is modeled by using two classical systems. The first is a set of three coupled harmonic oscillators subject to frictional forces and external drives and the second is a set of three coupled RLC circuits with electric resistors and alternating voltage sources. It is shown that both of the two classical systems have absorption spectra of DEIT similar to that of the four-level tripod-type atomic system. These classical analogies provide simple and intuitive physical description of quantum interference processes and can be used to illustrate experimental observations of the DEIT in quantum systems.

  11. Stress, stress-induced cortisol responses, and eyewitness identification performance.

    PubMed

    Sauerland, Melanie; Raymaekers, Linsey H C; Otgaar, Henry; Memon, Amina; Waltjen, Thijs T; Nivo, Maud; Slegers, Chiel; Broers, Nick J; Smeets, Tom

    2016-07-01

    In the eyewitness identification literature, stress and arousal at the time of encoding are considered to adversely influence identification performance. This assumption is in contrast with findings from the neurobiology field of learning and memory, showing that stress and stress hormones are critically involved in forming enduring memories. This discrepancy may be related to methodological differences between the two fields of research, such as the tendency for immediate testing or the use of very short (1-2 hours) retention intervals in eyewitness research, while neurobiology studies insert at least 24 hours. Other differences refer to the extent to which stress-responsive systems (i.e., the hypothalamic-pituitary-adrenal axis) are stimulated effectively under laboratory conditions. The aim of the current study was to conduct an experiment that accounts for the contemporary state of knowledge in both fields. In all, 123 participants witnessed a live staged theft while being exposed to a laboratory stressor that reliably elicits autonomic and glucocorticoid stress responses or while performing a control task. Salivary cortisol levels were measured to control for the effectiveness of the stress induction. One week later, participants attempted to identify the thief from target-present and target-absent line-ups. According to regression and receiver operating characteristic analyses, stress did not have robust detrimental effects on identification performance. Copyright © 2016 John Wiley & Sons, Ltd. © 2016 The Authors Behavioral Sciences & the Law Published by John Wiley & Sons Ltd. PMID:27417874

  12. Cortisol level

    MedlinePlus

    ... enable JavaScript. The cortisol blood test measures the level of cortisol in the blood. Cortisol is a ... in the morning. This is important, because cortisol level varies throughout the day. You may be asked ...

  13. Cortisol-induced enhancement of emotional face processing in social phobia depends on symptom severity and motivational context.

    PubMed

    van Peer, Jacobien M; Spinhoven, Philip; van Dijk, J Gert; Roelofs, Karin

    2009-05-01

    We investigated the effects of cortisol administration on approach and avoidance tendencies in 20 patients with social anxiety disorder (SAD). Event-related brain potentials (ERPs) were measured during a reaction time task, in which patients evaluated the emotional expression of photographs of happy and angry faces by making an approaching (flexion) or avoiding (extension) arm movement. Patients showed significant avoidance tendencies for angry but not for happy faces, both in the placebo and cortisol condition. Moreover, ERP analyses showed a significant interaction of condition by severity of social anxiety on early positive (P150) amplitudes during avoidance compared to approach, indicating that cortisol increases early processing of social stimuli (in particular angry faces) during avoidance. This result replicates previous findings from a non-clinical sample of high anxious individuals and demonstrates their relevance for clinical SAD. Apparently the cortisol-induced increase in processing of angry faces in SAD depends on symptom severity and motivational context. PMID:19428977

  14. Working hours, sleep, salivary cortisol, fatigue and neuro-behavior during Mars analog mission: five crews study.

    PubMed

    Rai, Balwant; Foing, Bernard H; Kaur, Jasdeep

    2012-05-16

    The buoyancy of humans in exploring extreme space environments has been established during missions to the moon. Long duration missions like mission to Mars however, requires humans to adapt to systemic and complex environments beyond the human body's capacity. Astronauts will encounter both physiological and psychological extremes during this trip. Very few studies are conducted on effect of long duration work and sleepiness on cognitive performance. So, this study was planned to find out effects of leadership responsibility, sleepiness and long duration working hours on cognitive performance. The 30 members (leadership: normal; 10:20) were selected from MDRS crews (Mars Desert Research Station, USA). Neurobehavioral test performance, self-ratings of fatigue and sleepiness, and salivary cortisol levels were evaluated during first day, mid and end day of mission. The leadership group did not show any signs of reduced test performance, even in elevated fatigue and sleepiness. The leadership group had faster reaction times on end of mission as compared to first and after 7 day of mission. Salivary cortisol levels were significantly higher in leadership group as compared to normal group. The results suggest that long duration work and sleepiness does not affect the cognitive performance of crew member. Further study is required while taking into account all factors and large sample size to prove this fact. PMID:22487731

  15. Parachute Jumping Induces More Sympathetic Activation Than Cortisol Secretion in First-Time Parachutists

    PubMed Central

    Messina, Giovanni; Chieffi, Sergio; Viggiano, Andrea; Tafuri, Domenico; Cibelli, Giuseppe; Valenzano, Anna; Triggiani, Antonio Ivano; Messina, Antonietta; De Luca, Vincenzo; Monda, Marcellino

    2016-01-01

    Background: The word “stress” describes the status of the body affected by external or internal forces, or “stressors”, threatening to alter its dynamic balance or homeostasis. The adaptive changes which occur in reply to stressors are either behavioral or physical. Once a given threshold is surpassed, a systemic reaction takes place involving the “stress system” in the brain together with its peripheral components, the hypothalamic-pituitary-adrenal axis and autonomic sympathetic. Objectives: Stress induces an activation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was to investigate whether the SNS and the HPA axis would show parallel or divergent stress response patterns in a session of first parachute jump. Patients and Methods: Activation of the SNS was evaluated by dosage of salivary alpha-amylase, galvanic skin responses, and heart rate in seven male novice parachutists. Activation of HPA axis was tested by dosage of cortisol. These variables were measured before and 1 minute and 90 minute after the jump. Results: All variables reached a peak at 1 minute post-jump. Salivary alpha-amylase, galvanic skin responses and heart rate did not return to basal value at 90 minutes post-jump, while cortisol returned to basal value at 90 minutes post-jump. Conclusions: This evidence indicates that parachute jumping is accompanied by a dissociation of SNS and HPA response patterns in novice parachutists, showing a slower recovery in sympathetic activity than in cortisol secretion. PMID:27217924

  16. Stress-induced salivary cortisol secretion during hypobaric hypoxia challenge and in vivo urinary thromboxane production in healthy male subjects.

    PubMed

    Simeoni, Simona; Biselli, Roberto; D'Amelio, Raffaele; Rocca, Bianca; Lattanzio, Stefano; Mucci, Luciana; Davì, Giovanni; Patacchioli, Francesca Romana

    2011-05-01

    Few studies have assessed the effects of stress on in vivo platelet activation. In the present study, hypobaric hypoxia induced by rapid decompression during high-altitude simulated flight in a hypobaric chamber was used to evaluate the effects of environmental stress on salivary cortisol and urinary thromboxane metabolite (TXM) excretion, a noninvasive marker of in vivo platelet function. Twenty-one male aviators (mean ± SD age = 36 ± 7 years) experiencing hypoxia by removing their oxygen mask for 4-5 min during a simulated flight to 25,000 ft (7,620 m; pO(2) = 59.17 mmHg) and a matched control group of thirteen flying instructors wearing oxygen masks during the challenge, were studied. Hypobaric hypoxia induced a transient significant increase (P < 0.001) in the aviators' salivary cortisol concentration; the overall pattern of diurnal cortisol fluctuation was maintained in both groups. Urinary TXM showed a significant ∼30% reduction (P < 0.01) after the chamber session in aviators exposed to hypobaric hypoxia, but not in controls. A significant inverse correlation was found between salivary cortisol and urinary TXM in aviators (r = - 0.64, P = 0.0015). Salivary cortisol was a significant predictor (P < 0.001) for urinary TXM concentrations in aviators. In conclusion, here we observed that an acute stress-induced salivary cortisol increase was associated with reduced urinary thromboxane biosynthesis, providing the first indirect evidence for an inhibitory effect of acute stress on in vivo platelet function. PMID:21434833

  17. Multiple Analogies for Complex Concepts: Antidotes for Analogy-Induced Misconception in Advanced Knowledge Acquisition. Technical Report No. 439.

    ERIC Educational Resources Information Center

    Spiro, Rand J.; And Others

    This report argues that there exists a pervasive tendency for analogies to contribute to the development of entrenched misconceptions in the form of reducing complex new knowledge to the core of a source analogy. The report presents a taxonomy of ways that simple analogy induces conceptual error and an alternative approach involving integrated…

  18. Intravenous tryptophan administration attenuates cortisol secretion induced by intracerebroventricular injection of noradrenaline.

    PubMed

    Sutoh, Madoka; Kasuya, Etsuko; Yayou, Ken-ichi; Ohtani, Fumihiro; Kobayashi, Yosuke

    2016-02-01

    This study was conducted to investigate the possibility of suppression of stress-induced cortisol (CORT) secretion by tryptophan (TRP) administration and to better understand its regulatory mechanisms by using a noradrenaline (NA) injection into the third ventricle (3V) as a stress model in cattle. A total of 25 Holstein steers with a cannula in the 3V were used. First, the increase in CORT secretion was observed following a NA injection into the 3V in a dose-dependent manner, verifying the appropriateness of this treatment as a stress model of CORT secretion (Experiment 1). The effect of prior-administration of TRP into peripheral blood with a dose that has been demonstrated to increase brain 5-hydroxytryptamine levels on the elevation of plasma CORT induced by NA or corticotropin-releasing hormone (CRH) was then examined (Experiment 2). The prior administration of TRP suppressed NA-induced, but not CRH-induced, CORT elevation. These results suggest that an increase in TRP absorption into peripheral blood could suppress the stress-induced CORT secretion in cattle via the attenuation of the stimulatory effect of NA on the hypothalamic CRH release. PMID:26260296

  19. Cortisol Test

    MedlinePlus

    ... is produced and secreted by the adrenal glands . Production of the hormone is regulated by the hypothalamus ... help determine its cause: Testing for Excess Cortisol Production If a person has a high blood cortisol ...

  20. The importance of the training-induced decrease in basal cortisol concentration in the improvement in muscular performance in humans.

    PubMed

    Grandys, M; Majerczak, J; Kulpa, J; Duda, K; Rychlik, U; Zoladz, J A

    2016-03-14

    Acute exercise-induced changes in cortisol concentration (C) and training related adaptation within hypothalamic-pituitary-adrenal (HPA) axis has been widely examined, but their influence on muscle strength performance is at best uncertain. Twenty four young healthy men were randomly assigned to an endurance training group (ET, n=12) or to a non-exercising controls (CON, n=12). ET performed supervised endurance training on cycle ergometer for 20 weeks. Endurance training program improved exercise capacity (14 % increase in power output generated at peak oxygen uptake - VO(2peak)), muscle strength performance (increase in MVC - maximal voluntary contraction - by 9 % and in TTF 50 % MVC - time to fatigue at 50 % MVC - by 21 %) and led to a decrease in basal serum C concentration (P=0.006) and an increase in basal testosterone to cortisol (T/C) and free testosterone to cortisol (fT/C) ratios (P=0.01 and P=0.02, respectively). It was found that the decrease in C concentration (deltaC) was positively correlated to the increase in local muscular endurance (deltaTTF 50 % MVC). No significant hormonal changes were seen in CON group. It is concluded that greater decrease in cortisol concentration after the endurance training is accompanied by poorer improvement in skeletal muscle performance in previously untrained subjects. PMID:26596321

  1. Effects of cortisol administration on craving in heroin addicts.

    PubMed

    Walter, M; Bentz, D; Schicktanz, N; Milnik, A; Aerni, A; Gerhards, C; Schwegler, K; Vogel, M; Blum, J; Schmid, O; Roozendaal, B; Lang, U E; Borgwardt, S; de Quervain, D

    2015-01-01

    Heroin dependence is a severe and chronically relapsing substance use disorder with limited treatment options. Stress is known to increase craving and drug-taking behavior, but it is not known whether the stress hormone cortisol mediates these stress effects or whether cortisol may rather reduce craving, for example, by interfering with addiction memory. The aim of the present study was to determine the effects of cortisol administration on craving in heroin-dependent patients and to determine whether the effects depend on the daily dose of heroin consumption. We used a double-blind, placebo-controlled, cross-over study in 29 heroin-dependent patients in a stable heroin-assisted treatment setting. A single oral dose of 20 mg of cortisol or placebo was administered 105 min before the daily heroin administration. The primary outcome measure was cortisol-induced change in craving. Secondary measures included anxiety, anger and withdrawal symptoms. For the visual analog scale for craving, we found a significant interaction (P = 0.0027) between study medication and heroin-dose group (that is, daily low, medium or high dose of heroin). Cortisol administration reduced craving in patients receiving a low dose of heroin (before heroin administration: P = 0.0019; after heroin administration: P = 0.0074), but not in patients receiving a medium or high dose of heroin. In a picture-rating task with drug-related pictures, cortisol administration did not affect the ratings for the picture-characteristic craving in all the three heroin-dose groups. Cortisol also did not significantly affect secondary outcome measures. In conclusion, a single administration of cortisol leads to reduced craving in low-dose heroin addicts. The present findings might have important clinical implications with regard to understanding stress effects and regarding treatment of addiction. PMID:26218852

  2. Stress-induced behavioral and metabolic adaptations lead to an obesity-prone phenotype in ewes with elevated cortisol responses.

    PubMed

    Lee, T Kevin; Lee, Caroline; Bischof, Robert; Lambert, Gavin W; Clarke, Iain J; Henry, Belinda A

    2014-09-01

    The underlying cause of predisposition to obesity is complex but one marker is cortisol responsiveness. Selection of sheep for high (HR) or low (LR) cortisol responses to adrenocorticotropin shows that HR are more likely to become obese. Increased propensity to obesity is associated with reduced skeletal muscle thermogenesis. We sought to determine whether metabolic or behavioral responses to stress also contribute to altered propensity to obesity in LR and HR. Animals (n=5-10/group) were exposed to 3 stressors and we measured food intake and thermogenesis (recorded with dataloggers implanted into muscle). Stressors were hypoglycaemia (0.125 units/kg insulin, IV), a barking dog and immune challenge (200 ng/kg lipopolysaccharide--LPS, IV). LR animals showed a greater catabolic state in response to both immune and psychosocial stressors. LPS reduced (P<0.01) food intake in both groups but LR showed a greater (P<0.05) reduction in food intake and a more substantial (P<0.05) rise in muscle temperature. Introduction of the barking dog reduced (P<0.05) food intake in LR only. These metabolic differences coincided with differences in cortisol responsiveness, where HR animals had increased (P<0.05) cortisol in response to both immune and psychosocial stressors. We also assessed behavior in the following paradigms: 1, isolation in the open field test; 2, response to a human intruder; and 3, food competition. LR had greater (P<0.05) activity, reduced fearfulness and displayed a proactive coping style of behavior. Thus we demonstrate that high cortisol responsiveness identifies animals with stress-induced metabolic and behavioral traits that may contribute to susceptibility to obesity. PMID:25001966

  3. An Analog of electrically induced transparency via surface delocalized modes

    NASA Astrophysics Data System (ADS)

    Xiao, Xiao; Zhou, Bingpu; Wang, Xinke; He, Jingwen; Hou, Bo; Zhang, Yan; Wen, Weijia

    2015-07-01

    We demonstrate theoretically and experimentally an interesting opaque state, which is based on an analog of electromagnetically induced transparency (EIT) in mechanism, in a metal hole array of the dimer lattice. By introducing a small difference to the dimer holes of each unit cell, the surface delocalized modes launching out from the dimer holes can have destructive interferences. Consequently, a narrow opaque window in the transparent background can be observed in the transmission spectrum. This surface-mode-induced opacity (SMIO) state is very sensitive to the difference of the dimer holes, which will promise various applications.

  4. Effects of Multimedia and Schema Induced Analogical Reasoning on Science Learning

    ERIC Educational Resources Information Center

    Zheng, R. Z.; Yang, W.; Garcia, D.; McCadden, E. P.

    2008-01-01

    The present study investigates the effects of multimedia and schema induced analogical reasoning on science learning. It involves 89 fourth grade elementary students in the north-east of the United States. Participants are randomly assigned into four conditions: (a) multimedia with analogy; (b) multimedia without analogy; (c) analogy without…

  5. Stress-induced cortisol facilitates threat-related decision making among police officers.

    PubMed

    Akinola, Modupe; Mendes, Wendy Berry

    2012-02-01

    Previous research suggests that cortisol can affect cognitive functions such as memory, decision making, and attentiveness to threat-related cues. Here, we examine whether increases in cortisol, brought on by an acute social stressor, influence threat-related decision making. Eighty-one police officers completed a standardized laboratory stressor and then immediately completed a computer simulated decision-making task designed to examine decisions to accurately shoot or not shoot armed and unarmed Black and White targets. Results indicated that police officers who had larger cortisol increases to the social-stress task subsequently made fewer errors when deciding to shoot armed Black targets relative to armed White targets, suggesting that hypothalamic pituitary adrenal (HPA) activation may exacerbate vigilance for threat cues. We conclude with a discussion of the implications of threat-initiated decision making. PMID:22141468

  6. Stress and the Hair Growth Cycle: Cortisol-Induced Hair Growth Disruption.

    PubMed

    Thom, Erling

    2016-08-01

    The stress hormone, cortisol, is known to affect the function and cyclic regulation of the hair follicle. When cortisol is present at high levels it has been demonstrated to reduce the synthesis and accelerate the degradation of important skin elements, namely hyaluronan and proteoglycans by approximately 40%. The following discussion outlines the relationship between stress, cortisol, and the effect on the normal function of the hair follicle. As a result of this connection, important correlations have been established in the literature to form a basis for novel, effective treatments of stress-related hair growth disorders.
    Amongst various treatment methods and substances, oral supplementation with a specific bioavailable proteoglycan stands out as a promising new therapeutic treatment method.

    J Drugs Dermatol. 2016;15(8):1001-1004. PMID:27538002

  7. Magnetically coupled electromagnetically induced transparency analogy of dielectric metamaterial

    SciTech Connect

    Zhang, Fuli He, Xuan; Zhao, Qian; Lan, Chuwen; Zhou, Ji; Zhang, Weihong Qiu, Kepeng

    2014-03-31

    In this manuscript, we experimentally demonstrate magnetically coupled electromagnetically induced transparency (EIT) analogy effect inside dielectric metamaterial. In contrast to previous studies employed different metallic topological microstructures to introduce dissipation loss change, barium strontium titanate, and calcium titanate (CaTiO{sub 3}) are chosen as the bright and dark EIT resonators, respectively, due to their different intrinsic dielectric loss. Under incident magnetic field excitation, dielectric metamaterial exhibits an EIT-type transparency window around 8.9 GHz, which is accompanied by abrupt change of transmission phase. Numerical calculations show good agreement with experiment spectra and reveal remarkably increased group index, indicating potential application in slow light.

  8. Maternal stress-associated cortisol stimulation may protect embryos from cortisol excess in zebrafish

    PubMed Central

    Faught, Erin; Best, Carol; Vijayan, Mathilakath M.

    2016-01-01

    Abnormal embryo cortisol level causes developmental defects and poor survival in zebrafish (Danio rerio). However, no study has demonstrated that maternal stress leads to higher embryo cortisol content in zebrafish. We tested the hypothesis that maternal stress-associated elevation in cortisol levels increases embryo cortisol content in this asynchronous breeder. Zebrafish mothers were fed cortisol-spiked food for 5 days, to mimic maternal stress, followed by daily breeding for 10 days to monitor temporal embryo cortisol content. Cortisol treatment increased mean embryo yield, but the daily fecundity was variable among the groups. Embryo cortisol content was variable in both groups over a 10-day period. A transient elevation in cortisol levels was observed in the embryos from cortisol-fed mothers only on day 3, but not on subsequent days. We tested whether excess cortisol stimulates 11βHSD2 expression in ovarian follicles as a means to regulate embryo cortisol deposition. Cortisol treatment in vitro increased 11β HSD2 levels sevenfold, and this expression was regulated by actinomycin D and cycloheximide suggesting tight regulation of cortisol levels in the ovarian follicles. We hypothesize that cortisol-induced upregulation of 11βHSD2 activity in the ovarian follicles is a mechanism restricting excess cortisol incorporation into the eggs during maternal stress. PMID:26998341

  9. Influence of gender and breed type on basal and induced secretion of cortisol in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the hypothesis that gender and breed type affect cortisol secretion, Angus (Bos taurus) and Brahman (Bos indicus) bulls (intact males), steers (castrate males), and heifers (intact females) were studied. Jugular venipuncture samples were taken from 900 cattle at: 28 days before weaning; wean...

  10. Cortisol - urine

    MedlinePlus

    ... is a steroid (glucocorticoid) hormone produced by the adrenal gland . Cortisol can also be measured using a blood ... is a glucocorticoid (steroid) hormone released from the adrenal gland in response to adrenocorticotropic hormone ( ACTH ). This is ...

  11. Dairy food consumption and meal-induced cortisol response interacted to influence weight loss in overweight women undergoing a 12-week, meal-controlled, weight loss intervention.

    PubMed

    Witbracht, Megan G; Van Loan, Marta; Adams, Sean H; Keim, Nancy L; Laugero, Kevin D

    2013-01-01

    Dairy food enhances weight loss in animal models, possibly by modifying the metabolic effects of cortisol. This study determined in overweight women (ages 20.0-45.9 y; n = 51) whether including dairy food in an energy-restricted diet affects cortisol concentrations and whether differences in provoked cortisol explain the magnitude of weight loss. Women received either an adequate amount of dairy food (AD), the equivalent of ≥711 mL/d milk, or a low amount of dairy food (LD), the equivalent to ≤238 mL/d milk, in a 12-wk, energy-restricted dietary intervention. Participants were tested in a 12-h laboratory visit, which included 2 standard meals and a dinner buffet that was consumed ad libitum. Salivary cortisol was measured from waking to bedtime. Energy restriction increased (P ≤ 0.04) the minimum and decreased (P ≤ 0.02) the diurnal amplitude in the salivary cortisol concentration from baseline to postintervention. Energy restriction enhanced the dinner meal-stimulated salivary cortisol response (DMR) (P ≤ 0.02) but only in the LD group. Compared with the LD treatment, the AD treatment induced (P ≤ 0.04) greater reductions in body weight and fat, but only in women characterized as having a baseline DMR (responders) (n = 26); weight and fat lost in the AD and LD groups were similar in nonresponders (n = 25). Overall, energy restriction dampened diurnal salivary cortisol fluctuations [symptomatic of hypothalamic-pituitary-adrenal (HPA) axis dysfunction] and enhanced dinner meal-stimulated salivary cortisol concentrations. The AD treatment prevented the latter. Furthermore, certain phenotypic markers of HPA axis function may help to expose the weight-reducing effects of consuming dairy food. PMID:23190756

  12. Cortisol regulates the paracrine action of macrophages by inducing vasoactive gene expression in endometrial cells.

    PubMed

    Thiruchelvam, Uma; Maybin, Jacqueline A; Armstrong, Gregory M; Greaves, Erin; Saunders, Philippa T K; Critchley, Hilary O D

    2016-06-01

    The human endometrium undergoes inflammation and tissue repair during menstruation. We hypothesized that the local availability of bioactive glucocorticoids plays an important role in immune cell-vascular cell interactions in endometrium during tissue repair at menstruation, acting either directly or indirectly via tissue resident macrophages. We sought to determine whether endometrial macrophages are direct targets for glucocorticoids; whether cortisol-treated macrophages have a paracrine effect on angiogenic gene expression by endometrial endothelial cells; and whether endometrial macrophages express angiogenic factors. Human endometrium (n = 41) was collected with ethical approval and subject consent. Donor peripheral blood monocyte-derived macrophages were treated with estradiol, progesterone, or cortisol. The effect of peripheral blood monocyte-derived macrophage secretory products on the expression of angiogenic RNAs by endothelial cells was examined. Immunofluorescence was used to examine localization in macrophages and other endometrial cell types across the menstrual cycle. Endometrial macrophages express the glucocorticoid receptor. In vitro culture with supernatants from cortisol-treated peripheral blood monocyte-derived macrophages resulted in altered endometrial endothelial cell expression of the angiogenic genes, CXCL2, CXCL8, CTGF, and VEGFC These data highlight the importance of local cortisol in regulating paracrine actions of macrophages in the endometrium. CXCL2 and CXCL8 were detected in endometrial macrophages in situ. The expression of these factors was highest in the endometrium during the menstrual phase, consistent with these factors having a role in endometrial repair. Our data have indicated that activation of macrophages with glucocorticoids might have paracrine effects by increasing angiogenic factor expression by endometrial endothelial cells. This might reflect possible roles for macrophages in endometrial repair of the vascular bed

  13. Pre-treatment waking cortisol response and vulnerability to interferon α induced depression.

    PubMed

    Eccles, Jessica; Lallemant, Camille; Mushtaq, Farrah; Greenwood, Matthew; Keller, Majella; Golding, Bruno; Tibble, Jeremy; Haq, Inam; Whale, Richard

    2012-12-01

    Depressive disorder is a common consequence of interferon α treatment. An understanding of the aetiological processes involved is evolving. HPA axis abnormalities are clearly described in community depressive disorder and represent vulnerability to depression development. We explored whether pre-treatment HPA axis abnormalities influence depression emergence during interferon α treatment. We examined waking HPA axis response via salivary cortisol sampling in 44 non-depressed, chronic hepatitis C infected patients due to commence standard interferon α treatment. Hamilton depression scales and the structured clinical interview for DSM-IV major depressive disorder status were administered monthly during treatment. Major depressive disorder developed in 26 of 44 subjects during interferon-α treatment. The pre-treatment waking cortisol response over 1h was significantly greater in the subsequent switch to depression group (F=4.23, p=0.046). The waking cortisol response pre-treatment with interferon α appears greater in those subsequently switching to depressive disorder during treatment. This waking response may join other vulnerability factors for depression emergence in this group. This model could prove a valuable tool in understanding non-iatrogenic depressive disorder in the general population and notably the role of cytokines. PMID:22571879

  14. Neurotensin analog NT77 induces regulated hypothermia in the rat.

    PubMed

    Gordon, Christopher J; McMahon, Beth; Richelson, Elliott; Padnos, Beth; Katz, Laurence

    2003-10-01

    The potential use of hypothermia as a therapeutic treatment for stroke and other pathological insults has prompted the search for drugs that can lower core temperature. Ideally, a drug is needed that reduces the set-point for control of core temperature (T(c)) and thereby induces a regulated reduction in T(c). To this end, a neurotensin analog (NT77) that crosses the blood brain barrier and induces hypothermia was assessed for its effects on the set-point for temperature regulation in the Sprague-Dawley rat by measuring behavioral and autonomic thermoregulatory responses. Following surgical implanation of radiotransmitters to monitor T(c), rats were placed in a temperature gradient and allowed to select from a range of ambient temperatures (T(a)) while T(c) was monitored by radiotelemetry. There was an abrupt decrease in selected T(a) from 29 to 16 degrees C and a concomitant reduction in T(c) from 37.4 to 34.0 degrees C 1 hr after IP injection of 5.0 mg/kg NT77. Selected T(a) and T(c) then recovered to control levels by 1.5 hr and 4 hr, respectively. Oxygen consumption (M) and heat loss (H) were measured in telemetered rats housed in a direct calorimeter maintained at a T(a) of 23.5 degrees C. Injection of NT77 initially led to a reduction in M, little change in H, and marked decrease in T(c). H initially rose but decreased around the time of the maximal decrease in T(c). Overall, NT77 appears to induce a regulated hypothermic response because the decrease in T(c) was preceded by a reduction in heat production, no change in heat loss, and preference for cold T(a)'s. Inducing a regulated hypothermic response with drugs such as NT77 may be an important therapy for ischemic disease and other insults. PMID:12967685

  15. Cortisol-induced inhibition of ovine renin and aldosterone responses to hypotension

    SciTech Connect

    Wood, C.E.; Silbiger, J.

    1987-03-01

    Previous studies from this laboratory have demonstrated that in preterm fetal sheep increases in plasma cortisol (F) concentration equal in amplitude to fetal F stress responses suppress plasma renin activity (PRA). The purpose of this study was to investigate the possibility that this negative interaction exists in adult sheep. Cortisol was measured by radioimmunoassay. Five conscious ewes with chronically prepared carotid arterial loops were infused intravenously with F or vehicle for 5 h. One hour after the end of F or vehicle infusion, renin secretion was stimulated by hypotension produced by infusion of sodium nitroprusside. F infusion increased plasma F; during vehicle infusion plasma F did not change. F infusion decreased hematocrit from 29 +/- 2 to 26 +/- 1%. Basal PRA in vehicle- and F-infused groups were 0.4 +/- 0 and 0.2 +/- 0.1 ng angiotensin I-ml/sup -1/-h/sup -1/ and did not change. In vehicle-infused ewes, PRA increased from 0.4 +/- 0 to 4.6 +/- 0.4 and plasma aldosterone from 26.0 +/- 1.0 to 173.1 +/- 21.8 pg/ml, while in F-infused ewes, PRA increased from 0.2 +/- 1 to 3.3 +/- 0.4 ng angiotensin I-ml/sup -1/-h/sup -1/ and aldosterone from 25.0 +/- 0 to 48.2 +/- 23.2 pg/ml, significantly smaller responses. These results suggest that repeated stress may modulate the responses of the renin-angiotensin system in this species.

  16. Imbalance between macrophage migration inhibitory factor and cortisol induces multiple organ dysfunction in patients with blunt trauma.

    PubMed

    Hayakawa, Mineji; Katabami, Kenichi; Wada, Takeshi; Minami, Yousuke; Sugano, Masahiro; Shimojima, Hidekazu; Kubota, Nobuhiko; Uegaki, Shinji; Sawamura, Atsushi; Gando, Satoshi

    2011-06-01

    Migration inhibitory factor (MIF) is associated with multiple organ dysfunction syndrome (MODS) in patients with systemic inflammatory response syndrome (SIRS). Our purposes were to determine the serum MIF, cortisol, and tumor narcosis factor-α (TNF-α) and to investigate the influences of the balance between the levels of MIF and cortisol in patients with blunt trauma. The cortisol levels were identical between the patients with and without MODS. However, the MIF and TNF-α levels in the patients with MODS were statistically higher than those of the patients without MODS. The cortisol/MIF ratios in the patients with MODS were statistically higher than those of the patients without MODS. The results show that MIF and TNF-α play an important role together in posttraumatic inflammatory response. An excessive serum MIF elevation overrides the anti-inflammatory effects of cortisol and leads to persistent SIRS followed by MODS in blunt trauma patients. PMID:20499270

  17. Species-specific sensitivity to selenium-induced impairment of cortisol secretion in adrenocortical cells of rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis)

    SciTech Connect

    Miller, L.L. Hontela, A.

    2011-06-01

    Species differences in physiological and biochemical attributes exist even among closely related species and may underlie species-specific sensitivity to toxicants. Rainbow trout (RT) are more sensitive than brook trout (BT) to the teratogenic effects of selenium (Se), but it is not known whether all tissues exhibit this pattern of vulnerability. In this study, primary cultures of RT and BT adrenocortical cells were exposed to selenite (Na{sub 2}SO{sub 3}) and selenomethionine (Se-Met) to compare cell viability and ACTH-stimulated cortisol secretion in the two fish species. Cortisol, the primary stress hormone in fish, facilitates maintenance of homeostasis when fish are exposed to stressors, including toxicants. Cell viability was not affected by Se, but selenite impaired cortisol secretion, while Se-Met did not (RT and BT EC{sub 50} > 2000 mg/L). RT cells were more sensitive (EC{sub 50} = 8.7 mg/L) to selenite than BT cells (EC{sub 50} = 90.4 mg/L). To identify the targets where Se disrupts cortisol synthesis, selenite-impaired RT and BT cells were stimulated with ACTH, dbcAMP, OH-cholesterol, and pregnenolone. Selenite acted at different steps in the cortisol biosynthesis pathway in RT and BT cells, confirming a species-specific toxicity mechanism. To test the hypothesis that oxidative stress mediates Se-induced toxicity, selenite-impaired RT cells were exposed to NAC, BSO and antioxidants (DETCA, ATA, Vit A, and Vit E). Inhibition of SOD by DETCA enhanced selenite-induced cortisol impairment, indicating that oxidative stress plays a role in Se toxicity; however, modifying GSH content of the cells did not have an effect. The results of this study, with two closely related salmonids, provided additional evidence for species-specific differences in sensitivity to Se which should be considered when setting thresholds and water quality guidelines. - Research Highlights: > We investigated species-specific sensitivity to Se in trout adrenocortical cells. > Selenite

  18. Two-Photon-Induced Fluorescence of Isomorphic Nucleobase Analogs

    PubMed Central

    Lane, Richard S. K.; Jones, Rosemary; Sinkeldam, Renatus W.

    2014-01-01

    Five isomorphic fluorescent uridine mimics have been subjected to two-photon (2P) excitation analysis to investigate their potential applicability as non-perturbing probes for the single-molecule detection of nucleic acids. We find that small structural differences can cause major changes in the two-photon excitation probability, with the 2P cross sections varying by over one order of magnitude. Two of the probes, both furan-modified uridine analogs, have the highest 2P cross sections (3.8 GM and 7.6 GM) reported for nucleobase analogs, using a conventional Ti:sapphire laser for excitation at 690 nm; they also have the lowest emission quantum yields. In contrast, the analogs with the highest reported quantum yields have the lowest 2P cross sections. The structure-photophysical property relationship presented here is a first step towards the rational design of emissive nucleobase analogs with controlled 2P characteristics. The results demonstrate the potential for major improvements through judicious structural modifications. PMID:24604669

  19. Psychophysiological evidence for cortisol-induced reduction in early bias for implicit social threat in social phobia.

    PubMed

    van Peer, Jacobien M; Spinhoven, Philip; Roelofs, Karin

    2010-01-01

    The stress hormone cortisol is important for the regulation of social motivational processes. High cortisol levels have been associated with social fear and avoidance, which play an important role in social anxiety disorder (SAD), as does hypervigilant processing of social threat. However, causal effects of cortisol on threat processing in SAD remain unclear. In an event-related potential (ERP) study we investigated the effects of cortisol on task-irrelevant (implicit) processing of social threat in SAD, exploring the temporal dynamics as well as the role of symptom severity and stimulus awareness. Angry face processing was measured in participants with clinical SAD after double-blind, within-subject oral administration of cortisol (50mg) and placebo, using a masked and an unmasked emotional Stroop task. Both tasks showed significantly increased P2 midline ERP amplitudes for angry compared to neutral and happy faces in the placebo condition, reflecting an early attentional bias for social threat in SAD. Furthermore, cortisol administration significantly decreased P2 amplitudes for masked angry faces. This effect correlated with social anxiety, showing stronger decreases in patients with higher levels of social anxiety. These results indicate a highly specific effect of cortisol on early motivated attention to social threat and, together with previous findings, highlight the importance of motivational context (stimulus- or task-relevance) as well as symptom severity. PMID:19836898

  20. Cortisol administration induces global down-regulation of the brain's reward circuitry.

    PubMed

    Montoya, Estrella R; Bos, Peter A; Terburg, David; Rosenberger, Lisa A; van Honk, Jack

    2014-09-01

    Research in rodents and humans has shown divergent effects of the glucocorticoids corticosterone and cortisol (CRT) on reward processing. In rodents, administration of CRT increases reward drive by facilitating dopamine release in the ventral striatum. In humans, correspondingly, risky decision-making increases when CRT levels are elevated. Human stress studies contrariwise show that elevated CRT is accompanied by a decrease in reward-related brain activity. There are however no direct insights into how CRT acts on the reward system in the human brain. Accordingly, we used pharmacological functional magnetic resonance imaging (pharmaco-fMRI) to investigate the effects of CRT on the brain's reward system. In a randomized within-subject design we administered a high dose of CRT (40 mg) and placebo to twenty healthy male volunteers on separate days, and used a monetary incentive delay task to assess the effects of the hormone on the striatum and the amygdala in anticipation of potential reward. In contrast to animal studies, we show that this high dose of CRT strongly decreases activity of the striatum in both reward and non-reward conditions. Furthermore, we observed reductions in activity in the basolateral amygdala, a key regulator of the brain's reward system. Crucially, the overall down-regulation of the brain's reward circuit was verified on the subjective level as subjects reported significantly reduced reward preference after CRT. In sum, we provide here direct evidence in humans that CRT acts on brain regions involved in reward-related behavior, that is, the basolateral amygdala and the striatum. Our findings suggest that CRT in the quantity and time course presently used globally down-regulates the reward system, and thereby decreases motivational processing in general. PMID:25001954

  1. Exploring Shamanic Journeying: Repetitive Drumming with Shamanic Instructions Induces Specific Subjective Experiences but No Larger Cortisol Decrease than Instrumental Meditation Music

    PubMed Central

    Gingras, Bruno; Pohler, Gerald; Fitch, W. Tecumseh

    2014-01-01

    Exposure to repetitive drumming combined with instructions for shamanic journeying has been associated with physiological and therapeutic effects, such as an increase in salivary immunoglobulin A. In order to assess whether the combination of repetitive drumming and shamanic instructions is specifically associated with these effects, we compared the effect of listening to either repetitive drumming or instrumental meditation music for 15 minutes on salivary cortisol concentration and on self-reported physiological and psychological states. For each musical style, two groups of participants were exposed to two conditions: instructions for shamanic journeying or relaxation instructions. A total of 39 participants (24 females) inexperienced in shamanic journeying completed the experiment. Salivary cortisol concentrations were measured before and after exposure to music. In addition, participants filled out a mood questionnaire before and after the experiment and completed a post experiment questionnaire on their experiences. A significant decrease in the concentration in salivary cortisol was observed across all musical styles and instructions, indicating that exposure to 15 minutes of either repetitive drumming or instrumental meditation music, while lying down, was sufficient to induce a decrease in cortisol levels. However, no differences were observed across conditions. Significant differences in reported emotional states and subjective experiences were observed between the groups. Notably, participants exposed to repetitive drumming combined with shamanic instructions reported experiencing heaviness, decreased heart rate, and dreamlike experiences significantly more often than participants exposed to repetitive drumming combined with relaxation instructions. Our findings suggest that the subjective effects specifically attributed to repetitive drumming and shamanic journeying may not be reflected in differential endocrine responses. PMID:24999623

  2. Exploring shamanic journeying: repetitive drumming with shamanic instructions induces specific subjective experiences but no larger cortisol decrease than instrumental meditation music.

    PubMed

    Gingras, Bruno; Pohler, Gerald; Fitch, W Tecumseh

    2014-01-01

    Exposure to repetitive drumming combined with instructions for shamanic journeying has been associated with physiological and therapeutic effects, such as an increase in salivary immunoglobulin A. In order to assess whether the combination of repetitive drumming and shamanic instructions is specifically associated with these effects, we compared the effect of listening to either repetitive drumming or instrumental meditation music for 15 minutes on salivary cortisol concentration and on self-reported physiological and psychological states. For each musical style, two groups of participants were exposed to two conditions: instructions for shamanic journeying or relaxation instructions. A total of 39 participants (24 females) inexperienced in shamanic journeying completed the experiment. Salivary cortisol concentrations were measured before and after exposure to music. In addition, participants filled out a mood questionnaire before and after the experiment and completed a post experiment questionnaire on their experiences. A significant decrease in the concentration in salivary cortisol was observed across all musical styles and instructions, indicating that exposure to 15 minutes of either repetitive drumming or instrumental meditation music, while lying down, was sufficient to induce a decrease in cortisol levels. However, no differences were observed across conditions. Significant differences in reported emotional states and subjective experiences were observed between the groups. Notably, participants exposed to repetitive drumming combined with shamanic instructions reported experiencing heaviness, decreased heart rate, and dreamlike experiences significantly more often than participants exposed to repetitive drumming combined with relaxation instructions. Our findings suggest that the subjective effects specifically attributed to repetitive drumming and shamanic journeying may not be reflected in differential endocrine responses. PMID:24999623

  3. Effects of smoking on ACTH and cortisol secretion

    SciTech Connect

    Seyler, L.E. Jr.; Fertig, J.; Pomerleau, O.; Hunt, D.; Parker, K.

    1984-01-02

    The relationships among changes in plasma nicotine, ACTH, and cortisol secretion after smoking were investigated. Ten male subjects smoked cigarettes containing 2.87 mg nicotine and 0.48 mg nicotine. No rises in cortisol or ACTH were detected after smoking 0.48 mg nicotine cigarettes. Cortisol rises were significant in 11 of 15 instances after smoking 2.87 mg nicotine cigarattes, but ACTH rose significantly in only 5 of the 11 instances where cortisol increased. Each ACTH rise occurred in a subject who reported nausea and was observed to be pale, sweaty, and tachycardic. Peak plasma nicotine concentrations were not significantly different in sessions when cortisol rose with or without ACTH increases, but cortisol increases were significantly greater in nauseated than in non-nauseated smokers. This data suggest that smoking-induced nausea stimulates cortisol release by stimulating ACTH secretion and that cortisol secretion in non-nauseated smokers may occur through a non-ACTH mechanism.

  4. CAPE Analogs Induce Growth Arrest and Apoptosis in Breast Cancer Cells.

    PubMed

    Beauregard, Annie-Pier; Harquail, Jason; Lassalle-Claux, Grégoire; Belbraouet, Mehdi; Jean-Francois, Jacques; Touaibia, Mohamed; Robichaud, Gilles A

    2015-01-01

    Breast cancer is the second leading cause of death amongst women worldwide. As a result, many have turned their attention to new alternative approaches to treat this disease. Caffeic acid phenylethyl ester (CAPE), a well-known active compound from bee propolis, has been previously identified as a strong antioxidant, anti-inflammatory, antiviral and anticancer molecule. In fact, CAPE is well documented as inducing cell death by inhibiting NFκB and by inducing pro-apoptotic pathways (i.e., p53). With the objective of developing stronger anticancer compounds, we studied 18 recently described CAPE derivatives for their ability to induce apoptosis in breast cancer cell lines. Five of the said compounds, including CAPE, were selected and subsequently characterised for their anticancer mechanism of action. We validated that CAPE is a potent inducer of caspase-dependent apoptosis. Interestingly, some newly synthesized CAPE derivatives also showed greater cell death activity than the lead CAPE structure. Similarly to CAPE, analog compounds elicited p53 activation. Interestingly, one compound in particular, analog 10, induced apoptosis in a p53-mutated cell line. These results suggest that our new CAPE analog compounds may display the capacity to induce breast cancer apoptosis in a p53-dependent and/or independent manner. These CAPE analogs could thus provide new therapeutic approaches for patients with varying genotypic signatures (such as p53 mutations) in a more specific and targeted fashion. PMID:26184141

  5. Novel thromboxane A2 analog-induced IUGR mouse model.

    PubMed

    Fung, C; Brown, A; Cox, J; Callaway, C; McKnight, R; Lane, R

    2011-10-01

    Rodents, particularly rats, are used in the majority of intrauterine growth restriction (IUGR) research. An important tool that is lacking in this field is the ability to impose IUGR on transgenic mice. We therefore developed a novel mouse model of chronic IUGR using U-46619, a thromboxane A2 (TXA2) analog, infusion. TXA2 overproduction is prevalent in human pregnancies complicated by cigarette smoking, diabetes mellitus and preeclampsia. In this model, U-46619 micro-osmotic pump infusion in the last week of C57BL/6J mouse gestation caused maternal hypertension. IUGR pups weighed 15% less, had lighter brain, lung, liver and kidney weights, but had similar nose-to-anus lengths compared with sham pups at birth. Metabolically, IUGR pups showed increased essential branched-chain amino acids. They were normoglycemic yet hypoinsulinemic. They showed decreased hepatic mRNA levels of total insulin-like growth factor-1 and its variants, but increased level of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha. IUGR offspring were growth restricted from birth (P1) through postnatal day 21 (P21). IUGR males caught up with sham males in weight by P28, whereas IUGR females caught up with sham females by P77. IUGR males surpassed sham males in weight by P238. In summary, we have a non-brain sparing IUGR mouse model that has a relative ease of surgical IUGR induction and exhibits features similar to the chronic IUGR offspring of humans and other animal models. As transgenic technology predominates in mice, this model now permits the imposition of IUGR on transgenic mice to interrogate mechanisms of fetal origins of adult disease. PMID:25141265

  6. Comparative hepatoprotective effects of tocotrienol analogs against drug-induced liver injury

    PubMed Central

    Tan, Cheau Yih; Saw, Tzuen Yih; Fong, Chee Wai; Ho, Han Kiat

    2015-01-01

    Oxidative stress plays a major part in the pathogenesis of drug-induced liver injury. Yet, overcoming it with other xenobiotics impose additional risks. In this study, we consider the use of natural-occurring and purified Vitamin E analogs as hepatoprotective agents. Vitamin E is well-known for its intrinsic antioxidant property even though the differential effect of specific analogs of tocopherol (TP) and tocotrienol (T3) is still not ascertained. This study investigates the protective effect of T3 analogs (α-, δ-, γ−) in comparison with α-TP followed by assessing the underlying mechanisms of the cytoprotective T3 analog(s) in two xenobiotics-induced liver injury models using (1) acetaminophen (APAP)- and (2) hydrogen peroxide (H2O2). Both α-TP and α-T3 exerted cytoprotective effects while only lower concentration of γ-T3 was effective in inhibiting both toxicants induced injury. α-TP/α-T3 protected hepatocytes from APAP and H2O2-induced liver injury through arresting free radicals and inhibiting oxidative stress (inhibition of reactive oxygen species, lipid peroxidation and mitochondrial permeability transition). There was also demonstrable inhibition of the apoptotic pathway (inhibition of caspse-3 activity and overexpression of Bcl-XL), accompanied with an induction of liver regeneration (PCNA and NF-kB). The cellular uptake of α-T3 was higher than α-TP at the same treatment dosage after 24 h. Overall, α-T3 seems to be a more potent hepatoprotective analog among the tocotrienols and α-TP at the same in vitro treatment dosage. In summary, these results suggest that α-TP/α-T3 elicit hepatoprotective effects against toxicants-induced damage mainly through activation of antioxidant responses at an early stage to prevent the exacerbation of injury. PMID:25637740

  7. The influence of temperament on transportation induced increases in body temperature and secretion of cortisol and epinephrine in bulls

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the influence of temperament on rectal temperature (RT) and secretion of cortisol (CS) and epinephrine (E) in response to transportation. Purebred Brahman bulls were selected based on temperament score measured at weaning [n=8 each: Calm (C), Intermediate (I), an...

  8. Cortisol coregulation in fish

    PubMed Central

    Fürtbauer, Ines; Heistermann, Michael

    2016-01-01

    Cortisol coregulation, which is the up- or down-regulation of partners’ physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children, and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner’s cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations. PMID:27458063

  9. Cortisol coregulation in fish.

    PubMed

    Fürtbauer, Ines; Heistermann, Michael

    2016-01-01

    Cortisol coregulation, which is the up- or down-regulation of partners' physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children, and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner's cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations. PMID:27458063

  10. Small interfering RNA suppression of polyamine analog-induced spermidine/spermine n1-acetyltransferase.

    PubMed

    Chen, Ying; Kramer, Debora L; Jell, Jason; Vujcic, Slavoljub; Porter, Carl W

    2003-11-01

    N1,N11-diethylnorspermine (DENSPM) is a polyamine analog that down-regulates polyamine biosynthesis and potently upregulates the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT). In certain cells, such as SKMEL-28 human melanoma cells, induction of SSAT is associated with rapid apoptosis. In this study, we used small interfering RNA (siRNA) to examine the role of SSAT induction in mediating polyamine pool depletion and apoptosis. siRNA duplexes were designed to target three independent sites in the SSAT mRNA coding region (siSSAT). When transfected under nontoxic conditions, two of the duplexes selectively reduced basal SSAT mRNA in HEK-293 cells by >80% and prevented DENSPM-induced SSAT mRNA by 95% in SK-MEL-28 cells. Treatment of SK-MEL-28 cells with 10 muM DENSPM in the presence of 83 nM siSSAT selectively prevented the 1400-fold induction of SSAT activity by approximately 90% and, in turn, prevented analog depletion of spermine (Spm) pools by approximately 35%. siSSAT also prevented DENSPM-induced cytochrome c release and caspase-3 cleavage at 36 h and apoptosis at 48 h as measured by annexin V staining. Overall, the data directly link analog induction of SSAT to Spm pool depletion and to caspase-dependent apoptosis in DENSPM-treated SK-MEL-28 cells. This represents the first use of siRNA technology directed toward a polyamine gene and the first unequivocal demonstration that SSAT induction initiates events leading to polyamine analog-induced apoptosis. PMID:14573765

  11. Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish

    PubMed Central

    Nesan, Dinushan; Vijayan, Mathilakath M.

    2016-01-01

    In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish. PMID:26940285

  12. Fasting and diet content affect stress-induced changes in plasma glucose and cortisol in Juvenile chinook salmon. [Oncorhynchus tshawytscha

    SciTech Connect

    Barton, B.A.; Schreck, C.B. ); Fowler, L.G. )

    1988-01-01

    Juvenile chinook salmon (Oncorhynchus tshawytscha) reared on low-, medium-, or high-lipid diets for 18 weeks were either kept on their respective diets or fasted for 20 d; then they were subjected to a 30-s handling stress or to handling plus continuous confinement. In fish that were handled but not confined, poststress hyperglycemia was greatest in fed fish that received the high-lipid diet and was generally lower in fasted than in fed fish. Plasma cortisol elevations in response to handling or handling plus confinement stress were not appreciably affected by diet type or fasting. The result indicated that prior feeding regimes and the types of diet fed should be considered when one is interpreting the magnitude of hyperglycemic stress responses in juvenile chinook salmon.

  13. Polyamine analog TBP inhibits proliferation of human K562 chronic myelogenous leukemia cells by induced apoptosis

    PubMed Central

    WANG, QING; WANG, YAN-LIN; WANG, KAI; YANG, JIAN-LIN; CAO, CHUN-YU

    2015-01-01

    The aim of the present study was to investigate the effects of the novel polyamine analog tetrabutyl propanediamine (TBP) on the growth of K562 chronic myelogenous leukemia (CML) cells and the underlying mechanism of these effects. MTT was used for the analysis of cell proliferation and flow cytometry was performed to analyze cell cycle distribution. DNA fragmentation analysis and Annexin V/propidium iodide double staining were used to identify apoptotic cells. The activity of the key enzymes in polyamine catabolism was detected using chemiluminescence. TBP can induce apoptosis and significantly inhibit K562 cell proliferation in a time- and dose-dependent manner. TBP treatment significantly induced the enzyme activity of spermine oxidase and acetylpolyamine oxidase in K562 cells, and also enhanced the inhibitory effect of the antitumor drug doxorubicin on K562 cell proliferation. As a novel polyamine analog, TBP significantly inhibited proliferation and induced apoptosis in K562 cells by upregulating the activity of the key enzymes in the polyamine catabolic pathways. TBP also increased the sensitivity of the K562 cells to the antitumor drug doxorubicin. These data indicate an important potential value of TBP for clinical therapy of human CML. PMID:25435975

  14. Superoxide generation catalyzed by the ozone-inducible plant peptides analogous to prion octarepeat motif.

    PubMed

    Yokawa, Ken; Kagenishi, Tomoko; Kawano, Tomonori

    2011-04-01

    Ozone-inducible (OI) peptides found in plants contain repeated sequences consisting of a hexa-repeat unit (YGH GGG) repeated 7-9 times in tandem, and each unit tightly binds copper. To date, the biochemical roles for OI peptides are not fully understood. Here, we demonstrated that the hexa-repeat unit from OI peptides behaves as metal-binding motif catalytically active in the O2•--generation. Lastly, possible mechanisms of the reaction and biological consequence of the reactions are discussed by analogy to the action of human prion octarepeat peptides. PMID:21350332

  15. Daily rhythm of cortisol, and evidence for a photo-inducible phase for prolactin secretion in nonpregnant mares housed under non-interrupted and skeleton photoperiods.

    PubMed

    Johnson, A L; Malinowski, K

    1986-07-01

    Studies were conducted in anestrous mares to characterize daily rhythms of cortisol in non-interrupted [ambient and 16 h light (L): 8 h dark (D)] and skeleton (10L:4D:2L:8D, 10L:6D:2L:6D and 10L:8D:2L:4D) photoperiods, and to determine if there exists a photosensitive phase for the secretion of prolactin. Neither peak or nadir concentrations of cortisol, nor the time of peak or nadir concentrations differed among photoperiod treatments. Highest concentrations (66 +/- 4.4 ng/ml, mean +/- SE) occurred between 0700 and 0900, whereas lowest concentrations (31 +/- 3.6 ng/ml) were found from 1900 to 2300. Mean daily concentrations of serum prolactin were significantly higher in mares housed under the 16L:8D and the 10L:8D:2L:4D photoperiods as compared with the remaining photoperiod treatments, and were lowest in the ambient photoperiod treatment. The mean daily concentration of prolactin in February among photoperiod treatments was inversely related to the number of days (from December 1) to first seasonal ovulation (r = -.92, P = .027). The results were interpreted to: 1) suggest that mares in the 10L:8D:2L:4D skeleton photoperiod do not phase-shift to interpret the 2-h light pulse as the beginning of their subjective day; and 2) provide further evidence that the photo-inducible phase for both prolactin secretion and the stimulation of seasonal reproductive activity occurs 8 to 10 h following the onset of the dark period (scotophase). PMID:3733571

  16. Dairy food consumption and meal-induced cortisol response interact to influence weight loss in overweight women undergoing a 12-week meal-controlled weight loss intervention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dairy foods enhance weight loss in animal models possibly by modifying the metabolic effects of cortisol. This study aimed to determine in overweight women (ages 20-45; n=51) whether inclusion of dairy foods in an energy-restricted diet affects basal and stimulated cortisol concentrations, and whet...

  17. Cortisol shifts financial risk preferences.

    PubMed

    Kandasamy, Narayanan; Hardy, Ben; Page, Lionel; Schaffner, Markus; Graggaber, Johann; Powlson, Andrew S; Fletcher, Paul C; Gurnell, Mark; Coates, John

    2014-03-01

    Risk taking is central to human activity. Consequently, it lies at the focal point of behavioral sciences such as neuroscience, economics, and finance. Many influential models from these sciences assume that financial risk preferences form a stable trait. Is this assumption justified and, if not, what causes the appetite for risk to fluctuate? We have previously found that traders experience a sustained increase in the stress hormone cortisol when the amount of uncertainty, in the form of market volatility, increases. Here we ask whether these elevated cortisol levels shift risk preferences. Using a double-blind, placebo-controlled, cross-over protocol we raised cortisol levels in volunteers over 8 d to the same extent previously observed in traders. We then tested for the utility and probability weighting functions underlying their risk taking and found that participants became more risk-averse. We also observed that the weighting of probabilities became more distorted among men relative to women. These results suggest that risk preferences are highly dynamic. Specifically, the stress response calibrates risk taking to our circumstances, reducing it in times of prolonged uncertainty, such as a financial crisis. Physiology-induced shifts in risk preferences may thus be an underappreciated cause of market instability. PMID:24550472

  18. The Postprandial Rise in Plasma Cortisol in Men Is Mediated by Macronutrient-Specific Stimulation of Adrenal and Extra-Adrenal Cortisol Production

    PubMed Central

    Bolton, Jennifer L.; Andrew, Ruth; Reynolds, Rebecca M.; Walker, Brian R.

    2015-01-01

    Context Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a postprandial rise in cortisol an important feature. The diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary-adrenal axis activity; however, cortisol is produced not only by the adrenal glands but also by regeneration from cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue. Objective We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans. Design This was a randomized, single-blinded, crossover study. Setting The study was conducted at a hospital research facility. Participants Eight normal-weight healthy men participated in the study. Interventions Subjects were given isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate, protein, fat, or low-calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol. Outcome Measures and Results Plasma cortisol increased similarly after all macronutrient meals (by ~90 nmol/L) compared with placebo. Carbohydrate stimulated adrenal secretion and extra-adrenal regeneration of cortisol to a similar degree. Protein and fat meals stimulated adrenal cortisol secretion to a greater degree than extra-adrenal cortisol regeneration. The increase in cortisol production by 11β-hydroxysteroid dehydrogenase type 1 was in proportion to the increase in insulin. The postprandial cortisol rise was not accounted for by decreased cortisol clearance. Conclusions Food-induced circadian variation in plasma cortisol is mediated by adrenal secretion and extra-adrenal regeneration of cortisol. Given that the latter has the more potent effect on tissue cortisol concentrations and that effects on adrenal and extra-adrenal cortisol production are macronutrient specific, this novel mechanism may contribute to the physiological interplay between insulin and

  19. Analog of microwave-induced resistance oscillations induced in GaAs heterostructures by terahertz radiation

    NASA Astrophysics Data System (ADS)

    Herrmann, T.; Dmitriev, I. A.; Kozlov, D. A.; Schneider, M.; Jentzsch, B.; Kvon, Z. D.; Olbrich, P.; Bel'kov, V. V.; Bayer, A.; Schuh, D.; Bougeard, D.; Kuczmik, T.; Oltscher, M.; Weiss, D.; Ganichev, S. D.

    2016-08-01

    We report on the study of terahertz radiation-induced MIRO-like oscillations of magnetoresistivity in GaAs heterostructures. Our experiments provide an answer on two most intriguing questions—effect of radiation helicity and the role of the edges—yielding crucial information for an understanding of the MIRO (microwave-induced resistance oscillations) origin. Moreover, we demonstrate that the range of materials exhibiting radiation-induced magneto-oscillations can be largely extended by using high-frequency radiation.

  20. Autophagy and Apoptosis in Hepatocellular Carcinoma Induced by EF25-(GSH)2: A Novel Curcumin Analog

    PubMed Central

    Zhou, Tao; Ye, Lili; Bai, Yu; Sun, Aiming; Cox, Bryan; Liu, Dahai; Li, Yong; Liotta, Dennis; Snyder, James P.; Fu, Haian; Huang, Bei

    2014-01-01

    Curcumin, a spice component as well as a traditional Asian medicine, has been reported to inhibit proliferation of a variety of cancer cells but is limited in application due to its low potency and bioavailability. Here, we have assessed the therapeutic effects of a novel and water soluble curcumin analog, 3,5-bis(2-hydroxybenzylidene)tetrahydro-4H-pyran-4-one glutathione conjugate [EF25-(GSH)2], on hepatoma cells. Using the MTT and colony formation assays, we determined that EF25-(GSH)2 drastically inhibits the proliferation of hepatoma cell line HepG2 with minimal cytotoxicity for the immortalized human hepatic cell line HL-7702. Significantly, EF25-(GSH)2 suppressed growth of HepG2 xenografts in mice with no observed toxicity to the animals. Mechanistic investigation revealed that EF25-(GSH)2 induces autophagy by means of a biphasic mechanism. Low concentrations (<5 µmol/L) induced autophagy with reversible and moderate cytoplasmic vacuolization, while high concentrations (>10 µmol/L) triggered an arrested autophagy process with irreversible and extensive cytoplasmic vacuolization. Prolonged treatment with EF25-(GSH)2 induced cell death through both an apoptosis-dependent and a non-apoptotic mechanism. Chloroquine, a late stage inhibitor of autophagy which promoted cytoplasmic vacuolization, led to significantly enhanced apoptosis and cytotoxicity when combined with EF25-(GSH)2. Taken together, these data imply a fail-safe mechanism regulated by autophagy in the action of EF25-(GSH)2, suggesting the therapeutic potential of the novel curcumin analog against hepatocellular carcinoma (HCC), while offering a novel and effective combination strategy with chloroquine for the treatment of patients with HCC. PMID:25268357

  1. Highly potent, synthetically accessible prostratin analogs induce latent HIV expression in vitro and ex vivo

    PubMed Central

    Beans, Elizabeth J.; Fournogerakis, Dennis; Gauntlett, Carolyn; Heumann, Lars V.; Kramer, Rainer; Marsden, Matthew D.; Murray, Danielle; Zack, Jerome A.; Wender, Paul A.

    2013-01-01

    Highly active antiretroviral therapy (HAART) decreases plasma viremia below the limits of detection in the majority of HIV-infected individuals, thus serving to slow disease progression. However, HAART targets only actively replicating virus and is unable to eliminate latently infected, resting CD4+ T cells. Such infected cells are potentially capable of reinitiating virus replication upon cessation of HAART, thus leading to viral rebound. Agents that would eliminate these reservoirs, when used in combination with HAART, could thus provide a strategy for the eradication of HIV. Prostratin is a preclinical candidate that induces HIV expression from latently infected CD4+ T cells, potentially leading to their elimination through a virus-induced cytopathic effect or host anti-HIV immunity. Here, we report the synthesis of a series of designed prostratin analogs and report in vitro and ex vivo studies of their activity relevant to induction of HIV expression. Members of this series are up to 100-fold more potent than the preclinical lead (prostratin) in binding to cell-free PKC, and in inducing HIV expression in a latently infected cell line and prostratin-like modulation of cell surface receptor expression in primary cells from HIV-negative donors. Significantly, selected members were also tested for HIV induction in resting CD4+ T cells isolated from infected individuals receiving HAART and were found to exhibit potent induction activity. These more potent agents and by extension related tunable analogs now accessible through the studies described herein should facilitate research and preclinical advancement of this strategy for HIV/AIDS eradication. PMID:23812750

  2. Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout.

    PubMed

    Sandhu, Navdeep; Vijayan, Mathilakath M

    2011-05-01

    Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000nM) for 4h either in the presence or absence of ACTH (0.5IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

  3. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

    SciTech Connect

    Abel, E.L.; Boulware, S.; Fields, T.; McIvor, E.; Powell, K.L.; DiGiovanni, J.; Vasquez, K.M.; MacLeod, M.C.

    2013-02-01

    Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

  4. Effects of season, age, sex, and housing on salivary cortisol concentrations in horses.

    PubMed

    Aurich, J; Wulf, M; Ille, N; Erber, R; von Lewinski, M; Palme, R; Aurich, C

    2015-07-01

    Analysis of salivary cortisol is increasingly used to assess stress responses in horses. Because spontaneous or experimentally induced increases in cortisol concentrations are often relatively small for stress studies, proper controls are needed. This requires an understanding of the factors affecting salivary cortisol over longer times. In this study, we have analyzed salivary cortisol concentration for 6 mo in horses (n = 94) differing in age, sex, reproductive state, and housing. Salivary cortisol followed a diurnal rhythm with the highest concentrations in the morning and a decrease throughout the day (P < 0.001). This rhythm was disrupted in individual groups on individual days; however, alterations remained within the range of diurnal changes. Comparison between months showed highest cortisol concentrations in December (P < 0.001). Cortisol concentrations increased in breeding stallions during the breeding season (P < 0.001). No differences in salivary cortisol concentrations between nonpregnant mares with and without a corpus luteum existed. In stallions, mean daily salivary cortisol and plasma testosterone concentrations were weakly correlated (r = 0.251, P < 0.01). No differences in salivary cortisol between female and male young horses and no consistent differences between horses of different age existed. Group housing and individual stabling did not affect salivary cortisol. In conclusion, salivary cortisol concentrations in horses follow a diurnal rhythm and are increased in active breeding sires. Time of the day and reproductive state of the horses are thus important for experiments that include analysis of cortisol in saliva. PMID:25700267

  5. The scent of wolves: pyrazine analogs induce avoidance and vigilance behaviors in prey.

    PubMed

    Osada, Kazumi; Miyazono, Sadaharu; Kashiwayanagi, Makoto

    2015-01-01

    The common gray wolf (Canis lupus) is an apex predator located at the top of the food chain in the Northern Hemisphere. It preys on rodents, rabbits, ungulates, and many other kinds of mammal. However, the behavioral evidence for, and the chemical basis of, the fear-inducing impact of wolf urine on prey are unclear. Recently, the pyrazine analogs 2, 6-dimethylpyrazine, 2, 3, 5-trimethylpyrazine and 3-ethyl-2, 5-dimethyl pyrazine were identified as kairomones in the urine of wolves. When mice were confronted with a mixture of purified pyrazine analogs, vigilance behaviors, including freezing and excitation of neurons at the accessory olfactory bulb, were markedly increased. Additionally, the odor of the pyrazine cocktail effectively suppressed the approach of deer to a feeding area, and for those close to the feeding area elicited fear-related behaviors such as the "tail-flag," "flight," and "jump" actions. In this review, we discuss the transfer of chemical information from wolf to prey through the novel kairomones identified in wolf urine and also compare the characteristics of wolf kairomones with other predator-produced kairomones that affect rodents. PMID:26500485

  6. The scent of wolves: pyrazine analogs induce avoidance and vigilance behaviors in prey

    PubMed Central

    Osada, Kazumi; Miyazono, Sadaharu; Kashiwayanagi, Makoto

    2015-01-01

    The common gray wolf (Canis lupus) is an apex predator located at the top of the food chain in the Northern Hemisphere. It preys on rodents, rabbits, ungulates, and many other kinds of mammal. However, the behavioral evidence for, and the chemical basis of, the fear-inducing impact of wolf urine on prey are unclear. Recently, the pyrazine analogs 2, 6-dimethylpyrazine, 2, 3, 5-trimethylpyrazine and 3-ethyl-2, 5-dimethyl pyrazine were identified as kairomones in the urine of wolves. When mice were confronted with a mixture of purified pyrazine analogs, vigilance behaviors, including freezing and excitation of neurons at the accessory olfactory bulb, were markedly increased. Additionally, the odor of the pyrazine cocktail effectively suppressed the approach of deer to a feeding area, and for those close to the feeding area elicited fear-related behaviors such as the “tail-flag,” “flight,” and “jump” actions. In this review, we discuss the transfer of chemical information from wolf to prey through the novel kairomones identified in wolf urine and also compare the characteristics of wolf kairomones with other predator-produced kairomones that affect rodents. PMID:26500485

  7. Behavior of processionary males (Thaumetopoea pityocampa) induced by sex pheromone and analogs in a wind tunnel.

    PubMed

    Quero, C; Camps, F; Guerrero, A

    1995-12-01

    The behavioral response of processionary males (Thaumetopoea pityocampa) to the natural pheromone (Z)-13-hexadecen-11-ynyl acetate (1) and structurally related analogs in a wind tunnel is presented. Stereomerically pureZ-1 and a mixture with theE isomer in 80:20 ratio elicited similar attraction responses at 1 µg and higher. The activity was dose-dependent, being optimum at 1 µg with 90% and 80% of males contacting with the source in the presence of theZ-1 andZ/E-1, respectively. 11-Hexadecynyl acetate (2) functioned as a pheromone mimic, being able to induce the complete mate-finding behavioral sequence, although its activity was much lower than that of the pheromone. (Z)-13-Hexadecen-11-ynyl alcohol (3) and, particularly, (Z)-13-hexadecen-11-ynal (4) were potent inhibitors of the upwind flight response in mixtures withZ-1 in 99:1, 95:5, and 91:9 ratios. (Z)-1,1,1-Trifluoro-16-nonadecen-14-yn-2-one (5) also inhibited the response of males to pheromone, particularly in the source contact behavior. Comparison with activity displayed by analogs in field tests is also reported. PMID:24233899

  8. Aggregation-Induced-Emission-Active Macrocycle Exhibiting Analogous Triply and Singly Twisted Möbius Topologies.

    PubMed

    Wang, Erjing; He, Zikai; Zhao, Engui; Meng, Luming; Schütt, Christian; Lam, Jacky W Y; Sung, Herman H Y; Williams, Ian D; Huang, Xuhui; Herges, Rainer; Tang, Ben Zhong

    2015-08-10

    Molecules with Möbius topology have drawn increasing attention from scientists in a variety of fields, such as organic chemistry, inorganic chemistry, and material science. However, synthetic difficulties and the lack of functionality impede their fundamental understanding and practical applications. Here, we report the facile synthesis of an aggregation-induced-emission (AIE)-active macrocycle (TPE-ET) and investigate its analogous triply and singly twisted Möbius topologies. Because of the twisted and flexible nature of the tetraphenylethene units, the macrocycle adjusts its conformations so as to accommodate different guest molecules in its crystals. Moreover, theoretical studies including topological and electronic calculations reveal the energetically favorable interconversion process between triply and singly twisted topologies. PMID:26177730

  9. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes.

    PubMed

    Abdel-Malek, Zalfa A; Ruwe, Andrew; Kavanagh-Starner, Renny; Kadekaro, Ana Luisa; Swope, Viki; Haskell-Luevano, Carrie; Koikov, Leonid; Knittel, James J

    2009-10-01

    One skin cancer prevention strategy that we are developing is based on synthesizing and testing melanocortin analogs that reduce and repair DNA damage resulting from exposure to solar ultraviolet (UV) radiation, in addition to stimulating pigmentation. Previously, we reported the effects of tetrapeptide analogs of alpha-melanocortin (alpha-MSH) that were more potent and stable than the physiological alpha-MSH, and mimicked its photoprotective effects against UV-induced DNA damage in human melanocytes. Here, we report on a panel of tripeptide analogs consisting of a modified alpha-MSH core His(6)-d-Phe(7)-Arg(8), which contained different N-capping groups, C-terminal modifications, or arginine mimics. The most potent tripeptides in activating cAMP formation and tyrosinase of human melanocytes were three analogs with C-terminal modifications. The most effective C-terminal tripeptide mimicked alpha-MSH in reducing hydrogen peroxide generation and enhancing nucleotide excision repair following UV irradiation. The effects of these three analogs required functional MC1R, as they were absent in human melanocytes that expressed non-functional receptor. These results demonstrate activation of the MC1R by tripeptide melanocortin analogs. Designing small analogs for topical delivery should prove practical and efficacious for skin cancer prevention. PMID:19558415

  10. New-to-nature sophorose analog: a potent inducer for gene expression in Trichoderma reesei.

    PubMed

    Huang, Tom Tao; Wages, John M

    2016-04-01

    Controlled hydrolysis of lactonic sophorolipids from Starmerella bombicola yields a previously undescribed sophorose analog that potently induces cellulase in Trichoderma reesei Rut-C30. Acid treatment of natural sophorolipids results in a mixture of monoacetylated, deacetylated, and diacetylated sophorolipids in acidic and lactonic forms. Isolation of the active components of the mixture, followed by structure determination by MS and NMR, reveals a new chemical entity, in which the lactone ring has been opened at the C-1' rather than at the C-4″ position of the sophorose moiety. This sophorose ester is resistant to degradation by the host and is at least 28 times more powerful an inducer than sophorose in shake-flask culture. Even at low concentrations (0.05 mM), the chemically modified sophorolipid effectively induces cellulase. With further improvements, this highly enabling technology can potentially reduce the cost of enzymes produced in T. reesei and can facilitate the rapid deployment of enzyme plants to support the nascent cellulosic biofuels and biochemicals industries. PMID:26920480

  11. Testosterone Suppression of CRH-stimulated Cortisol in Men

    PubMed Central

    Rubinow, David R.; Roca, Catherine A.; Schmidt, Peter J.; Danaceau, Merry A.; Putnam, Karen; Cizza, Giovanni; Chrousos, George; Nieman, Lynnette

    2005-01-01

    Despite observations of age-dependent sexual dimorphisms in hypothalamic-pituitary-adrenal (HPA) axis activity, the role of androgens in the regulation of HPA axis activity in men has not been examined. We assessed this role by performing CRH stimulation tests in ten men (ages 18–45) during gonadal suppression with leuprolide acetate and during testosterone addition to leuprolide. CRH-stimulated cortisol levels as well as peak cortisol and greatest cortisol excursion were significantly lower (p < .05, .005, and .01, respectively) during testosterone replacement compared with the induced hypogonadal condition (leuprolide plus placebo); cortisol area under the curve was lower at a trend level (p < .1). Paradoxically, CRH-stimulated ACTH was increased significantly during testosterone replacement (p < .05). The cortisol:ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (p < .1). A mixed effects regression model showed that testosterone but not estradiol or CBG significantly contributed to the variance of cortisol. These data demonstrate that testosterone regulates CRH-stimulated HPA axis activity in men, with the divergent effects on ACTH and cortisol suggesting a peripheral (adrenal) locus for the suppressive effects on cortisol. Our results further demonstrate that the enhanced stimulated HPA axis activity previously described in young men compared with young women cannot be ascribed to an activational upregulation of the axis by testosterone. PMID:15841103

  12. Electrode-induced digital-to-analog resistive switching in TaO x -based RRAM devices

    NASA Astrophysics Data System (ADS)

    Li, Xinyi; Wu, Huaqiang; Gao, Bin; Wu, Wei; Wu, Dong; Deng, Ning; Cai, Jian; Qian, He

    2016-07-01

    In RRAM devices, electrodes play a significant role during the switching process. In this paper, different top electrodes are used for TaO y /Ta2O5‑x /AlO σ triple-oxide-layer devices. Top electrode-induced digital resistive switching to analog resistive switching was observed. For Pt top electrode (TE) devices, abrupt digital resistive switching behavior was observed, while Al TE devices showed gradual analog resistive switching behavior. Devices with various AlO σ thicknesses and sizes were fabricated and characterized to evaluate the reliability of the analog resistive switching. The physical mechanisms responsible for this electrode-induced resistive switching behavior were discussed.

  13. Electrode-induced digital-to-analog resistive switching in TaO x -based RRAM devices.

    PubMed

    Li, Xinyi; Wu, Huaqiang; Bin Gao; Wu, Wei; Wu, Dong; Deng, Ning; Cai, Jian; Qian, He

    2016-07-29

    In RRAM devices, electrodes play a significant role during the switching process. In this paper, different top electrodes are used for TaO y /Ta2O5-x /AlO σ triple-oxide-layer devices. Top electrode-induced digital resistive switching to analog resistive switching was observed. For Pt top electrode (TE) devices, abrupt digital resistive switching behavior was observed, while Al TE devices showed gradual analog resistive switching behavior. Devices with various AlO σ thicknesses and sizes were fabricated and characterized to evaluate the reliability of the analog resistive switching. The physical mechanisms responsible for this electrode-induced resistive switching behavior were discussed. PMID:27302281

  14. Selenium-Containing Analogs of SAHA Induce Cytotoxicity in Lung Cancer Cells

    PubMed Central

    Karelia, Nilkamal; Desai, Dhimant; Hengst, Jeremy A.; Amin, Shantu; Rudrabhatla, Sairam V.; Yun, Jong

    2010-01-01

    Cancer therapy has moved beyond conventional chemotherapeutics to more mechanism-based targeted approaches. Studies demonstrate that histone deacetylase (HDAC) is a promising target for anticancer agents. Numerous, structurally diverse, hydroxamic acid derivative, HDAC inhibitors have been reported and have been shown to induce growth arrest, differentiation, autophagy and/or apoptotic cell death by inhibiting multiple signaling pathways in cancer cells. Suberoylanilide hydroxamic acid (SAHA) has emerged as an effective anticancer therapeutic agent and was recently approved by the FDA for the treatment of advanced cutaneous T- cell lymphoma. In our previous study, we reported the development of the novel, potent, selenium containing HDAC inhibitors (SelSA-1 and SelSA-2). In this study, the effects of SelSA-1 and SelSA-2 on signaling pathways and cytotoxicity were compared with the known HDAC inhibitor, SAHA, in lung cancer cell lines. After 24 hours of treatment, SelSA-1 and SelSA-2 inhibited lung cancer cell growth to a greater extent than SAHA in a dose-dependent manner with IC50 values at low micromolar concentrations. SelSA-1 and SelSA-2 inhibited ERK and PI3K-AKT signaling pathways while simultaneously increasing in autophagy in A549 cells in a time dependent manner. This preliminary study demonstrates the effectiveness of the selenium-containing analogs of SAHA, SelSA-1 and SelSA-2, as HDAC inhibitors and provides insight into the improvement and/or development of these analogs as a therapeutic approach for the treatment of lung cancer. PMID:20855208

  15. Selenium-containing analogs of SAHA induce cytotoxicity in lung cancer cells.

    PubMed

    Karelia, Nilkamal; Desai, Dhimant; Hengst, Jeremy A; Amin, Shantu; Rudrabhatla, Sairam V; Yun, Jong

    2010-11-15

    Cancer therapy has moved beyond conventional chemotherapeutics to more mechanism-based targeted approaches. Studies demonstrate that histone deacetylase (HDAC) is a promising target for anticancer agents. Numerous, structurally diverse, hydroxamic acid derivative, HDAC inhibitors have been reported and have been shown to induce growth arrest, differentiation, autophagy, and/or apoptotic cell death by inhibiting multiple signaling pathways in cancer cells. Suberoylanilide hydroxamic acid (SAHA) has emerged as an effective anticancer therapeutic agent and was recently approved by the FDA for the treatment of advanced cutaneous T-cell lymphoma. In our previous study, we reported the development of the novel, potent, selenium-containing HDAC inhibitors (SelSA-1 and SelSA-2). In this study, the effects of SelSA-1 and SelSA-2 on signaling pathways and cytotoxicity were compared with the known HDAC inhibitor, SAHA, in lung cancer cell lines. After 24 h of treatment, SelSA-1 and SelSA-2 inhibited lung cancer cell growth to a greater extent than SAHA in a dose-dependent manner with IC(50) values at low micromolar concentrations. SelSA-1 and SelSA-2 inhibited ERK and PI3K-AKT signaling pathways while simultaneously increasing in autophagy in A549 cells in a time dependent manner. This preliminary study demonstrates the effectiveness of the selenium-containing analogs of SAHA, SelSA-1, and SelSA-2, as HDAC inhibitors and provides insight into the improvement and/or development of these analogs as a therapeutic approach for the treatment of lung cancer. PMID:20855208

  16. Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.

    PubMed

    Jang, S; Yu, X-M; Odorico, S; Clark, M; Jaskula-Sztul, R; Schienebeck, C M; Kupcho, K R; Harrison, A D; Winston-McPherson, G N; Tang, W; Chen, H

    2015-08-01

    To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy. PMID:26251030

  17. Altered stress-induced cortisol levels in goats exposed to polychlorinated biphenyls (PCB 126 and PCB 153) during fetal and postnatal development.

    PubMed

    Zimmer, Karin E; Gutleb, Arno C; Lyche, Jan L; Dahl, Ellen; Oskam, Irma C; Krogenaes, Anette; Skaare, Janneche Utne; Ropstad, Erik

    2009-01-01

    Short-term stress exposure is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis and a consequent rise in blood glucocorticoids and catecholamines, from the adrenal cortex and medulla, respectively. The HPA axis is a potential target for some persistent organic pollutants, among which polychlorinated biphenyls (PCB) were found to be modulators of the mammalian endocrine system. PCB are distributed globally in the environment, in food chains, and are transferred to the fetuses of pregnant animals and via mother's milk to suckling offspring. In the present study it was postulated that intrauterine and lactational exposure to either of two single congeners of PCB (PCB 153 and PCB 126, respectively) might affect basal cortisol concentrations, and also the cortisol response to short-term stress in adulthood. Thus, pregnant goats were orally exposed to one of these PCB congeners from d 60 of gestation until delivery, and their offspring studied. Low-dose exposure to PCB 153 and PCB 126 resulted in significantly lower mean basal cortisol concentrations in goat offspring during certain periods of pubertal development and their first breeding season. Male goat kids exposed to either PCB congener showed a greater and more prolonged rise in plasma cortisol levels than controls when animals were subjected to mild stress at 9 mo of age using frequent blood sampling. Neither the basal maternal cortisol plasma level nor goat kid adrenal masses were affected by PCB exposure. PMID:19184731

  18. Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

    SciTech Connect

    Wang, Tingting; Chen, Man; Liu, Lian; Cheng, Huaiyan; Yan, You-E; Feng, Ying-Hong; Wang, Hui

    2011-12-15

    Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt -377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. -- Highlights: Black-Right-Pointing-Pointer Nicotine-induced StAR inhibition in two human adrenal cell models. Black-Right-Pointing-Pointer Nicotine-induced single CpG site methylation in StAR promoter. Black-Right-Pointing-Pointer Persistent StAR inhibition and single CpG methylation after nicotine termination

  19. Rayleigh-Scattering-Induced Noise in Analog RF-Photonic Links

    NASA Astrophysics Data System (ADS)

    Cahill, James P.

    Analog RF-photonic links hold the potential to increase the precision of time and frequency synchronization in commercial applications by orders of magnitude. However, current RF-photonic links that are used for synchronization must suppress optical-fiber-induced noise by using bi-directional active feedback schemes, in which light must travel through the optical fiber in both directions. These schemes are incompatible with most existing fiber-optic networks. Unless this noise can be suppressed using different methods, RF-photonic time and frequency synchronization will remain accessible only to the research community. As a first step towards identifying alternate means of suppressing the optical-fiber-induced noise, this dissertation presents an extensive experimental characterization and limited theoretical discussion of the dominant optical-intensity and RF-phase noise source in a laboratory setting, where environmental fluctuations are small. The experimental results indicate that the optical-fiber-induced RF-phase noise and optical-intensity noise are caused by the same physical mechanism. The experimental results demonstrate that this mechanism is related to the laser-phase noise but not the laser intensity noise. The bandwidth of the optical-fiber-induced noise depends on the optical-fiber length for lasers with low phase noise, while for lasers with high phase noise, the bandwidth is constant. I demonstrate that the optical-intensity and RF-phase noise can be mitigated by dithering the laser frequency. Based on these results, I hypothesize that interference from Rayleigh scattering is the underlying mechanism of the optical-intensity and RF-phase noise. Prior theoretical work, carried out with high phase noise lasers, predicts that the noise induced by this process will have a bandwidth that is proportional to the laser linewidth and that is constant with respect to the optical-fiber length, for lasers with high-phase noise, which is consistent with the

  20. Analogy of transistor function with modulating photonic band gap in electromagnetically induced grating

    PubMed Central

    Wang, Zhiguo; Ullah, Zakir; Gao, Mengqin; Zhang, Dan; Zhang, Yiqi; Gao, Hong; Zhang, Yanpeng

    2015-01-01

    Optical transistor is a device used to amplify and switch optical signals. Many researchers focus on replacing current computer components with optical equivalents, resulting in an optical digital computer system processing binary data. Electronic transistor is the fundamental building block of modern electronic devices. To replace electronic components with optical ones, an equivalent optical transistor is required. Here we compare the behavior of an optical transistor with the reflection from a photonic band gap structure in an electromagnetically induced transparency medium. A control signal is used to modulate the photonic band gap structure. Power variation of the control signal is used to provide an analogy between the reflection behavior caused by modulating the photonic band gap structure and the shifting of Q-point (Operation point) as well as amplification function of optical transistor. By means of the control signal, the switching function of optical transistor has also been realized. Such experimental schemes could have potential applications in making optical diode and optical transistor used in quantum information processing. PMID:26349444

  1. Analogy of transistor function with modulating photonic band gap in electromagnetically induced grating

    NASA Astrophysics Data System (ADS)

    Wang, Zhiguo; Ullah, Zakir; Gao, Mengqin; Zhang, Dan; Zhang, Yiqi; Gao, Hong; Zhang, Yanpeng

    2015-09-01

    Optical transistor is a device used to amplify and switch optical signals. Many researchers focus on replacing current computer components with optical equivalents, resulting in an optical digital computer system processing binary data. Electronic transistor is the fundamental building block of modern electronic devices. To replace electronic components with optical ones, an equivalent optical transistor is required. Here we compare the behavior of an optical transistor with the reflection from a photonic band gap structure in an electromagnetically induced transparency medium. A control signal is used to modulate the photonic band gap structure. Power variation of the control signal is used to provide an analogy between the reflection behavior caused by modulating the photonic band gap structure and the shifting of Q-point (Operation point) as well as amplification function of optical transistor. By means of the control signal, the switching function of optical transistor has also been realized. Such experimental schemes could have potential applications in making optical diode and optical transistor used in quantum information processing.

  2. Theoretical understanding of two-photon-induced fluorescence of isomorphic nucleoside analogs.

    PubMed

    Samanta, Pralok K; Pati, Swapan K

    2015-04-21

    We use ab initio Density Functional Theory (DFT) and Time-dependent DFT (TDDFT) calculations for a detailed understanding of one-photon absorption (1PA) and two-photon absorption (2PA) cross sections of eight different nucleoside analogs. The results are compared and contrasted with the available experimental data. Our calculated results show that the low energy peaks in the absorption spectra mainly arise because of the π-π* electronic transition of the nucleoside analogs. The emission spectra of the nucleoside analogs are also calculated using TDDFT methods. The calculated absorption and emission spectra in the presence of a solvent follow the same trend as those found experimentally. Our results demonstrate that the nucleoside analogs show significantly different electronic and optical properties, although their bonding aspects towards Watson-Crick base pairing remain the same. We also derive the microscopic details of the origin of nonlinear optical properties of the nucleoside analogs. PMID:25785569

  3. The influence of temperament on endotoxin-induced changes in body temperature, sickness behavior, and secretion of cortisol and epinephrine in bulls

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine the influence of temperament on body temperature, sickness behavior, and the secretion of cortisol and epinephrine in response to an endotoxin challenge. Purebred Brahman bulls were selected based on temperament score measured at weaning [n=8 each Calm (C), Inter...

  4. Yawning, fatigue, and cortisol: expanding the Thompson Cortisol Hypothesis.

    PubMed

    Thompson, Simon B N

    2014-10-01

    Yawning and its involvement in neurological disorders has become the new scientific conundrum. Cortisol levels are known to rise during stress and fatigue; yawning may occur when we are under stress or tired. However, the link between yawning, fatigue, and cortisol has not been fully understood. Expansion of the Thompson Cortisol Hypothesis proposes that the stress hormone, cortisol, is responsible for yawning and fatigue especially in people with incomplete innervation such as multiple sclerosis. This informs our understanding of the functional importance of the brain stem region of the brain in regulating stress and fatigue. PMID:25169036

  5. Syrbactin Structural Analog TIR-199 Blocks Proteasome Activity and Induces Tumor Cell Death.

    PubMed

    Bachmann, André S; Opoku-Ansah, John; Ibarra-Rivera, Tannya R; Yco, Lisette P; Ambadi, Sudhakar; Roberts, Christopher C; Chang, Chia-En A; Pirrung, Michael C

    2016-04-15

    Multiple myeloma is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade®), carfilzomib (Kyprolis®), and ixazomib (Ninlaro®), confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory multiple myeloma and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog. Molecular modeling and simulation suggested that TIR-199 covalently binds each of the three catalytic subunits (β1, β2, and β5) and revealed key interaction sites. In vitro and cell culture-based proteasome activity measurements confirmed that TIR-199 inhibits the proteasome in a dose-dependent manner and induces tumor cell death in multiple myeloma and neuroblastoma cells as well as other cancer types in the NCI-60 cell panel. It is particularly effective against kidney tumor cell lines, with >250-fold higher anti-tumor activities than observed with the natural product syringolin A. In vivo studies in mice revealed a maximum tolerated dose of TIR-199 at 25 mg/kg. The anti-tumor activity of TIR-199 was confirmed in hollow fiber assays in mice. Adverse drug reaction screens in a kidney panel revealed no off-targets of concern. This is the first study to examine the efficacy of a syrbactin in animals. Taken together, the results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer. PMID:26907687

  6. Triptycene analogs

    NASA Technical Reports Server (NTRS)

    Hua, Duy (Inventor); Perchellet, Jean-Pierre (Inventor)

    2004-01-01

    This invention provides analogs of triptycene which are useful as anticancer drugs, as well as for other uses. The potency of these compounds is in a similar magnitude as daunomycin, a currently used anticancer drug. Each compound of the invention produces one or more desired effects (blocking nucleoside transport, inhibiting nucleic acid or protein syntheses, decreasing the proliferation and viability of cancer cells, inducing DNA fragmentation or retaining their effectiveness against multidrug-resistant tumor cells).

  7. Shiftwork Duration and the Awakening Cortisol Response Among Police Officers

    PubMed Central

    Wirth, Michael; Burch, James; Violanti, John; Burchfiel, Cecil; Fekedulegn, Desta; Andrew, Michael; Zhang, Hongmei; Miller, Diane B.; Hébert, James R.; Vena, John E.

    2013-01-01

    Police officers are required to work irregular hours, which induces stress, fatigue, and sleep disruption, and they have higher rates of chronic disease and mortality. Cortisol is a well-known “stress hormone” produced via activation of the hypothalamic-pituitary-adrenal axis. An abnormal secretion pattern has been associated with immune system dysregulation and may serve as an early indicator of disease risk. This study examined the effects of long- and short-term shiftwork on the cortisol awakening response among officers (n = 68) in the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study (2001–2003). The time each officer spent on day (start time: 04:00–11:59 h), afternoon (12:00–19:59 h), or night (20:00–03:59 h) shifts was summarized from 1994 to examination date to characterize long-term (mean: 14 ± 9 yrs) and short-term (3, 5, 7, or 14 days prior to participation) shiftwork exposures. The cortisol awakening response was characterized by summarizing the area under the curve (AUC) for samples collected on first awakening, and at 15-, 30-, and 45-min intervals after waking. Data were collected on a scheduled training or off day. The cortisol AUC with respect to ground (AUCG) summarized total cortisol output after waking, and the cortisol AUC with respect to increase (AUCI) characterized the waking cortisol response. Officers also completed the Center for Epidemiologic Studies Depression scale. Waking cortisol AUC values were lower among officers working short-term night or afternoon shifts than day shifts, with maximal differences occurring after 5 days of shiftwork. The duration of long-term shiftwork was not associated with the cortisol awakening response, although values were attenuated among officers with more career shift changes. PMID:21721860

  8. Lipid droplet binding thalidomide analogs activate endoplasmic reticulum stress and suppress hepatocellular carcinoma in a chemically induced transgenic mouse model

    PubMed Central

    2013-01-01

    Background Hepatocellular carcinoma (HCC) is the most frequent and aggressive primary tumor of the liver and it has limited treatment options. Results In this study, we report the in vitro and in vivo effects of two novel amino-trifluoro-phtalimide analogs, Ac-915 and Ac-2010. Both compounds bind lipid droplets and endoplasmic reticulum membrane, and interact with several proteins with chaperone functions (HSP60, HSP70, HSP90, and protein disulfide isomerase) as determined by affinity chromatography and resonant waveguide optical biosensor technology. Both compounds inhibited protein disulfide isomerase activity and induced cell death of different HCC cells at sub or low micromolar ranges detected by classical biochemical end-point assay as well as with real-time label-free measurements. Besides cell proliferation inhibiton, analogs also inhibited cell migration even at 250 nM. Relative biodistribution of the analogs was analysed in native tissue sections of different organs after administration of drugs, and by using fluorescent confocal microscopy based on the inherent blue fluorescence of the compounds. The analogs mainly accumulated in the liver. The effects of Ac-915 and Ac-2010 were also demonstrated on the advanced stages of hepatocarcinogenesis in a transgenic mouse model of N-nitrosodiethylamine (DEN)-induced HCC. Significantly less tumor development was found in the livers of the Ac-915- or Ac-2010-treated groups compared with control mice, characterized by less liver tumor incidence, fewer tumors and smaller tumor size. Conclusion These results imply that these amino-trifluoro-phthalimide analogs could serve potent clinical candidates against HCC alone or in combination with dietary polyunsaturated fatty acids. PMID:24268070

  9. Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone

    SciTech Connect

    Paz-Bouza, J.I.; Redding, T.W.; Schally, A.V.

    1987-02-01

    Pancreatic ductal adenocarcinoma was induced in female Syrian golden hamsters by injecting N-nitrosobis(2-oxopropyl)amine (BOP) once a week at a dose of 10 mg per kg of body weight for 18 weeks. Hamsters were then treated with somatostatin analog (RC-160) or with (6-D-tryptophan)luteinizing hormone-releasing hormone ((D-Trp/sup 6/)LH-RH) delayed delivery systems. After 18 weeks of BOP administration, the hamsters were divided into three groups of 10-20 animals each. Group I consisted of untreated controls, group II was injected with RC-160, and group III was injected with (D-Trp/sub 2/)LH-RH. A striking decrease in tumor weight and volume was obtained in animals treated with (D-Trp/sup 6/)LH-RH or with the somatostatin analog RC-160. After 45 days of treatment with either analog, the survival rate was significantly higher in groups II and III (70%), as compared with the control group (35%). The studies, done by light microscopy, high-resolution microscopy, and electron microscopy, showed a decrease in the total number of cancer cells and changes in the epithelium, connective tissue, and cellular organelles in groups II and III treated with the hypothalamic analogs as compared to controls. These results in female hamsters with induced ductal pancreatic tumors confirm and extend the authors findings, obtained in male animals with transplanted tumors, that (D-Trp/sub 6/)LH-RH and somatostatin analogs inhibit the growth of pancreatic cancers.

  10. Performance on the Iowa Gambling Task is related to magnitude of weight loss and salivary cortisol in a diet-induced weight loss intervention in overweight women.

    PubMed

    Witbracht, Megan G; Laugero, Kevin D; Van Loan, Marta D; Adams, Sean H; Keim, Nancy L

    2012-05-15

    The overall objective of this study was to examine the relationship between executive function, specifically decision-making, and weight loss. We used the Iowa Gambling Task (IGT) to characterize decision-making and compared performance on this task to weight loss in obese women (n=29) participating in a 12-week controlled, calorie-reduced intervention. We hypothesized that a greater amount of weight loss over the course of the intervention would be associated with better performance on the IGT, assessed at the end of the intervention. The intervention led to significant weight loss of 5.8±3.1 kg (p<0.05) and fat loss of 5.1±3.0 kg (p<0.05). Body weight and fat mass losses over the 12-week intervention varied widely, ranging from -12.5 kg to 0.0 kg for body weight and -10.4 kg to +0.8 kg for fat mass. A greater amount of body weight loss was correlated (r=0.425; p<0.01) with a higher total score on the IGT. Similarly, the reduction in body fat mass was also correlated with the IGT score (r=0.408; p<0.05). We examined other physiological (salivary cortisol), metabolic (resting energy expenditure), and behavioral (food intake; dietary restraint) factors that might be related to differences in the magnitude of weight loss. Of these variables, ad libitum consumption of energy, fat and protein during a buffet meal was inversely related to weight loss (r=-0.428; p<0.05; r=-0.375; p<0.05 and r=-0.472; p=0.01, respectively). The present study is the first to report an association between diet-induced weight loss and performance on the IGT, and this association was specific to the loss of body fat. Our results suggest that differences in weight loss may be linked to executive function that involves decision-making about events that have emotionally or socially salient ramifications. These findings underscore the need to further investigate higher cognitive and neuroendocrine pathways that may influence or be altered by the process of dieting and weight loss. PMID:21565212

  11. Degradation and aggregation of delta sleep-inducing peptide (DSIP) and two analogs in plasma and serum

    SciTech Connect

    Graf, M.V.; Saegesser, B.; Schoenenberger, G.A.

    1987-07-01

    The biostability of DSIP (delta sleep-inducing peptide) and two analogs in blood was investigated in order to determine if rates of inactivation contribute to variable effects in vivo. Incubation of DSIP in human or rat blood led to release of products having retention times on a gel filtration column equivalent to Trp. Formation of products was dependent on temperature, time, and species. Incubation of /sup 125/I-N-Tyr-DSIP and /sup 125/I-N-Tyr-P-DSIP, a phosphorylated analog, revealed slower degradation and, in contrast to DSIP, produced complex formation. An excess of unlabeled material did not displace the radioactivity supporting the assumption of non-specific binding/aggregation. It was concluded that the rapid disappearance of injected DSIP in blood was due to degradation, whereas complex formation together with slower degradation resulted in longer persistence of apparently intact analogs. Whether this could explain the sometimes stronger and more consistent effects of DSIP-analogs remains to be examined.

  12. Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis[OPEN

    PubMed Central

    Liu, Chun-Hsin; Finke, Andreas; Díaz, Mariana; Rozhon, Wilfried; Poppenberger, Brigitte; Baubec, Tuncay; Pecinka, Ales

    2015-01-01

    DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway. PMID:26023162

  13. Data and results of a laboratory investigation of microprocessor upset caused by simulated lightning-induced analog transients

    NASA Technical Reports Server (NTRS)

    Belcastro, C. M.

    1984-01-01

    A methodology was developed a assess the upset susceptibility/reliability of a computer system onboard an aircraft flying through a lightning environment. Upset error modes in a general purpose microprocessor were studied. The upset tests involved the random input of analog transients which model lightning induced signals onto interface lines of an 8080 based microcomputer from which upset error data was recorded. The program code on the microprocessor during tests is designed to exercise all of the machine cycles and memory addressing techniques implemented in the 8080 central processing unit. A statistical analysis is presented in which possible correlations are established between the probability of upset occurrence and transient signal inputs during specific processing states and operations. A stochastic upset susceptibility model for the 8080 microprocessor is presented. The susceptibility of this microprocessor to upset, once analog transients have entered the system, is determined analytically by calculating the state probabilities of the stochastic model.

  14. The receptor binding affinity of monocyclic [Ala3,Xaa11]endothelin-1 analogs correlates with inducible helix length.

    PubMed

    Andersen, N H; Harris, S M; Lee, V G; Liu, E C; Moreland, S; Hunt, J T

    1995-02-01

    Endothelin-1, a bicyclic 21-amino acid peptide with disulfide bridges between cysteines 1 and 15 as well as between cysteines 3 and 11, has been reported to be partially helical based on both CD and NMR data. However, this remains an area of controversy with some claims that CD data indicate no alpha-helical structure (Calas, B.; Harricane, M.-C.; Gulmard, L.; Heitz, F.; Mendre, C.; Chabrier, P.E.; Bennes, R. Peptide Res. 1992, 5, 97) and a recent X-ray crystal structure placing the helix at a different locus (Janes, R.W.; Peapus, D.H.; Wallace, B.A. Structural Biology 1994, 1, 311). The CD studies reported herein indicate that the helical structures reported in NMR studies (e.g. Andersen, N.H.; Chen, C.; Marschner, T.M.; Krystek, Jr. S.R.; Bassolino, D.A. Biochemistry 1992, 31, 1280) apply to pure aqueous media as well. The helix located from Lys9 to the Cys15/His16 juncture is ca 75% populated in pH 4 aqueous buffer. Titration difference CDs reveal that the helix extent increases by one to two residues and that the 'helical conformation' is more completely populated upon addition of TFE to 50+ volume-%. Comparison with a more helical analog suggests that the helix propagates towards (but not to the end of) the C-terminus upon fluoroalcohol addition. A variety of monocyclic derivatives of [Nle7] ET-1 lacking the 3,11-disulfide were evaluated for biological activity and examined by TFE titration difference CD. The series included an Aib11 and a Pro11 analog. The helix promoting Aib analog was the most active while the Pro analog exhibited significantly lower vasoconstrictor activity and binding affinity for the ETA receptor. All of the monocyclic analogs became significantly more helical upon addition of fluoroalcohols. The inclusion of a proline residue at position 11 does not preclude helix formation upon addition of fluoroalcohols. Rather, helix formation is relatively easily induced but limited to a 5 residue span. Apparently this is insufficient to orient

  15. Parotid fluid cortisol and cortisone

    PubMed Central

    Katz, Fred H.; Shannon, Ira L.

    1969-01-01

    Parotid fluid corticosteroids, substantially comprised of cortisol and cortisone, were previously demonstrated to rise to far greater levels 4 hr after administration of ACTH than they did in the third trimester of pregnancy, although the plasma total corticosteroid concentrations were similar in these two states. It was therefore suggested that only nonproteinbound corticosteroid gains access to parotid fluid. In the present study parotid fluid cortisol and cortisone and plasma dialyzable cortisol concentrations have been measured in normal men before and 2 hr after 40 U ACTH, and, in another group, before and after 10 days of diethystilbestrol (5 mg daily). Total plasma cortisol rose from a mean of 6.3 to 17.9 μg/100 ml after ACTH and from 14.6 to 39.4 mg/100 ml after the estrogen. However parotid fluid cortisol plus cortisone rose from 0.8 to 2.6 μg/100 ml after ACTH and to only 2.2 after estrogen. This rise resembled that of the plasma dialyzable cortisol (control 0.4, ACTH 1.8, estrogen 1.2 μg/100 ml) rather than the increase in total plasma cortisol which was over twice as high after estrogen as after ACTH. Thus parotid fluid corticosteroids seem to be a good measure of nonprotein-bound corticosteroid, the cortisol available to the cell. The total amount of cortisol plus cortisone excreted is approximately constant, independent of parotid fluid flow rate. Cortisone exceeds cortisol in parotid fluid in the basal state, but after ACTH the situation is reversed. PMID:4305375

  16. Liquid methionine hydroxy analog (free acid) and DL-methionine attenuate calcium-induced kidney damage in domestic fowl.

    PubMed

    Wideman, R F; Ford, B C; Leach, R M; Wise, D F; Robey, W W

    1993-07-01

    To evaluate the possibility that kidney damage may be induced by the commercial practice of feeding high-Ca (HCa) prelayer rations, and to evaluate the protective efficacy of supplementing HCa diets with liquid methionine hydroxy analog free acid or DL-methionine, 12-wk-old female Single Comb White Leghorn pullets were fed one of the following corn-soybean meal-based diets until they reached 22 wk of age: normal-Ca (NC, 1% Ca); HCa (HC, 3.5% Ca); HCa supplemented with .34 or .68% liquid methionine hydroxy analog free acid (HC3A or HC6A); or HCa supplemented with .3 or .6% DL-methionine (HC3DL or HC6DL). The unsupplemented HC diet caused a significant reduction in kidney mass and a significant increase in the incidence of gross kidney damage and urolithiasis in pullets necropsied at 22 wk of age. Calcium-induced kidney damage was attenuated in a dose-response fashion by supplementing the HC diet with liquid methionine hydroxy analog and DL-methionine. None of the diets caused a significant metabolic acidosis. Plasma uric acid concentrations were not predictive of the extent of Ca-induced kidney damage. Analyses of glomerular size distributions indicated that subclinical or "hidden" kidney damage may not progressively develop into urolithiasis as hens mature. When compared with hens reared on the NC diet, rearing hens on the HC, HC3A, HC3DL, HC6A, or HC6DL diets did not consistently affect hen-day egg production, egg mass, eggshell mass, percentage eggshell, or bone mineralization. PMID:8346150

  17. New bichalcone analogs as NF-κB inhibitors and as cytotoxic agents inducing Fas/CD95-dependent apoptosis

    PubMed Central

    Vijaya Bhaskar Reddy, M.; Shen, Yuh-Chiang; Hwang, Tsong-Long; Bastow, Kenneth F.; Qian, Keduo; Lee, Kuo-Hsiung; Wu, Tian-Shung

    2011-01-01

    A series of novel bichalcone analogs were synthesized and evaluated in lipopolysaccharide (LPS)-activated microglial cells as inhibitors of nitric oxide (NO) and for in vitro anticancer activity using a limited panel of four human cancer cell lines. All analogs inhibited NO production. Compounds 4 and 11 exhibited optimal activity with IC50 values of 0.3 and 0.5 µM, respectively, and were at least 38-fold better than the positive control. A mechanism of action study showed that both compounds significantly blocked the nuclear translocation of NF-κB p65 and up-regulation of iNOS at 1.0 µM. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI50 values ranging from 0.70~13.10 µM. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling. PMID:21377368

  18. Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

    PubMed

    Kuehl, Linn K; Hinkelmann, Kim; Muhtz, Christoph; Dettenborn, Lucia; Wingenfeld, Katja; Spitzer, Carsten; Kirschbaum, Clemens; Wiedemann, Klaus; Otte, Christian

    2015-01-01

    Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, p<.01). In contrast, mean CAR values correlated negatively with diastolic (r=-.29, p=.03) and systolic blood pressure (r=-.32, p=.02). Our results indicate that higher hair cortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile. PMID:25462908

  19. Saliva collection by using filter paper for measuring cortisol levels in dogs.

    PubMed

    Oyama, D; Hyodo, M; Doi, H; Kurachi, T; Takata, M; Koyama, S; Satoh, T; Watanabe, G

    2014-01-01

    Four experiments were conducted to evaluate the accuracy and reliability of noninvasive evaluation of cortisol in saliva of dogs. In experiment 1, we measured the cortisol concentration in the filter paper on which 250-μL cortisol solutions had been quantitatively pipetted and in filter papers dipped in cortisol solution. In experiment 2, we collected the blood and saliva of dogs 3 times at 30-min intervals and compared the cortisol concentrations to examine whether the dynamics of cortisol in the blood and saliva are similar. The results of experiments 1 and 2 showed that the cortisol concentration can be quantitatively measured with this method and that the dynamics of cortisol concentration in the plasma and saliva collected by using filter paper are not different (P = 0.14 for experiment 1 and P = 0.51 for experiment 2). In experiment 3, to investigate the factors related to inducing stress in dogs by using the filter-paper method of collecting saliva, we compared the cortisol concentrations at 0 and 30 min after collecting the saliva of pet dogs. The dog owners completed a survey on their dogs, providing basic information and reporting the collection of their dog's saliva. We found that the cortisol concentrations increased significantly in dogs whose owners spent >2 min collecting saliva (P = 0.005), suggesting that prompt collection of saliva is necessary for accurate assessment of cortisol without induction of a stress response. In addition, the cortisol concentrations increased significantly in dogs whose teeth were not regularly brushed (P = 0.04), suggesting that regular teeth brushing mitigates the effect of the collection process on cortisol concentrations in the saliva, with minimal stress to the dogs. In experiment 4, we measured cortisol concentrations in pet dogs accustomed to having their teeth brushed by their owners, before and after interaction with their owners, to assess whether brushing induces stress in dogs. We detected that the

  20. Impaired Memory Retrieval Correlates with Individual Differences in Cortisol Response but Not Autonomic Response

    ERIC Educational Resources Information Center

    Tranel, Daniel; Adolphs, Ralph; Buchanan, Tony W.

    2006-01-01

    Stress can enhance or impair memory performance. Both cortisol release and sympathetic nervous system responses have been implicated in these differential effects. Here we investigated how memory retrieval might be affected by stress-induced cortisol release, independently of sympathetic nervous system stress responses. Thirty-two healthy…

  1. Evaluation of the circadian profiles of serum dehydroepiandrosterone (DHEA), cortisol, and cortisol/DHEA molar ratio after a single oral administration of DHEA in elderly subjects.

    PubMed

    Ceresini, G; Morganti, S; Rebecchi, I; Freddi, M; Ceda, G P; Banchini, A; Solerte, S B; Ferrari, E; Ablondi, F; Valenti, G

    2000-04-01

    Aging is associated with a selective decline in circulating levels of dehydroepiandrosterone (DHEA) and its sulfate, with no major changes in cortisol secretion. In young subjects, serum levels of both DHEA and cortisol are regulated according to a circadian rhythm, and an age-related attenuation of DHEA, but not cortisol, circadian rhythmicity has been reported. Several trials have evaluated the effects of DHEA supplementation in elderly subjects, although the results are still controversial. However, no data are available on the 24-hour profile of DHEA circulating levels in elderly subjects with DHEA administration. In the present study, we evaluated the circadian rhythms of DHEA, cortisol, and the cortisol/DHEA molar ratio in old subjects treated with either placebo (old-PL) or a single 50-mg dose of DHEA (old-D), both administered orally at 0700 hours. For each variable, the circadian profiles were compared with those obtained in young control subjects. The group of young subjects displayed a circadian rhythm for both DHEA and cortisol serum concentrations but no rhythm for the cortisol/DHEA molar ratio. In the old-PL group, the circadian rhythm of DHEA was completely abolished, whereas significant rhythms for both cortisol and the cortisol/DHEA molar ratio were observed. Particularly, at each time point, the cortisol/DHEA molar ratio was significantly higher in these subjects versus the young group. In the old-D group, the circadian rhythm of DHEA was completely restored and was comparable to that observed in the young group. Analogous to the observations in young subjects, the profile of the cortisol/DHEA molar ratio in old-D subjects did not display any circadian rhythmicity, the values being almost completely comparable to those observed in young controls. Our data demonstrate that the circadian rhythm of DHEA is totally abolished in elderly subjects. A single 50-mg dose of DHEA administered orally at 0700 hours restores the circadian rhythmicity of serum

  2. Protective Effects of Vitamin E Analogs against Carbon Tetrachloride-Induced Fatty Liver in Rats

    PubMed Central

    Yachi, Rieko; Igarashi, Osamu; Kiyose, Chikako

    2010-01-01

    Recently, it has been reported that α-tocopherol (α-Toc) is effective for amelioration of liver damage. However, it is unknown whether other vitamin E analogs are effective. In this study, we investigated the effects of γ-tocopherol (γ-Toc) and tocotrienols (T3) in rats with fatty liver. Rats fed a vitamin E-deficient diet for four weeks were divided into eight groups: Control, carbon tetrachloride (CCl4), α-Toc, α-Toc + CCl4, γ-Toc, γ-Toc + CCl4, T3 mix, T3 mix + CCl4. After a 24 h fast, the rats were administered 20 mg of each of the vitamin E analogs, respectively. Moreover, the CCl4 group were given 0.5 ml/kg body weight corn oil preparation containing CCl4 6 h after vitamin E administration. We measured the activities of aspartate aminotransferase and alanine aminotransferase (ALT) in plasma, and the contents of triglyceride (TG), total cholesterol (T-Chol) and vitamin E analogs in the liver. Also, we determined the hepatic expression of mRNA for inflammatory cytokines. The liver TG content in the γ-Toc + CCl4 and T3 mix + CCl4 groups was decreased in comparison with the CCl4 group. Moreover, ALT activity in the T3 mix + CCl4 group was significantly lower than CCl4 group. These findings suggest that γ-Toc and T3 are effective for amelioration of fatty liver. PMID:20838570

  3. Lunar Analog

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2009-01-01

    In this viewgraph presentation, a ground-based lunar analog is developed for the return of manned space flight to the Moon. The contents include: 1) Digital Astronaut; 2) Bed Design; 3) Lunar Analog Feasibility Study; 4) Preliminary Data; 5) Pre-pilot Study; 6) Selection of Stockings; 7) Lunar Analog Pilot Study; 8) Bed Design for Lunar Analog Pilot.

  4. The association between cortisol and the BOLD response in male adolescents undergoing fMRI.

    PubMed

    Keulers, Esther H H; Stiers, Peter; Nicolson, Nancy A; Jolles, Jelle

    2015-02-19

    MRI participation has been shown to induce subjective and neuroendocrine stress reactions. A recent aging study showed that cortisol levels during fMRI have an age-dependent effect on cognitive performance and brain functioning. The present study examined whether this age-specific influence of cortisol on behavioral and brain activation levels also applies to adolescence. Salivary cortisol as well as subjective experienced anxiety were assessed during the practice session, at home, and before, during and after the fMRI session in young versus old male adolescents. Cortisol levels were enhanced pre-imaging relative to during and post-imaging in both age groups, suggesting anticipatory stress and anxiety. Overall, a negative correlation was found between cortisol output during the fMRI experiment and brain activation magnitude during performance of a gambling task. In young but not in old adolescents, higher cortisol output was related to stronger deactivation of clusters in the anterior and posterior cingulate cortex. In old but not in young adolescents, a negative correlation was found between cortisol and activation in the inferior parietal and in the superior frontal cortex. In sum, cortisol increased the deactivation of several brain areas, although the location of the affected areas in the brain was age-dependent. The present findings suggest that cortisol output during fMRI should be considered as confounder and integrated in analyzing developmental changes in brain activation during adolescence. PMID:25514334

  5. Flexing is Not Stretching: An Analog Study of Flexure-Induced Fault Growth

    NASA Astrophysics Data System (ADS)

    Supak, S. K.; Bohnenstiehl, D. R.; Buck, W. R.

    2003-12-01

    A thin (5 mm thick) plaster layer floating on a foam rubber substrate is bent and fractured in an analog model of extensional fault growth during lithospheric flexing. The size-frequency scaling of the resulting crack populations were analyzed. Unlike lithospheric stretching models, crack populations formed during these experiments indicate that length- and spacing- frequency distributions are not well described by a power-law model. Rather, these size-frequency data are better described by a negative exponential distribution. The absence of a power-law fault distribution reflects the preferential nucleation and growth of faults in association with stress maxima along the axis of the flexing plate. In contrast, the cracks formed in response to stretching evolve, due to elastic interaction during simultaneous growth, from an initially random distribution of nucleation points to form a self-similar network of fractures. The model predicts a non-power-law fault distribution for any area of moderate or large magnitude lithospheric flexure. The outer rise of trenches is an area of undisputed flexural faulting; however, in these environments, fault distributions have not yet been analyzed. A recent model for axial highs of fast-spreading ridges suggests that lithosphere is flexed significantly as it rafts away from ridge axes. Several studies of ocean floor fault populations near axial highs report non-power-law scaling, consistent with our analog model predictions for plate flexure.

  6. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    SciTech Connect

    Yoon, Deok Hyo; Lim, Mi-Hee; Lee, Yu Ran; Sung, Gi-Ho; Lee, Tae-Ho; Jeon, Byeong Hwa; Cho, Jae Youl; Song, Won O.; Park, Haeil; Choi, Sunga; Kim, Tae Woong

    2013-12-15

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by

  7. Cortisol directly impacts Flavobacterium columnare in vitro growth characteristics.

    PubMed

    Declercq, Annelies Maria; Aerts, Johan; Ampe, Bart; Haesebrouck, Freddy; De Saeger, Sarah; Decostere, Annemie

    2016-01-01

    Teleost fish faced with stressful stimuli launch an endocrine stress response through activation of the hypothalamic-pituitary-interrenal axis to release glucocorticoids, in particular cortisol, into the blood. For the majority of bacterial fish pathogens, stress is considered a key factor in disease outbreaks. Based upon studies in mammals, there is considerable evidence to suggest that, besides impairing the immune system, cortisol can have a direct effect on bacterial cells. Hitherto, this intriguing field of microbial endocrinology has remained largely unexplored in aquatic diseases. The present study investigated in vitro the impact of cortisol on phenotypic traits of the fresh water fish pathogen Flavobacterium columnare. Colonies obtained from the highly virulent (HV) isolates resulted in significantly larger and more spreading colonies compared to those from the low virulent (LV) isolates. High cortisol doses added displayed a direct effect on the bacterial cells and induced a significant decrease in colony size. An additional intriguing finding was the inverse relationship between cortisol concentrations added to the broth and the spreading character of colonies retrieved, with higher cortisol doses resulting in less rhizoid to rough and even smooth colony formation (the latter only in the LV trout isolate), suggesting a dose-response effect. The loss of the rhizoid appearance of the F. columnare colonies upon administration of cortisol, and hence the loss of motility, might indicate a phenotypic change to the biofilm state. These findings form the basis for further research on the impact of glucocorticoids on other virulence factors and biofilm formation of F. columnare. PMID:27530746

  8. Hypoxia-induced changes in recovery sleep, core body temperature, urinary 6-sulphatoxymelatonin and free cortisol after a simulated long-duration flight.

    PubMed

    Coste, Olivier; Van Beers, Pascal; Touitou, Yvan

    2009-12-01

    Fatigue and sleep disorders often occur after long-haul flights, even when no time zones are crossed. In this controlled study, we assessed the effects of two levels of hypoxia (at 8000 ft and 12 000 ft) on recovery sleep. Core body temperature (CBT), a circadian marker, urinary 6-sulphatoxymelatonin and free cortisol were studied in 20 young healthy male volunteers exposed for 8 h (08:00-16:00 hours) in a hypobaric chamber to a simulated cabin altitude of 8000 ft and, 4 weeks later, 12 000 ft. Each subject served as his own control. Sleep was recorded by polysomnography for three consecutive nights for each exposure. CBT was monitored by telemetry during the three 24-h cycles (control, hypoxic exposure and recovery). Free urinary cortisol and 6-sulphatoxymelatonin levels were assayed twice daily between 08:00 and 20:00 hours (day) and between 20:00 and 08:00 hours (night). We showed significant changes in circadian patterns of CBT at both altitudes, suggesting a phase delay, and changes in recovery sleep but only at 12 000 ft. We observed an increase in sleep onset latency which correlated positively with the increase in CBT levels during the first recovery night and a decrease in the duration of stage N(2) (formerly S(2)), which correlated negatively with the mid-range crossing time, a reliable phase marker of CBT rhythm. This study shows clearly the impact of hypobaric hypoxia on circadian time structure during air flights leading to a phase delay of CBT, independent of jet lag and consequences on sleep during recovery. PMID:19765206

  9. Toward a theory of the general-anesthetic-induced phase transition of the cerebral cortex. I. A thermodynamics analogy

    NASA Astrophysics Data System (ADS)

    Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Sleigh, J. W.; Wilcocks, Lara C.

    2001-07-01

    In a recent paper the authors developed a stochastic model for the response of the cerebral cortex to a general anesthetic agent. The model predicted that there would be an anesthetic-induced phase change at the point of transition into unconsciousness, manifested as a divergence in the electroencephalogram spectral power, and a change in spectral energy distribution from being relatively broadband in the conscious state to being strongly biased towards much lower frequencies in the unconscious state. Both predictions have been verified in recent clinical measurements. In the present paper we extend the model by calculating the equilibrium distribution function for the cortex, allowing us to establish a correspondence between the cortical phase transition and the more familiar thermodynamic phase transitions. This correspondence is achieved by first identifying a cortical free energy function, then by postulating that there exists an inverse relationship between an anesthetic effect and a quantity we define as cortical excitability, which plays a role analogous to temperature in thermodynamic phase transitions. We follow standard thermodynamic theory to compute a cortical entropy and a cortical ``heat capacity,'' and we investigate how these will vary with anesthetic concentration. The significant result is the prediction that the entropy will decrease discontinuously at the moment of induction into unconsciousness, concomitant with a release of ``latent heat'' which should manifest as a divergence in the analogous heat capacity. There is clear clinical evidence of heat capacity divergence in historical anesthetic-effect measurements performed in 1977 by Stullken et al. [Anesthesiology 46, 28 (1977)]. The discontinuous step change in cortical entropy suggests that the cortical phase transition is analogous to a first-order thermodynamic transition in which the comatose-quiescent state is strongly ordered, while the active cortical state is relatively disordered.

  10. Gender specific effect of psychological stress and cortisol reactivity on adolescent risk taking.

    PubMed

    Daughters, Stacey B; Gorka, Stephanie M; Matusiewicz, Alexis; Anderson, Katelyn

    2013-07-01

    The purpose of this study was to evaluate how psychological stress, gender and cortisol response to stress relate to risk behavior among 132 14-18 year old adolescents. Participants completed a laboratory based risk task prior to and immediately after a computerized psychological stress task, and salivary cortisol was collected from pre-stress to 60 min following initial stress exposure. Results indicate that adolescent boys (n = 59) and girls (n = 73) demonstrate different patterns of risk taking (RT) in response to stress, such that boys evidenced an increase in RT following stress exposure, whereas girls evidenced a decrease in RT. In addition, a gender by cortisol interaction demonstrated that for boys, both a smaller total cortisol output (AUCg) and peak cortisol response to stress (PC) was associated with greater stress-induced RT. Both cortisol measures were unrelated to stress-induced RT among girls. Taken together, data suggest that among boys, a blunted cortisol response to stress underlies an increase in risk taking in the context of psychological stress. Further research with an additional behavioral stress task is needed prior to drawing conclusions regarding the relation between female gender, cortisol response to stress, and risk taking in the context of psychological stress. PMID:23338478

  11. Novel Pactamycin Analogs Induce p53 Dependent Cell-Cycle Arrest at S-Phase in Human Head and Neck Squamous Cell Carcinoma (HNSCC) Cells

    PubMed Central

    Guha, Gunjan; Liang, Xiaobo; Kulesz-Martin, Molly F.; Mahmud, Taifo; Indra, Arup Kumar; Ganguli-Indra, Gitali

    2015-01-01

    Pactamycin, although putatively touted as a potent antitumor agent, has never been used as an anticancer drug due to its high cytotoxicity. In this study, we characterized the effects of two novel biosynthetically engineered analogs of pactamycin, de-6MSA-7-demethyl-7-deoxypactamycin (TM-025) and 7-demethyl-7-deoxypactamycin (TM-026), in head and neck squamous cell carcinoma (HNSCC) cell lines SCC25 and SCC104. Both TM-025 and TM-026 exert growth inhibitory effects on HNSCC cells by inhibiting cell proliferation. Interestingly, unlike their parent compound pactamycin, the analogs do not inhibit synthesis of nascent protein in a cell-based assay. Furthermore, they do not induce apoptosis or autophagy in a dose- or a time-dependent manner, but induce mild senescence in the tested cell lines. Cell cycle analysis demonstrated that both analogs significantly induce cell cycle arrest of the HNSCC cells at S-phase resulting in reduced accumulation of G2/M-phase cells. The pactamycin analogs induce expression of cell cycle regulatory proteins including master regulator p53, its downstream target p21Cip1/WAF1, p27kip21, p19, cyclin E, total and phospho Cdc2 (Tyr15) and Cdc25C. Besides, the analogs mildly reduce cyclin D1 expression without affecting expression of cyclin B, Cdk2 and Cdk4. Specific inhibition of p53 by pifithrin-α reduces the percentage of cells accumulated in S-phase, suggesting contribution of p53 to S-phase increase. Altogether, our results demonstrate that Pactamycin analogs TM-025 and TM-026 induce senescence and inhibit proliferation of HNSCC cells via accumulation in S-phase through possible contribution of p53. The two PCT analogs can be widely used as research tools for cell cycle inhibition studies in proliferating cancer cells with specific mechanisms of action. PMID:25938491

  12. Pyrazine analogs are active components of wolf urine that induce avoidance and fear-related behaviors in deer

    PubMed Central

    Osada, Kazumi; Miyazono, Sadaharu; Kashiwayanagi, Makoto

    2014-01-01

    Our previous studies indicated that a cocktail of pyrazine analogs, identified in wolf urine, induced avoidance and fear behaviors in mice. The effects of the pyrazine cocktail on Hokkaido deer (Cervus nippon yesoensis) were investigated in field bioassays at a deer park in Hokkaido, Japan. A set of feeding bioassay trials tested the effects of the pyrazine cocktail odor on the behavior of the deer located around a feeding area in August and September 2013. This odor effectively suppressed the approach of the deer to the feeding area. In addition, the pyrazine cocktail odor provoked fear-related behaviors, such as “tail-flag”, “flight” and “jump” actions, of the deer around the feeding area. This study is the first experimental demonstration that the pyrazine analogs in wolf urine have robust and continual fearful aversive effects on ungulates as well as mice. The pyrazine cocktail might be suitable for a chemical repellent that could limit damage to forests and agricultural crops by wild ungulates. PMID:25177281

  13. Novel Benzo[a]quinolizidine Analogs Induce Cancer Cell Death through Paraptosis and Apoptosis.

    PubMed

    Zheng, Hongbo; Dong, Yiwen; Li, Lin; Sun, Bin; Liu, Lei; Yuan, Huiqing; Lou, Hongxiang

    2016-05-26

    Paraptosis is nonapoptotic cell death characterized by massive endoplasmic reticulum (ER)- or mitochondria-derived vacuoles. Induction of paraptosis offers significant advantages for the treatment of chemotherapy-resistant tumors compared with anticancer drugs that rely on apoptosis. Because some natural alkaloids induce paraptotic cell death, a novel series of benzo[a]quinolizidine derivatives were synthesized, and their antiproliferative activity and ability to induce cytoplasmic vacuolation were analyzed. Structural optimization led to the identification of the potent compound 22b, which inhibited cancer cell proliferation in vitro and in vivo and profoundly facilitated paraptosis-like cell death and induced caspase-dependent apoptosis. Further investigation revealed that 22b-mediated vacuolation originated from persistent ER stress and upregulation of LC3B. Paraptosis induced by benzo[a]quinolizidine derivatives thus represents an alternative strategy for cancer chemotherapy. PMID:27077446

  14. 5-FU-induced hyperammonemic encephalopathy in a case of metastatic rectal adenocarcinoid successfully rechallenged with the fluoropyrimidine analog, capecitabine.

    PubMed

    Advani, Pooja P; Fakih, Marwan G

    2011-01-01

    Neurological complications of both fluorouracil (5-FU) and its oral prodrug, capecitabine, have been described in the literature. This study reported the case of a 70-year-old female with metastatic adenocarcinoid of the rectum who developed hyperammonemic encephalopathy, following infusional 5-FU therapy, manifesting itself as intractable nausea, vomiting, confusion and disorientation. Interestingly, when the patient was rechallenged with the fluoropyrimidine analog, capecitabine, neither hyperammonemia nor symptom recurrence was observed. 5-FU is an integral component of effective anti-neoplastic treatment for metastatic colorectal cancer, but is often discontinued when neurotoxicity develops. This case highlighted the use of capecitabine as an alternative for patients who have demonstrated evidence of 5-FU-induced hyperammonemic encephalopathy. Re-challenging the patient with capecitabine, at a low daily dose intensity, accounted for the overall tolerability of the treatment, as demonstrated by normal ammonia levels and the lack of neurological symptoms. PMID:21273620

  15. The investigation of resveratrol and analogs as potential inducers of fetal hemoglobin.

    PubMed

    Theodorou, Andria; Phylactides, Marios; Forti, Luca; Cramarossa, Maria Rita; Spyrou, Pantelis; Gambari, Roberto; Thein, Swee Lay; Kleanthous, Marina

    2016-05-01

    Βeta-thalassemia, is a hemoglobinopathy characterized by reduced beta-globin chain synthesis, leading to imbalanced globin chain production, ineffective erythropoiesis and anemia. Increasing gamma-globin gene expression is a promising therapeutic approach as it reduces this imbalance by combining with the excess alpha globin chains and producing fetal hemoglobin (HbF). Furthermore, increased iron absorption and repeated blood transfusions lead to iron overload and tissue damage secondary to reactive oxygen species. Compounds exhibiting both antioxidant and HbF inducing activities are, therefore, highly desirable therapeutic agents. Resveratrol, a natural phytoalexin, combines these two activities but is also cytotoxic. Nine hydroxystilbenic resveratrol derivatives were synthesized in an attempt to identify compounds that retain the HbF-inducing and antioxidant activities of resveratrol but exhibit reduced cytotoxicity. Three derivatives (P1, P4 and P11) exhibited similar hemoglobin-inducing properties to resveratrol in K562 cells, however, only P11 showed reduced cytotoxicity. All three derivatives demonstrated variable HbF-inducing activity in primary erythroid progenitor cells from healthy donors. Resveratrol and P11 increased HbF induction significantly, with P11 having the highest activity. Additionally, P4 significantly increased progenitor numbers. A combinatorial treatment in K562 cells using resveratrol and decitabine resulted in a statistically significant increase in hemoglobin-inducing activity only above the level shown by resveratrol alone. PMID:27067481

  16. Vitamin D3 analog maxacalcitol (OCT) induces hCAP-18/LL-37 production in human oral epithelial cells.

    PubMed

    Tada, Hiroyuki; Shimizu, Takamitsu; Nagaoka, Isao; Takada, Haruhiko

    2016-01-01

    Maxacalcitol (22-oxacalcitriol: OCT) is a synthetic vitamin D3 analog with a limited calcemic effect. In this study, we investigated whether OCT increases the production of LL-37/CAP-18, a human cathelicidin antimicrobial peptide, in human gingival/oral epithelial cells. A human gingival epithelial cell line (Ca9-22) and human oral epithelial cell lines (HSC-2, HSC-3, and HSC-4) exhibited the enhanced expression of LL-37 mRNA upon stimulation with OCT as well as active metabolites of vitamins D3 and D2. Among the human epithelial cell lines, Ca9-22 exhibited the strongest response to these vitamin D-related compounds. OCT induced the higher production of CAP-18 (ng/mL order) until 6 days time-dependently in Ca9-22 cells in culture. The periodontal pathogen Porphyromonas gingivalis was killed by treatment with the LL-37 peptide. These findings suggest that OCT induces the production of hCAP-18/LL-37 in a manner similar to that induced by the active metabolite of vitamin D3. PMID:27356607

  17. Dust Bowl migration as an analog for possible global warming-induced migration from Mexico

    SciTech Connect

    Turner, M.H.; Longstreth, J.D.; Johnson, A.K.; Rosenberg, N.J.

    1994-06-01

    As a result of increases in CO{sub 2} and other radiatively important trace gases, scientists have predicted increases in mean worldwide temperatures of 2--5 degrees C over the next 50 to 100 years. Such temperature increases may result in climate modifications that would in turn be associated with increases in drought and desertification and could even change the patterns of the monsoons and tropical rains, which are important to agriculture throughout the world. They predicted that the rise in sea level caused by melting and thermal expansion of glaciers and polar icecaps could flood large population centers, destroying habitation and displacing populations. This will result in approximately 50 million ``environmental refugees`` worldwide, triple the number of today. The expected shifts in precipitation are also likely to result in (1) increased runoff contaminated with pesticides, salts, garbage, sewage, and eroded soil, and (2) drought also leading to increased soil erosion and salinization, as well as depletion of limited water resources. The total impact of global warming on agriculture and human habitation could considerably slow the economic development of some nations and would particularly affect agricultural production. Loss of homes, the inability to raise food, an increased prevalence of disease and worsened economic conditions may drive people to leave their homelands, seeking entry into countries which have more resources and greater resistance to the economic consequences of climatic change. This report looks at the possible environmental impacts and economic impacts of the greenhouse effect on Mexico while using the American Dust Bowl event as an analog.

  18. A C-TERMINAL INSECT KININ ANALOG ENHANCES INHIBITION OF WEIGHT GAIN AND INDUCES SIGNIFICANT MORTALITY IN HELICOVERPA ZEA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The first reported examples of C-terminal aldehyde analogs of an insect neuropeptide are described. They are hexapeptide insect kinin analogs Boc-VFFPWG-H and Fmoc-RFFPWG-H. Activity observed for these modified analogs in an in vitro insect diuretic assay confirms that the C-terminal aldehyde group...

  19. Cortisol and PTSD symptoms among male and female high-exposure 9/11 survivors.

    PubMed

    Dekel, Sharon; Ein-Dor, Tsachi; Gordon, Kathleen M; Rosen, Jeffrey B; Bonanno, George A

    2013-10-01

    Only a few studies have examined cortisol response to trauma-related stressors in relation to posttraumatic stress disorder (PTSD). We followed a sample of high-exposure survivors of the attacks on September 11, 2001 (9/11; 32 men and 29 women) and examined their cortisol response after recalling the escape from the attack, 7 and 18 months post-9/11. PTSD symptoms and saliva cortisol levels were assessed before and after trauma recollection. Hierarchical regression analyses revealed that PTSD symptoms and male sex predicted increased cortisol response following recollections. For men, elevated cortisol was associated with greater severity of reexperiencing symptoms (p < .001) and lower severity of avoidance symptoms (p < .001). For women, recall-induced cortisol was minimal and unrelated to PTSD symptoms (p = .164 and p = .331, respectively). These findings suggest that augmented cortisol response to trauma-related stressors may be evident in men reporting symptoms of PTSD. Thus, as cortisol abnormalities related to PTSD symptoms appear sex-specific, future research on mechanisms of sex differences in response to trauma is warranted. PMID:24030869

  20. Cortisol and testosterone increase financial risk taking and may destabilize markets

    PubMed Central

    Cueva, Carlos; Roberts, R. Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N.; Herbert, Joe; Rustichini, Aldo

    2015-01-01

    It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders’ financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways. PMID:26135946

  1. Cortisol and testosterone increase financial risk taking and may destabilize markets.

    PubMed

    Cueva, Carlos; Roberts, R Edward; Spencer, Tom; Rani, Nisha; Tempest, Michelle; Tobler, Philippe N; Herbert, Joe; Rustichini, Aldo

    2015-01-01

    It is widely known that financial markets can become dangerously unstable, yet it is unclear why. Recent research has highlighted the possibility that endogenous hormones, in particular testosterone and cortisol, may critically influence traders' financial decision making. Here we show that cortisol, a hormone that modulates the response to physical or psychological stress, predicts instability in financial markets. Specifically, we recorded salivary levels of cortisol and testosterone in people participating in an experimental asset market (N = 142) and found that individual and aggregate levels of endogenous cortisol predict subsequent risk-taking and price instability. We then administered either cortisol (single oral dose of 100 mg hydrocortisone, N = 34) or testosterone (three doses of 10 g transdermal 1% testosterone gel over 48 hours, N = 41) to young males before they played an asset trading game. We found that both cortisol and testosterone shifted investment towards riskier assets. Cortisol appears to affect risk preferences directly, whereas testosterone operates by inducing increased optimism about future price changes. Our results suggest that changes in both cortisol and testosterone could play a destabilizing role in financial markets through increased risk taking behaviour, acting via different behavioural pathways. PMID:26135946

  2. Muramyl-dipeptide and its synthetic analog as possible inducers of interleukin-2 production

    SciTech Connect

    Malaitsev, V.V.; Andronova, T.M.; Bogdanova, I.M.; Sukhikh, G.T.

    1986-01-01

    This paper studies the action of muramyl-dipeptide (MDP) and its synthetic derivative N-acetylglucosaminyl-N-acetyl-muramyl-alanyl-D-isoglutamine (GMDP) on IL2 production in a population of BALB/c mouse spleen cells. Tritium-thymidine was added to the wells in the flat-bottomed culture panes and the radioactivity of the samples was measured on a scintillation beta-counter after deposition of material was precipitated with TCA on the filters. The supernatant of the culture of activated spleen cells, stimulated by MDP or GMDP induced a proliferative response of the con A blast cells. The effectiveness of the stimulating action of MDP and GMDP, and of the classical IL2 inducer, con A, was compared.

  3. Analog of the spin-orbit-induced anomalous Hall effect with quantized radiation

    SciTech Connect

    Larson, Jonas

    2010-05-15

    We demonstrate how the term describing the interaction between a single two-level atom and two cavity field modes may attain a Rashba form. As an outcome, cavity QED provides a testbed for studies of phenomena reminiscent of the spin-orbit induced anomalous Hall effect. The effective magnetic field, deriving from the non-Abelian gauge potentials rendered by the Rashba coupling, induces a transverse force acting on the phase space distributions. Thereby, the phase space distributions build up a transverse motion manifesting itself in spiral trajectories, rather than circular ones obtained for a zero magnetic field as one would acquire for the corresponding Abelian gauge potentials. Utilizing realistic experimental parameters, the phenomenon is numerically verified, ascertain that it should be realizable with current techniques.

  4. Mind your thoughts: associations between self-generated thoughts and stress-induced and baseline levels of cortisol and alpha-amylase.

    PubMed

    Engert, Veronika; Smallwood, Jonathan; Singer, Tania

    2014-12-01

    Stress is a major health burden in today's society. Research shows that negative cognitive styles are associated with increased stress reactivity, low mood and accelerated cellular aging. Our study sought to unravel the relationship between the content of self-generated thoughts and psychosocial stress measured in terms of hypothalamic-pituitary-adrenal axis and sympathetic activity. Features of self-generated thoughts were assessed using thought sampling while participants performed cognitive tasks following a stress induction or in a baseline condition. More negatively toned emotional thoughts and more social temporal thoughts with a past focus were associated with increased cortisol and alpha-amylase levels, both after stress and at baseline. More social temporal thoughts with a future focus, on the other hand, had an overall attenuating effect on the levels of both stress markers. Our results indicate a fundamental link between the thoughts and stress levels we experience. Understanding the mechanisms governing this mind-body association may have important implications for understanding and counteracting the high incidence of stress-related disorders in today's society. PMID:25457636

  5. Bisphenol A and its analogs induce morphological and biochemical alterations in human peripheral blood mononuclear cells (in vitro study).

    PubMed

    Michałowicz, Jaromir; Mokra, Katarzyna; Bąk, Agata

    2015-10-01

    Few studies have addressed the cellular effects of bisphenol S (BPS) and bisphenol AF (BPAF) on cells, and no study has been conducted to analyze the mechanism of action of bisphenols in blood cells. In this study, the effect of bisphenol A (BPA), bisphenol F (BPF), BPS and BPAF on human peripheral blood mononuclear cells (PBMCs) was analyzed. It was shown that BPA, BPF and BPAF in particular, decreased cell viability, which was associated with depletion of intracellular ATP level and alterations in PBMCs size and granulation. Bisphenols enhanced ROS (including OH˙) formation, which led to damage to lipids and proteins in PBMCs. The most significant alterations in ROS level were induced by BPF, and particularly BPAF. Moreover, it was shown that BPAF most strongly provoked lipid peroxidation, while BPA and BPS caused the greatest damage to proteins. It may be concluded that BPA and its analogs were capable of inducing oxidative stress and damage in PBMCs in the concentrations ranging from 0.06 to 0.5 μM (0.02-0.1 μg/ml), which may be present in human blood as a result of environmental exposure. Although, most of bisphenols studied decreased cell viability, size and ATP level at higher concentrations, BPAF exhibited its cytotoxic potential at low concentrations ranging from 0.3 to 3 μM (0.1-1.0 μg/ml) that may correspond to concentrations in humans following occupational exposure. PMID:26028149

  6. Using Electron Induced Dissociation (EID) on an LC Time-Scale to Characterize a Mixture of Analogous Small Organic Molecules

    NASA Astrophysics Data System (ADS)

    Prakash, Aruna S.; Smith, Michael J. P.; Kaabia, Zied; Hurst, Glenn; Yan, Ci; Sims, Martin; Bristow, Anthony W. T.; Stokes, Peter; Parker, David; Mosely, Jackie A.

    2012-05-01

    LC ESI FTICR MS of a sample of cediranib identified this pharmaceutical target molecule plus an additional 10 compounds of interest, all of which were less than 10% total ion current (TIC) peak intensity relative to cediranib. LC FTICR tandem mass spectrometry using electron induced dissociation (EID) has been achieved and has proven to be the best way to generate useful product ion information for all of these singly protonated molecules. Cediranib [M + H]+ fragmented by EID to give 29 product ions whereas QTOF-CID generated only one very intense product ion, and linear ion trap-CID, which generated 10 product ions, but all with poor S/N. Twenty-six of the EID product ions were unique to this fragmentation technique alone. By considering the complementary LC-EID and LC-CID data together, all 10 unknown compounds were structurally characterized and proven to be analogous to cediranib. Of particular importance, EID produced unique product ion information for one of the low level cediranib analogues that enabled full characterization of the molecule such that the presence of an extra propylpyrrolidine group was discovered and proven to be located on the pyrrolidine ring of cediranib, solving an analytical problem that could not be solved by collision induced dissociation (CID). Thus, it has been demonstrated that EID is in harmony with the chromatography duty-cycle and the dynamic concentration range of synthetic compounds containing trace impurities, providing crucial analytical information that cannot be obtained by more traditional methodologies.

  7. Tuning all-Optical Analog to Electromagnetically Induced Transparency in nanobeam cavities using nanoelectromechanical system

    PubMed Central

    Shi, Peng; Zhou, Guangya; deng, Jie; Tian, Feng; Chau, Fook Siong

    2015-01-01

    We report the observations of all-optical electromagnetically induced transparency in nanostructures using waveguide side-coupled with photonic crystal nanobeam cavities, which has measured linewidths much narrower than individual resonances. The quality factor of transparency resonance can be 30 times larger than those of measured individual resonances. When the gap between cavity and waveguide is reduced to 10 nm, the bandwidth of destructive interference region can reach 10 nm while the width of transparency resonance is 0.3 nm. Subsequently, a comb-drive actuator is introduced to tune the line shape of the transparency resonance. The width of the peak is reduced to 15 pm and the resulting quality factor exceeds 105. PMID:26415907

  8. Novel Carvedilol Analogs that Suppress Store Overload Induced Ca2+ Release

    PubMed Central

    Smith, Chris D.; Wang, Aixia; Vembaiyan, Kannan; Zhang, Jingqun; Xie, Cuihong; Zhou, Qiang; Wu, Guogen; Wayne Chen, S. R.; Back, Thomas G.

    2013-01-01

    Carvedilol is a uniquely effective drug for the treatment of cardiac arrhythmias in patients with heart failure. This activity is in part due to its ability to inhibit store overload-induced calcium release (SOICR) through the RyR2 channel. We describe the synthesis, characterization and bioassay of ca. 100 compounds based on the carvedilol motif in order to identify features that correlate with and optimize SOICR inhibition. A single cell bioassay was employed based on the RyR2-R4496C mutant HEK-293 cell line, in which calcium release from the endoplasmic reticulum through the defective channel was measured. IC50 values for SOICR inhibition were thus obtained. The compounds investigated contained modifications to the three principal subunits of carvedilol, including the carbazole and catechol moieties, as well as the linker chain containing the β-amino alcohol functionality. The SAR results indicate that significant alterations are tolerated in each of the three subunits. PMID:24124794

  9. Elevated hair cortisol concentrations in endurance athletes.

    PubMed

    Skoluda, Nadine; Dettenborn, Lucia; Stalder, Tobias; Kirschbaum, Clemens

    2012-05-01

    Engaging in intensive aerobic exercise, specifically endurance sports, is associated with HPA axis activation indicated by elevated cortisol levels. Whether the repeated short-term elevations in cortisol levels result in higher long-term cortisol exposure of endurance athletes has been difficult to examine since traditional methods of cortisol assessments (saliva, blood, urine) reflect only relatively short time periods. Hair segment analysis provides a new method to assess cumulative cortisol secretion over prolonged time periods in a retrospective fashion. The aim of this study was to investigate cumulative cortisol secretion over several months reflecting intensive training and competitive races by examining hair cortisol levels of endurance athletes. Hair samples were obtained from 304 amateur endurance athletes (long-distance runners, triathletes, cyclists) and 70 controls. Cortisol concentrations were determined in the first to third 3-cm hair segments most proximal to the scalp. In addition, self-report measures of training volume were obtained. Endurance athletes exhibited higher cortisol levels in all three hair segments compared to controls (p<.001). Positive correlations between the cortisol concentration in the first hair segment and each indicator of training volume were found (all p<.01). These data suggest that repeated physical stress of intensive training and competitive races among endurance athletes is associated with elevated cortisol exposure over prolonged periods of time. These findings may have important implications with regard to somatic and mental health of athletes which should be investigated in future research. PMID:21944954

  10. LZ-106, a novel analog of enoxacin, inducing apoptosis via activation of ROS-dependent DNA damage response in NSCLCs.

    PubMed

    Yang, Lin; Yuan, Yinan; Fu, Chengyu; Xu, Xuefen; Zhou, Jieying; Wang, Shuhao; Kong, Lingyi; Li, Zhiyu; Guo, Qinglong; Wei, Libin

    2016-06-01

    Lung cancer, especially non-small-cell lung cancer (NSCLC), plays the leading role in cancer which is closely related to a myriad of fatal results. Unfortunately, current molecular mechanisms and clinical treatment of NSCLC still remain to be explored despite the fact that intensive investigations have been carried out in the last two decades. Recently, growing attention to finding exploitable sources of anticancer agents is refocused on quinolone compounds, an antibiotic with a long period of clinic application, for their remarkable cell-killing activity against not only bacteria, but eukaryotes as well. In this study, we found LZ-106, an analog of enoxacin, exhibiting potent inhibitory effects on NSCLC in both cultured cells and xenograft mouse model. We identified apoptosis-inducing action of LZ-106 in NSCLC cells through the mitochondrial and endoplasmic reticulum (ER)-stress apoptotic pathways via Annexin-V/PI double-staining assay, membrane potential detection, calcium level detection and the expression analysis of the key apoptotic proteins. Through comet assay, reactive oxygen species (ROS) detection, the expression analysis of DNA damage response (DDR) marker γ-H2AX and other DDR-related proteins, we also demonstrated that LZ-106 notably induced ROS overproduction and DDR. Interestingly, additional evidence in our findings revealed that DDR and apoptosis could be alleviated in the presence of ROS scavenger N-acetyl-cysteine (NAC), indicating ROS-dependent DDR involvement in LZ-106-induced apoptosis. Thus our data not only offered a new therapeutic candidate for NSCLC, but also put new insights into the pharmacological research of quinolones. PMID:27012423

  11. Ultra-narrow band perfect absorbers based on plasmonic analog of electromagnetically induced absorption.

    PubMed

    He, Jinna; Ding, Pei; Wang, Junqiao; Fan, Chunzhen; Liang, Erjun

    2015-03-01

    A novel plasmonic metamaterial consisting of the solid (bar) and the inverse (slot) compound metallic nanostructure for electromagnetically induced absorption (EIA) is proposed in this paper, which is demonstrated to achieve an ultra-narrow absorption peak with the linewidth less than 8 nm and the absorptivity exceeding 97% at optical frequencies. This is attributed to the plasmonic EIA resonance arising from the efficient coupling between the magnetic response of the slot (dark mode) and the electric resonance of the bar (bright mode). To the best of our knowledge, this is the first time that the plasmonic EIA is used to realize the narrow-band perfect absorbers. The underlying physics are revealed by applying the two-coupled-oscillator model. The near-perfect-absorption resonance also causes an enhancement of about 50 times in H-field and about 130 times in E-field within the slots. Such absorber possesses potential for applications in filter, thermal emitter, surface enhanced Raman scattering, sensing and nonlinear optics. PMID:25836832

  12. Shell-crosslinked knedel-like nanoparticles induce lower immunotoxicity than their non-crosslinked analogs

    PubMed Central

    Elsabahy, Mahmoud; Samarajeewa, Sandani; Raymond, Jeffery E.; Clark, Corrie; Wooley, Karen L.

    2013-01-01

    The development of stable nanoparticles that can withstand the changing conditions experienced in a biological setting and also be of low toxicity and immunogenicity is of particular importance to address the problems associated with currently utilized nanotechnology-based therapeutics and diagnostics. The use of crosslinked nanoparticles continues to receive special impetus, due to their robust structure and high kinetic stability, and they have recently been shown to induce lower cytotoxicity than their non-crosslinked micellar counterparts. In the current study, poly(acrylamidoethylamine)-block-poly(DL-lactide) (PAEA90-b-PDLLA40) copolymers were synthesized, self-assembled in water to yield nanoscopic polymeric micelles, and the effects of decorating the micellar surface with poly(ethylene glycol) (i.e. PEGylation) and crosslinking the PAEA layer to varying extents on the physicochemical characteristics, cytotoxicity and immunotoxicity of the nanoparticles were studied. Herein, we report for the first time that crosslinking can efficiently reduce the immunotoxicity of polymeric nanomaterials. In addition, increasing the degree of crosslinking further reduced the accessibility of biomolecules to the core of the nanoparticles and decreased their cytotoxicity and immunotoxicity. It is also highlighted that crosslinking can be more efficient than PEGylation in reducing the immunotoxicity of nanomaterials. Shell-crosslinking of block copolymer micelles, therefore, is expected to advance their clinical development beyond the earlier known effects, and to broaden the implications in the field of nanomedicine. PMID:24187610

  13. Rational design of triazololipopeptides analogs of kisspeptin inducing a long-lasting increase of gonadotropins.

    PubMed

    Beltramo, Massimiliano; Robert, Vincent; Galibert, Mathieu; Madinier, Jean-Baptiste; Marceau, Philippe; Dardente, Hugues; Decourt, Caroline; De Roux, Nicolas; Lomet, Didier; Delmas, Agnès F; Caraty, Alain; Aucagne, Vincent

    2015-04-23

    New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-resistant amide mimic and a serum albumin-binding motif, respectively. These triazololipopeptides are highly potent full agonists of KISS1R and are >100 selective over the closely related NPFF1R. When injected in ewes with a quiescent reproductive system, the best compound of our series induced a much prolonged increase of luteinizing hormone release compared to KP10 and increased follicle-stimulating hormone plasma concentration. Hence, this KISS1R agonist is a new valuable pharmacological tool to explore the potential of KP system in reproduction control. Furthermore, it represents the first step to develop drugs treating reproductive system disorders due to a reduced activity of the hypothalamo-pituitary-gonadal axis such as delayed puberty, hypothalamic amenorrhea, and hypogonadotropic hypogonadism. PMID:25811530

  14. In vitro assay for drug-induced hepatosteatosis using rat primary hepatocytes, a fluorescent lipid analog and gene expression analysis.

    PubMed

    Fujimura, Hisako; Murakami, Naoko; Kurabe, Michie; Toriumi, Wataru

    2009-05-01

    To evaluate new drugs' potential for hepatosteatosis, we developed a cell-based assay using a fluorescent fatty acid analog: BODIPY558/568 C12. Rat primary hepatocytes were exposed to positive reference compounds [cyclosporine A (CsA), clofibrate (CFR), tetracycline (TC), valproic acid (VPA), carbon tetrachloride (CCl4), tamoxifen (TMX)] in the presence of BODIPY558/568 C12. The formation of fluorscecent particles or lipid droplets in the cytoplasm was confirmed by confocal laser scanning microscopy and electron microscopy respectively. The accumulation of BODIPY558/568 C12 was measured by fluorometry and high content imaging method. All positive reference compounds increased fluorescent particles in number and fluorescence intensity. High content imaging was more sensitive and selective method than fluorometry to detect fluorescent particles. Gene expression analysis of the hepatocytes showed two patterns: genes related to lipid metabolism/synthesis were down-regulated by oxidative stress inducing compounds: CsA, TC and TMX, and up-regulated by peroxisome proliferator-activated receptor-alpha agonists: CFR and VPA. From these findings, we concluded that the cell-based assay developed in this study is an appropriate method to predict drugs' potential for hepatosteatosis, and gene expression analysis is useful to profile the mechanism of the hepatosteatosis. PMID:19224547

  15. Control of slab width on subduction-induced upper mantle flow and associated upwellings: Insights from analog models

    NASA Astrophysics Data System (ADS)

    Strak, Vincent; Schellart, Wouter P.

    2016-06-01

    The impact of slab width W (i.e., trench-parallel extent) on subduction-induced upper mantle flow remains uncertain. We present a series of free subduction analog models where W was systematically varied to upscaled values of 250-3600 km to investigate its effect on subducting plate kinematics and upper mantle return flow around the lateral slab edges. We particularly focused on the upwelling component of mantle flow, which might promote decompression melting and could thereby produce intraplate volcanism. The models show that W has a strong control on trench curvature and on the trench retreat, subducting plate, and subduction velocities, generally in good agreement with previous modeling studies. Upper mantle flow velocity maps produced by means of a stereoscopic particle image velocimetry technique indicate that the magnitude of the subduction-induced mantle flow around the lateral slab edges correlates positively with the product of W and trench retreat velocity. For all models an important upwelling component is always produced close to the lateral slab edges, with higher magnitudes for wider slabs. The trench-parallel lateral extent of this upwelling component is the same irrespective of W, but its maximum magnitude gets located closer to the subducting plate in the trench-normal direction and it is more focused when W increases. For W ≤ 2000 km the upwelling occurs laterally (in the trench-parallel direction) next to the subslab domain and the mantle wedge domain, while for W ≥ 2000 km it is located only next to the subslab domain and focuses closer to the trench tip, because of stronger poloidal flow in the mantle wedge extending laterally.

  16. Systematic review and meta-analysis reveals acutely elevated plasma cortisol following fasting but not less severe calorie restriction.

    PubMed

    Nakamura, Yuko; Walker, Brian R; Ikuta, Toshikazu

    2016-03-01

    Elevated plasma cortisol has been reported following caloric restriction, and may contribute to adverse effects including stress-induced overeating, but results from published studies are inconsistent. To clarify the effects of caloric restriction on plasma cortisol, and to assess cortisol as an indicator of stress during caloric restriction, we conducted a systematic review and meta-analysis of published studies in which cortisol was measured following caloric restriction without other manipulations in humans. We further compared effects of fasting, very low calorie diet (VLCD), and other less intense low calorie diet (LCD), as well as the duration of caloric restriction by meta-regression. Overall, caloric restriction significantly increased serum cortisol level in 13 studies (357 total participants). Fasting showed a very strong effect in increasing serum cortisol, while VLCD and LCD did not show significant increases. The meta-regression analysis showed a negative association between the serum cortisol level and the duration of caloric restriction, indicating serum cortisol is increased in the initial period of caloric restriction but decreased to the baseline level after several weeks. These results suggest that severe caloric restriction causes activation of the hypothalamic-pituitary-adrenal axis, which may be transient, but results in elevated cortisol which could mediate effects of starvation on brain and metabolic function as well as ameliorate weight loss. PMID:26586092

  17. Crowding increases salivary cortisol but not self-directed behavior in captive baboons.

    PubMed

    Pearson, Brandon L; Reeder, DeeAnn M; Judge, Peter G

    2015-04-01

    Reduced space can lead to crowding in social animals. Crowding increases the risk of agonistic interactions that, in turn, may require additional physiological defensive coping mechanisms affecting health. To determine the stress induced from increased social density in a group of nineteen baboons living in an indoor/outdoor enclosure, saliva cortisol levels and rates of anxiety-related behavior were analyzed across two unique crowding episodes. Initially, mean salivary cortisol levels when animals were restricted to their indoor quarters were compared to those when they also had access to their larger outdoor enclosure. Then, mean cortisol levels were compared before, during, and after two distinct crowding periods of long and short duration. Crowding resulted in significantly elevated cortisol during crowding periods compared to non-crowded periods. Cortisol levels returned to baseline following two crowding episodes contrasting in their length and ambient climate conditions. These cortisol elevations indicate greater metabolic costs of maintaining homeostasis under social stress resulting from reduced space. Self-directed behavior, conversely, was not reliably elevated during crowding. Results suggest that the potential for negative social interactions, and/or the uncertainty associated with social threat can cause physiological stress responses detected by salivary cortisol. Self-directed behavioral measures of stress may constitute inadequate indicators of social stress in colony-housed monkeys or represent subjective emotional arousal unrelated to hypothalamic-pituitary adrenal axis activation. PMID:25598488

  18. Cortisol responses to naturalistic and laboratory stress in student teachers: comparison with a non-stress control day.

    PubMed

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

    2013-04-01

    Ambulatory assessments of hypothalamus-pituitary-adrenal axis responses to acute natural stressors yield evidence on stress regulation with high ecological validity. Sampling of salivary cortisol is a standard technique in this field. In 21 healthy student teachers, we assessed cortisol responses to a demonstration lesson. On a control day, sampling was repeated at analogous times. Additionally, the cortisol awakening response (CAR) was assessed on both days. Participants were also exposed to a laboratory stressor, the Trier Social Stress Test, and rated their individual levels of chronic work stress. In pre-to-post-stress assessment, cortisol levels declined after the lesson. However, post-stress cortisol levels were significantly higher compared with those on the control day. Also, the Trier Social Stress Test yielded higher cortisol responses when using the control day as reference baseline. Associations between the CAR and chronic stress measures were observed solely on the control day. There were no significant associations between cortisol responses to the natural and laboratory stressors. Our results indicate that a control day might be an important complement in laboratory but especially in ambulatory stress research. Furthermore, associations between chronic stress measures and the CAR might be obscured by acute stress exposure. Finally, responses to the laboratory stressor do not seem to mirror natural stress responses. PMID:22888074

  19. Positive upshots of cortisol in everyday life.

    PubMed

    Hoyt, Lindsay T; Zeiders, Katharine H; Ehrlich, Katherine B; Adam, Emma K

    2016-06-01

    Cortisol, the major physiological end product of the hypothalamic-pituitary-adrenal axis, is usually associated with stress and negative affect. However, a new body of research highlights the complex, adaptive significance of elevated cortisol within individuals in everyday life. Whereas most studies do not have the power to test the dynamic transactions between cortisol and affect within a person throughout the entire waking day, we employed an intensive study protocol analyzing hourly diary reports of affect in relation to hourly salivary cortisol samples among 24 healthy adults from morning to bedtime, across 2 consecutive weekdays (N = 862 total samples). Utilizing multileveling modeling and focusing on within-person effects, we examined whether momentary increases in cortisol could be mood protective, or energy enhancing, in everyday life, supporting the cortisol boost hypothesis. Results revealed no significant associations between cortisol and current affective state; however, within-person increases in cortisol were significantly associated with subsequent rises in activeness, alertness, and relaxation, and trend-level reductions in stress and nervousness. This study adds to growing evidence that cortisol plays a positive role in regulating affect in everyday life. (PsycINFO Database Record PMID:26950364

  20. The effect of chronic stress on plasma cortisol concentrations in cyclic female pigs depends on the time of day.

    PubMed

    Janssens, C J; Helmond, F A; Wiegant, V M

    1995-04-01

    The influence of tethered housing (a condition of chronic stress) on morning and evening basal plasma cortisol levels was investigated in a longitudinal study in cyclic female nulliparous pigs (gilts). After a period of loose housing in individual pens ("nonstress" estrous cycles), six cannulated gilts were tethered by a neck chain and housed for a period of 20 wk (chronic stress estrous cycles). Blood was sampled twice daily (1000 and 1800 hr) for cortisol determination. Plasma cortisol levels showed a diurnal rhythm with significantly higher levels at 1000 hr than at 1800 hr. Tethered housing induced a significant increase in the 1800-hr plasma cortisol concentrations during the first three estrous cycles after tethering, whereas the 1000-hr plasma cortisol concentrations did not change throughout the experimental period. During the period of increased 1800-hr levels, cortisol was still released in a circadian fashion, albeit, the rhythm was flattened. In control gilts, housed loose during the entire experimental period, plasma cortisol concentrations at 1000 hr and at 1800 hr remained unaltered and 1000-hr cortisol concentrations were significantly higher than the 1800-hr concentrations during the experimental period. Therefore, possible effects of the experimental procedure or age-related effects could be excluded. These data indicate that, in tethered gilts, the chronic stress-induced hypercortisolemia is of transient nature, suggesting adaptive changes in the regulation of the hypothalamic-pituitary-adrenocortical axis. In addition, the data reveal circadian differences in the effect of chronic stress on hypothalamic-pituitary- adrenocortical function. PMID:7600767

  1. Relationship between serum cortisol levels and some physiological parameters following reining training session in horse.

    PubMed

    Casella, Stefania; Vazzana, Irene; Giudice, Elisabetta; Fazio, Francesco; Piccione, Giuseppe

    2016-05-01

    The changes of cortisol, red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), heart rate (HR), respiratory rate (RR) and rectal temperature (RT) were evaluated after a reining training session in eight Quarter Horses. All parameters were measured before exercise (T0), immediately after exercise (T1), 1 h after exercise (T2), 2 h after exercise (T3) and 24 h after exercise (T4). One-way analysis of variance (ANOVA) for repeated measures, followed Bonferroni's post hoc test, showed a significant effect of the reining training session (P < 0.0001) on cortisol, RBC, Hb, Hct, HR, RR and RT. Simple linear regression analysis showed the positive correlation (P < 0.05) between cortisol changes and variations of studied parameters in T1, T3 and T4. Exercise-induced cortisol concentrations reflect the physiological response of reining training, suggesting that the changes observed are useful to assess the performance in reining horses and their reining training adaptability. PMID:26419874

  2. Having your cake and eating it too: A habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases mesenteric fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of...

  3. Characterization of inhibitory T cells induced by an analog of type II collagen in an HLA-DR1 humanized mouse model of autoimmune arthritis

    PubMed Central

    2012-01-01

    Introduction We used DR1 transgenic mice and covalently linked DR1 multimers to characterize analog-specific inhibitory T cells in collagen-induced arthritis (CIA). Because of the low numbers of antigen-specific T cells in wild-type mice, functional T-cell studies in autoimmune arthritis have been challenging. The use of T-cell receptor (TCR) transgenic mice has provided useful information, but such T cells may not represent the heterogeneous T-cell response that occurs in natural settings. Our focus was to develop tools to identify and characterize the population of immunoregulatory T cells induced in wild-type mice by an analog peptide of CII259-273, which contains amino acid substitutions at positions 263 (N) and 266 (D) (analog peptide A12). Methods DR1 multimers, developed by loading empty class II molecules with exogenous peptide, provide a method for visualizing antigen-specific T cells with flow cytometry. However, the low binding avidity of A12 for the major histocompatibility complex (MHC) made this strategy untenable. To overcome this problem, we generated DR1 multimers in which the analog peptide A12 was covalently linked, hoping that the low-avidity analog would occupy enough binding clefts to allow detection of the responsive T cells. Results Staining with the tetramer revealed that A12-specific T cells were readily detectable at 10 days after immunization. These CD4(+) T cells are a highly selective subset of the TCR repertoire and have a limited clonality. Analysis of cytokine expression showed that cells detected by tetramer (A12) expressed primarily suppressive cytokines (interleukin-4 (IL-4) and IL-10) in response to collagen, compared with control cells. Although they did not express Fox-p3, they were extremely effective in preventing and suppressing inflammatory arthritis. Conclusions In summary, our studies showed that the use of covalently linked multimers allows characterization of analog-specific T cells that are otherwise difficult to

  4. Analog earthquakes

    SciTech Connect

    Hofmann, R.B.

    1995-09-01

    Analogs are used to understand complex or poorly understood phenomena for which little data may be available at the actual repository site. Earthquakes are complex phenomena, and they can have a large number of effects on the natural system, as well as on engineered structures. Instrumental data close to the source of large earthquakes are rarely obtained. The rare events for which measurements are available may be used, with modfications, as analogs for potential large earthquakes at sites where no earthquake data are available. In the following, several examples of nuclear reactor and liquified natural gas facility siting are discussed. A potential use of analog earthquakes is proposed for a high-level nuclear waste (HLW) repository.

  5. MATERNAL SELF-REPORTED DEPRESSIVE SYMPTOMS AND MATERNAL CORTISOL LEVELS INTERACT TO PREDICT INFANT CORTISOL LEVELS.

    PubMed

    Khoury, Jennifer E; Gonzalez, Andrea; Levitan, Robert; Masellis, Mario; Basile, Vincenzo; Atkinson, Leslie

    2016-01-01

    Three basic findings have emerged from research on maternal depressive symptoms and offspring hypothalamic-pituitary-adrenal functioning: (a) Mothers' depressive symptoms are positively associated with their offsprings' cortisol stress response, (b) numerous individual and interpersonal maternal characteristics moderate this association, and (c) maternal and infant cortisol levels are highly correlated. In combination, these findings have suggested that maternal cortisol levels may moderate the relation between maternal depressive symptoms and infant cortisol responsivity; the current study assessed this hypothesis. Participants were 297 mother-infant dyads who were recruited from the community. Maternal depressive symptoms were assessed via self-report. Dyads participated in two differentially stressful infant challenges when infants were 16 and 17 months old. Mother and infant salivary cortisol was collected before and after challenges. Results indicate that maternal cortisol levels moderated associations between maternal depressive symptoms and infant cortisol levels across both challenges. Infants showed higher cortisol levels if their mothers had both higher depressive symptoms and higher cortisol levels, as compared to infants of mothers with higher depressive symptoms and lower cortisol, and to infants of mothers with lower depressive symptoms and either higher or lower cortisol levels. We discuss findings in relation to environmental and biological factors that may contribute to the intergenerational transmission of depressive symptoms. PMID:26939829

  6. Cyclane-aminol 10-hydroxycamptothecin analogs as novel DNA topoisomerase I inhibitors induce apoptosis selectively in tumor cells.

    PubMed

    Zhang, Shixuan; Geng, Tao; Jiang, Bo; Song, Ge; Ha, Lisha; Sun, Chenguang; Qian, Yuan; Fan, Qingyu; Guo, Hongmin

    2014-07-01

    A novel series of cyclane-aminol 10-hydroxycamptothecin (HCPT) analogs was designed and synthesized through the Mannich reaction using HCPT as the lead compound, such as 10-hydroxyl-9-L-prolinol (+) methylcamptothecin (PRPT), 10-hydroxyl-9-(4'-hydroxy) piperidinylmethylcamptothecin (PPPT), and 10-hydroxy-9-(4'-hydroxyethyl)-piperazinylmethycamptothecin (QPPT). Three kinds of new cyclane-aminols were introduced into the structure of HCPT, which modified strong cytotoxic HCPT into cyclane-aminol HCPT analogs with moderate cytotoxicity and improved selectivity toward DNA topoisomerase I inhibition in tumor cells. Special metabolic pathways for cyclane-aminol HCPT analogs in rats were discovered, which differed from other HCPT analogs. Cyclane-aminol HCPT analogs can capture O2 and cause an increase in intracellular hydrogen peroxide levels with selective induction of apoptosis in tumor cells rather than in normal peripheral blood mononuclear cells. Among them, PPPT has a much better druggability than topotecan (TPT) and has the potential to be developed into an antitumor agent. PMID:24525588

  7. Diurnal cortisol variation and cortisol response to an MRI stressor in schizophrenia and bipolar disorder.

    PubMed

    Girshkin, Leah; O'Reilly, Nicole; Quidé, Yann; Teroganova, Nina; Rowland, Jesseca E; Schofield, Peter R; Green, Melissa J

    2016-05-01

    Markers of HPA axis function, including diurnal cortisol rhythm and cortisol responses to stress or pharmacological manipulation, are increasingly reported as disrupted in schizophrenia (SZ) and bipolar disorder (BD). However, there has been no direct comparison of cortisol responses to stress in SZ and BD in the same study, and associations between cortisol dysfunction and illness characteristics remain unclear. In this study we used spline embedded linear mixed models to examine cortisol levels of SZ and BD participants at waking, during the first 45min after waking (representing the cortisol awakening response; CAR), during the period of rapid cortisol decline post the awakening response, and in reaction to a stressor (MRI scan), relative to healthy controls (HC). Contrary to expectations, neither SZ nor BD showed differences in waking cortisol levels, CAR, or immediate post-CAR decline compared to HC; however, waking cortisol levels were greater in BD relative to SZ. In response to the MRI stressor, the SZ group showed a significant absence of the expected increase in cortisol responsivity to stress, which was seen in both the BD and HC groups. Clinical factors affecting the CAR differed between SZ and BD. In SZ, higher antipsychotic medication dosage was associated with a steeper incline of the CAR, while greater positive symptom severity was associated with a more blunted CAR, and greater levels of anxiety were associated with the blunted cortisol response to stress. In BD, longer illness duration was associated with a steeper incline in CAR and lower levels of waking cortisol. These results suggest that cortisol responses may normalize with medication (in SZ) and longer illness duration (in BD), in line with findings of aberrant cortisol levels in the early stages of psychotic disorders. PMID:26874562

  8. Correspondence between hair cortisol concentrations and 30-day integrated daily salivary and weekly urinary cortisol measures.

    PubMed

    Short, Sarah J; Stalder, Tobias; Marceau, Kristine; Entringer, Sonja; Moog, Nora K; Shirtcliff, Elizabeth A; Wadhwa, Pathik D; Buss, Claudia

    2016-09-01

    Characterization of cortisol production, regulation and function is of considerable interest and relevance given its ubiquitous role in virtually all aspects of physiology, health and disease risk. The quantification of cortisol concentration in hair has been proposed as a promising approach for the retrospective assessment of integrated, long-term cortisol production. However, human research is still needed to directly test and validate current assumptions about which aspects of cortisol production and regulation are reflected in hair cortisol concentrations (HCC). Here, we report findings from a validation study in a sample of 17 healthy adults (mean±SD age: 34±8.6 yrs). To determine the extent to which HCC captures cumulative cortisol production, we examined the correspondence of HCC, obtained from the first 1cm scalp-near hair segment, assumed to retrospectively reflect 1-month integrated cortisol secretion, with 30-day average salivary cortisol area-under-the curve (AUC) based on 3 samples collected per day (on awakening, +30min, at bedtime) and the average of 4 weekly 24-h urinary free cortisol (UFC) assessments. To further address which aspects of cortisol production and regulation are best reflected in the HCC measure, we also examined components of the salivary measures that represent: (1) production in response to the challenge of awakening (using the cortisol awakening response [CAR]), and (2) chronobiological regulation of cortisol production (using diurnal slope). Finally, we evaluated the test-retest stability of each cortisol measure. Results indicate that HCC was most strongly associated with the prior 30-day integrated cortisol production measure (average salivary cortisol AUC) (r=0.61, p=0.01). There were no significant associations between HCC and the 30-day summary measures using CAR or diurnal slope. The relationship between 1-month integrated 24-h UFC and HCC did not reach statistical significance (r=0.30, p=0.28). Lastly, of all cortisol

  9. Intraindividual stability of hair cortisol concentrations.

    PubMed

    Stalder, Tobias; Steudte, Susann; Miller, Robert; Skoluda, Nadine; Dettenborn, Lucia; Kirschbaum, Clemens

    2012-05-01

    The analysis of cortisol in human hair constitutes a promising method for the retrospective assessment of cumulative cortisol secretion over extended periods of time. An implicit assumption underlying the use of this method is that in the absence of major life changes hair cortisol concentrations show a high level of intraindividual stability, i.e. single hair cortisol assessments exhibit considerable trait-specificity and are only to a smaller extent influenced by state-dependent factors. Here, we present data from two independent studies examining patterns of intraindividual stability in hair cortisol levels. In study I, 45 participants were examined at two sampling points carried out one year apart from each other. In study II, 64 individuals provided data at three sampling points which occurred at two-month intervals. In both studies, at each time point hair was sampled and relevant psychosocial and hair-related variables were assessed. Results of both studies consistently revealed strong test-retest associations for repeated hair cortisol measurements ('r's between 0.68 and 0.79, 'p's <0.0001). Findings of structural equation modelling applied to data of study II showed that single hair cortisol assessments comprise a strong trait component, explaining between 59 and 82% of variance, and are only to a lesser extent influenced by state-related factors. Only inconsistent evidence for covariation of changes in hair cortisol concentrations and simultaneous changes in perceived stress or other relevant variables was seen across the two studies. The current findings suggest a considerable degree of intraindividual stability in hair cortisol levels which highlights the utility of this method for obtaining trait estimates of long-term cortisol secretion in psychoneuroendocrinological research. PMID:21917384

  10. Protein-Protein Interactions in high moisture-extruded meat analogs and heat-induce soy Protein Gels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two commercial soy protein isolates were made into fibrous meat analogs by high moisture extrusion or into gels by heating and cooling, at varying concentrations and/or temperatures. Protein-protein interactions by extrusion or gelation were investigated through protein solubility studies of raw an...

  11. A beta-amino acid pyrokinin analog induces irregular pupariation behavior in larvae of the flesh fly Sarcophaga bullata

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The developmental process of pupariation is accelerated by members of the pyrokinin class of neuropeptides in larvae of the flesh fly Sarcophaga bullata. A pyrokinin analog (Ac-Y[beta-3-Phe]TPRLamide), in which a Phe residue is replaced with a beta-amino acid, accelerates pupariation in this fly at...

  12. Antifeedant activity and high mortality in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae) induced by biostable insect kinin analogs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The insect kinins are multifunctional neuropeptides found in a variety of arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). A series of biostable insect kinin analogs based on the shared C-terminal pentapeptide core region were fed in solutions of artificial diet t...

  13. The Effects of Race-related Stress on Cortisol Reactivity in the Laboratory

    PubMed Central

    Richman, Laura Smart; Jonassaint, Charles

    2009-01-01

    Background The experience of race-related stressors is associated with physiological stress responses. However, much is unknown still about the complex relationship between how race-related stressors are perceived and experienced and potential moderators such as strength of racial identity. Purpose This research examines the impact of a real-life stressor and strength of race identity on physiological responses to a social evaluative threat induced in the laboratory. Methods Salivary cortisol measures were collected throughout a stressor protocol. African-American participants were also randomized to one of two conditions designed to promote either racial identification or student identification, before the experimental task. Unexpectedly, a highly publicized real-life racial stressor, the Duke Lacrosse (LaX) scandal, occurred during the course of the data collection. This allowed for pre-post LaX comparisons to be made on cortisol levels. Results These comparisons showed that across both priming conditions, participants post-LaX had highly elevated cortisol levels that were nonresponsive to the experimental stress task, while their pre-LaX counterparts had lower cortisol levels that exhibited a normal stress response pattern. Furthermore, this effect of LaX was significantly moderated by gender, with women having lower mean cortisol levels pre-LaX but significantly greater cortisol levels than all other groups post-LaX. Conclusions These results suggest that recent exposure to race-related stress can have a sustained impact on physiological stress responses for African Americans. PMID:18347910

  14. Effects of copper on the acute cortisol response and associated physiology in rainbow trout.

    PubMed

    Tellis, Margaret S; Alsop, Derek; Wood, Chris M

    2012-03-01

    The aim of this study was to determine the effects of chronic waterborne copper (Cu) exposure on the acute stress-induced cortisol response and associated physiological consequences in rainbow trout (Oncorhynchus mykiss). Trout were exposed to 30 μg Cu/L in moderately hard water (120 mg/L as CaCO(3)) for 40 days, following which time the acute cortisol response was examined with a series of stressors. At 40 days, a 65% increase in Cu was observed in the gill, but no accumulation was observed in the liver, brain or head kidney. Stressors such as air exposure or confinement did not elicit an increase in circulating cortisol levels for Cu-exposed fish, in contrast to controls. However, this inhibitory effect on the acute cortisol response appeared to have few implications on the ability of Cu-exposed fish to maintain ion and carbohydrate homeostasis. For example, plasma Na(+), Ca(2+) and glucose levels as well as hepatic glycogen levels were the same post-stress in control and Cu-exposed fish. Trout were also challenged with exposure to 50% seawater for 48 h, where Cu-exposed trout maintained plasma Na(+), glucose and hepatic glycogen levels. However, Cu-exposed fish experienced decreased plasma K(+) levels throughout the Cu exposure and stress tests. In conclusion, chronic Cu exposure resulted in the abolition of an acute cortisol response post-stress. There was no Cu accumulation in the hypothalamus-pituitary-interrenal axis (HPI axis) suggesting this was not a direct toxic effect of Cu on the cortisol regulatory pathway. However, the lack of an acute cortisol response in Cu-exposed fish did not impair the ability of the fish to maintain ion and carbohydrate homeostasis. This effect on cortisol may be a strategy to reduce costs during the chronic stress of Cu exposure, and not endocrine disruption as a result of toxic injury. PMID:21964321

  15. [Respective roles of cortisol, aldosterone and angiotensin II during pathophysiology of atherosclerosis].

    PubMed

    Ayari, Hanène

    2013-01-01

    The involvement of angiotensin II, cortisol and aldosterone in increased cardiovascular risk is well known but their interactions within arterial wall and during atheroma formation are not established. In fact, mild cortisol excess is associated with a higher prevalence of cardiovascular events, increased intima media thickness, a higher frequency of atherosclerotic plaques and increased mortality. Conversely, remission from hypercortisolism is followed by improvement in cardiovascular risk markers as intima-media thickness or arterial distensibility, suggesting a strong link between cortisol excess and adverse vascular remodeling. On the other hand, implication of renin-angiotensin system (RAS) in atheromatous remodeling is well documented. The RAS also includes aldosterone, a mineralocorticoid which secretion is mainly and strongly stimulated by angiotensin II, and which receptor (MR) can also be activated by cortisol given that MR affinity is similar for both aldosterone and cortisol. The role of aldosterone in arterial remodeling is still very controversial. Aldosterone treatment associated with a high salt diet induced not only hypertension but also oxidative stress, collagen synthesis and vascular inflammation. However in models without salt loading or arterial hypertension, such as the treatment with deoxycorticosterone acetate in dogs, no alterations in aortic structure were observed and moreover, the MR blockade with eplerenone did not attenuate atherosclerosis in the aorta of diabetic Apo-E KO mice. It stems that among the different effects and mechanisms described in cell experiments, it is not known which are indeed operating in situ in human vessels and thus, if local cortisol is deleterious or beneficial and, if activation of MR by aldosterone or cortisol is important in vascular remodeling and atherogenesis. RAS blocker treatment would be particularly beneficial in essential hypertensive patients with low plasma renin, to attenuate both angiotensin

  16. 2-Substituted 3β-Aryltropane Cocaine Analogs Produce Atypical Effects without Inducing Inward-Facing Dopamine Transporter Conformations

    PubMed Central

    Hong, Weimin C.; Kopajtic, Theresa A.; Xu, Lifen; Lomenzo, Stacey A.; Jean, Bernandie; Madura, Jeffry D.; Surratt, Christopher K.; Trudell, Mark L.

    2016-01-01

    Previous structure-activity relationship studies indicate that a series of cocaine analogs, 3β-aryltropanes with 2β-diarylmethoxy substituents, selectively bind to the dopamine transporter (DAT) with nanomolar affinities that are 10-fold greater than the affinities of their corresponding 2α-enantiomers. The present study compared these compounds to cocaine with respect to locomotor effects in mice, and assessed their ability to substitute for cocaine (10 mg/kg, i.p.) in rats trained to discriminate cocaine from saline. Despite nanomolar DAT affinity, only the 2β-Ph2COCH2-3β-4-Cl-Ph analog fully substituted for cocaine-like discriminative effects. Whereas all of the 2β compounds increased locomotion, only the 2β-(4-ClPh)PhCOCH2-3β-4-Cl-Ph analog had cocaine-like efficacy. None of the 2α-substituted compounds produced either of these cocaine-like effects. To explore the molecular mechanisms of these drugs, their effects on DAT conformation were probed using a cysteine-accessibility assay. Previous reports indicate that cocaine binds with substantially higher affinity to the DAT in its outward (extracellular)- compared with inward-facing conformation, whereas atypical DAT inhibitors, such as benztropine, have greater similarity in affinity to these conformations, and this is postulated to explain their divergent behavioral effects. All of the 2β- and 2α-substituted compounds tested altered cysteine accessibility of DAT in a manner similar to cocaine. Furthermore, molecular dynamics of in silico inhibitor-DAT complexes suggested that the 2-substituted compounds reach equilibrium in the binding pocket in a cocaine-like fashion. These behavioral, biochemical, and computational results show that aryltropane analogs can bind to the DAT and stabilize outward-facing DAT conformations like cocaine, yet produce effects that differ from those of cocaine. PMID:26769919

  17. Estimation of glucose utilization in a type 2 diabetes mellitus patient on insulin analogs with tumor hypoglycemia induced by IGF-II.

    PubMed

    Chode, Suresh; Albert, Stewart G; Shoemaker, James D; Green, Aileen L

    2016-02-01

    We present a 38-year-old male patient with insulin requiring type 2 diabetes mellitus (DM) who had fasting hypoglycemia caused by a non-pancreatic-islet-cell mesenchymal tumor producing IGF-II. The evaluation was confounded in that there was pre-existing DM being treated with insulin analogs. Insulin levels were assessed with an immunoassay with cross reactivity with the insulin analogs. An 18-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) scan localized the 19.7×18.0×17.8cm retroperitoneal mass. A 3.25kg tumor was resected. Post-operatively insulin treatment was resumed and circulating IGF-II levels returned to normal. The maximum standardized uptake values of FDG (SUVmax) along with a steady state glucose infusion of 17.5g/h were used to determine the components of glucose utilization due to IGF-II induced muscle glucose uptake (utilization, 62%) whereas the tumor itself was responsible for approximately 22% of measurable glucose uptake. Whereas tumor induced hypoglycemia has been ascribed to preferential glucose utilization by the tumor, the predominant hypoglycemic effect was due to hormonal IGF-II induced total body glucose uptake. PMID:26774399

  18. Eryptosis-inducing activity of bisphenol A and its analogs in human red blood cells (in vitro study).

    PubMed

    Maćczak, Aneta; Cyrkler, Monika; Bukowska, Bożena; Michałowicz, Jaromir

    2016-04-15

    Bisphenols are important chemicals that are widely used in the manufacturing of polycarbonates, epoxy resin and thermal paper, and thus the exposure of humans to these substances has been noted. The purpose of this study was to assess eryptotic changes in human erythrocytes exposed (in vitro) to bisphenol A (BPA) and its selected analogs, i.e.,bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF). The erythrocytes were incubated with compounds studied at concentrations ranging from 1 to 250μg/mL for 4, 12 or 24h. The results showed that BPA and its analogs increased cytosolic calcium ions level with the strongest effect noted for BPAF. It has also been revealed that all bisphenols analyzed, and BPAF and BPF in particular increased phosphatidylserine translocation in red blood cells, which confirmed that they exhibited eryptotic potential in this cell type. Furthermore, it was shown that BPA and its analogs caused significant increase in calpain and caspase-3 activities, while the strongest effect was noted for BPAF. BPS, which is the main substituent of bisphenol A in polymers and thermal paper production exhibited similar eryptotic potential to BPA. Eryptotic changes in human erythrocytes were provoked by bisphenols at concentrations, which may influence the human body during occupational exposure or subacute poisoning with these compounds. PMID:26799224

  19. Cortisol promotes endoplasmic glucose production via pyridine nucleotide redox.

    PubMed

    Wang, Zengmin; Mick, Gail J; Xie, Rongrong; Wang, Xudong; Xie, Xuemei; Li, Guimei; McCormick, Kenneth L

    2016-04-01

    Both increased adrenal and peripheral cortisol production, the latter governed by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), contribute to the maintenance of fasting blood glucose. In the endoplasmic reticulum (ER), the pyridine nucleotide redox state (NADP/NADPH) is dictated by the concentration of glucose-6-phosphate (G6P) and the coordinated activities of two enzymes, hexose-6-phosphate dehydrogenase (H6PDH) and 11β-HSD1. However, luminal G6P may similarly serve as a substrate for hepatic glucose-6-phophatase (G6Pase). A tacit belief is that the G6P pool in the ER is equally accessible to both H6PDH and G6Pase. Based on our inhibition studies and kinetic analysis in isolated rat liver microsomes, these two aforesaid luminal enzymes do share the G6P pool in the ER, but not equally. Based on the kinetic modeling of G6P flux, the ER transporter for G6P (T1) preferentially delivers this substrate to G6Pase; hence, the luminal enzymes do not share G6P equally. Moreover, cortisol, acting through 11β-HSD1, begets a more reduced pyridine redox ratio. By altering this luminal redox ratio, G6P flux through H6PDH is restrained, allowing more G6P for the competing enzyme G6Pase. And, at low G6P concentrations in the ER lumen, which occur during fasting, this acute cortisol-induced redox adjustment promotes glucose production. This reproducible cortisol-driven mechanism has been heretofore unrecognized. PMID:26860459

  20. Testosterone, cortisol, and human competition.

    PubMed

    Casto, Kathleen V; Edwards, David A

    2016-06-01

    Testosterone and cortisol figure prominently in the research literature having to do with human competition. In this review, we track the history of this literature, concentrating particularly on major theoretical and empirical contributions, and provide commentary on what we see as important unresolved issues. In men and women, athletic competition is typically associated with an increase in testosterone (T) and cortisol (C). Hormone changes in response to non-athletic competition are less predictable. Person (e.g., power motivation, mood, aggressiveness, social anxiety, sex, and baseline levels of T and C) and context (e.g., whether a competition is won or lost, the closeness of the competition, whether the outcome is perceived as being influenced by ability vs. chance, provocations) factors can influence hormone responses to competition. From early on, studies pointed to a positive relationship between T and dominance motivation/status striving. Recent research, however, suggests that this relationship only holds for individuals with low levels of C - this is the core idea of the dual-hormone hypothesis, and it is certain that the broadest applications of the hypothesis have not yet been realized. Individuals differ with respect to the extent to which they embrace competition, but the hormonal correlates of competitiveness remain largely unexplored. Although rapid increases in both T and C associated with competition are likely adaptive, we still know very little about the psychological benefits of these hormonal changes. Administration studies have and will continue to contribute to this inquiry. We close with a discussion of what, we think, are important methodological and mechanistic issues for future research. PMID:27103058

  1. ABCC1 confers tissue-specific sensitivity to cortisol versus corticosterone: A rationale for safer glucocorticoid replacement therapy.

    PubMed

    Nixon, Mark; Mackenzie, Scott D; Taylor, Ashley I; Homer, Natalie Z M; Livingstone, Dawn E; Mouras, Rabah; Morgan, Ruth A; Mole, Damian J; Stimson, Roland H; Reynolds, Rebecca M; Elfick, Alistair P D; Andrew, Ruth; Walker, Brian R

    2016-08-17

    The aim of treatment in congenital adrenal hyperplasia is to suppress excess adrenal androgens while achieving physiological glucocorticoid replacement. However, current glucocorticoid replacement regimes are inadequate because doses sufficient to suppress excess androgens almost invariably induce adverse metabolic effects. Although both cortisol and corticosterone are glucocorticoids that circulate in human plasma, any physiological role for corticosterone has been neglected. In the brain, the adenosine 5'-triphosphate-binding cassette transporter ABCB1 exports cortisol but not corticosterone. Conversely, ABCC1 exports corticosterone but not cortisol. We show that ABCC1, but not ABCB1, is expressed in human adipose and that ABCC1 inhibition increases intracellular corticosterone, but not cortisol, and induces glucocorticoid-responsive gene transcription in human adipocytes. Both C57Bl/6 mice treated with the ABCC1 inhibitor probenecid and FVB mice with deletion of Abcc1 accumulated more corticosterone than cortisol in adipose after adrenalectomy and corticosteroid infusion. This accumulation was sufficient to increase glucocorticoid-responsive adipose transcript expression. In human adipose tissue, tissue corticosterone concentrations were consistently low, and ABCC1 mRNA was up-regulated in obesity. To test the hypothesis that corticosterone effectively suppresses adrenocorticotropic hormone (ACTH) without the metabolic adverse effects of cortisol, we infused cortisol or corticosterone in patients with Addison's disease. ACTH suppression was similar, but subcutaneous adipose transcripts of glucocorticoid-responsive genes were higher after infusion with cortisol rather than with corticosterone. These data indicate that corticosterone may be a metabolically favorable alternative to cortisol for glucocorticoid replacement therapy when ACTH suppression is desirable, as in congenital adrenal hyperplasia, and justify development of a pharmaceutical preparation. PMID

  2. Breastfeeding, Bed-Sharing, and Maternal Cortisol.

    PubMed

    Simon, Clarissa D; Adam, Emma K; McKinney, Chelsea O; Krohn, Julie B; Shalowitz, Madeleine U

    2016-05-01

    Prior studies have found that close mother-child sleep proximity helps increase rates of breastfeeding, and breastfeeding itself is linked to better maternal and infant health. In this study, we examine whether breastfeeding and infant bed-sharing are related to daily rhythms of the stress-responsive hormone cortisol. We found that bed-sharing was related to flatter diurnal cortisol slopes, and there was a marginal effect for breastfeeding to predict steeper cortisol slopes. Furthermore, mothers who breastfeed but do not bed-share had the steepest diurnal cortisol slopes, whereas mothers who bed-shared and did not breastfeed had the flattest slopes (P < .05). These results were significant after controlling for subjective sleep quality, perceived stress, depression, socioeconomic status, race, and maternal age. Findings from this study indicate that infant parenting choices recommended for infants (breastfeeding and separate sleep surfaces for babies) may also be associated with more optimal stress hormone profiles for mothers. PMID:26330120

  3. Stress-related cortisol response and laboratory eating behavior in obese women.

    PubMed

    Lorig, Fabian; Kießl, Gundula Rebecca Raphaela; Laessle, Reinhold Gustav

    2016-06-01

    Stress-related cortisol secretion has been linked to increased appetite and subsequent food intake in overweight individuals. The present study addresses this relationship in a repeated-measures randomized controlled laboratory experiment. Nineteen obese women were compared to 36 normal weight controls with respect to stress-induced salivary cortisol and laboratory eating behavior, measured by a universal eating monitor. The trier social stress test served as stressor. Stress-induced cortisol levels were significantly higher in the obese compared to the normal weight controls. Unexpectedly, a corresponding increase in laboratory food intake was not detected. The results are interpreted and discussed with regard to restrained eating, which was found to be present to a significant degree in the obese women. PMID:25827493

  4. Study of the photon-induced formation and subsequent desorption of CH3OH and H2CO in interstellar ice analogs

    NASA Astrophysics Data System (ADS)

    Martín-Doménech, R.; Muñoz Caro, G. M.; Cruz-Díaz, G. A.

    2016-05-01

    Context. Methanol and formaldehyde are two simple organic molecules that are ubiquitously detected in the interstellar medium, in both the solid and gaseous phases. An origin in the solid phase and a subsequent nonthermal desorption into the gas phase is often invoked to explain their abundances in some of the environments where they are found. Experimental simulations under astrophysically relevant conditions have been carried out in the past four decades in order to find a suitable mechanism for that process. Aims: In particular, photodesorption from pure methanol ice (and presumably from pure formaldehyde ice) has been found to be negligible in previous works, probably because both molecules are very readily dissociated by vacuum-UV photons. Therefore, we explore the in situ formation and subsequent photon-induced desorption of these species, studying the UV photoprocessing of pure ethanol ice, and a more realistic binary H2O:CH4 ice analog. Methods: Experimental simulations were performed in an ultra-high vacuum chamber. Pure ethanol and binary H2O:CH4 ice samples deposited onto an infrared transparent window at 8 K were UV-irradiated using a microwave-discharged hydrogen flow lamp. Evidence of photochemical production of these two species and subsequent UV-photon-induced desorption into the gas phase were searched for by means of a Fourier transform infrared spectrometer and a quadrupole mass spectrometer, respectively. After irradiation, ice samples were warmed up to room temperature until complete sublimation was attained for detection of volatile products. Results: Formation of CH3OH was only observed during photoprocessing of the H2O:CH4 ice analog, accounting for ~4% of the initial CH4 ice column density, but no photon-induced desorption was detected. Photochemical production of H2CO was observed in both series of experiments. Formation of formaldehyde accounted for ≤45% conversion of the initial ethanol ice, but it could not be quantified during

  5. Study of the photon-induced formation and subsequent desorption of CH3OH and H2CO in interstellar ice analogs

    NASA Astrophysics Data System (ADS)

    Martín-Doménech, R.; Muñoz Caro, G. M.; Cruz-Díaz, G. A.

    2016-04-01

    Context. Methanol and formaldehyde are two simple organic molecules that are ubiquitously detected in the interstellar medium, in both the solid and gaseous phases. An origin in the solid phase and a subsequent nonthermal desorption into the gas phase is often invoked to explain their abundances in some of the environments where they are found. Experimental simulations under astrophysically relevant conditions have been carried out in the past four decades in order to find a suitable mechanism for that process. Aims: In particular, photodesorption from pure methanol ice (and presumably from pure formaldehyde ice) has been found to be negligible in previous works, probably because both molecules are very readily dissociated by vacuum-UV photons. Therefore, we explore the in situ formation and subsequent photon-induced desorption of these species, studying the UV photoprocessing of pure ethanol ice, and a more realistic binary H2O:CH4 ice analog. Methods: Experimental simulations were performed in an ultra-high vacuum chamber. Pure ethanol and binary H2O:CH4 ice samples deposited onto an infrared transparent window at 8 K were UV-irradiated using a microwave-discharged hydrogen flow lamp. Evidence of photochemical production of these two species and subsequent UV-photon-induced desorption into the gas phase were searched for by means of a Fourier transform infrared spectrometer and a quadrupole mass spectrometer, respectively. After irradiation, ice samples were warmed up to room temperature until complete sublimation was attained for detection of volatile products. Results: Formation of CH3OH was only observed during photoprocessing of the H2O:CH4 ice analog, accounting for ~4% of the initial CH4 ice column density, but no photon-induced desorption was detected. Photochemical production of H2CO was observed in both series of experiments. Formation of formaldehyde accounted for ≤45% conversion of the initial ethanol ice, but it could not be quantified during

  6. Cortisol levels at baseline and under stress in adolescent males with attention-deficit hyperactivity disorder, with or without comorbid conduct disorder.

    PubMed

    Northover, Clare; Thapar, Anita; Langley, Kate; Fairchild, Graeme; van Goozen, Stephanie H M

    2016-08-30

    Reported findings on cortisol reactivity to stress in young people with ADHD are very variable. This inconsistency may be explained by high rates of comorbidity with Conduct Disorder (CD). The present study examined cortisol responses to a psychosocial stressor in a large sample of adolescent males with ADHD (n=202), with or without a comorbid diagnosis of Conduct Disorder (CD). Associations between stress reactivity and callous-unemotional traits and internalizing symptoms were also assessed. The ADHD only (n=95) and ADHD+CD (n=107) groups did not differ in baseline cortisol, but the ADHD+CD group showed significantly reduced cortisol stress reactivity relative to the ADHD only group. Regression analyses indicated that ADHD symptom severity predicted reduced baseline cortisol, whereas CD symptom severity predicted increased baseline cortisol (ADHD β=-0.24, CD β=0.16, R=0.26) and reduced cortisol stress reactivity (β=-0.17, R=0.17). Callous-unemotional traits and internalizing symptoms were not significantly related to baseline or stress-induced cortisol. Impaired cortisol reactivity is hypothesised to reflect fearlessness and is associated with deficient emotion regulation and inhibition of aggressive and antisocial behaviour. Consequently, it may partly explain the greater severity of problems seen in those with comorbid ADHD and CD. PMID:27280522

  7. Modeling from Local to Subsystem Level Effects in Analog and Digital Circuits Due to Space Induced Single Event Transients

    NASA Technical Reports Server (NTRS)

    Perez, Reinaldo J.

    2011-01-01

    Single Event Transients in analog and digital electronics from space generated high energetic nuclear particles can disrupt either temporarily and sometimes permanently the functionality and performance of electronics in space vehicles. This work first provides some insights into the modeling of SET in electronic circuits that can be used in SPICE-like simulators. The work is then directed to present methodologies, one of which was developed by this author, for the assessment of SET at different levels of integration in electronics, from the circuit level to the subsystem level.

  8. Mechanisms of cortisol action in fish hepatocytes.

    PubMed

    Faught, Erin; Vijayan, Mathilakath M

    2016-09-01

    Here we provide an overview of the mechanistic characterization of the hepatic action of cortisol during stress in fish. Cortisol is the main circulating glucocorticoid in fish and its action is mediated through its cytosolic receptor, the glucocorticoid receptor (GR), and regulates the expression of genes involved in growth, metabolism and immune function. When taken together, the data suggests that cortisol may be playing a key role in the energy substrate re-partitioning in hepatocytes to cope with stress. The proposed model is that cortisol upregulates pathways involved in energy substrate mobilization, including gluconeogenesis, while downregulating energy demanding pathways, including growth and immune function. Recent work also points to a role for cortisol in mediating rapid action that is non-genomic and includes modulation of secondary signalling cascades; however, the physiological relevance of these studies remains to be determined. Altogether, studies carried out in hepatocytes are bringing to fore the complex nature of the cortisol signalling pathways in the organismal stress response. The mode of actions and their physiological implications for stress coping awaits further study. PMID:27445122

  9. Relation of inflammation and liver function with the plasma cortisol response to adrenocorticotropin in early lactating dairy cows.

    PubMed

    Trevisi, E; Bertoni, G; Lombardelli, R; Minuti, A

    2013-09-01

    In this study we examined the relationship between cortisol and inflammatory status in early lactating dairy cows after a stimulation test of the adrenal cortex. Twenty-four cows were grouped into quartiles (6 cows per each quartile) in accordance with the liver activity index (based on plasma concentration of negative acute phase proteins in early lactation); the quartiles were lower (LO; cows with the lowest liver functionality), intermediate lower, intermediate upper, and upper (UP; cows with the highest liver functionality). Each cow was injected i.v. with 20 µg of a synthetic analog of ACTH at 35 d in milk (DIM). Blood samples were taken to assess inflammatory status, and at 0, 30, and 60 min after ACTH challenge to measure total cortisol. The free cortisol fraction was analyzed in the LO and UP quartiles and the bound cortisol fraction was estimated as the difference between total and free cortisol. The LO, in comparison with the other quartiles, suffered a more severe inflammatory status, with the highest values of haptoglobin, reactive oxygen metabolites, and total nitric oxide metabolites and the lowest concentration of direct or indirect markers of negative acute phase proteins. The cows in the LO quartile had the highest values of plasma nonesterified fatty acids and β-hydroxybutyrate at 7 DIM, suggesting a more severe body lipid mobilization. The LO quartile cows showed the highest frequency of health problems and the lowest milk yield in the first 35 DIM. Thirty minutes after the ACTH treatment, the concentration of total cortisol was lower in LO in comparison to other groups. Similarly, the bound cortisol fraction was lower in LO versus UP. The adrenal response appeared inversely related with health status after calving (e.g., lower in LO cows, experiencing the most severe inflammatory status). The lower increase in cortisol after the ACTH challenge in cows with greater inflammation (LO quartile) seems a consequence of the lower availability of

  10. Extraneuronal Monoamine Transporter Mediates the Permissive Action of Cortisol in the Guinea Pig Trachea: Possible Involvement of Tracheal Chondrocytes

    PubMed Central

    Wang, Chen; Qiu, Wenying; Zheng, Yiqing; Li, Hui; Li, Yijia; Feng, Bing; Guo, Shu; Yan, Li; Cao, Ji-Min

    2013-01-01

    Cortisol, a member of glucocorticoids, could potentiate the action of catecholamine by a non-genomic mechanism. Although this permissive effect has been well appreciated in the anti-asthmatic medication, the underlying signaling pathway has remained mysterious. Here, we show that extraneuronal monoamine transporter (EMT), a membraneous reuptake transporter for circulating catecholamine clearance, is the direct target of cortisol in its permissive effect. We found that BSA-conjugated cortisol, which functions as a cortisol but cannot penetrate cell membrane, enhanced the spasmolytic effect of β-adrenoceptor agonist (isoprenaline) in histamine-sensitized tracheal spirals of guinea pigs, and pharmacological inhibition of EMT with famotidine was powerful enough to imitate the permissive action of cortisol. To our surprise, EMT protein expression was high in the chondrocytes of tracheal cartilage, but was undetectable in tracheal smooth muscle cells. The functionality of EMT was further confirmed with measurement of catecholamine uptake by tracheal chondrocytes. Moreover, cortisol-initiated membrane signaling could activate protein kinase C (PKC), which phosphorylates EMT and induces its internalization via a lipid raft-dependent pathway. Both of the mechanisms slow down the reuptake process by chondrocytes, leading to extracellular catecholamine accumulation and results in a more profound adrenergic signaling activation in tracheal smooth muscle cells. Thus, an EMT-centered pathway was proposed to explain the permissive action of cortisol. Collectively, our results highlight the role of EMT in the crosstalk between glucocorticoid and catecholamine. EMT may represent a promising target for adrenergic signaling modulation. PMID:24098439

  11. Effects of coupled dose and rhythm manipulation of plasma cortisol levels on leukocyte transcriptional response to endotoxin challenge in humans.

    PubMed

    Kamisoglu, Kubra; Sleight, Kirsten; Nguyen, Tung T; Calvano, Steve E; Coyle, Susette M; Corbett, Siobhan A; Androulakis, Ioannis P

    2014-10-01

    Severe traumas are associated with hypercortisolemia due to both disruption of cortisol secretion rhythm and increase in its total concentration. Understanding the effects of altered cortisol levels and rhythms on immune function is of great clinical interest, to prevent conditions such as sepsis from complicating the recovery. This in vivo study assesses the responses of circulating leukocytes to coupled dose and rhythm manipulation of cortisol, preceding an immune challenge induced by endotoxin administration. Through continuous infusion, plasma cortisol concentration was increased to and kept constant at a level associated with major physiologic stress. In response, transcriptional programming of leukocytes was altered to display a priming response before endotoxin exposure. Enhanced expression of a number of receptors and signaling proteins, as well as lowered protein translation and mitochondrial function indicated a sensitization against potential infectious threats. Despite these changes, response to endotoxin followed very similar patterns in both cortisol and saline pre-treated groups except one cluster including probe sets associated with major players regulating inflammatory response. In sum, altered dose and rhythm of plasma cortisol levels engendered priming of circulating leukocytes when preceded an immune challenge. This transcriptional program change associated with stimulated surveillance function and suppressed energy-intensive processes, emphasized permissive actions of cortisol on immune function. PMID:24217219

  12. 4-Amino-2-arylamino-5-indoloyl/cinnamoythiazoles, analogs of topsentin-class of marine alkaloids, induce apoptosis in HeLa cells.

    PubMed

    Juneja, Manisha; Vanam, Uma; Paranthaman, Sripriya; Bharathan, Asha; Keerthi, Venugopal S; Reena, Justus K; Rajaram, Rama; Rajasekharan, Kallikat N; Karunagaran, Devarajan

    2013-05-01

    Marine organisms provide several biologically active compounds that include alkaloids with high cytotoxic activity but only a few of them have so far reached clinical stage, due partly to their limited supply and complex structural features. In an attempt to develop novel anticancer compounds, we have now synthesized diaminoindoloylthiazoles (4a-c; DIT1-3) and diaminocinnamoylthiazoles (5a,b; DCT1-2) as analogs based on a topsentin scaffold and investigated the cytotoxic and apoptotic activities of these compounds in HeLa cells. The results suggest that diaminoindoloylthiazoles (DIT1-3) inhibit cell growth and among these, DIT3 is the most cytotoxic against HeLa cells (IC50 1 μM). The diaminocinnamoylthiazoles DCT1 and DCT2, which can be viewed as curcumin-diaminothiazole hybrids, also inhibited cell growth but at relatively higher concentrations with IC50 values of 60 and 30 μM, respectively. These compounds induced apoptosis through the intrinsic pathway by reducing the mitochondrial membrane potential and activating caspases, 9 and 3, but not caspase 8. Among the marine alkaloid analogs tested in this study, DIT1-3 are very effective in inducing apoptosis of HeLa cells followed by DCT2 and DCT1. The treated cells were arrested in G2/M phase followed by accumulation of the cells in the Sub G0 phase. The curcumin-diaminothiazole hybrid DCT1 had the maximum effect in downregulating TNF-induced NF-κB activation among the compounds tested in this study. Thus, we demonstrate that diaminoindoloylthiazoles and diaminocinnamoylthiazoles induce apoptosis, regulate cell cycle and NF-κB signaling and thus show promising anticancer effects that warrant further investigation. PMID:23524113

  13. TM-233, a novel analog of 1′-acetoxychavicol acetate, induces cell death in myeloma cells by inhibiting both JAK/STAT and proteasome activities

    PubMed Central

    Sagawa, Morihiko; Tabayashi, Takayuki; Kimura, Yuta; Tomikawa, Tatsuki; Nemoto-Anan, Tomoe; Watanabe, Reiko; Tokuhira, Michihide; Ri, Masaki; Hashimoto, Yuichi; Iida, Shinsuke; Kizaki, Masahiro

    2015-01-01

    Although the introduction of bortezomib and immunomodulatory drugs has led to improved outcomes in patients with multiple myeloma, the disease remains incurable. In an effort to identify more potent and well-tolerated agents for myeloma, we have previously reported that 1′-acetoxychavicol acetate (ACA), a natural condiment from South-East Asia, induces apoptotic cell death of myeloma cells in vitro and in vivo through inhibition of NF-κB-related functions. Searching for more potent NF-κB inhibitors, we developed several ACA analogs based on quantitative structure–activity relationship analysis. TM-233, one of these ACA analogs, inhibited cellular proliferation and induced cell death in various myeloma cell lines with a lower IC50 than ACA. Treatment with TM-233 inhibited constitutive activation of JAK2 and STAT3, and then downregulated the expression of anti-apoptotic Mcl-1 protein, but not Bcl-2 and Bcl-xL proteins. In addition, TM-233 rapidly decreased the nuclear expression of NF-κB and also decreased the accumulation of cytosolic NF-κB. We also examined the effects of TM-233 on bortezomib-resistant myeloma cells that we recently established, KMS-11/BTZ and OPM-2/BTZ. TM-233, but not bortezomib, inhibited cellular proliferation and induced cell death in KMS-11/BTZ and OPM-2/BTZ cells. Interestingly, the combination of TM-233 and bortezomib significantly induced cell death in these bortezomib-resistant myeloma cells through inhibition of NF-κB activity. These results indicate that TM-233 could overcome bortezomib resistance in myeloma cells mediated through different mechanisms, possibly inhibiting the JAK/STAT pathway. In conclusion, TM-233 might be a more potent NF-κB inhibitor than ACA, and could overcome bortezomib resistance in myeloma cells. PMID:25613668

  14. Immunosensor with Fluid Control Mechanism for Salivary Cortisol Analysis

    PubMed Central

    Yamaguchi, Masaki; Matsuda, Yohei; Sasaki, Shohei; Sasaki, Makoto; Kadoma, Yoshihiro; Imai, Yoshikatsu; Niwa, Daisuke; Shetty, Vivek

    2012-01-01

    The purpose of this research is to demonstrate a new design for a cortisol immunosensor for the noninvasive and quantitative analysis of salivary cortisol. We propose a cortisol immunosensor with a fluid control mechanism which has both a vertical flow and a lateral flow. The detected current resulting from a competitive reaction between the sample cortisol and a glucose oxidase (GOD)-labeled cortisol conjugate was found to be inversely related to the concentration of cortisol in the sample solution. A calibration curve using the relative detected current showed an R2 = 0.98 and CV = 14% for a range of standard cortisol solutions corresponding to the concentrations of native salivary cortisol (0.1 – 10 ng/ml). The measurement could be accomplished within 35 minutes and the cortisol immunosensor could be reused. These results show promise for realizing an on-site and easy-to-use biosensor for cortisol. Used for evaluation of human salivary cortisol levels, the cortisol immunosensor measurement corresponded closely with commercially available ELISA method (R2 = 0.92). Our results indicate the promise of the new cortisol immunosensor for noninvasive, point-of care measurement of human salivary cortisol levels. PMID:22939507

  15. Cortisol Regulates Acid Secretion of H+-ATPase-rich Ionocytes in Zebrafish (Danio rerio) Embryos

    PubMed Central

    Lin, Chia-Hao; Shih, Tin-Han; Liu, Sian-Tai; Hsu, Hao-Hsuan; Hwang, Pung-Pung

    2015-01-01

    Systemic acid-base regulation is vital for physiological processes in vertebrates. Freshwater (FW) fish live in an inconstant environment, and thus frequently face ambient acid stress. FW fish have to efficiently modulate their acid secretion processes for body fluid acid-base homeostasis during ambient acid challenge; hormonal control plays an important role in such physiological regulation. The hormone cortisol was previously proposed to be associated with acid base regulation in FW fish; however, the underlying mechanism has not been fully described. In the present study, mRNA expression of acid-secreting related transporters and cyp11b (encoding an enzyme involved in cortisol synthesis) in zebrafish embryos was stimulated by treatment with acidic FW (AFW, pH 4.0) for 3 d. Exogenous cortisol treatment (20 mg/L, 3 d) resulted in upregulated expression of transporters related to acid secretion and increased acid secretion function at the organism level in zebrafish embryos. Moreover, cortisol treatment also significantly increased the acid secretion capacity of H+-ATPase-rich cells (HRCs) at the cellular level. In loss-of-function experiments, microinjection of glucocorticoid receptor (GR) morpholino (MO) suppressed the expression of acid-secreting related transporters, and decreased acid secretion function at both the organism and cellular levels; on the other hand, mineralocorticoid receptor (MR) MO did not induce any effects. Such evidence supports the hypothesized role of cortisol in fish acid-base regulation, and provides new insights into the roles of cortisol; cortisol-GR signaling stimulates zebrafish acid secretion function through transcriptional/translational regulation of the transporters and upregulation of acid secretion capacity in each acid-secreting ionocyte. PMID:26635615

  16. Interactive effects of early and recent exposure to stressful contexts on cortisol reactivity in middle childhood

    PubMed Central

    Jaffee, Sara R; McFarquhar, Tara; Stevens, Suzanne; Ouellet-Morin, Isabelle; Melhuish, Edward; Belsky, Jay

    2015-01-01

    Background Given mixed findings as to whether stressful experiences and relationships are associated with increases or decreases in children's cortisol reactivity, we tested whether a child's developmental history of risk exposure explained variation in cortisol reactivity to an experimentally induced task. We also tested whether the relationship between cortisol reactivity and children's internalizing and externalizing problems varied as a function of their developmental history of stressful experiences and relationships. Method Participants included 400 children (M = 9.99 years, SD = 0.74 years) from the Children's Experiences and Development Study. Early risk exposure was measured by children's experiences of harsh, nonresponsive parenting at 3 years. Recent risk exposure was measured by children's exposure to traumatic events in the past year. Children's cortisol reactivity was measured in response to a social provocation task and parents and teachers described children's internalizing and externalizing problems. Results The effect of recent exposure to traumatic events was partially dependent upon a child's early experiences of harsh, nonresponsive parenting: the more traumatic events children had recently experienced, the greater their cortisol reactivity if they had experienced lower (but not higher) levels of harsh, nonresponsive parenting at age 3. The lowest levels of cortisol reactivity were observed among children who had experienced the most traumatic events in the past year and higher (vs. lower) levels of harsh, nonresponsive parenting in early childhood. Among youth who experienced harsh, nonresponsive parent–child relationships in early childhood and later traumatic events, lower levels of cortisol reactivity were associated with higher levels of internalizing and externalizing problems. Conclusions Hypothalamic–pituitary–adrenal (HPA) axis reactivity to psychological stressors and the relationship between HPA axis reactivity and children

  17. Maternal transfer of bisphenol A impacts the ontogeny of cortisol stress response in rainbow trout.

    PubMed

    Birceanu, Oana; Mai, Trinh; Vijayan, Mathilakath M

    2015-11-01

    Bisphenol A (BPA) is widespread in the aquatic environment, and early life-stage exposure to this chemical affects growth and development in fish. We tested the hypothesis that BPA accumulation in eggs, mimicking maternal transfer, impacts the development and function of the hypothalamus-pituitary-interrenal (HPI) axis in rainbow trout (Oncorhynchus mykiss). To mimic maternal transfer, oocytes were loaded with 0 (control), 1, 4 and 40ng BPA embryo(-1). We measured the temporal changes in whole body cortisol content, transcript levels of corticosteroidogenesis-related genes and glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) protein expressions during early development. In addition, trout larvae were subjected to an acute stressor at key developmental stages (at hatch, just prior to first feed and post hatch) and whole body cortisol levels measured to assess the functional integrity of the HPI axis. The developmental profile of whole body cortisol content was altered in the 1 and 40ng BPA groups compared to the control group. Also, the two key rate-limiting steps in steroidogenesis, the steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage (P450scc) enzyme transcript levels were disrupted in the larvae originating from BPA accumulated eggs prior to first feed. Whole body GR and MR protein expressions were higher in the 40ng BPA group compared to other groups prior to first feed. Stressor-induced elevation in whole body cortisol levels were evident at 65 days post-fertilization (dpf) and later, but not at 42 dpf in trout larvae. This cortisol response to a stressor exposure was attenuated in the 4 and 40ng BPA groups at 65 dpf, but not at 140 dpf. Together, accumulation of BPA in eggs, mimicking maternal transfer of this chemical, disrupts the ontogeny of cortisol stress response in trout larvae and may compromise the target tissue responsiveness to cortisol stimulation during early development. PMID:26398930

  18. Suitability of saliva cortisol as a biomarker for hypothalamic-pituitary-adrenal axis activation assessment, effects of feeding actions, and immunostimulatory challenges in dairy cows.

    PubMed

    Schwinn, A-C; Knight, C H; Bruckmaier, R M; Gross, J J

    2016-06-01

    One of the most prominent physiological responses to stressors is the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, currently assessed by measuring cortisol concentration in blood plasma. To reduce animal discomfort during sampling, which negatively affects stress biomarkers, current research focuses on noninvasive sampling of media other than blood, for example, saliva. The aim of this study was to assess the suitability of saliva cortisol as a biomarker under different physiological and immunological states in dairy cows. Our objectives were to 1) evaluate the relationship between HPA axis activation and saliva cortisol concentration, 2) investigate effects of some feeding action (as influenced by feed and water consumption) on saliva cortisol concentration, and 3) evaluate the time lag between plasma and saliva cortisol during induced inflammatory conditions by intramammary lipopolysaccharide (LPS) and lipoteichoic acid (LTA) injection. During a specific activation of the HPA axis, a positive correlation ( = 0.75, < 0.0001) between saliva and blood cortisol concentrations was observed with increased ( < 0.01) plasma cortisol concentrations following ACTH administration. Saliva and blood samples were taken before, during, and after drinking, feeding, and ruminating. Only a low correlation between saliva and plasma cortisol concentrations ( = 0.03, = 0.83) but no significant effects of the different feeding actions on saliva cortisol were observed. When compared with basal concentrations, cortisol concentrations in plasma significantly increased during inflammatory responses following LPS and LTA injection. Compared with plasma cortisol, changes in saliva cortisol concentrations occurred at a much lower level within a narrow range and did not necessarily follow changes in plasma. In conclusion, the positive correlation between saliva and plasma cortisol concentration in response to ACTH and inflammation suggests the suitability of saliva

  19. Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses: do stereotypic horses cope better with poor environmental conditions?

    PubMed Central

    2013-01-01

    Background Stereotypic behaviours, i.e. repetitive behaviours induced by frustration, repeated attempts to cope and/or brain dysfunction, are intriguing as they occur in a variety of domestic and captive species without any clear adaptive function. Among the different hypotheses, the coping hypothesis predicts that stereotypic behaviours provide a way for animals in unfavourable environmental conditions to adjust. As such, they are expected to have a lower physiological stress level (glucocorticoids) than non-stereotypic animals. Attempts to link stereotypic behaviours with glucocorticoids however have yielded contradictory results. Here we investigated correlates of oral and motor stereotypic behaviours and glucocorticoid levels in two large samples of domestic horses (NStudy1 = 55, NStudy2 = 58), kept in sub-optimal conditions (e.g. confinement, social isolation), and already known to experience poor welfare states. Each horse was observed in its box using focal sampling (study 1) and instantaneous scan sampling (study 2). Plasma samples (collected in study 1) but also non-invasive faecal samples (collected in both studies) were retrieved in order to assess cortisol levels. Results Results showed that 1) plasma cortisol and faecal cortisol metabolites concentrations did not differ between horses displaying stereotypic behaviours and non-stereotypic horses and 2) both oral and motor stereotypic behaviour levels did not predict plasma cortisol or faecal cortisol metabolites concentrations. Conclusions Cortisol measures, collected in two large samples of horses using both plasma sampling as well as faecal sampling (the latter method minimizing bias due to a non-invasive sampling procedure), therefore do not indicate that stereotypic horses cope better, at least in terms of adrenocortical activity. PMID:23289406

  20. Sublethal responses of the striped mullet (Mugil cephalus L. ) to fluorene analogs

    SciTech Connect

    Wofford, H.W.

    1981-01-01

    Juvenile striped mullet (Mugil cephalus) were exposed for up to 12 days to 10 to 10,000 ..mu..g/l fluorene and three fluorene analogs (dibenzofuran, carbazole, and dibenzothiophene). These constituents of oil and coal were all acutely toxic to mullet at concentrations below their maximum solubility in seawater. The relative toxicity of the four analogs was related to their lipophilic nature and chemical reactivity. These pollutants were capable of inducing the corticosteroid stress response and resulting secondary stress responses in mullet. Plasma cortisol concentrations were significantly elevated, followed by a rise in plasma glucose. Responses were mild compared to those elicited by physical stress. Liver glycogen content was initially depressed, and later was restored to levels higher than the controls. Minor changes were observed in plasma lipids, with plasma triglyceride concentrations showing a consistent elevation upon exposure to dibenzofuran. Plasma osmolality was not significantly altered. Components of the xenobiotic metabolizing system of mullet were also affected by exposure to the four compounds. Large increases in liver glutathione concentration were observed, along with slight elevations in liver ascorbic acid content and ..beta..-glucuronidase activity. The fluorene analogs caused profound behavioral changes, which appeared to be related to a pharmacological effect on brain biogenic amine levels.

  1. Salivary Cortisone Reflects Cortisol Exposure Under Physiological Conditions and After Hydrocortisone.

    PubMed

    Debono, Miguel; Harrison, Robert F; Whitaker, Martin J; Eckland, David; Arlt, Wiebke; Keevil, Brian G; Ross, Richard J

    2016-04-01

    In this study we tested the use of salivary cortisol and cortisone as alternatives to serum cortisol. Salivary cortisol is often undetectable and contaminated by hydrocortisone. Salivary cortisone strongly reflects serum cortisol. PMID:26812690

  2. Summary cortisol reactivity indicators: Interrelations and meaning.

    PubMed

    Khoury, Jennifer E; Gonzalez, Andrea; Levitan, Robert D; Pruessner, Jens C; Chopra, Kevin; Basile, Vincenzo Santo; Masellis, Mario; Goodwill, Alasdair; Atkinson, Leslie

    2015-01-01

    Research on the hypothalamic pituitary adrenal (HPA) axis has involved a proliferation of cortisol indices. We surveyed recently published HPA-related articles and identified 15 such indices. We sought to clarify their biometric properties, specifically, how they interrelate and what they mean, because such information is rarely offered in the articles themselves. In the present article, the primary samples consist of community mothers and their infants (N = 297), who participated in two challenges, the Toy Frustration Paradigm and the Strange Situation Procedure. We sought to cross-validate findings from each of these samples against the other, and also against a clinically depressed sample (N = 48) and a sample of healthy older adults (N = 51) who participated in the Trier Social Stress Test. Cortisol was collected from all participants once before and twice after the challenges. These heterogenous samples were chosen to obtain the greatest possible range in cortisol levels and stress response regulation. Using these data, we computed the 15 summary cortisol indices identified in our literature survey. We assessed inter-relations amongst indices and determined their underlying dimensions via principal component analysis (PCA). The PCAs consistently extracted two components, accounting for 79%-93% of the variance. These components represent "total cortisol production" and "change in cortisol levels." The components were highly congruent across challenge, time, and sample. High variable loadings and explained factor variance suggest that all indices represent their underlying dimensions very well. Thus the abundance of summary cortisol indices currently represented in the literature appears superfluous. PMID:26844238

  3. Summary cortisol reactivity indicators: Interrelations and meaning

    PubMed Central

    Khoury, Jennifer E.; Gonzalez, Andrea; Levitan, Robert D.; Pruessner, Jens C.; Chopra, Kevin; Basile, Vincenzo Santo; Masellis, Mario; Goodwill, Alasdair; Atkinson, Leslie

    2015-01-01

    Research on the hypothalamic pituitary adrenal (HPA) axis has involved a proliferation of cortisol indices. We surveyed recently published HPA-related articles and identified 15 such indices. We sought to clarify their biometric properties, specifically, how they interrelate and what they mean, because such information is rarely offered in the articles themselves. In the present article, the primary samples consist of community mothers and their infants (N = 297), who participated in two challenges, the Toy Frustration Paradigm and the Strange Situation Procedure. We sought to cross-validate findings from each of these samples against the other, and also against a clinically depressed sample (N = 48) and a sample of healthy older adults (N = 51) who participated in the Trier Social Stress Test. Cortisol was collected from all participants once before and twice after the challenges. These heterogenous samples were chosen to obtain the greatest possible range in cortisol levels and stress response regulation. Using these data, we computed the 15 summary cortisol indices identified in our literature survey. We assessed inter-relations amongst indices and determined their underlying dimensions via principal component analysis (PCA). The PCAs consistently extracted two components, accounting for 79%–93% of the variance. These components represent “total cortisol production” and “change in cortisol levels.” The components were highly congruent across challenge, time, and sample. High variable loadings and explained factor variance suggest that all indices represent their underlying dimensions very well. Thus the abundance of summary cortisol indices currently represented in the literature appears superfluous. PMID:26844238

  4. The rapid immunosuppression in phytohemagglutinin-activated human T cells is inhibited by the proliferative Ca(2+) influx induced by progesterone and analogs.

    PubMed

    Lin, Veronica Hui-Chen; Chen, Jiann-Jong; Liao, Chen-Chung; Lee, Shinn-Shing; Chien, Eileen Jea

    2016-07-01

    Progesterone, an endogenous immunomodulator, suppresses human T-cell activation during pregnancy. A sustained Ca(2 +) influx is an important signal for T-cell proliferation after crosslinking of T-cell receptor/CD3 complexes by anti-CD3 antibodies or phytohemagglutinin (PHA). Progesterone targets cell membrane sites inducing rapid responses including elevated intracellular free calcium concentration ([Ca(2+)]i) and suppressed T-cell PHA-activated proliferation. Interestingly, both PHA and progesterone induce [Ca(2+)]i elevation, but it remains unclear whether the PHA-induced Ca(2+) influx is affected by progesterone leading to T-cell immunosuppression. Primary T-cells were isolated from human peripheral blood and the quench effect on intracellular fura-2 fluorescence of Mn(2+) was used to explore the responses to Ca(2+) influx with cell proliferation being determined by MTT assay. PHA-stimulated Ca(2+) influx was dose-dependently suppressed by progesterone and its agonist R5020, which correlated with PHA-activated T-cell proliferation inhibition. A similar dose-dependent suppression effect on cellular Ca(2+) influx and proliferation occurred with the TRPC channel inhibitor BTP2 and selective TRPC3 channel inhibitor Pyr3. In addition, two progesterone analogs, Org OD 02-0 and 20α-hydroxyprogesterone (20α-OHP), also produced dose-dependent suppression of Ca(2+) influx, but had no effect on proliferation. Finally, inhibition of PHA-activated T-cell proliferation by progesterone is further suppressed by 20α-OHP, but not by Org OD 02-0. Overall, progesterone and R5020 are able to rapidly decrease PHA-stimulated sustained Ca(2+) influx, probably via blockade of TRPC3 channels, which suppresses T-cell proliferation. Taken together, the roles of progesterone and its analogs regarding the rapid response Ca(2+) influx need to be further explored in relation to cytokine secretion and proliferation in activated T-cells. PMID:26808612

  5. Cytotoxicity Induced by a Redox-silent Analog of Tocotrienol in Human Mesothelioma H2452 Cell Line via Suppression of Cap-dependent Protein Translation.

    PubMed

    Sato, Ayami; Ueno, Haruka; Takase, Akari; Ando, Akira; Sekine, Yuko; Yano, Tomohiro

    2016-04-01

    De novo synthesis of proteins is regulated by cap-dependent protein translation. Aberrant activation of the translation is a hallmark of many cancer types including malignant mesothelioma (MM). We previously reported that a redox-silent analog of α-tocotrienol, 6-O-carboxypropyl-α-tocotrienol (T3E) induces potent cytotoxicity against human MM cells. However, the detailed mechanism of cytotoxicity of T3E remains unclear. In this study, we investigated if T3E induced potent cytotoxicity aganist MM cells. T3E reduced the formation of the cap-dependent translation complex and induced inactivation of oncogene from rat sarcoma virus (RAS). These events were associated with T3E cytotoxicity in MM cells. Furthermore, atorvastatin, an inhibitor of RAS function, had similar effects on MM cells. Moreover, 4EGI-1, a specific inhibitor of the cap-dependent translation complex, induced severe cytotoxicity in MM cells. Overall, T3E had a cytotoxic effect on MM cells via disruption of the activated cap-dependent translation complex through inactivation of RAS. PMID:27069128

  6. A novel double carbonyl analog of curcumin induces the apoptosis of human lung cancer H460 cells via the activation of the endoplasmic reticulum stress signaling pathway.

    PubMed

    Ye, Hui; Wei, Xiaoyan; Wang, Zhankun; Zhang, Shanshan; Ren, Jiye; Yao, Song; Shi, Lingyi; Yang, Lizhu; Qiu, Peihong; Wu, Jianzhang; Liang, Guang

    2016-09-01

    Curcumin can inhibit the growth of a variety of cancer cells; however, its poor bioavailability and pharmacokinetic profiles, which are attributed to its instability under physiological conditions, have limited its application in anticancer therapy. In the present study, we screened a double carbonyl analog of curcumin (A17) and analyzed its effects and mechanism of inducing apoptosis in human lung cancer H460 cells. The results showed that A17 not only induced CHOP expression in human lung cancer H460 cells, but also induced the apoptosis of H460 cells in a dose-responsive manner, and this effect was related to corresponding activation of some important components in the endoplasmic reticulum (ER) stress-mediated apoptosis pathway. When CHOP was knocked down by specific siRNA, A17-induced cell apoptosis was attenuated, thereby further demonstrating that the apoptotic pathway is ER stress‑dependent. Our studies demonstrated that A17 has better stability and antitumor activity than curcumin in H460 cells via an ER stress-mediated mechanism. These results imply that A17 could be further explored as a potential anticancer agent for the treatment of human non-small cell lung cancer (NSCLC). PMID:27431486

  7. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

    SciTech Connect

    Cheng, Li-Chuan; Li, Lih-Ann

    2012-02-01

    CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

  8. Daily or thrice weekly handling of eland antelope (Taurotragus oryx): effects on serum cortisol level.

    PubMed

    Pennington, P M; Pope, C E; MacLean, R A; Galiguis, J; Gentry, L R; Godke, R A; Wirtu, G

    2013-06-01

    We evaluated the cortisol response of adult female eland (n=8) that were handled in hydraulic chute daily or 3×/week. Females were divided into two groups and each group (n=4) successively received two estrous cycle synchronization treatments: (1) two injections of prostaglandin (PG-PG) F2α at 11 day intervals and (2) oral administration of altrenogest for 7 days and an injection of PGF2α on day 7 (Alt-PG). Blood samples were collected 3×/week during the synchronization (Synch) and expected luteal phase (Nonintensive) periods, and daily during the expected time of induced (Intensive 1) or natural (Intensive 2) estrus. Overall, mean cortisol levels were highest during Intensive 1, followed by Intensive 2, Synch and Nonintensive periods. Individual eland were the most significant source of variation for cortisol level. The frequency of handling and the synchronization treatment significantly affected cortisol levels in 3/8 and 4/8 females, respectively. In conclusion, in response to increased frequency of handling, eland cortisol levels rose transiently and returned to baseline within few days after more intensive handling. Thus, the eland females were tolerant to and recovered from the effects of repeated daily handling. PMID:23290948

  9. Impaired memory retrieval correlates with individual differences in cortisol response but not autonomic response

    PubMed Central

    Buchanan, Tony W.; Tranel, Daniel; Adolphs, Ralph

    2006-01-01

    Stress can enhance or impair memory performance. Both cortisol release and sympathetic nervous system responses have been implicated in these differential effects. Here we investigated how memory retrieval might be affected by stress-induced cortisol release, independently of sympathetic nervous system stress responses. Thirty-two healthy participants (16 women) learned emotionally arousing and neutral words. One hour later, half of the participants underwent a stressor (cold pressor test) and the other half, a control warm water exposure, both followed by a delayed free recall task. The stressed participants were split into those who did (responders, N = 8) and those who did not (nonresponders, N = 6) show a cortisol response. Both responders and nonresponders showed comparable sympathetic nervous system activity (skin conductance level) during the cold pressor. The cortisol responders recalled significantly fewer words compared to nonresponders, and compared to control participants; this effect was most pronounced for moderately arousing words (compared to highly arousing and neutral words). These results suggest that individual differences in cortisol reactivity affect memory retrieval performance, and help to explain the differential effects of stress on memory. PMID:16741288

  10. Technical and clinical aspects of cortisol as a biochemical marker of chronic stress

    PubMed Central

    Lee, Do Yup; Kim, Eosu; Choi, Man Ho

    2015-01-01

    Stress is now recognized as a universal premorbid factor associated with many risk factors of various chronic diseases. Acute stress may induce an individual’s adaptive response to environmental demands. However, chronic, excessive stress causes cumulative negative impacts on health outcomes through “allostatic load”. Thus, monitoring the quantified levels of long-term stress mediators would provide a timely opportunity for prevention or earlier intervention of stressrelated chronic illnesses. Although either acute or chronic stress could be quantified through measurement of changes in physiological parameters such as heart rate, blood pressure, and levels of various metabolic hormones, it is still elusive to interpret whether the changes in circulating levels of stress mediators such as cortisol can reflect the acute, chronic, or diurnal variations. Both serum and salivary cortisol levels reveal acute changes at a single point in time, but the overall long-term systemic cortisol exposure is difficult to evaluate due to circadian variations and its protein-binding capacity. Scalp hair has a fairy predictable growth rate of approximately 1 cm/month, and the most 1 cm segment approximates the last month’s cortisol production as the mean value. The analysis of cortisol in hair is a highly promising technique for the retrospective assessment of chronic stress. [BMB Reports 2015; 48(4): 209-216] PMID:25560699

  11. Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation.

    PubMed

    Hartig, Ellen I; Zhu, Shusen; King, Benjamin L; Coffman, James A

    2016-01-01

    Chronic early-life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with cortisol and examined the effects on both larvae and adults. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and upregulated genes associated with defense response and immune system processes. In adulthood the treated fish maintained elevated basal cortisol levels in the absence of exogenous cortisol, and constitutively mis-expressed genes involved in defense response and its regulation. Adults derived from cortisol-treated embryos displayed defective tailfin regeneration, heightened basal expression of pro-inflammatory genes, and failure to appropriately regulate those genes following injury or immunological challenge. These results support the hypothesis that chronically elevated glucocorticoid signaling early in life directs development of a pro-inflammatory adult phenotype, at the expense of immunoregulation and somatic regenerative capacity. PMID:27444789

  12. Cortisol-treated zebrafish embryos develop into pro-inflammatory adults with aberrant immune gene regulation

    PubMed Central

    Hartig, Ellen I.; Zhu, Shusen; King, Benjamin L.

    2016-01-01

    ABSTRACT Chronic early-life stress increases adult susceptibility to numerous health problems linked to chronic inflammation. One way that this may occur is via glucocorticoid-induced developmental programming. To gain insight into such programming we treated zebrafish embryos with cortisol and examined the effects on both larvae and adults. Treated larvae had elevated whole-body cortisol and glucocorticoid signaling, and upregulated genes associated with defense response and immune system processes. In adulthood the treated fish maintained elevated basal cortisol levels in the absence of exogenous cortisol, and constitutively mis-expressed genes involved in defense response and its regulation. Adults derived from cortisol-treated embryos displayed defective tailfin regeneration, heightened basal expression of pro-inflammatory genes, and failure to appropriately regulate those genes following injury or immunological challenge. These results support the hypothesis that chronically elevated glucocorticoid signaling early in life directs development of a pro-inflammatory adult phenotype, at the expense of immunoregulation and somatic regenerative capacity. PMID:27444789

  13. Celastrol Analogs as Inducers of the Heat Shock Response. Design and Synthesis of Affinity Probes for the Identification of Protein Targets

    PubMed Central

    Klaić, Lada; Morimoto, Richard I.; Silverman, Richard B.

    2012-01-01

    The natural product celastrol (1) possesses numerous beneficial therapeutic properties and affects numerous cellular pathways. The mechanism of action and cellular target(s) of celastrol, however, remain unresolved. While a number of studies have proposed that the activity of celastrol is mediated through reaction with cysteine residues, these observations have been based on studies with specific proteins or by in vitro analysis of a small fraction of the proteome. In this study, we have investigated the spatial and structural requirements of celastrol for the design of suitable affinity probes to identify cellular binding partners of celastrol. Although celastrol has several potential sites for modification, some of these were not synthetically amenable or yielded unstable analogs. Conversion of the carboxylic acid functionality to amides and long-chain analogs, however, yielded bioactive compounds that induced the heat shock response (HSR) and antioxidant response and inhibited Hsp90 activity. This led to the synthesis of biotinylated celastrols (23 and 24) that were used as affinity reagents in extracts of human Panc-1 cells to identify Annexin II, eEF1A, and β-tubulin as potential targets of celastrol. PMID:22380712

  14. Homocysteine, Cortisol, Diabetes Mellitus, and Psychopathology

    PubMed Central

    Kontoangelos, K.; Papageorgiou, C. C.; Raptis, A. E.; Tsiotra, P.; Lambadiari, V.; Papadimitriou, G. N.; Rabavilas, A. D.; Dimitriadis, G.; Raptis, S. A.

    2015-01-01

    Objective. This study investigates the association of homocysteine and cortisol with psychological factors in type 2 diabetic patients. Method. Homocysteine, cortisol, and psychological variables were analyzed from 131 diabetic patients. Psychological factors were assessed with the Eysenck Personality Questionnaire (EPQ), Hostility and Direction of Hostility Questionnaire (HDHQ), the Symptom Checklist 90-R (SCL 90-R), the Zung Self-Rating Depression Scale (ZDRS), and the Maudsley O-C Inventory Questionnaire (MOCI). Blood samples were taken by measuring homocysteine and cortisol in both subgroups during the initial phase of the study (T0). One year later (T1), the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments and with an identical blood analysis. Results. The relation of psychoticism and homocysteine is positive among controlled diabetic patients (P value = 0.006 < 0.05) and negative among uncontrolled ones (P value = 0.137). Higher values of cortisol correspond to lower scores on extraversion subscale (rp = −0.223, P value = 0.010). Controlled diabetic patients showed a statistically significant negative relationship between homocysteine and the act-out hostility subscale (rsp = −0.247, P = 0.023). There is a statistically significant relationship between homocysteine and somatization (rsp = −0.220, P = 0.043). Conclusions. These findings support the notion that homocysteine and cortisol are related to trait and state psychological factors in patients with diabetes mellitus type 2. PMID:25722989

  15. Relationships among salivary immunoglobulin A, lactoferrin and cortisol in basketball players during a basketball season.

    PubMed

    He, Cheng-Shiun; Tsai, Min-Lung; Ko, Miau-Hwa; Chang, Chen-Kang; Fang, Shih-Hua

    2010-11-01

    The aim of this study was to examine the changes and relationships of immune and stress parameters of basketball players during a basketball season. Eight members of National Taichung University basketball team volunteered to participate. Saliva samples were collected at rest and before the start of practice or competition at seven time points during the intense training, competition and recovery period. Salivary immunoglobulin A (sIgA), cortisol, and lactoferrin were measured during training and competition period and compared with those measured at the fourth recovery week. Relationships among immune and stress parameters were evaluated. Compared with those detected at the fourth recovery week, significant decreases in secretion rates and absolute concentrations of sIgA and lactoferrin were observed at times of intense training and competition. In addition, significant increases in secretion rates and absolute concentrations of salivary cortisol were observed during intense training and competition period and the first week of recovery. Moreover, a significant inverse correlation (r = -0.28; P < 0.05) that existed between secretion rates of sIgA and cortisol as well as a positive correlation (r = 0.32; P < 0.05) that existed between secretion rates of sIgA and lactoferrin was measured. Our results demonstrated that the secreted cortisol was induced and the mucosal immunity of the participants was suppressed during the basketball season. The inverse correlation existed between secretion rates of sIgA and cortisol may indicate a possible role of cortisol in the strenuous exercise-induced immunosuppression. Our results also suggest that a delicate balance may exist between mucosal innate and adaptive immune responses. PMID:20668874

  16. Cortisol affects metabolic and ionoregulatory responses to a different extent depending on feeding ration in common carp, Cyprinus carpio.

    PubMed

    Liew, Hon Jung; Fazio, Angela; Faggio, Caterina; Blust, Ronny; De Boeck, Gudrun

    2015-11-01

    Interacting effects of feeding and stress on corticoid responses in fish were investigated in common carp fed 3.0% or 0.5% body mass (BM) which received no implant, a sham or a cortisol implant (250 mg/kg BM) throughout a 168 hour post-implant period (168 h-PI). At 12h-PI, cortisol implants elevated plasma cortisol, glucose and lactate. Plasma osmolality and ions remained stable, but cortisol increased gill and kidney Na(+)/K(+) ATPase (NKA) and H(+) ATPase activities. Gill NKA activities were higher at 3%-BM, whereas kidney H(+) ATPase activity was greater at 0.5%-BM. Cortisol induced liver protein mobilization and repartitioned liver and muscle glycogen. At 3%-BM, this did not increase plasma ammonia, reflecting improved excretion efficiency concomitant with upregulation of Rhesus glycoprotein Rhcg-1 in gill. Responses in glucocorticoid receptors (GR1/GR2) and mineralocorticoid receptor (MR) to cortisol elevation were most prominent in kidney with increased expression of all receptors at 24 h-PI at 0.5%-BM, but only GR2 and MR at 0.5%-BM. In the liver, upregulation of all receptors occurred at 24 h-PI at 3%-BM, whilst only GR2 and MR were upregulated at 0.5%-BM. In the gill, there was a limited upregulation: GR2 and MR at 72 h-PI and GR1 at 168 h-PI at 3%-BM but only GR2 at 72 h-PI at 0.5%-BM. Thus cortisol elevation led to similar expression patterns of cortisol receptors in both feeding regimes, while feeding affected the type of receptor that was induced. Induction of corticoid receptors occurred simultaneously with increases in Rhcg-1 mRNA expression (gill) but well after NKA and H(+) ATPase activities increased (gill/kidney). PMID:26219478

  17. Phase shift multiplication effect of all-optical analog to electromagnetically induced transparency in two micro-cavities side coupled to a waveguide system

    SciTech Connect

    Wang, Boyun; Wang, Tao Tang, Jian; Li, Xiaoming; Dong, Chuanbo

    2014-01-14

    We propose phase shift multiplication effect of all-optical analog to electromagnetically induced transparency in two photonic crystal micro-cavities side coupled to a waveguide system through external optical pump beams. With dynamically tuning the propagation phase of the line waveguide, the phase shift of the transmission spectrum in two micro-cavities side coupled to a waveguide system is doubled along with the phase shift of the line waveguide. π-phase shift and 2π-phase shift of the transmission spectrum are obtained when the propagation phase of the line waveguide is tuned to 0.5π-phase shift and π-phase shift, respectively. All observed schemes are analyzed rigorously through finite-difference time-domain simulations and the coupled-mode formalism. These results show a new direction to the miniaturization and the low power consumption of microstructure integration photonic devices in optical communication and quantum information processing.

  18. All-optical Mach-Zehnder interferometer switching based on the phase-shift multiplication effect of an analog on the electromagnetically induced transparency effect

    NASA Astrophysics Data System (ADS)

    Wang, Boyun; Xiong, Liangbin; Zeng, Qingdong; Chen, Zhihong; Lv, Hao; Ding, Yaoming; Du, Jun; Yu, Huaqing

    2016-06-01

    We theoretically and numerically investigate all-optical Mach-Zehnder interferometer switching based on the phase-shift multiplication effect of an all-optical analog on the electromagnetically induced transparency effect. The free-carrier plasma dispersion effect modulation method is applied to improve the tuning rate with a response time of picoseconds. All observed schemes are analyzed rigorously through finite-difference time-domain simulations and coupled-mode formalism. Compared with no phase-shift multiplication effect, the average pump power of all-optical switching required to yield the π-phase shift difference decreases by 55.1%, and the size of the modulation region is reduced by 50.1% when the average pump power reaches 60.8 mW. This work provides a new direction for low-power consumption and miniaturization of microstructure integration light-controlled switching devices in optical communication and quantum information processing.

  19. Effects of Binary Mixtures of Inducers (Toluene Analogs) and of Metals on Bioluminescence Induction of a Recombinant Bioreporter Strain

    PubMed Central

    Kong, In Chul

    2014-01-01

    This paper investigated the effects of binary mixtures of bioluminescence inducers (toluene, xylene isomers, m-toluate) and of metals (Cu, Cd, As(III), As(V), and Cr) on bioluminescence activity of recombinant (Pm-lux) strain KG1206. Different responses and sensitivities were observed depending on the types and concentrations of mixtures of inducers or metals. In the case of inducer mixtures, antagonistic and synergistic modes of action were observed, whereas metal mixtures showed all three modes of action. Antagonistic mode of action was most common for mixtures of indirect inducers, which showed bioluminescence ranging from 29% to 62% of theoretically expected effects (P(E)). On the other hand, synergistic mode of action was observed for mixtures of direct and indirect inducers, which showed bioluminescence between 141% and 243% of P(E).In the case of binary metal mixtures, bioluminescence activities were ranged from 62% to 75% and 113% to 164% of P(E) for antagonistic and synergistic modes of action, respectively (p-values 0.0001–0.038). Therefore, mixture effects could not be generalized since they were dependent on both the types and concentrations of chemicals, suggesting that biomonitoring may constitute a better strategy by investigating types and concentrations of mixture pollutants at contaminated sites. PMID:25313497

  20. Stress, cortisol, and obesity: a role for cortisol responsiveness in identifying individuals prone to obesity.

    PubMed

    Hewagalamulage, S D; Lee, T K; Clarke, I J; Henry, B A

    2016-07-01

    There is a strong inter-relationship between activation of the hypothalamo-pituitary-adrenal axis and energy homeostasis. Patients with abdominal obesity have elevated cortisol levels. Furthermore, stress and glucocorticoids act to control both food intake and energy expenditure. In particular, glucocorticoids are known to increase the consumption of foods enriched in fat and sugar. It is well-known that, in all species, the cortisol response to stress or adrenocorticotropin is highly variable. It has now emerged that cortisol responsiveness is an important determinant in the metabolic sequelae to stress. Sheep that are characterized as high-cortisol responders (HRs) have greater propensity to weight gain and obesity than low-cortisol responders (LRs). This difference in susceptibility to become obese is associated with a distinct metabolic, neuroendocrine, and behavioral phenotype. In women and ewes, HR individuals eat more in response to stress than LR. Furthermore, HR sheep have impaired melanocortin signaling and reduced skeletal muscle thermogenesis. High-cortisol responder sheep exhibit reactive coping strategies, whereas LRs exhibit proactive coping strategies. This complex set of traits leads to increased food intake and reduced energy expenditure in HR and thus, predisposition to obesity. We predict that cortisol responsiveness may be used as a marker to identify individuals who are at risk of weight gain and subsequent obesity. PMID:27345309

  1. Enantiomeric Excesses Induced in Amino Acids by Ultraviolet Circularly Polarized Light Irradiation of Extraterrestrial Ice Analogs: A Possible Source of Asymmetry for Prebiotic Chemistry

    NASA Astrophysics Data System (ADS)

    Modica, Paola; Meinert, Cornelia; de Marcellus, Pierre; Nahon, Laurent; Meierhenrich, Uwe J.; Le Sergeant d'Hendecourt, Louis

    2014-06-01

    The discovery of meteoritic amino acids with enantiomeric excesses of the L-form (ee L) has suggested that extraterrestrial organic materials may have contributed to prebiotic chemistry and directed the initial occurrence of the ee L that further led to homochirality of amino acids on Earth. A proposed mechanism for the origin of ee L in meteorites involves an asymmetric photochemistry of extraterrestrial ices by UV circularly polarized light (CPL). We have performed the asymmetric synthesis of amino acids on achiral extraterrestrial ice analogs by VUV CPL, investigating the chiral asymmetry transfer at two different evolutionary stages at which the analogs were irradiated (regular ices and/or organic residues) and at two different photon energies (6.6 and 10.2 eV). We identify 16 distinct amino acids and precisely measure the L-enantiomeric excesses using the enantioselective GC × GC-TOFMS technique in five of them: α-alanine, 2,3-diaminopropionic acid, 2-aminobutyric acid, valine, and norvaline, with values ranging from ee L = -0.20% ± 0.14% to ee L = -2.54% ± 0.28%. The sign of the induced ee L depends on the helicity and the energy of CPL, but not on the evolutionary stage of the samples, and is the same for all five considered amino acids. Our results support an astrophysical scenario in which the solar system was formed in a high-mass star-forming region where icy grains were irradiated during the protoplanetary phase by an external source of CPL of a given helicity and a dominant energy, inducing a stereo-specific photochemistry.

  2. Enantiomeric excesses induced in amino acids by ultraviolet circularly polarized light irradiation of extraterrestrial ice analogs: A possible source of asymmetry for prebiotic chemistry

    SciTech Connect

    Modica, Paola; De Marcellus, Pierre; D'Hendecourt, Louis Le Sergeant; Meinert, Cornelia; Meierhenrich, Uwe J.; Nahon, Laurent E-mail: ldh@ias.u-psud.fr

    2014-06-10

    The discovery of meteoritic amino acids with enantiomeric excesses of the L-form (ee {sub L}) has suggested that extraterrestrial organic materials may have contributed to prebiotic chemistry and directed the initial occurrence of the ee {sub L} that further led to homochirality of amino acids on Earth. A proposed mechanism for the origin of ee {sub L} in meteorites involves an asymmetric photochemistry of extraterrestrial ices by UV circularly polarized light (CPL). We have performed the asymmetric synthesis of amino acids on achiral extraterrestrial ice analogs by VUV CPL, investigating the chiral asymmetry transfer at two different evolutionary stages at which the analogs were irradiated (regular ices and/or organic residues) and at two different photon energies (6.6 and 10.2 eV). We identify 16 distinct amino acids and precisely measure the L-enantiomeric excesses using the enantioselective GC × GC-TOFMS technique in five of them: α-alanine, 2,3-diaminopropionic acid, 2-aminobutyric acid, valine, and norvaline, with values ranging from ee {sub L} = –0.20% ± 0.14% to ee {sub L} = –2.54% ± 0.28%. The sign of the induced ee {sub L} depends on the helicity and the energy of CPL, but not on the evolutionary stage of the samples, and is the same for all five considered amino acids. Our results support an astrophysical scenario in which the solar system was formed in a high-mass star-forming region where icy grains were irradiated during the protoplanetary phase by an external source of CPL of a given helicity and a dominant energy, inducing a stereo-specific photochemistry.

  3. Ventral Midbrain NTS1 Receptors Mediate Conditioned Reward Induced by the Neurotensin Analog, D-Tyr[11]neurotensin

    PubMed Central

    Rouibi, Khalil; Bose, Poulomee; Rompré, Pierre-Paul; Warren, Richard A.

    2015-01-01

    The present study was aimed at characterizing the mechanisms by which neurotensin (NT) is acting within the ventral midbrain to induce a psychostimulant-like effect. In a first experiment, we determine which subtype(s) of NT receptors is/are involved in the reward-inducing effect of ventral midbrain microinjection of NT using the conditioned place-preference (CPP) paradigm. In a second study, we used in vitro patch clamp recording technique to characterize the NT receptor subtype(s) involved in the modulation of glutamatergic neurotransmission (excitatory post-synaptic current, EPSC) in ventral tegmental neurons that expressed (Ih+), or do not express (Ih-), a hyperpolarization-activated cationic current. Behavioral studies were performed with adult male Long-Evans rats while electrophysiological recordings were obtained from brain slices of rat pups aged between 14 and 21 days. Results show that bilateral ventral midbrain microinjections of 1.5 and 3 nmol of D-Tyr[11]NT induced a CPP that was respectively attenuated or blocked by co-injection with 1.2 nmol of the NTS1/NTS2 antagonist, SR142948, and the preferred NTS1 antagonist, SR48692. In electrophysiological experiments, D-Tyr[11]NT (0.01-0.5 μM) attenuated glutamatergic EPSC in Ih+ but enhanced it in Ih- neurons. The attenuation effect (Ih+ neurons) was blocked by SR142948 (0.1 μM) while the enhancement effect (Ih- neurons) was blocked by both antagonists (0.1 μM). These findings suggest that (i) NT is acting on ventral midbrain NTS1 receptors to induce a rewarding effect and (ii) that this psychostimulant-like effect could be due to a direct action of NT on dopamine neurons and/or an enhancement of glutamatergic inputs to non-dopamine (Ih-) neurons. PMID:26733785

  4. Acute stress differentially affects spatial configuration learning in high and low cortisol-responding healthy adults

    PubMed Central

    Meyer, Thomas; Smeets, Tom; Giesbrecht, Timo; Quaedflieg, Conny W. E. M.; Merckelbach, Harald

    2013-01-01

    Background Stress and stress hormones modulate memory formation in various ways that are relevant to our understanding of stress-related psychopathology, such as posttraumatic stress disorder (PTSD). Particular relevance is attributed to efficient memory formation sustained by the hippocampus and parahippocampus. This process is thought to reduce the occurrence of intrusions and flashbacks following trauma, but may be negatively affected by acute stress. Moreover, recent evidence suggests that the efficiency of visuo-spatial processing and learning based on the hippocampal area is related to PTSD symptoms. Objective The current study investigated the effect of acute stress on spatial configuration learning using a spatial contextual cueing task (SCCT) known to heavily rely on structures in the parahippocampus. Method Acute stress was induced by subjecting participants (N = 34) to the Maastricht Acute Stress Test (MAST). Following a counterbalanced within-subject approach, the effects of stress and the ensuing hormonal (i.e., cortisol) activity on subsequent SCCT performance were compared to SCCT performance following a no-stress control condition. Results Acute stress did not impact SCCT learning overall, but opposing effects emerged for high versus low cortisol responders to the MAST. Learning scores following stress were reduced in low cortisol responders, while high cortisol-responding participants showed improved learning. Conclusions The effects of stress on spatial configuration learning were moderated by the magnitude of endogenous cortisol secretion. These findings suggest a possible mechanism by which cortisol responses serve an adaptive function during stress and trauma, and this may prove to be a promising route for future research in this area. PMID:23671762

  5. Administration of somatostatin analog octreotide in the ventrolateral orbital cortex produces sex-related antinociceptive effects on acute and formalin-induced nociceptive behavior in rats.

    PubMed

    Qu, Chao-Ling; Dang, Yong-Hui; Tang, Jing-Shi

    2015-08-01

    The present study was designed to examine whether somatostatin analog octreotide (OCT) was involved in antinociception in the ventrolateral orbital cortex (VLO) and determine whether this effect had a sex difference between male and female rats. The radiant heat-evoked tail flick (TF) reflex was used as an index of acute nociceptive response in lightly anesthetized rats. The number of flinches evoked by formalin injection into the hindpaw was used to evaluate inflammatory persistent pain in conscious rats. Administration of OCT (2.0, 5.0 10.0 ng in 0.5 µl) into the VLO depressed the TF reflex in a dose-dependent manner only in female rats, but not male rats. Pretreatment with a nonselective somatostatin receptor antagonist cyclo-somatostatin (c-SOM) (25.0 µg in 0.5 µl) into the VLO antagonized 10.0 ng OCT-induced inhibition of the TF reflex in female rats. Similarly, application of high dose of OCT (10.0 ng in 0.5 µl) into the VLO depressed formalin-induced flinching response in the early and late phases only in female rats, and had no any effects in male rats. Pretreatment with c-SOM (25.0 µg in 0.5 µl) into the VLO totally antagonized the 10 ng OCT-induced inhibition of the flinches in both phases in female rats. Additionally, single administration of c-SOM into the VLO failed to alter tail reflex latencies and formalin-induced nociceptive behaviors in female rats. The results provide the first valuable evidence that somatostatin and its receptors are involved in antinociception in acute heat-evoked nociception and inflammatory persistent pain only in female rats, not male rats, in the VLO. PMID:26055971

  6. Analogs of the novel phytohormone, strigolactone, trigger apoptosis and synergize with PARP inhibitors by inducing DNA damage and inhibiting DNA repair

    PubMed Central

    Ryan, Colin P.; Wang, Victor S.; Lapier, Jennifer; Schlarbaum, Jamie P.; Dayani, Yaron; Artuso, Emma; Prandi, Cristina; Koltai, Hinanit; Agama, Keli; Pommier, Yves; Chen, Yu; Tricoli, Lucas; LaRocque, Jeannine R.; Albanese, Christopher; Yarden, Ronit I.

    2016-01-01

    Strigolactones are a novel class of plant hormones produced in roots that regulate shoot and root development. We previously reported that strigolactone analogs (SLs) induce G2/M cell cycle arrest and apoptosis in a variety of human cancer cells and inhibit tumor growth of human breast cancer xenografts in mice. SLs had no significant influences on non-transformed cells. Here we report for the first time that SLs induce DNA damage in the form of DNA double-strand breaks (DSBs) and activate the DNA damage response signaling by inducing phosphorylation of ATM, ATR and DNA-PKcs and co-localization of the DNA damage signaling protein, 53BP1, with γH2AX nuclear foci. We further report that in addition to DSBs induction, SLs simultaneously impair DSBs repair, mostly homology-directed repair (HDR) and to a lesser extent non-homologous end joining (NHEJ). In response to SLs, RAD51, the homologous DSB repair protein, is ubiquitinated and targeted for proteasomal degradation and it fails to co-localize with γH2AX foci. Interestingly, SLs synergize with DNA damaging agents-based therapeutics. The combination of PARP inhibitors and SLs showed an especially potent synergy, but only in BRCA1-proficient cells. No synergy was observed between SLs and PARP inhibitors in BRCA1-deficient cells, supporting a role for SLs in HDR impairment. Together, our data suggest that SLs increase genome instability and cell death by a unique mechanism of inducing DNA damage and inhibiting DNA repair. PMID:26910887

  7. Analogs of the novel phytohormone, strigolactone, trigger apoptosis and synergize with PARP inhibitors by inducing DNA damage and inhibiting DNA repair.

    PubMed

    Croglio, Michael P; Haake, Jefferson M; Ryan, Colin P; Wang, Victor S; Lapier, Jennifer; Schlarbaum, Jamie P; Dayani, Yaron; Artuso, Emma; Prandi, Cristina; Koltai, Hinanit; Agama, Keli; Pommier, Yves; Chen, Yu; Tricoli, Lucas; LaRocque, Jeannine R; Albanese, Christopher; Yarden, Ronit I

    2016-03-22

    Strigolactones are a novel class of plant hormones produced in roots that regulate shoot and root development. We previously reported that strigolactone analogs (SLs) induce G2/M cell cycle arrest and apoptosis in a variety of human cancer cells and inhibit tumor growth of human breast cancer xenografts in mice. SLs had no significant influences on non-transformed cells. Here we report for the first time that SLs induce DNA damage in the form of DNA double-strand breaks (DSBs) and activate the DNA damage response signaling by inducing phosphorylation of ATM, ATR and DNA-PKcs and co-localization of the DNA damage signaling protein, 53BP1, with γH2AX nuclear foci. We further report that in addition to DSBs induction, SLs simultaneously impair DSBs repair, mostly homology-directed repair (HDR) and to a lesser extent non-homologous end joining (NHEJ). In response to SLs, RAD51, the homologous DSB repair protein, is ubiquitinated and targeted for proteasomal degradation and it fails to co-localize with γH2AX foci. Interestingly, SLs synergize with DNA damaging agents-based therapeutics. The combination of PARP inhibitors and SLs showed an especially potent synergy, but only in BRCA1-proficient cells. No synergy was observed between SLs and PARP inhibitors in BRCA1-deficient cells, supporting a role for SLs in HDR impairment. Together, our data suggest that SLs increase genome instability and cell death by a unique mechanism of inducing DNA damage and inhibiting DNA repair. PMID:26910887

  8. Photoperiod effects on plasma cortisol levels in Gasterosteus aculeatus.

    PubMed

    Audet, C; FitzGerald, G J; Guderley, H

    1986-01-01

    No diel variations of plasma cortisol levels were found in Gasterosteus aculeatus acclimated to two different photoperiod conditions: 14L:10D and 9L:15D. However, under long photoperiods, G. aculeatus exhibited higher plasma cortisol levels than under short photoperiods, suggesting that elevated plasma cortisol levels are associated with the spring migration and/or reproductive activities. This decrease of plasma cortisol levels is particularly marked in male G. aculeatus. Under the 9L:15D photoperiod, males had lower plasma cortisol levels than females, in contrast to 14L:10D, where no significant sex differences were found. PMID:3940931

  9. Gliptin and GLP-1 analog treatment improves survival and vascular inflammation/dysfunction in animals with lipopolysaccharide-induced endotoxemia.

    PubMed

    Steven, Sebastian; Hausding, Michael; Kröller-Schön, Swenja; Mader, Michael; Mikhed, Yuliya; Stamm, Paul; Zinßius, Elena; Pfeffer, Amanda; Welschof, Philipp; Agdauletova, Saule; Sudowe, Stephan; Li, Huige; Oelze, Matthias; Schulz, Eberhard; Klein, Thomas; Münzel, Thomas; Daiber, Andreas

    2015-03-01

    Dipeptidyl peptidase (DPP)-4 inhibitors are used to treat hyperglycemia by increasing the incretin glucagon-like peptide-1 (GLP-1). Previous studies showed anti-inflammatory and antiatherosclerotic effects of DPP-4 inhibitors. Here, we compared the effects of linagliptin versus sitagliptin and liraglutide on survival and vascular function in animal models of endotoxic shock by prophylactic therapy and treatment after lipopolysaccharide (LPS) injection. Gliptins were administered either orally or subcutaneously: linagliptin (5 mg/kg/day), sitagliptin (50 mg/kg/day) or liraglutide (200 µg/kg/day). Endotoxic shock was induced by LPS injection (mice 17.5-20 mg/kg i.p., rats 10 mg/kg/day). Linagliptin and liraglutide treatment or DPP-4 knockout improved the survival of endotoxemic mice, while sitagliptin was ineffective. Linagliptin, liraglutide and sitagliptin ameliorated LPS-induced hypotension and vascular dysfunction in endotoxemic rats, suppressed inflammatory parameters such as whole blood nitrosyl-iron hemoglobin (leukocyte-inducible nitric oxide synthase activity) or aortic mRNA expression of markers of inflammation as well as whole blood and aortic reactive oxygen species formation. Hemostasis (tail bleeding time, activated partial thromboplastin time) was impaired in endotoxemic rats and recovered under cotreatment with linagliptin and liraglutide. Finally, the beneficial effects of linagliptin on vascular function and inflammatory parameters in endotoxemic mice were impaired in AMP-activated kinase (alpha1) knockout mice. The improved survival of endotoxemic animals and other data shown here may warrant further clinical evaluation of these drugs in patients with septic shock beyond the potential improvement of inflammatory complications in diabetic individuals with special emphasis on the role of AMP-activated kinase (alpha1) in the DPP-4/GLP-1 cascade. PMID:25600227

  10. Effect of ACTH on plasma corticosterone and cortisol in eagles and condors

    USGS Publications Warehouse

    Zenoble, R.D.; Kemppainen, R.J.; Young, D.W.; Carpenter, J.W.

    1985-01-01

    The effect of ACTH on plasma corticosterone and cortisol was determined in 12 eagles (Haliaeetus leucocephalus) and in 6 Andean condors (Vultur gryphus). In all raptors, the concentration of plasma corticosterone was substantially greater than that of cortisol. After ACTH administration, the eagles had a marked increase (P less than 0.001) in plasma corticosterone concentrations, but not in plasma cortisol. Administration of saline solution did not induce increased plasma corticosterone concentrations in the eagles. The condors had a smaller increase (P less than 0.002) in plasma corticosterone concentrations after ACTH administration, as compared with that of the eagles. However, administration of saline solution in 2 condors resulted in an increase in corticosterone similar to the increase after ACTH administration. In the condor, a stress-related release of endogenous ACTH may have an effect similar to that induced by exogenously administered ACTH. Plasma cortisol concentrations did not increase significantly after administration of ACTH or saline solution in either raptor species.

  11. Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva.

    PubMed

    Atsumi, Toshiko; Tonosaki, Keiichi

    2007-02-28

    Free radicals/reactive oxygen species are related to many biological phenomena such as inflammation, aging, and carcinogenesis. The body possesses various antioxidative systems (free radical scavenging activity, FRSA) for preventing oxidative stress, and saliva contains such activity. In the present study, we measured the total salivary FRSA induced after the smelling of lavender and rosemary essential oils that are widely used in aromatherapy. Various physiologically active substances in saliva such as cortisol, secretory IgA, and alpha-amylase activity were found to be correlated with aroma-induced FRSA. The subjects (22 healthy volunteers) sniffed aroma for 5 min, and each subject's saliva was collected immediately. FRSA was measured using 1,1-diphenyl-2-picrylhydrazyl. The FRSA values were increased by stimulation with low concentrations (1000 times dilution) of lavender or by high-concentrations (10 times dilution) of rosemary. In contrast, both lavender and rosemary stimulations decreased cortisol levels. A significant inverse correlation was observed between the FRSA values and the cortisol levels with each concentration of rosemary stimulation. No significant changes were noted in sIgA or alpha-amylase. These findings clarify that lavender and rosemary enhance FRSA and decrease the stress hormone, cortisol, which protects the body from oxidative stress. PMID:17291597

  12. Testosterone, cortisol, and psychopathic traits in men and women.

    PubMed

    Welker, Keith M; Lozoya, Elianna; Campbell, Jocelyn A; Neumann, Craig S; Carré, Justin M

    2014-04-22

    Cortisol and testosterone are theorized to independently and jointly influence antisocial behaviors. The current research examined the independent and interactive effects of baseline testosterone and cortisol on individual differences in psychopathic traits in a relatively large non-clinical sample (N=237). Participants completed the Self-Report Psychopathy - Short Form (SRP; Paulhus, Neumann, & Hare, in press) and provided saliva samples. Analyses indicated that testosterone and cortisol were positively correlated with psychopathic traits in men, but beyond these effects, cortisol moderated the relationship between testosterone and psychopathy in men. The relationship between testosterone and psychopathy within men was positive when cortisol levels were high, but negative when cortisol levels were low. These results have implications for work surrounding the dual hormone hypothesis and suggest that nonclinical variability in psychopathy can be predicted by baseline testosterone and cortisol. PMID:24631306

  13. Subjective Stress, Salivary Cortisol, and Electrophysiological Responses to Psychological Stress

    PubMed Central

    Qi, Mingming; Gao, Heming; Guan, Lili; Liu, Guangyuan; Yang, Juan

    2016-01-01

    The present study aimed to investigate the subjective stress, salivary cortisol, and electrophysiological responses to psychological stress induced by a modified version of a mental arithmetic task. Fifteen participants were asked to estimate whether the multiplication product of two-decimal numbers was above 10 or not either with a time limit (the stress condition) or without a time limit (the control condition). The results showed that participants reported higher levels of stress, anxiety, and negative affect in the stress condition than they did in the control condition. Moreover, the salivary cortisol level continued to increase after the stress condition but exhibited a sharp decrease after the control condition. In addition, the electrophysiological data showed that the amplitude of the frontal-central N1 component was larger for the stress condition than it was for the control condition, while the amplitude of the frontal-central P2 component was larger for the control condition than it was for the stress condition. Our study suggests that the psychological stress characteristics of time pressure and social-evaluative threat caused dissociable effects on perception and on the subsequent attentional resource allocation of visual information. PMID:26925026

  14. Intra- and interspecific challenges modulate cortisol but not androgen levels in a year-round territorial damselfish.

    PubMed

    Ros, Albert F H; Vullioud, Philippe; Bruintjes, Rick; Vallat, Armelle; Bshary, Redouan

    2014-05-15

    Interactions between individuals of different species are commonplace in animal communities. Some behaviors displayed during these interspecific social interactions may be very similar to those displayed during intraspecific social interactions. However, whether functional analogies between intra- and interspecific behaviors translate at the proximate level into an overlap in their underlying endocrine mechanisms remains largely unknown. Because steroids both mediate social behaviors and respond to them, we approached this question by comparing the behavioral and steroid response of free-living dusky gregories (Stegastes nigricans) to standardized territorial intrusions (sTI) of either conspecific or heterospecific food competitors. Stegastes nigricans is a year-round territorial fish that 'cultivates' the algae on which it feeds and is highly aggressive to both intra- and interspecific intruders. Behavioral differences between intra- and interspecific aggressive responses to sTI were marginal, and sTI tests caused an increase in cortisol levels that was positively related with the levels of aggression. In contrast, androgen levels did not increase in response to sTI, yet they showed a positive relationship with agonistic behavior. These results parallel a pattern that was first described for year-round territorial bird species. Furthermore, they suggest that changes in endocrine-hormone levels during territoriality might be independent of the species that induces the territorial response. PMID:24577440

  15. Introducing a novel method to assess cumulative steroid concentrations: increased hair cortisol concentrations over 6 months in medicated patients with depression.

    PubMed

    Dettenborn, Lucia; Muhtz, Christoph; Skoluda, Nadine; Stalder, Tobias; Steudte, Susann; Hinkelmann, Kim; Kirschbaum, Clemens; Otte, Christian

    2012-05-01

    Depression has been linked to increased cortisol concentrations using point measures taken from urine, blood, or saliva samples. However, with regard to hypercortisolism-induced consequences, long-term cumulative cortisol burden is of relevance. Our objective was to use hair analysis as a new method to assess cortisol exposure over 6 months in depressed patients and healthy controls. We examined 23 depressed patients (8 men and 15 women, mean age: 41.6 years ( ± standard deviation (SD), 13.1 years); mean duration of current depressive episode 9 months ( ± SD, 13 months)) and 64 healthy controls, matched for age and gender. Cortisol concentrations in two 3-cm hair segments from near to the scalp were analyzed, representing cortisol secretion during the 6 months prior to sampling. Compared with healthy individuals, depressed patients had higher hair cortisol concentrations in the first (mean ± SD: 26.7 ± 20.8 vs. 18.7 ± 11.5 pg/mg, p < 0.05) and second hair segment (mean ±  SD: 21.9 ± 23.7 vs. 13.4 ± 9.6 pg/mg, p < 0.05). In conclusion, hair cortisol analysis confirmed enhanced cortisol secretion in depressed patients over a prolonged time period. Because of the retrospective and cumulative nature of cortisol in hair, the assessment of hair cortisol concentration may help in addressing unanswered questions regarding hypothalamic-pituitary-adrenal axis overactivity and associated health consequences in psychiatric disorders. PMID:22043813

  16. A day-centered approach to modeling cortisol: Diurnal cortisol profiles and their associations among U.S. adults

    PubMed Central

    Dmitrieva, Natalia O.; Almeida, David M.; Dmitrieva, Julia; Loken, Eric; Pieper, Carl F.

    2013-01-01

    Summary Diurnal cortisol is a marker of HPA-axis activity that may be one of the biological mechanisms linking stressors to age-related health declines. The current study identified day-centered profiles of diurnal cortisol among 1,101 adults living in the United States. Participants took part in up to four consecutive days of salivary cortisol collection, assessed at waking, 30 minutes post-waking, before lunch, and before bedtime. Growth Mixture Modeling with latent time basis was used to estimate common within-day trajectories of diurnal cortisol among 2,894 cortisol days. The 3-class solution provided the best model fit, showing that the majority of study days (73%) were characterized by a Normative cortisol pattern, with a robust cortisol awakening response (CAR), a steep negative diurnal slope, coupled with low awakening and bedtime levels. Relative to this profile, diurnal cortisol on the remainder of days appeared either Elevated throughout the day (20% of days) or Flattened (7% of days). Relative to the Normative trajectory, the Elevated trajectory was distinguished by a higher morning cortisol level, whereas the Flattened trajectory was characterized by a high bedtime level, with weaker CAR and diurnal slope parameters. Relative to the Normative profile, Elevated profile membership was associated with older age and cigarette smoking. Greater likelihood of the Flattened cortisol pattern was observed among participants who were older, male, smoked cigarettes, used medications that are known to affect cortisol output, and reported poorer health. The current study demonstrates the value of a day-centered Growth Mixture Modeling approach to the study of diurnal cortisol, showing that deviations from the classic robust rhythm of diurnal cortisol are associated with older age, male sex, use of medications previously shown to affect cortisol levels, poorer health behaviors, and poorer self-reported health. PMID:23770247

  17. Relationships between leptin, HCG, cortisol, and psychosocial stress and nausea and vomiting throughout pregnancy.

    PubMed

    Kuo, Shih-Hsien; Yang, Yi-Hsin; Wang, Ruey-Hsia; Chan, Te-Fu; Chou, Fan-Hao

    2010-07-01

    The purposes of this prospective, longitudinal study were to examine the relationships between leptin, human chorionic gonadotropin (hCG), cortisol, and psychosocial stress and nausea and vomiting (NV) in women with mild-to-moderate NV throughout pregnancy. Participants comprised 91 pregnant women recruited from prenatal clinics in southern Taiwan. Data analysis using one-way analysis of variance (ANOVA) indicated that leptin, hCG, cortisol levels, and Index of Nausea, Vomiting, and Retching (INVR) scores, but not stress (measured with the Visual Analog Scale, VAS) scores, were significantly different among the three trimesters. The average INVR score and hCG level decreased from the first to third trimesters (p < .0001 for both). The average leptin and cortisol levels increased from the first to third trimesters (p = .001 and p < .0001, respectively). Analysis using mixed models indicated that the INVR scores decreased significantly in a progressive manner through the stages of pregnancy and were significantly lower in the second and third trimesters. Findings reveal that stress/VAS and hCG may both be significantly and independently associated with INVR scores. Future research should examine psychosocial reactions in addition to exploring other biochemical markers related to NV and stress. PMID:20453023

  18. Stronger Pharmacological Cortisol Suppression and Anticipatory Cortisol Stress Response in Transient Global Amnesia

    PubMed Central

    Griebe, Martin; Nees, Frauke; Gerber, Benjamin; Ebert, Anne; Flor, Herta; Wolf, Oliver T.; Gass, Achim; Hennerici, Michael G.; Szabo, Kristina

    2015-01-01

    Transient global amnesia (TGA) is a disorder characterized by a sudden attack of severe anterograde memory disturbance that is frequently preceded by emotional or physical stress and resolves within 24 h. By using MRI following the acute episode in TGA patients, small lesions in the hippocampus have been observed. Hence, it has been hypothesized that the disorder is caused by a stress-related transient inhibition of memory formation in the hippocampus. To study the factors that may link stress and TGA, we measured the cortisol day-profile, the dexamethasone feedback inhibition and the effect of experimental exposure to stress on cortisol levels (using the socially evaluated cold pressor test and a control procedure) in 20 patients with a recent history of TGA and in 20 healthy controls. We used self-report scales of depression, anxiety and stress, and a detailed neuropsychological assessment to characterize our collective. We did not observe differences in mean cortisol levels in the cortisol day-profile between the two groups. After administration of low-dose dexamethasone, TGA patients showed significantly stronger cortisol suppression in the daytime profile compared to the control group (p = 0.027). The mean salivary cortisol level was significantly higher in the TGA group prior to and after the experimental stress exposure (p = 0.008 and 0.010 respectively), as well as prior to and after the control condition (p = 0.022 and 0.024, respectively). The TGA group had higher scores of depressive symptomatology (p = 0.021) and anxiety (p = 0.007), but the groups did not differ in the neuropsychological assessment. Our findings of a stronger pharmacological suppression and higher cortisol levels in anticipation of experimental stress in participants with a previous TGA indicate a hypersensitivity of the HPA axis. This suggests that an individual stress sensitivity might play a role in the pathophysiology of TGA. PMID:25805980

  19. Decreased hair cortisol concentrations in generalised anxiety disorder.

    PubMed

    Steudte, Susann; Stalder, Tobias; Dettenborn, Lucia; Klumbies, Elisabeth; Foley, Paul; Beesdo-Baum, Katja; Kirschbaum, Clemens

    2011-04-30

    Previous research examining hypothalamic-pituitary-adrenal (HPA) axis activity in generalised anxiety disorder (GAD) has suggested a general hypercortisolism. These studies have mostly relied on salivary, plasma or urinary assessments, reflecting cortisol secretion over short time periods. The current study utilised the novel method of cortisol assessment in hair to obtain a retrospective index of cortisol secretion over a prolonged period of time. Hair cortisol levels were determined in 15 GAD patients and in 15 age- and gender-matched controls. In addition, participants collected six saliva samples (on awakening, +30 min, 12:00, 16:00, 20:00 h and at bedtime) on two consecutive weekdays for the assessment of the diurnal cortisol profile. Results revealed significantly lower (50-60%) cortisol levels in the first and second 3-cm hair segments of GAD patients compared to those of controls. No significant between-group differences were seen in diurnal cortisol profiles. The hair cortisol findings tentatively suggest that under naturalistic conditions GAD is associated with hypocortisolism. If corroborated by future research, this demonstrates the important qualities of cortisol measurement in hair as an ecologically valid, retrospective index of long-term cortisol secretion and as a marker for psychiatric disorders associated with hypo- or hypercortisolism. PMID:20889215

  20. Predictors of anticipatory cortisol reactivity to subsequent stressors.

    PubMed

    Turan, Bulent

    2015-10-01

    Understanding the nature, predictors, and consequences of anticipatory biological stress responses are important in understanding long-term effects of repeated stressors. We examined anticipatory cortisol responses after an individual has actually experienced and reacted to a stressor once and is anticipating a second similar stressor. We hypothesized that how an individual reacts to the first stressor may predict that individual's anticipatory responses to further stressors. In Session 1, 77 male participants delivered speeches and performed arithmetic tasks in front of two evaluators. In Session 2 one week later, participants were told that they would do the same tasks again in front of evaluators. Stress cortisol reactivity in Session 1 (increase in cortisol from pre-stressor to post-stressor) predicted anticipatory cortisol reactivity in Session 2 (increase in cortisol from baseline to immediately pre-stressor). In addition, trait measures of low self-esteem and a "Submissive and Disconnected" interpersonal orientation predicted stronger anticipatory cortisol reactivity in Session 2. If the cortisol response to an initial stressor does in fact shape consequent anticipatory cortisol responses, this self-perpetuating nature of the initial cortisol response may contribute to negative long-term effects of repeated stressors on health. One factor that may be able to counteract this effect is a dominant and confident interpersonal orientation, which may lead to lower anticipatory cortisol reactions regardless of the response to the initial stressor. PMID:26071396

  1. Cortisol elimination from plasma in premenopausal women with rheumatoid arthritis

    PubMed Central

    Rovensky, J; Imrich, R; Koska, J; Kovalancik, M; Killinger, Z; Payer, J; Vigas, M; Jezova, D

    2003-01-01

    Methods: Twelve premenopausal female patients with RA (39.8 (1.8) years) and nine healthy control women matched for age and body mass index (42 (3.3) years) were enrolled in the study. None of the patients had previously been receiving treatment with glucocorticoids. After dexamethasone suppression (2 mg by mouth) the evening before the study, 20 mg of hydrocortisone was given. Blood and saliva samples were drawn six hours after injection of hydrocortisone. Plasma and salivary cortisol were measured. Results: Dexamethasone administration suppressed plasma cortisol concentrations to an almost undetectable level in all subjects, except one with RA. In this subject, a raised concentration of plasma cortisol was verified by repeated analysis despite the fact that cortisol concentration in the saliva sample measured simultaneously was not raised. No significant difference in the disappearance curve of cortisol in plasma or in salivary cortisol levels was found between the patients with RA and the healthy controls. Conclusions: The profile of disappearance of total cortisol from plasma, and salivary cortisol levels during the elimination phase after its intravenous administration, are unchanged in premenopausal women with RA. Alterations in cortisol clearance are not likely to have a role in cortisol availability in patients with RA. PMID:12810434

  2. Science Teachers' Analogical Reasoning

    NASA Astrophysics Data System (ADS)

    Mozzer, Nilmara Braga; Justi, Rosária

    2013-08-01

    Analogies can play a relevant role in students' learning. However, for the effective use of analogies, teachers should not only have a well-prepared repertoire of validated analogies, which could serve as bridges between the students' prior knowledge and the scientific knowledge they desire them to understand, but also know how to introduce analogies in their lessons. Both aspects have been discussed in the literature in the last few decades. However, almost nothing is known about how teachers draw their own analogies for instructional purposes or, in other words, about how they reason analogically when planning and conducting teaching. This is the focus of this paper. Six secondary teachers were individually interviewed; the aim was to characterize how they perform each of the analogical reasoning subprocesses, as well as to identify their views on analogies and their use in science teaching. The results were analyzed by considering elements of both theories about analogical reasoning: the structural mapping proposed by Gentner and the analogical mechanism described by Vosniadou. A comprehensive discussion of our results makes it evident that teachers' content knowledge on scientific topics and on analogies as well as their pedagogical content knowledge on the use of analogies influence all their analogical reasoning subprocesses. Our results also point to the need for improving teachers' knowledge about analogies and their ability to perform analogical reasoning.

  3. High cortisol responses identify propensity for obesity that is linked to thermogenesis in skeletal muscle.

    PubMed

    Lee, T Kevin; Clarke, Iain J; St John, Justin; Young, I Ross; Leury, Brian L; Rao, Alexandra; Andrews, Zane B; Henry, Belinda A

    2014-01-01

    Subjects characterized as cortisol high responders (HRs) consume more calories after stress, but it is unknown whether cortisol responsiveness predicts a propensity for obesity. Female sheep with either high or low cortisol responses to adrenocorticotropin (ACTH) were identified. Body composition was similar in HRs and cortisol low responders (LRs), but the HRs had greater (P<0.01) adiposity than did the LRs (40.5±0.7 vs. 35.8±1.4%) after high-energy feeding, despite comparable food intake. Postprandial thermogenesis in muscle temperature was 0.8 ± 0.08°C higher in the LRs than in the HRs (P<0.01), whereas feeding-induced changes in fat temperature were similar. Leptin and insulin sensitivity were similar in the HRs and LRs. Feeding lowered (P<0.001) the respiratory control ratio in muscle (HRs 9.2±0.8-5.2±1.2; LRs 8.4±0.5-5.2±0.7), indicative of increased uncoupled respiration. Also in muscle, the feeding-induced increases in uncoupling protein (UCP)-3 (fold increase: HRs, 2.4; LRs, 2.0), ryanodine 1 receptor (RyR1; fold increase: HRs 3.1; LRs 2.1), and sarcoendoplasmic reticulum Ca(2+)-dependent ATPase (fold increase: HRs 1.5; LRs 1.6) were equivalent in the HRs and LRs. Sequencing of mitochondrial DNA revealed no haplotypic differences between the 2 groups. We conclude that predisposition to obesity can be predicted by cortisol responsiveness to an ACTH challenge and that the response is due to innate differences in muscle thermogenesis. PMID:24022403

  4. Stronger cortisol response to acute psychosocial stress is correlated with larger decrease in temporal sensitivity

    PubMed Central

    Yao, Zhuxi; Jiang, Caihong; Zhang, Kan; Wu, Jianhui

    2016-01-01

    As a fundamental dimension of cognition and behavior, time perception has been found to be sensitive to stress. However, how one’s time perception changes with responses to stress is still unclear. The present study aimed to investigate the relationship between stress-induced cortisol response and time perception. A group of 40 healthy young male adults performed a temporal bisection task before and after the Trier Social Stress Test for a stress condition. A control group of 27 male participants completed the same time perception task without stress induction. In the temporal bisection task, participants were first presented with short (400 ms) and long (1,600 ms) visual signals serving as anchor durations and then required to judge whether the intermediate probe durations were more similar to the short or the long anchor. The bisection point and Weber ratio were calculated and indicated the subjective duration and the temporal sensitivity, respectively. Data showed that participants in the stress group had significantly increased salivary cortisol levels, heart rates, and negative affects compared with those in the control group. The results did not show significant group differences for the subjective duration or the temporal sensitivity. However, the results showed a significant positive correlation between stress-induced cortisol responses and decreases in temporal sensitivity indexed by increases in the Weber ratio. This correlation was not observed for the control group. Changes in subjective duration indexed by temporal bisection points were not correlated with cortisol reactivity in both the groups. In conclusion, the present study found that although no significant change was observed in time perception after an acute stressor on the group-level comparison (i.e., stress vs. nonstress group), individuals with stronger cortisol responses to stress showed a larger decrease in temporal sensitivity. This finding may provide insight into the understanding of

  5. Inhibition of NF-κB translocation by curcumin analogs induces G0/G1 arrest and downregulates thymidylate synthase in colorectal cancer.

    PubMed

    Rajitha, Balney; Belalcazar, Astrid; Nagaraju, Ganji Purnachandra; Shaib, Walid L; Snyder, James P; Shoji, Mamoru; Pattnaik, Subasini; Alam, Afroz; El-Rayes, Bassel F

    2016-04-10

    Cell cycle progression and DNA synthesis are essential steps in cancer cell growth and resistance. Thymidylate synthase (TS) is a therapeutic target for 5FU. Curcumin is a potent inhibitor of NF-κB. EF31 and UBS109 are potent synthetic analogues of curcumin. We tested the hypothesis that inhibition of NF-κB translocation by curcumin and its analogs EF31 and UBS109 can inhibit cell cycle progression and downregulate TS levels in colorectal cancer (CRC) cell lines. Two CRC cell lines (HCT116 and HT-29) were either untreated (control) or treated with IC50 concentrations of curcumin, EF31 UBS109 led to G0/G1 cell cycle arrest. Treatment with curcumin, EF31 or UBS109 inhibited NF-κB, downregulated survival pathways and inhibited cell cycle progression. Arrest in the G0/G1 phase was associated with downregulation of the transcription factor E2F-1 and its target gene TS. NF-κB over-expression induced E2F-1 and TS protein and mRNA levels in both cell lines. EF31 and UBS109 treatment significantly decreased tumor growth in compared to untreated tumors. EF31 and UBS109 are promising agents for the prevention and treatment of CRC. PMID:26850372

  6. Low-power, ultrafast, and dynamic all-optical tunable plasmonic analog to electromagnetically induced transparency in two resonators side-coupled with a waveguide system

    SciTech Connect

    Wang, Boyun; Wang, Tao Li, Xiaoming; Han, Xu; Zhu, Youjiang

    2015-06-07

    We theoretically and numerically investigate a low-power, ultrafast, and dynamic all-optical tunable plasmonic analog to electromagnetically induced transparency (EIT) in two nanodisk resonators side-coupled to a metal-insulator-metal plasmonic waveguide system. The optical Kerr effect is enhanced by the slow light effect of the plasmonic EIT-like effect and the plasmonic waveguide based on graphene-Ag composite material structures with giant effective Kerr nonlinear coefficient. The optical Kerr effect modulation method is applied to improve tuning rate with response time of subpicoseconds or even femtoseconds. With dynamically tuning the propagation phase of the plasmonic waveguide, π-phase shift of the transmission spectrum in the plasmonic EIT-like system is achieved under excitation of a pump light with an intensity as low as 5.85 MW/cm{sup 2}. The group delay is controlled between 0.09 and 0.4 ps. All observed schemes are analyzed rigorously through finite-difference time-domain simulations and coupled-mode formalism. Results show a new direction toward the low power consumption and ultrafast responses of integration plasmonic photonic devices and all-optical dynamical storage of light devices in optical communication and quantum information processing.

  7. Clozapine and risperidone influence on cortisol and estradiol levels in male patients with schizophrenia.

    PubMed

    Piriu, G; Torac, E; Gaman, L E; Iosif, L; Tivig, I C; Delia, C; Gilca, M; Stoian, I; Atanasiu, V

    2015-01-01

    Estrogens role in schizophrenia patients is a subject, which has gained an increased attention from the medical community. Estrogens have been shown to inhibit dopamine actions, improve neuronal regeneration, and overall, have a protective role in the pathology of schizophrenia. The adjunctive estrogen therapy for men is currently under debate. Antipsychotic medication is known to influence the hypothalamo-hypophyseal - gonadal axis by inducing variable degrees of hyperprolactinemia. Several studies have found that some of the atypical antipsychotics lower cortisol levels in patients and also in healthy controls. We have investigated the effects of clozapine and risperidone on estradiol levels in men with schizophrenia. We have also evaluated the levels of prolactin and cortisol, taking into account the possible influence of antipsychotic drugs on both these hormones. Both prolactin and cortisol also have the potential to regulate sexual hormones biosynthesis. Our study found decreased estradiol levels in men with schizophrenia treated with clozapine and risperidone, while prolactin levels were increased only in the risperidone treated group. Cortisol levels are not statistically significant different between groups. PMID:26664488

  8. Common oxytocin receptor gene variant interacts with rejection sensitivity to influence cortisol reactivity during negative evaluation.

    PubMed

    Auer, Brandon J; Byrd-Craven, Jennifer; Grant, DeMond M; Granger, Douglas A

    2015-09-01

    The study tested the hypothesis that variation in the oxytocin receptor gene (OXTR rs53576) and self-report of rejection sensitivity are associated with adrenocortical reactivity to social stress. Participants (N=94; 36.17% male; Mage=20.18yrs; 62.8% Caucasian) completed a writing task on a salient problem in society, provided self-report via questionnaire of rejection sensitivity, and were then informed that a committee of peers would evaluate their written comments. Participants received either scripted praise or criticism as a way to induce social evaluative threat. Saliva was collected before and after the stress task and assayed for cortisol. Results revealed that cortisol levels increased in participants with moderate levels of social rejection sensitivity-inferred by rs53576 genotype and reported rejection sensitivity-while cortisol levels decreased in participants with high and low levels of social rejection sensitivity. Our findings suggest a curvilinear relationship between social rejection sensitivity and cortisol reactivity in the context of social rejection, warranting further consideration in future studies. PMID:26241486

  9. Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model.

    PubMed

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

    2014-01-01

    Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. This study compared the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50-150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6-12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients. PMID:24025564

  10. Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model

    PubMed Central

    Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

    2014-01-01

    Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. To compare the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50–150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6–12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients. PMID:24025564

  11. Huggable communication medium decreases cortisol levels

    PubMed Central

    Sumioka, Hidenobu; Nakae, Aya; Kanai, Ryota; Ishiguro, Hiroshi

    2013-01-01

    Interpersonal touch is a fundamental component of social interactions because it can mitigate physical and psychological distress. To reproduce the psychological and physiological effects associated with interpersonal touch, interest is growing in introducing tactile sensations to communication devices. However, it remains unknown whether physical contact with such devices can produce objectively measurable endocrine effects like real interpersonal touching can. We directly tested this possibility by examining changes in stress hormone cortisol before and after a conversation with a huggable communication device. Participants had 15-minute conversations with a remote partner that was carried out either with a huggable human-shaped device or with a mobile phone. Our experiment revealed significant reduction in the cortisol levels for those who had conversations with the huggable device. Our approach to evaluate communication media with biological markers suggests new design directions for interpersonal communication media to improve social support systems in modern highly networked societies. PMID:24150186

  12. Inactivity amplifies the catabolic response of skeletal muscle to cortisol

    NASA Technical Reports Server (NTRS)

    Ferrando, A. A.; Stuart, C. A.; Sheffield-Moore, M.; Wolfe, R. R.

    1999-01-01

    Severe injury or trauma is accompanied by both hypercortisolemia and prolonged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Although BR alone can result in a 2-3% loss of lean body mass, the effects of severe trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were also directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 microg/kg x h), resulting in blood cortisol concentrations that mimic severe injury (approximately 31 microg/dL). After 14 days of strict BR, hypercortisolemia increased phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented negative amino acid balance was the result of an increased muscle protein breakdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed rest due to a significant increase in de novo synthesis (P < 0.05). Thus, inactivity sensitizes skeletal muscle to the catabolic effects of hypercortisolemia. Furthermore, these effects on healthy volunteers are analogous to those seen after severe injury.

  13. Diurnal Cortisol and Survival in Epithelial Ovarian Cancer

    PubMed Central

    Schrepf, Andrew; Thaker, Premal H.; Goodheart, Michael J.; Bender, David; Slavich, George M.; Dahmoush, Laila; Penedo, Frank; DeGeest, Koen; Mendez, Luis; Lubaroff, David M.; Cole, Steven W.; Sood, Anil K.; Lutgendorf, Susan K.

    2015-01-01

    Introduction Hypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment. Materials and Methods Participants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables. Results Each cortisol measure was associated with decreased survival time, adjusting for covariates (all p<.041). A one standard deviation increase in night cortisol was associated with a 46% greater likelihood of death. Patients in the high night cortisol group survived an estimated average of 3.3 years compared to 7.3 years for those in the low night cortisol group. Elevated ascites IL-6 was associated with each cortisol measure (all r >.36, all p<.017). Discussion Abnormal cortisol rhythms assessed prior to treatment are associated with decreased survival in ovarian cancer and increased inflammation in the vicinity of the tumor. HPA abnormalities may reflect poor endogenous control of inflammation, dysregulation caused by tumor-associated inflammation, broad circadian disruption, or some combination of these factors. Nocturnal cortisol may have utility as a non-invasive measure of HPA function and/or disease severity. PMID:25647344

  14. The effects of an anticipated challenge on diurnal cortisol secretion.

    PubMed

    Wetherell, Mark A; Lovell, Brian; Smith, Michael A

    2015-01-01

    In healthy, non-challenged individuals, the secretion of cortisol typically follows a diurnal profile characterized by a peak in the period following waking (cortisol awakening response) and a gradual decline throughout the day. In addition, cortisol secretion is increased in response to acutely stressful stimuli, particularly stressors involving social evaluation. The current study is the first to assess the impact of an anticipated acute laboratory stressor upon the typical diurnal pattern of HPA activation and relationship to acute cortisol secretion. A sample of 23 healthy young adults provided salivary cortisol samples at four time points (immediately upon awakening, 30-min post-awakening, 1200 h and before bed) on 2 consecutive days. On the second day, participants attended the laboratory and undertook an anticipated acute socially evaluative stressor immediately following provision of their 1200 h saliva sample. Heart rate, blood pressure and mood were recorded immediately before and after the stressor and at 10 and 20 min post-stressor along with additional salivary cortisol samples. Typical patterns of cortisol secretion were observed on both days and exposure to the laboratory stressor was associated with the expected increases in cortisol, heart rate, blood pressure and negative mood. However, significant differences in diurnal cortisol secretion were observed between the two days with greater secretion, in particular, during the period following awakening, evident on the day of the anticipated laboratory stressor. Furthermore, secretion of cortisol during the period following awakening was positively related to secretion during the acute reactivity periods. This is the first study to integrate a laboratory stressor into a typical day and assess its impact on indices of diurnal cortisol secretion in an ambulatory setting. The current findings support the notion that the cortisol awakening response is associated with anticipation of the upcoming day

  15. An optimization formulation for characterization of pulsatile cortisol secretion

    PubMed Central

    Faghih, Rose T.; Dahleh, Munther A.; Brown, Emery N.

    2015-01-01

    Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an ℓ0-norm cost function for this controller, and solve a reweighed ℓ1-norm minimization algorithm for obtaining the solution to this optimization problem. We use four examples to illustrate the performance of this approach: (i) a toy problem that achieves impulse control, (ii) two examples that achieve physiologically plausible pulsatile cortisol release, (iii) an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications. PMID:26321898

  16. Daily variations in cortisol levels and binge eating disorder.

    PubMed

    Sitton, Sarah; Porn, Patricia M; Shaeffer, Stephanie

    2002-12-01

    Morning and afternoon levels of cortisol for 73 volunteers (67 women and 6 men) were compared in relation to their Binge Eating Disorder scores, Body Mass Indexes, and self-reports of mood and hunger. Cortisol level was not significantly correlated with binge eating or mood or hunger for either time period. However, it was inversely related to body mass, with lower cortisol levels associated with greater body mass. PMID:12530732

  17. An optimization formulation for characterization of pulsatile cortisol secretion.

    PubMed

    Faghih, Rose T; Dahleh, Munther A; Brown, Emery N

    2015-01-01

    Cortisol is released to relay information to cells to regulate metabolism and reaction to stress and inflammation. In particular, cortisol is released in the form of pulsatile signals. This low-energy method of signaling seems to be more efficient than continuous signaling. We hypothesize that there is a controller in the anterior pituitary that leads to pulsatile release of cortisol, and propose a mathematical formulation for such controller, which leads to impulse control as opposed to continuous control. We postulate that this controller is minimizing the number of secretory events that result in cortisol secretion, which is a way of minimizing the energy required for cortisol secretion; this controller maintains the blood cortisol levels within a specific circadian range while complying with the first order dynamics underlying cortisol secretion. We use an ℓ0-norm cost function for this controller, and solve a reweighed ℓ1-norm minimization algorithm for obtaining the solution to this optimization problem. We use four examples to illustrate the performance of this approach: (i) a toy problem that achieves impulse control, (ii) two examples that achieve physiologically plausible pulsatile cortisol release, (iii) an example where the number of pulses is not within the physiologically plausible range for healthy subjects while the cortisol levels are within the desired range. This novel approach results in impulse control where the impulses and the obtained blood cortisol levels have a circadian rhythm and an ultradian rhythm that are in agreement with the known physiology of cortisol secretion. The proposed formulation is a first step in developing intermittent controllers for curing cortisol deficiency. This type of bio-inspired pulse controllers can be employed for designing non-continuous controllers in brain-machine interface design for neuroscience applications. PMID:26321898

  18. The cortisol awakening response and cognition across the adult lifespan.

    PubMed

    Ennis, Gilda E; Moffat, Scott D; Hertzog, Christopher

    2016-06-01

    Although the hippocampus is thought to play a central role in the regulation of the cortisol awakening response (CAR), results from past studies examining the relationship between the CAR and hippocampal-mediated memory and cognition have been mixed. Inconsistent findings may be due to the use of cortisol samples collected on only 1-2days since reduced sampling can permit unstable situational factors to bias results. We used cortisol assessments from 10 consecutive days to test the relationship of the CAR to episodic memory, working memory, and processing speed in a sample of healthy young, middle-aged, and older adults (age range: 23-79years; N=56). We tested if the relationship between the CAR and cognition would depend upon age and also tested if other cortisol measures, specifically waking cortisol, diurnal cortisol output (i.e., area under the curve) and diurnal cortisol slope (linear and quadratic), would be related to cognition. We found that a more positive CAR slope was related to better episodic memory and that this relationship did not depend upon age. The CAR was not significantly related to working memory. The relationship of the CAR to processing speed was not significant when using a CAR measure that corrected for non-compliant cortisol sampling. We also found that higher waking cortisol was significantly related to better working memory, but not episodic memory or processing speed. Neither diurnal cortisol output nor diurnal linear cortisol slope was significantly related to cognitive functioning. Future work should investigate the mechanisms underpinning the relationship of the cortisol awakening process to cognitive functioning. PMID:27105036

  19. Cortisol levels in hair of East Greenland polar bears

    PubMed Central

    Bechshøft, TØ; Sonne, C; Dietz, R; Born, EW; Novak, MA; Henchey, E; Meyer, JS

    2010-01-01

    To demonstrate the ability to assess long-term hypothalamic-pituitary-adrenocortical (HPA) axis activity in polar bears (Ursus maritimus), a pilot study was conducted in which cortisol concentrations was analyzed in hair from 7 female (3–19 years) and 10 male (6-19 years) East Greenland polar bears sampled 1994–2006. Hair was chosen as matrix as it is non-invasive, seasonally harmonized, and has been validated as an index of long-term changes in cortisol levels. Samples were categorized according to contamination: Eight were clean (2 females, 6 males), 5 had been contaminated with bear blood (2 F, 3 M), and 4 with bear fat (3 F, 1 M). There was no significant difference in cortisol concentration between the three categories after external contamination was removed. However, contaminated hair samples should be cleaned before cortisol determination. Average hair cortisol concentration was 8.90 pg/mg (range: 5.5 to 16.4 pg/mg). There was no significant correlation between cortisol concentration and age (p = 0.81) or sampling year (p = 0.11). However, females had higher mean cortisol concentration than males (females mean: 11.0 pg/mg, males: 7.3 pg/mg; p = 0.01). The study showed that polar bear hair contains measurable amounts of cortisol and that cortisol in hair may be used in studies of long-term stress in polar bears. PMID:21144554

  20. Individual differences in cortisol stress response predict increases in voice pitch during exam stress.

    PubMed

    Pisanski, Katarzyna; Nowak, Judyta; Sorokowski, Piotr

    2016-09-01

    Despite a long history of empirical research, the potential vocal markers of stress remain unclear. Previous studies examining speech under stress most consistently report an increase in voice pitch (the acoustic correlate of fundamental frequency, F0), however numerous studies have failed to replicate this finding. In the present study we tested the prediction that these inconsistencies are tied to variation in the severity of the stress response, wherein voice changes may be observed predominantly among individuals who show a cortisol stress response (i.e., an increase in free cortisol levels) above a critical threshold. Voice recordings and saliva samples were collected from university psychology students at baseline and again immediately prior to an oral examination. Voice recordings included both read and spontaneous speech, from which we measured mean, minimum, maximum, and the standard deviation in F0. We observed an increase in mean and minimum F0 under stress in both read and spontaneous speech, whereas maximum F0 and its standard deviation showed no systematic changes under stress. Our results confirmed that free cortisol levels increased by an average of 74% (ranging from 0 to 270%) under stress. Critically, increases in cortisol concentrations significantly predicted increases in mean F0 under stress for both speech types, but did not predict variation in F0 at baseline. On average, stress-induced increases in voice pitch occurred only when free cortisol levels more than doubled their baseline concentrations. Our results suggest that researchers examining speech under stress should control for individual differences in the magnitude of the stress response. PMID:27188981

  1. Elevated cortisol during play is associated with age and social engagement in children with autism

    PubMed Central

    2010-01-01

    Background The hallmark characteristic of autism is impaired reciprocal social interaction. While children find social interaction stress-reducing, many children with autism may find social interaction stress-inducing. The current study was designed to examine stress responsivity as measured by cortisol by comparing children with autism to neurotypical peers during an ecologically valid 20-minute playground paradigm. Methods The experiment involved sets of three children: a child with autism, a neurotypical child, and a confederate. Participants included 45 prepubescent males between 8 and 12 years of age (21 with autism and 24 neurotypical children). Results Children with autism showed fewer initiations (χ²(1) = 4.03, P = 0.044), rejected initiations from others more (χ²(1) = 7.10, P = 0.008) and spent less time interacting during motor (F(1,43) = 16.7, P = 0.0002) and cooperative (F(1,43) = 14.78, P = 0.0004) play. Repeated measures analysis of the cortisol values revealed a significant model (χ²(4) = 22.76, P < 0.0005) that included time of measurement, diagnosis and age as main effects and an interaction between diagnosis and age. Thus, as age increased among children with autism, they experienced enhanced cortisol levels while age did not modify expected cortisol levels for typical children. Stress responsivity was associated with more peripheral equipment play for motor (χ²(3) = 12.3, P = 0.006) and cooperative (χ²(3) = 8.24, P = 0.04) play as well as reduced nonverbal social skills during motor (χ²(1) = 5.52, P = 0.018) and cooperative play (χ²(1) = 4.53, P = 0.033). Conclusions Overall, children with autism engaged in fewer social overtures and spent less time interacting than typically developing peers during play. The peer interaction paradigm resulted in significantly higher levels of cortisol in many children with autism. Distinct patterns emerged within the autism group based on developmental (older), biological (cortisol responder) and

  2. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells.

    PubMed

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B

    2014-08-25

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24 h significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention. PMID:25038520

  3. The effect of pioglitazone on aldosterone and cortisol production in HAC15 human adrenocortical carcinoma cells

    PubMed Central

    Pan, Zhi-qiang; Xie, Ding; Choudhary, Vivek; Seremwe, Mutsa; Tsai, Ying-Ying; Olala, Lawrence; Chen, Xunsheng; Bollag, Wendy B.

    2014-01-01

    Pioglitazone belongs to the class of drugs called thiazolidinediones (TZDs), which are widely used as insulin sensitizers in the treatment of diabetes. A major side effect of TZDs is fluid retention. The steroid hormone aldosterone also promotes sodium and fluid retention; however, the effect of pioglitazone on aldosterone production is controversial. We analyzed the effect of pioglitazone alone and in combination with angiotensin II (AngII) on the late rate-limiting step of adrenocortical steroidogenesis in human adrenocortical carcinoma HAC15 cells. Treatment with pioglitazone for 24hr significantly increased the expression of CYP11B2 and enhanced AngII-induced CYP11B2 expression. Despite the observed changes in mRNA levels, pioglitazone significantly inhibited AngII-induced aldosterone production and CYP11B2 protein levels. On the other hand, pioglitazone stimulated the expression of the unfolded protein response (UPR) marker DDIT3, with this effect occurring at early times and inhibitable by the PPARγ antagonist GW9962. The levels of DDIT3 (CHOP) and phospho-eIF2α (Ser51), a UPR-induced event that inhibits protein translation, were also increased. Thus, pioglitazone promotes CYP11B2 expression but nevertheless inhibits aldosterone production in AngII-treated HAC15 cells, likely by blocking global protein translation initiation through DDIT3 and phospho-eIF2α. In contrast, pioglitazone promoted AngII-induced CYP11B1 expression and cortisol production. Since cortisol enhances lipolysis, this result suggests the possibility that PPARs, activated by products of fatty acid oxidation, stimulate cortisol secretion to promote utilization of fatty acids during fasting. In turn, the ability of pioglitazone to stimulate cortisol production could potentially underlie the effects of this drug on fluid retention. PMID:25038520

  4. Biomimetic Analogs for Collagen Biomineralization

    PubMed Central

    Gu, L.; Kim, Y.K.; Liu, Y.; Ryou, H.; Wimmer, C.E.; Dai, L.; Arola, D.D.; Looney, S.W.; Pashley, D.H.; Tay, F.R.

    2011-01-01

    Inability of chemical phosphorylation of sodium trimetaphosphate to induce intrafibrillar mineralization of type I collagen may be due to the failure to incorporate a biomimetic analog to stabilize amorphous calcium phosphates (ACP) as nanoprecursors. This study investigated adsorption/desorption characteristics of hydrolyzed and pH-adjusted sodium trimetaphosphate (HPA-Na3P3O9) to collagen. Based on those results, a 5-minute treatment time with 2.8 wt% HPA-Na3P3O9 was used in a single-layer reconstituted collagen model to confirm that both the ACP-stabilization analog and matrix phosphoprotein analog must be present for intrafibrillar mineralization. The results of that model were further validated by complete remineralization of phosphoric-acid-etched dentin treated with the matrix phosphoprotein analog and lined with a remineralizing lining composite, and with the ACP-stabilization analog supplied in simulated body fluid. An understanding of the basic processes involved in intrafibrillar mineralization of reconstituted collagen fibrils facilitates the design of novel tissue engineering materials for hard tissue repair and regeneration. PMID:20940362

  5. Central activation by histamine-induced itch: analogies to pain processing: a correlational analysis of O-15 H2O positron emission tomography studies.

    PubMed

    Drzezga, A; Darsow, U; Treede, R D; Siebner, H; Frisch, M; Munz, F; Weilke, F; Ring, J; Schwaiger, M; Bartenstein, P

    2001-05-01

    The aim of this study was to identify the functional cerebral network involved in the central processing of itch and to detect analogies and differences to previously identified cerebral activation patterns triggered by painful noxious stimuli. Repeated positron emission tomography regional cerebral blood flow (rCBF) measurements using O15-labeled water were performed in six healthy right-handed male subjects (mean age 32 +/- 2 years). Each subject underwent 12 sequential rCBF measurements. In all subjects a standardized skin prick test was performed on the right forearm 2 min before each rCBF measurement. For activation, histamine was applied in nine tests in logarithmically increasing concentrations from 0.03 to 8%. Three tests were performed with isotonic saline solution serving as a control condition. Itch intensity and unpleasantness were registered with a visual analogue scale during each test. Subtraction analysis between activation and control conditions as well as correlation analysis with covariates were performed. Itch induced a significant activation in the predominantly contralateral somatosensory cortex and in the ipsilateral and contralateral motor areas (supplementary motor area (SMA), premotor cortex, primary motor cortex). Additional significant activations were found in the prefrontal cortex and the cingulate gyrus, but not in subcortical structures nor in the secondary somatosensory cortex. In correlation analyses, several cortical areas showed a graded increase in rCBF with the logarithm of the histamine concentration (bilateral sensorimotor areas and cingulate cortex; contralateral insula, superior temporal cortex and prefrontal cortex) and with itch unpleasantness (contralateral sensorimotor cortex, prefrontal cortex and posterior insula; ipsilateral SMA). Induction of itch results in the activation of a distributed cerebral network. Itch and pain seem to share common pathways (a medial and a lateral processing pathway and a strong projection

  6. Longitudinal mediators of a randomized prevention program effect on cortisol for youth from parentally-bereaved families

    PubMed Central

    Luecken, Linda J.; Hagan, Melissa J.; Sandler, Irwin N.; Tein, Jenn-Yun; Ayers, Tim S.; Wolchik, Sharlene A.

    2013-01-01

    Objective We recently reported that a randomized controlled trial of a family-focused intervention for parentally-bereaved youth predicted higher cortisol output 6 years later relative to a control group of bereaved youth (Luecken et al., 2010). The current study evaluated longitudinal mediators of the preventive intervention effect on cortisol 6 years later. Method Parentally bereaved children (N=139; mean age 11.4, SD = 2.4; age range = 8-16 years; 54% male; 61% Caucasian, 17% Hispanic, 7% African American, 15% other ethnicities) were randomly assigned to the 12-week preventive intervention (n=78) or a self-study control (n=61) condition. Six years later (mean age 17.5, SD 2.4), cortisol was sampled as youth participated in a parent-child conflict interaction task. Using 4 waves of data across the 6 years, longitudinal mediators of the program impact on cortisol were evaluated. Results Program-induced increases in positive parenting, decreases in child exposure to negative life events, and lower externalizing symptoms significantly mediated the intervention effect on cortisol 6 years later. Conclusions An intervention targeting improved parenting and reduced child exposure to additional life stressors following the death of a parent may have long-term neuroendocrine effects. PMID:23529870

  7. Seasonal variations of basal cortisol and high stress response to captivity in Octodon degus, a mammalian model species.

    PubMed

    Quispe, Rene; Villavicencio, Camila P; Addis, Elizabeth; Wingfield, John C; Vasquez, Rodrigo A

    2014-02-01

    Across vertebrates, the hypothalamic-pituitary-adrenal axis is a conserved neuroendocrine network that responds to changing environments and involves the release of glucocorticoids into the blood. Few studies have been carried out concerning mammalian adrenal regulation in wild species either in the laboratory or field, and even fewer have been able to determine true glucocorticoid baselines. We studied the South-American caviomorph rodent Octodon degus, a diurnal and social mammal that has become an important species in the biological research. First, we determined the plasma cortisol baseline and the acute stress concentrations during the non-reproductive and mating seasons in free-living individuals. Second, using the same protocol we assessed the impact of long-term captivity on the adrenal function in wild-caught degus and degus born in laboratory. Third, we examined laboratory groups formed with degus taken from two distant natural populations; one of them originally occurs at the Andes Mountains in high altitude conditions. The data revealed seasonal modulation of basal cortisol in the wild associated with mating. In laboratory, degus presented higher cortisol stress responses, with greater magnitudes shown in degus born and reared in captivity. No differences between populations were found. The results suggest differential regulatory mechanisms between basal and stress-induced cortisol levels, and context dependence of cortisol modulation in a mammalian species. PMID:24368258

  8. Radioactive Decay - An Analog.

    ERIC Educational Resources Information Center

    McGeachy, Frank

    1988-01-01

    Presents an analog of radioactive decay that allows the student to grasp the concept of half life and the exponential nature of the decay process. The analog is devised to use small, colored, plastic poker chips or counters. Provides the typical data and a graph which supports the analog. (YP)

  9. Chemical processing and shampooing impact cortisol measured in human hair

    PubMed Central

    Hoffman, M. Camille; Karban, Laura V.; Benitez, Patrick; Goodteacher, Angela; Laudenslager, Mark L.

    2015-01-01

    Purpose The assessment of cortisol in hair has gained popularity as a means to measure retrospective hypothalamic-pituitary-adrenal activity in a number of species; however, cortisol levels from human hair subjected to typical chemicals for cosmetic or hygienic purposes may be altered by the chemicals used. The purposed of this study was to determine if exposure of hair to chemical processing or shampooing impacts cortisol values. Methods Human hair not exposed to prior chemical processing was cut from the posterior vertex region of the head of 106 human subjects as close to the scalp as possible. The hair sample was divided into 4-6 full-length clusters depending on quantity of hair available. Each hair sample was processed for baseline (native) cortisol and remaining clusters were exposed to five standard chemical hair treatments (Experiment 1) or were shampooed 15 or 30 times (Experiment 2). Hair was ground and cortisol levels were determined by enzyme immunoassay (EIA). Comparisons were made between native hair and processed hair using paired t-tests and Pearson correlation. Results Hair cortisol as assessed by EIA was significantly altered by chemical processing but in somewhat different ways. Exposure to bleach (harshest exposure), demi-perm (least exposure) or 15-30 shampoos resulted in a significant decrease in cortisol level while exposure to varying percentages of peroxides increased cortisol measured. There were no differences in cortisol levels associated with sex, age or tobacco use in the native hair for this particular group. Conclusion Chemical processing and frequent shampooing affect cortisol levels measured in hair. Chemically processed or excessively shampooed hair should be avoided when recruiting subjects for hair cortisol studies. PMID:25090265

  10. Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity

    PubMed Central

    Vaisvaser, Sharon; Lin, Tamar; Admon, Roee; Podlipsky, Ilana; Greenman, Yona; Stern, Naftali; Fruchter, Eyal; Wald, Ilan; Pine, Daniel S.; Tarrasch, Ricardo; Bar-Haim, Yair; Hendler, Talma

    2013-01-01

    Stressful experiences modulate neuro-circuitry function, and the temporal trajectory of these alterations, elapsing from early disturbances to late recovery, heavily influences resilience and vulnerability to stress. Such effects of stress may depend on processes that are engaged during resting-state, through active recollection of past experiences and anticipation of future events, all known to involve the default mode network (DMN). By inducing social stress and acquiring resting-state functional magnetic resonance imaging (fMRI) before stress, immediately following it, and 2 h later, we expanded the time-window for examining the trajectory of the stress response. Throughout the study repeated cortisol samplings and self-reports of stress levels were obtained from 51 healthy young males. Post-stress alterations were investigated by whole brain resting-state functional connectivity (rsFC) of two central hubs of the DMN: the posterior cingulate cortex (PCC) and hippocampus. Results indicate a ’recovery’ pattern of DMN connectivity, in which all alterations, ascribed to the intervening stress, returned to pre-stress levels. The only exception to this pattern was a stress-induced rise in amygdala-hippocampal connectivity, which was sustained for as long as 2 h following stress induction. Furthermore, this sustained enhancement of limbic connectivity was inversely correlated to individual stress-induced cortisol responsiveness (AUCi) and characterized only the group lacking such increased cortisol (i.e., non-responders). Our observations provide evidence of a prolonged post-stress response profile, characterized by both the comprehensive balance of most DMN functional connections and the distinct time and cortisol dependent ascent of intra-limbic connectivity. These novel insights into neuro-endocrine relations are another milestone in the ongoing search for individual markers in stress-related psychopathologies. PMID:23847492

  11. Cortisol and Politics: Variance in Voting Behavior is Predicted by Baseline Cortisol Levels

    PubMed Central

    French, Jeffrey A.; Smith, Kevin B.; Alford, John R.; Guck, Adam; Birnie, Andrew K.; Hibbing, John R.

    2014-01-01

    Participation in electoral politics is affected by a host of social and demographics variables, but there is growing evidence that biological predispositions may also play a role in behavior related to political involvement. We examined the role of individual variation in hypothalamic-pituitary-adrenal (HPA) stress axis parameters in explaining differences in self-reported and actual participation in political activities. Self-reported political activity, religious participation, and verified voting activity in U.S. national elections were collected from 105 participants, who were subsequently exposed to a standardized (nonpolitical) psychosocial stressor. We demonstrated that lower baseline salivary cortisol in the late afternoon was significantly associated with increased actual voting frequency in six national elections, but not with self-reported non-voting political activity. Baseline cortisol predicted significant variation in voting behavior above and beyond variation accounted for by traditional demographic variables (particularly age of participant in our sample). Participation in religious activity was weakly (and negatively) associated with baseline cortisol. Our results suggest that HPA-mediated characteristics of social, cognitive, and emotional processes may exert an influence on a trait as complex as voting behavior, and that cortisol is a better predictor of actual voting behavior, as opposed to self-reported political activity. PMID:24835544

  12. Cortisol and politics: variance in voting behavior is predicted by baseline cortisol levels.

    PubMed

    French, Jeffrey A; Smith, Kevin B; Alford, John R; Guck, Adam; Birnie, Andrew K; Hibbing, John R

    2014-06-22

    Participation in electoral politics is affected by a host of social and demographics variables, but there is growing evidence that biological predispositions may also play a role in behavior related to political involvement. We examined the role of individual variation in hypothalamic-pituitary-adrenal (HPA) stress axis parameters in explaining differences in self-reported and actual participation in political activities. Self-reported political activity, religious participation, and verified voting activity in U.S. national elections were collected from 105 participants, who were subsequently exposed to a standardized (nonpolitical) psychosocial stressor. We demonstrated that lower baseline salivary cortisol in the late afternoon was significantly associated with increased actual voting frequency in six national elections, but not with self-reported non-voting political activity. Baseline cortisol predicted significant variation in voting behavior above and beyond variation accounted for by traditional demographic variables (particularly age of participant in our sample). Participation in religious activity was weakly (and negatively) associated with baseline cortisol. Our results suggest that HPA-mediated characteristics of social, cognitive, and emotional processes may exert an influence on a trait as complex as voting behavior, and that cortisol is a better predictor of actual voting behavior, as opposed to self-reported political activity. PMID:24835544

  13. Female breakfast skippers display a disrupted cortisol rhythm and elevated blood pressure.

    PubMed

    Witbracht, Megan; Keim, Nancy L; Forester, Shavawn; Widaman, Adrianne; Laugero, Kevin

    2015-03-01

    Chronic stress and over-activity in the hypothalamic-pituitary-adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it's normally decreasing. To extend these findings to humans, we hypothesized that habitual breakfast skippers would display a similar pattern of circulating cortisol and alterations in meal and stress-induced cortisol reactions. Normal weight to obese women aged 18-45 years old who were strictly defined as either breakfast skippers (n=30) or breakfast eaters (n=35) were invited to participate in our study. Normal breakfast habits were maintained for the entire study period and each participant attended 4 lab visits. Over the first 2 lab visits, body composition, fasting clinical chemistries, and self-reports of chronic stress were assessed. On each of 2 additional days (lab visits 3 and 4), salivary free cortisol was measured at home upon waking and at bedtime, and in the lab in response to a standard lunch, ad libitum afternoon snack buffet, and stress and control (relaxation) tasks. The order of the control and stress test visits was randomized. While body weight, body composition, HOMA-IR, total and HDL cholesterol did not statistically differ (p>0.05), both diastolic and systolic blood pressure was elevated (p<0.01) and LDL cholesterol was lower (p=0.04) in the breakfast skipper group. Compared to the breakfast eaters and on the control task visit only, breakfast skippers had higher circulating cortisol from arrival to midafternoon (p<0.01) and during the snack buffet (p<0.05). Furthermore, the lunch-induced cortisol reaction was larger in the 'skippers' (p=0.03). On both stress and control visit days, the diurnal cortisol amplitude was significantly (p=0.02) blunted in breakfast skippers. Self-reports of chronic stress did not differ between the groups. These data indicate that habitually skipping breakfast is

  14. Effects of Shampoo and Water Washing on Hair Cortisol Concentrations

    PubMed Central

    Hamel, Amanda F.; Meyer, Jerrold S.; Henchey, Elizabeth; Dettmer, Amanda M.; Suomi, Stephen J.; Novak, Melinda A.

    2010-01-01

    Background Measurement of cortisol in hair is an emerging biomarker for chronic stress in human and nonhuman primates. Currently unknown, however, is the extent of potential cortisol loss from hair that has been repeatedly exposed to shampoo and/or water. Methods Pooled hair samples from 20 rhesus monkeys were subjected to five treatment conditions: 10, 20, or 30 shampoo washes, 20 water-only washes, or a no-wash control. For each wash, hair was exposed to a dilute shampoo solution or tap water for 45 s, rinsed 4 times with tap water, and rapidly dried. Samples were then processed for cortisol extraction and analysis using previously published methods. Results Hair cortisol levels were significantly reduced by washing, with an inverse relationship between number of shampoo washes and the cortisol concentration. This effect was mainly due to water exposure, as cortisol levels following 20 water-only washes were similar to those following 20 shampoo treatments. Conclusions Repeated exposure to water with or without shampoo appears to leach cortisol from hair, yielding values that underestimate the amount of chronic hormone deposition within the shaft. Collecting samples proximal to the scalp and obtaining hair washing frequency data may be valuable when conducting human hair cortisol studies. PMID:21034727

  15. Longitudinal Associations among Child Maltreatment, Social Functioning, and Cortisol Regulation

    ERIC Educational Resources Information Center

    Alink, Lenneke R. A.; Cicchetti, Dante; Kim, Jungmeen; Rogosch, Fred A.

    2012-01-01

    Child maltreatment increases the risk for impaired social functioning and cortisol regulation. However, the longitudinal interplay among these factors is still unclear. This study aimed to shed light on the effect of maltreatment on social functioning and cortisol regulation over time. The sample consisted of 236 children (mean age 7.64 years, SD…

  16. Cortisol Release in Infants in Response to Inoculation.

    ERIC Educational Resources Information Center

    Lewis, Michael; Thomas, David

    1990-01-01

    Data provide strong evidence that studies of stress and cortisol release in infants must take into account basal level, circadian rhythm, and behavioral effects and employ appropriate statistical procedures. Participants were infants of two, four, and six months of age from whom salivary cortisol was obtained before and 15 minutes after an…

  17. Enhanced Cortisol Response to Stress in Children in Autism

    ERIC Educational Resources Information Center

    Spratt, Eve G.; Nicholas, Joyce S.; Brady, Kathleen T.; Carpenter, Laura A.; Hatcher, Charles R.; Meekins, Kirk A.; Furlanetto, Richard W.; Charles, Jane M.

    2012-01-01

    Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a…

  18. Father Contributions to Cortisol Responses in Infancy and Toddlerhood

    ERIC Educational Resources Information Center

    Mills-Koonce, W. Roger; Garrett-Peters, Patricia; Barnett, Melissa; Granger, Douglas A.; Blair, Clancy; Cox, Martha J.

    2011-01-01

    The current study is one of the first prospective examinations of longitudinal associations between observed father caregiving behaviors and child cortisol reactivity and regulation in response to emotional arousal. Observations of father and mother caregiving behaviors and child cortisol levels in response to challenges at 7 months and 24 months…

  19. Suppressing the Morning Rise in Cortisol Impairs Free Recall

    ERIC Educational Resources Information Center

    Rimmele, Ulrike; Meier, Flurina; Lange, Tanja; Born, Jan

    2010-01-01

    Elevated glucocorticoid levels impair memory retrieval. We investigated whether retrieval under naturally elevated glucocorticoid levels, i.e., during the morning rise in cortisol can be improved by suppressing cortisol. In a crossover study 16 men retrieved emotional and neutral texts and pictures (learned 3 d earlier) 30 min after morning…

  20. Cortisol Levels and Conduct Disorder in Adolescent Mothers

    ERIC Educational Resources Information Center

    Azar, Rima; Zoccolillo, Mark; Paquette, Daniel; Quiros, Elsa; Baltzer, Franziska; Tremblay, Richard E.

    2004-01-01

    Objective: To examine the association between cortisol levels and conduct disorder (CD) in adolescent mothers. Past research has shown that low levels of cortisol were associated with CD, particularly with its aggressive symptoms. The authors tested the hypothesis that adolescent mothers with CD would show lower levels of salivary cortisol…

  1. Salivary cortisol levels in athletes and nonathletes: a systematic review.

    PubMed

    Cevada, T; Vasques, P E; Moraes, H; Deslandes, A

    2014-12-01

    High performance athletes are constantly facing different situations involving stress. Salivary cortisol has been used as a physiological measure to verify high performance athlete and mental health, in spite of research that has shown that comparisons between cortisol levels in athletes and nonathletes are inconclusive. The purpose of this study was to review articles that investigated salivary cortisol levels at rest in high performance athletes in comparison to physically active or sedentary nonathlete individuals. PubMed, ISI Web of Knowledge, SciELO, LILACS, and Scopus databases were searched for studies on salivary cortisol in athletes and the size effect was calculated. Although 3 articles reported higher salivary cortisol levels in female athletes compared to a control group, the results showed homogeneity among baseline groups or groups in resting conditions, suggesting a lack of discriminative capacity. These results should be interpreted with caution, due to the presence of substantial methodological bias. PMID:25230328

  2. The cocoa flavanol (-)-epicatechin protects the cortisol response.

    PubMed

    Ruijters, Erik J B; Haenen, Guido R M M; Weseler, Antje R; Bast, Aalt

    2014-01-01

    Various health benefits of the cocoa flavanol (-)-epicatechin (EC) have been attributed to its antioxidant and anti-inflammatory potency. In the present study we investigated whether EC is able to prevent deterioration of the anti-inflammatory effect of the glucocorticoid (GC) cortisol in the presence of oxidative stress. It was found that cortisol reduces inflammation in differentiated monocytes. Oxidative stress extinguishes the anti-inflammatory effect of cortisol, leading to cortisol resistance. EC reduces intracellular oxidative stress as well as the development of cortisol resistance. This further deciphers the enigmatic mechanism of EC by which it exerts its anti-inflammatory and antioxidant action. The observed effect of the cocoa flavanol EC will especially be of relevance in pathophysiological conditions with increased oxidative stress and consequential GC resistance and provides a fundament for the rational use of dietary antioxidants. PMID:24269961

  3. Resetting of circadian melatonin and cortisol rhythms in humans by ordinary room light

    NASA Technical Reports Server (NTRS)

    Boivin, D. B.; Czeisler, C. A.

    1998-01-01

    The present study was designed to investigate whether a weak photic stimulus can reset the endogenous circadian rhythms of plasma melatonin and plasma cortisol in human subjects. A stimulus consisting of three cycles of 5 h exposures to ordinary room light (approximately 180 lux), centered 1.5 h after the endogenous temperature nadir, significantly phase-advanced the plasma melatonin rhythm in eight healthy young men compared with the phase delays observed in eight control subjects who underwent the same protocol but were exposed to darkness (p < or = 0.003). After light-induced phase advances, the circadian rhythms of plasma melatonin and plasma cortisol maintained stable temporal relationships with the endogenous core body temperature cycle, consistent with the conclusion that exposure to ordinary indoor room light had shifted a master circadian pacemaker.

  4. Bayesian analogy with relational transformations.

    PubMed

    Lu, Hongjing; Chen, Dawn; Holyoak, Keith J

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. PMID:22775500

  5. Analysis of hair cortisol levels in captive chimpanzees: Effect of various methods on cortisol stability and variability

    PubMed Central

    Yamanashi, Yumi; Teramoto, Migaku; Morimura, Naruki; Hirata, Satoshi; Suzuki, Juri; Hayashi, Misato; Kinoshita, Kodzue; Murayama, Miho; Idani, Gen’ichi

    2016-01-01

    Hair cortisol has been reported to be a useful measure of long-term hypothalamic–pituitary–adrenal (HPA) axis activation in several species. It serves as a practical tool for long-term stress assessment, but it is important to understand the methodological factors that can affects hair cortisol assays to avoid methodological artifacts. To that end, we tested several procedures for measuring cortisol levels in hair collected from captive chimpanzees. The results showed that reproducibility was high, and we found no differences in cortisol levels among the various storage, drying, and sampling methods. However, the fineness of homogenized hair, sample weight, and extraction time affected absolute hair cortisol concentration. Although hair cortisol levels were stable over time, factors that may influence measurement results should be kept constant throughout a study.•We modified and validated a methodology involving enzyme immunoassays to reliably measure the hair cortisol levels of captive chimpanzees.•The results revealed that the fineness of homogenized hair, sample weight, and extraction time caused variations in absolute hair cortisol concentrations in chimpanzees. In contrast, storage, drying, and sampling from similar body parts did not affect the results. PMID:26870668

  6. Analysis of hair cortisol levels in captive chimpanzees: Effect of various methods on cortisol stability and variability.

    PubMed

    Yamanashi, Yumi; Teramoto, Migaku; Morimura, Naruki; Hirata, Satoshi; Suzuki, Juri; Hayashi, Misato; Kinoshita, Kodzue; Murayama, Miho; Idani, Gen'ichi

    2016-01-01

    Hair cortisol has been reported to be a useful measure of long-term hypothalamic-pituitary-adrenal (HPA) axis activation in several species. It serves as a practical tool for long-term stress assessment, but it is important to understand the methodological factors that can affects hair cortisol assays to avoid methodological artifacts. To that end, we tested several procedures for measuring cortisol levels in hair collected from captive chimpanzees. The results showed that reproducibility was high, and we found no differences in cortisol levels among the various storage, drying, and sampling methods. However, the fineness of homogenized hair, sample weight, and extraction time affected absolute hair cortisol concentration. Although hair cortisol levels were stable over time, factors that may influence measurement results should be kept constant throughout a study.•We modified and validated a methodology involving enzyme immunoassays to reliably measure the hair cortisol levels of captive chimpanzees.•The results revealed that the fineness of homogenized hair, sample weight, and extraction time caused variations in absolute hair cortisol concentrations in chimpanzees. In contrast, storage, drying, and sampling from similar body parts did not affect the results. PMID:26870668

  7. Regulation of gill claudin paralogs by salinity, cortisol and prolactin in Mozambique tilapia (Oreochromis mossambicus).

    PubMed

    Tipsmark, Christian K; Breves, Jason P; Rabeneck, D Brett; Trubitt, Rebecca T; Lerner, Darren T; Grau, E Gordon

    2016-09-01

    In euryhaline teleosts, reorganization of gill tight junctions during salinity acclimation involves dynamic expression of specific claudin (Cldn) paralogs. We identified four transcripts encoding Cldn tight junction proteins in the tilapia gill transcriptome: cldn10c, cldn10e, cldn28a and cldn30. A tissue distribution experiment found cldn10c and cldn10e expression levels in the gill to be 100-fold higher than any other tissues examined. cldn28a and cldn30 levels in the gill were 10-fold greater than levels in other tissues. Expression of these genes in Mozambique tilapia was examined during acclimation to fresh water (FW), seawater (SW), and in response to hormone treatments. Transfer of tilapia from FW to SW elevated cldn10c and cldn10e, while cldn28a and cldn30 were stimulated following transfer from SW to FW. In hypophysectomized tilapia transferred to FW, pituitary extirpation induced reduced expression of cldn10c, cldn10e and cldn28a; these effects were mitigated equally by either prolactin or cortisol replacement. In vitro experiments with gill filaments showed that cortisol stimulated expression of all four cldns examined, suggesting a direct action of cortisol in situ. Our data indicate that elevated cldn10c and cldn10e expression is important during acclimation of tilapia to SW possibly by conferring ion specific paracellular permeability. On the other hand, expression of cldn28a and cldn30 appears to contribute to reorganization of branchial epithelium during FW acclimation. Hormone treatment experiments showed that particular FW- and SW-induced cldns are controlled by cortisol and prolactin. PMID:27210417

  8. Nonvolatile Analog Memory

    NASA Technical Reports Server (NTRS)

    MacLeod, Todd C. (Inventor)

    2007-01-01

    A nonvolatile analog memory uses pairs of ferroelectric field effect transistors (FFETs). Each pair is defined by a first FFET and a second FFET. When an analog value is to be stored in one of the pairs, the first FFET has a saturation voltage applied thereto, and the second FFET has a storage voltage applied thereto that is indicative of the analog value. The saturation and storage voltages decay over time in accordance with a known decay function that is used to recover the original analog value when the pair of FFETs is read.

  9. Analog synthetic biology.

    PubMed

    Sarpeshkar, R

    2014-03-28

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  10. The effect of luteinizing hormone releasing hormone analog regime and stage of oocyte maturity for induced ovulation of channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effective LHRHa (luteinizing hormone releasing hormone analog) dose based on the gonadal maturity of channel catfish, Ictalurus punctatus to optimize channel x blue hybrid catfish production was evaluated in 4 trials (twice in early part of the season and twice in the peak spawning season) in a ...

  11. Biostable and PEG polymer-conjugated insect pyrokinin analogs demonstrate antifeedant activity and induce high mortality in the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The pyrokinins are multifunctional neuropeptides found in a variety of arthropod species, including the pea aphid Acyrthosiphon pisum (Hemiptera: Aphidae). A series of biostable pyrokinin analogs based on the shared C-terminal pentapeptide core region were fed in solutions of artificial diet to the ...

  12. Tissue-specific induction of Hsp90 mRNA and plasma cortisol response in chinook salmon following heat shock, seawater challenge, and handling challenge

    USGS Publications Warehouse

    Palmisano, Aldo N.; Winton, J.R.; Dickhoff, Walton W.

    2000-01-01

    In studying the whole-body response of chinook salmon (Oncorhynchus tshawytscha) to various stressors, we found that 5-hour exposure to elevated temperature (mean 21.6??C; + 10.6??C over ambient) induced a marked increase in Hsp90 messenger RNA accumulation in heart, brain, gill, muscle, liver, kidney, and tail fin tissues. The most vital tissues (heart, brain, gill, and muscle) showed the greatest Hsp90-mRNA response, with heart tissue increasing approximately 35-fold, Heat shock induced no increase in plasma cortisol. In contrast, a standard handling challenge induced high plasma cortisol levels, but no elevation in Hsp90 mRNA in any tissue, clearly separating the physiological and cellular stress responses. We saw no increase either in tissue Hsp90 mRNA levels or in plasma cortisol concentrations after exposing the fish to seawater overnight.

  13. Plasma cortisol levels and illness appraisal in deficit syndrome schizophrenia.

    PubMed

    White, Ross G; Lysaker, Paul; Gumley, Andrew I; McLeod, Hamish; McCleery, Muriel; O'Neill, Donnacha; MacBeth, Angus; Giurgi-Oncu, Catalina; Mulholland, Ciaran C

    2014-12-30

    Research investigating the association between negative symptoms and plasma cortisol levels in individuals with schizophrenia has produced inconsistent findings. This study investigated whether deficit syndrome schizophrenia (characterized by high levels of primary negative symptoms) is associated with comparatively high morning plasma cortisol levels, more negative appraisals about illness and higher levels of depression. Participants were 85 individuals diagnosed with schizophrenia and 85 individuals with no history of contact with psychiatric services matched for age and gender. All participants provided fasting 9.00a.m. plasma cortisol samples. There were no significant differences between the schizophrenia and control participants in plasma cortisol levels. The Proximal Deficit Syndrome method was used to identify individuals with deficit syndrome schizophrenia. Contrary to what had been hypothesized, participants with deficit syndrome schizophrenia had significantly lower plasma cortisol levels than both non-deficit syndrome participants and control participants. Participants with the deficit syndrome reported significantly less negative appraisals about illness (assessed by PBIQ) and lower levels of depression (assessed by BDI-II). Differences in cortisol levels continued to trend toward significance when levels of depression were controlled for. The patterns of illness-related appraisals and plasma cortisol levels raise the possibility that the deficit syndrome could be a form of adaptation syndrome. PMID:25262562

  14. Acute effects of bright light exposure on cortisol levels.

    PubMed

    Jung, Christopher M; Khalsa, Sat Bir S; Scheer, Frank A J L; Cajochen, Christian; Lockley, Steven W; Czeisler, Charles A; Wright, Kenneth P

    2010-06-01

    Multisynaptic neural and endocrine pathways from the suprachiasmatic nucleus of the hypothalamus have been hypothesized to communicate circadian and photic information to the adrenal glands. In humans, light exposure has been reported to have no effect, increase, or decrease cortisol levels. These inconsistent findings in humans may be related to differences among studies including the intensity (approximately 500 to 5500 lux), duration (15 min to 4 h), and circadian phase of light exposure. The authors assessed the influence of exposure to bright light on cortisol levels in humans during the rising and descending phases of the circadian rhythm of cortisol, that is, when cortisol levels are high. Twenty healthy men and women were studied using a within-subject research design. Subjects were studied in an environment free of time cues for 9 to 10 days. Subjects received a 6.7-h exposure of bright light (approximately 10,000 lux; equivalent to ambient light intensity just after sunrise or just before sunset) or dim light (approximately 3 lux; equivalent to candle light) during the biological night and morning. Bright light exposure significantly reduced plasma cortisol levels at both circadian phases studied, whereas dim light exposure had little effect on cortisol levels. The finding of an acute suppressive effect of bright light exposure on cortisol levels supports the existence of a mechanism by which photic information can acutely influence the human adrenal glands. PMID:20484692

  15. Increased serum cortisol binding in chronic active hepatitis

    SciTech Connect

    Orbach, O.; Schussler, G.C.

    1989-01-01

    A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG.

  16. Elevated cortisol content in dog hair with atopic dermatitis.

    PubMed

    Park, Seol-Hee; Kim, Sun-A; Shin, Nam-Shik; Hwang, Cheol-Yong

    2016-05-01

    Canine atopic dermatitis (CAD) is a chronic relapsing inflammatory skin disease occurring in 10% of the canine population. Although most studies have focused on the pathophysiological mechanism involved in CAD, the detrimental impact of CAD on quality of life has received only little attention. Hair cortisol analysis is becoming a valuable tool in monitoring chronic stress. To further validate this approach in CAD, we compared the hair cortisol concentration of atopic dogs with that of healthy conditioned dogs. The extent and severity of cutaneous lesions of atopic dermatitis were assessed according to modified CADESI-03 scores. In addition, skin barrier function was evaluated by measuring transepidermal water loss (TEWL) and stratum corneum conductance. The correlation between CAD severity and hair cortisol concentration was evaluated. The level of hair cortisol evaluated by ELISA assay showed that the atopic dermatitis group had significantly increased cortisol levels compared to that of the healthy control group. A significant positive correlation was identified between hair cortisol level and the CADESI score in CAD patients. The TEWL value of the cubital flexor of the forelimb in the atopic group was significantly higher compared to the healthy controls. These findings imply that the hair cortisol analysis can be an effective and objective biomarker in assessment of long-term stress of CAD patients. PMID:27506086

  17. Human Milk Cortisol is Associated With Infant Temperament

    PubMed Central

    Grey, Katherine R.; Davis, Elysia Poggi; Sandman, Curt A.; Glynn, Laura M.

    2012-01-01

    The implications of the biologically active elements in milk for the mammalian infant are largely unknown. Animal models demonstrate that transmission of glucocorticoids through milk influences behavior and modifies brain development in offspring. The aim of this study was to determine the relation between human milk cortisol levels and temperament of the breastfed infant. Fifty-two mother and infant pairs participated when the infants were three-months old. Milk cortisol levels were assessed and each mother completed the Infant Behavior Questionnaire (IBQ), a widely used parent-report measure of infant temperament. Analyses revealed a positive association between milk cortisol and the Negative Affectivity dimension of the IBQ (partial r =.37, p < .01). No correlation was found between elevated cortisol levels and the Surgency/Extraversion or the Orienting/Regulation dimensions. Further, the positive association between increased maternal milk cortisol and Negative Affectivity was present among girls (β = .59, p < .01), but not among boys. (Although, the sex by milk cortisol interaction term was not statistically significant, suggesting that these results require replication.) Environmental factors such as maternal demographics and negative maternal affect (depression and perceived stress) at the time of assessment did not account for the positive association. The findings support the proposal that exposure to elevated levels of cortisol in human milk influences infant temperament. The findings further suggest that mothers have the ability shape offspring phenotype through the transmission of biologically active components in milk. PMID:23265309

  18. Cortisol alters reward processing in the human brain.

    PubMed

    Kinner, Valerie L; Wolf, Oliver T; Merz, Christian J

    2016-08-01

    Dysfunctional reward processing is known to play a central role for the development of psychiatric disorders. Glucocorticoids that are secreted in response to stress have been shown to attenuate reward sensitivity and thereby might promote the onset of psychopathology. However, the underlying neurobiological mechanisms mediating stress hormone effects on reward processing as well as potential sex differences remain elusive. In this neuroimaging study, we administered 30mg cortisol or a placebo to 30 men and 30 women and subsequently tested them in the Monetary Incentive Delay Task. Cortisol attenuated anticipatory neural responses to a verbal and a monetary reward in the left pallidum and the right anterior parahippocampal gyrus. Furthermore, in men, activation in the amygdala, the precuneus, the anterior cingulate, and in hippocampal regions was reduced under cortisol, whereas in cortisol-treated women a signal increase was observed in these regions. Behavioral performance also indicated that reward learning in men is impaired under high cortisol concentrations, while it is augmented in women. These findings illustrate that the stress hormone cortisol substantially diminishes reward anticipation and provide first evidence that cortisol effects on the neural reward system are sensitive to sex differences, which might translate into different vulnerabilities for psychiatric disorders. PMID:27170428

  19. The Impact of PTSD Treatment on the Cortisol Awakening Response

    PubMed Central

    Pacella, Maria L.; Feeny, Norah; Zoellner, Lori; Delahanty, Douglas L.

    2015-01-01

    Background Posttraumatic stress disorder (PTSD) is associated with abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis; however, limited research has examined whether cortisol levels change following successful PTSD treatment. The current study examined the impact of successful PTSD treatment on the cortisol awakening response (CAR). Method Twenty-nine adults participating in a treatment trial for chronic PTSD provided saliva samples (upon waking, and 30, 45, and 60-min post-waking) before and after receiving either prolonged exposure therapy or sertraline. PTSD responder status (i.e., loss or retention of a PTSD diagnosis) served as the predictor variable. Outcome measures included area under the curve with respect to ground and increase, reflecting total cortisol output and HPA axis reactivity, respectively. Results A series of hierarchical regressions revealed no significant main effects of PTSD responder status for either CAR outcome. However, a significant gender by treatment response interaction for cortisol reactivity revealed that female treatment non-responders displayed higher cortisol reactivity following treatment than female responders, whereas cortisol reactivity did not change pre- to post-treatment for male responders. Findings remained after controlling for age, trauma history, baseline medication status, baseline PTSD, and baseline depressive symptoms. Conclusion Loss of a PTSD diagnosis may contribute to decreased cortisol reactivity in females. Neuroendocrine changes following treatment may emerge only for specific subgroups, highlighting the importance of exploring treatment moderators. PMID:25327949

  20. Violence exposure and cortisol responses in urban youth.

    PubMed

    Kliewer, Wendy

    2006-01-01

    I examined the physiological costs associated with exposure to violence in 101 African American youth (55% male; M age = 11.14 years) living in high-violence areas of a midsized southern city in the United States. Salivary cortisol was measured before and after a laboratory task (viewing and discussing a video depicting community violence) and on waking 1 morning in the week following the laboratory assessment. Overall, cortisol levels were low. Analyses controlling for age, gender, negative affect, and major life events revealed that peer victimization was associated with lower basal cortisol values obtained from home assessments. Witnessed violence predicted a cortisol awakening response (CAR) but only in girls; girls with a typical CAR had lower levels of witnessing violence than girls with an atypical pattern. Witnessed violence also was associated with lower baseline cortisol levels measured in the laboratory and with increases in cortisol from baseline to posttask for boys but not girls. Peer victimization was associated with increases in cortisol from pretask to posttask for both genders. I discuss implications for research and prevention. PMID:16712428

  1. A systematic review of the effects of mindfulness interventions on cortisol.

    PubMed

    O'Leary, Karen; O'Neill, Siobhan; Dockray, Samantha

    2016-09-01

    Cortisol is increasingly included in examinations of mindfulness intervention effects as an indicator of efficacy; however, the association of cortisol and mindfulness has yet to be rigorously evaluated. A systematic review of six studies examining mindfulness intervention effects on cortisol was conducted. Inconsistent results were found for mindfulness effects on cortisol. Significant changes in cortisol levels were observed in within-participants studies but not observed in randomised controlled trial designs. Mindfulness may influence cortisol, but findings are inconclusive. Mindfulness pathways and methodological differences influence variations in mindfulness effects. Robust protocols are needed to adequately examine mindfulness effects on cortisol. PMID:25673371

  2. Influence of external factors on hair cortisol concentrations.

    PubMed

    Salaberger, Theresa; Millard, Marlon; Makarem, Samy El; Möstl, Erich; Grünberger, Viktoria; Krametter-Frötscher, Reinhild; Wittek, Thomas; Palme, Rupert

    2016-07-01

    Measuring hair cortisol has attracted interest as a long term parameter for chronic stress evaluation. However, some studies support the hypothesis that locally produced cortisol, originating from the hair follicle or skin cells, affects concentrations in the hair. In an animal model the influence of different treatments (extensive brushing, administration of a hyperemising fluid that enhances blood circulation or a synthetic glucocorticoid) on the local cortisol production of hair was evaluated. Therefore eight sheep were sheared and the area of the skin surface of the back was quartered, with three quarters being daily subjected to a certain treatment and one quarter remaining untreated. The skin areas were sheared again after three weeks and cortisol concentrations of all wool samples were determined by immunoassay. Systemic cortisol concentrations were additionally monitored with faecal samples, indicating a significant decline in concentrations of glucocorticoid metabolites between week 1 and 2 or 3, respectively. We found no significant difference in hair cortisol concentrations between fields before treatment (p=0.310). Comparing matched fields before and after treatment, we found no significant differences in wool cortisol concentrations for fields treated with hyperemising fluid as well as for the control fields (p=0.329, p=0.097). Hairs exposed to either extensive brushing or dexamethasone fluid had significantly higher immunoreactive cortisol concentrations after three weeks of treatment (p=0.016, p=0.01). We therefore advise cautious interpretation when measuring hair cortisol concentrations as a parameter for chronic stress, because external factors may have a significant influence on the results. PMID:27167500

  3. Deconvolution of Serum Cortisol Levels by Using Compressed Sensing

    PubMed Central

    Faghih, Rose T.; Dahleh, Munther A.; Adler, Gail K.; Klerman, Elizabeth B.; Brown, Emery N.

    2014-01-01

    The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropin hormone (ACTH) from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on this problem, a complete satisfactory solution has been elusive. We formulate this question as a non-convex optimization problem, and solve it using a coordinate descent algorithm that has a principled combination of (i) compressed sensing for recovering the amplitude and timing of the secretory events, and (ii) generalized cross validation for choosing the regularization parameter. Using only the observed serum cortisol levels, we model cortisol secretion from the adrenal glands using a second-order linear differential equation with pulsatile inputs that represent cortisol pulses released in response to pulses of ACTH. Using our algorithm and the assumption that the number of pulses is between 15 to 22 pulses over 24 hours, we successfully deconvolve both simulated datasets and actual 24-hr serum cortisol datasets sampled every 10 minutes from 10 healthy women. Assuming a one-minute resolution for the secretory events, we obtain physiologically plausible timings and amplitudes of each cortisol secretory event with R2 above 0.92. Identification of the amplitude and timing of pulsatile hormone release allows (i) quantifying of normal and abnormal secretion patterns towards the goal of understanding pathological neuroendocrine states, and (ii) potentially designing optimal approaches for treating hormonal disorders. PMID:24489656

  4. Hair cortisol and cognitive performance in working age adults.

    PubMed

    McLennan, Skye N; Ihle, Andreas; Steudte-Schmiedgen, Susann; Kirschbaum, Clemens; Kliegel, Matthias

    2016-05-01

    It has been hypothesized that prolonged exposure to high cortisol levels results in cognitive impairment. However, previous research into the relationship between cortisol and cognition has produced mixed results, most likely due to difficulties achieving valid estimates of long-term cortisol exposure based on salivary or plasma cortisol assessments at a single time point. Furthermore, there has been little research on the cognitive effects of long-term cortisol exposure in working-age adults. In the present study, hair samples were collected from 246 nurses (89.8% female) aged from 21 to 62 (M=42.0, SD=11.2). Hair cortisol concentrations (HCC) in the proximal 3-cm hair segment were analyzed providing an estimate of integrated cortisol secretion over the 3 month-period prior to hair sampling. Cognition was measured using a battery of 15 neuropsychological tests, measuring core dimensions of memory, inductive reasoning, processing speed, crystalized intelligence and major aspects of executive functioning. HCC was not significantly related to any of the cognitive abilities measured, either before or after controlling for potential moderators such as age, sex, education, health, well-being, work ability and burnout. Tests for nonlinear relationships also yielded non-significant results. Thus, despite the study being well powered, long term cortisol exposure did not appear to be related to cognitive performance in this sample of working-age adults, suggesting that long term cortisol exposure may be less relevant to cognition in younger and middle-aged adults than was previously thought. PMID:26881835

  5. Cortisol in human tissues at different stages of life.

    PubMed

    Costa, A; Benedetto, C; Fabris, C; Giraudi, G F; Testori, O; Bertino, E; Marozio, L; Varvello, G; Arisio, R; Ariano, M; Emanuel, A

    1996-01-01

    Aim of the work was to measure the cortisol level in human tissues at different stages of life, by means of radioimmunoassay and by chromatography. Viable samples of 13 different tissues were obtained during surgical intervention from 30 to 70 years old patients of either sex. Mean tissue cortisol concentration was 78 +/- 35 ng/g, ranging from 20 +/- 10 ng/g in the thyroid to 124 +/- 76 ng/g in the kidney. Similar values were measured in the corresponding tissues from not decayed corpses, so that paired values could be mediated. However the pancreas, and corrupted autopsy tissues, gave nil or exceedingly high cortisol concentration values; in some cases, opposite extreme values were measured in different organs of the same body. Cortisol concentration was also measured in 11 sound different tissues of spontaneously aborted or stillbirth fetuses, between 16 and 36 weeks of gestation. Mean value was 63 +/- 27 ng/g, ranging from 30 +/- 25 ng/g in the liver to 104 +/- 52 ng/g in the lungs. Also in fetuses nil or exceedingly high cortisol values occurred in altered tissues. One hundred and fourteen samples of limbs and carcasses of 7 to 12 gestational weeks embryos, obtained from voluntary abortions, were also examined: 20% gave nil result, in the remaining mean cortisol concentration was 32 ng/g. In 33 samples of embryos' mixed viscera, RIA and chromatography gave unreliable exceedingly high values. The nil and the exceedingly high values measured in the altered autoptic tissue specimens were inconsistent with the cortisol blood level measured in the patients, as were those measured in embryonic tissues with the acknowledged blood and adrenals cortisol levels at that stage of life. Thus cortisol may be measured by RIA and by chromatography in sound tissues, while the values obtained in the pancreas, in corrupted tissues, and in embryonal viscera do not represent the hormonal milieu, but are likely artifacts due to impeachment of the diagnostic system. PMID:8884541

  6. Interventions to Improve Cortisol Regulation in Children: A Systematic Review

    PubMed Central

    McLaughlin, Katie A.; Shonkoff, Jack P.

    2014-01-01

    Childhood adversity is associated with physiologic dysregulation across multiple biological systems; however, relatively little is known about whether these changes are reversible with intervention. The objective of this review was to examine evidence for the effectiveness of interventions to promote healthy cortisol regulation in children. We selected articles from English-language publications in PubMed and EBSCO databases through 2012. Two independent reviewers assessed articles against eligibility criteria. Eligible studies were randomized controlled or quasi-experimental studies designed to improve relationships, environments, or psychosocial functioning in children and examined cortisol as an outcome. We identified 19 articles. There was substantial heterogeneity across studies with regard to age, selection criteria, intervention design, cortisol assessment, and follow-up duration. Eighteen of the 19 articles reported at least 1 difference in baseline cortisol, diurnal cortisol, or cortisol responsivity between intervention and control participants. Importantly, however, there was remarkable inconsistency with regard to how the interventions influenced cortisol. Therefore, studies that included a low-risk comparison group (n = 8) provided critical insight, and each found some evidence that postintervention cortisol levels in the intervention group approximated the low-risk comparison group and differed from children receiving usual care. In conclusion, existing studies show that cortisol activity can be altered by psychosocial interventions. These findings are promising, not only because they indicate physiologic plasticity that can be leveraged by interventions but also because they suggest it may be possible to repair regulatory systems after childhood adversity, which could inform strategies for reducing health disparities and promoting lasting improvements in health. PMID:24420810

  7. Deconvolution of serum cortisol levels by using compressed sensing.

    PubMed

    Faghih, Rose T; Dahleh, Munther A; Adler, Gail K; Klerman, Elizabeth B; Brown, Emery N

    2014-01-01

    The pulsatile release of cortisol from the adrenal glands is controlled by a hierarchical system that involves corticotropin releasing hormone (CRH) from the hypothalamus, adrenocorticotropin hormone (ACTH) from the pituitary, and cortisol from the adrenal glands. Determining the number, timing, and amplitude of the cortisol secretory events and recovering the infusion and clearance rates from serial measurements of serum cortisol levels is a challenging problem. Despite many years of work on this problem, a complete satisfactory solution has been elusive. We formulate this question as a non-convex optimization problem, and solve it using a coordinate descent algorithm that has a principled combination of (i) compressed sensing for recovering the amplitude and timing of the secretory events, and (ii) generalized cross validation for choosing the regularization parameter. Using only the observed serum cortisol levels, we model cortisol secretion from the adrenal glands using a second-order linear differential equation with pulsatile inputs that represent cortisol pulses released in response to pulses of ACTH. Using our algorithm and the assumption that the number of pulses is between 15 to 22 pulses over 24 hours, we successfully deconvolve both simulated datasets and actual 24-hr serum cortisol datasets sampled every 10 minutes from 10 healthy women. Assuming a one-minute resolution for the secretory events, we obtain physiologically plausible timings and amplitudes of each cortisol secretory event with R (2) above 0.92. Identification of the amplitude and timing of pulsatile hormone release allows (i) quantifying of normal and abnormal secretion patterns towards the goal of understanding pathological neuroendocrine states, and (ii) potentially designing optimal approaches for treating hormonal disorders. PMID:24489656

  8. Are we missing a mineralocorticoid in teleost fish? Effects of cortisol, deoxycorticosterone and aldosterone on osmoregulation, gill Na+,K+-ATPase activity and isoform mRNA levels in Atlantic salmon

    USGS Publications Warehouse

    McCormick, S.D.; Regish, A.; O'Dea, M. F.; Shrimpton, J.M.

    2008-01-01

    It has long been held that cortisol, acting through a single receptor, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. The recent finding that fish express a gene with high sequence similarity to the mammalian mineralocorticoid receptor (MR) suggests the possibility that a hormone other than cortisol carries out some mineralocorticoid functions in fish. To test for this possibility, we examined the effect of in vivo cortisol, 11-deoxycorticosterone (DOC) and aldosterone on salinity tolerance, gill Na+,K+-ATPase (NKA) activity and mRNA levels of NKA α1a and α1b in Atlantic salmon. Cortisol treatment for 6–14 days resulted in increased, physiological levels of cortisol, increased gill NKA activity and improved salinity tolerance (lower plasma chloride after a 24 h seawater challenge), whereas DOC and aldosterone had no effect on either NKA activity or salinity tolerance. NKA α1a and α1b mRNA levels, which increase in response to fresh water and seawater acclimation, respectively, were both upregulated by cortisol, whereas DOC and aldosterone were without effect. Cortisol, DOC and aldosterone had no effect on gill glucocorticoid receptor GR1, GR2 and MR mRNA levels, although there was some indication of possible upregulation of GR1 by cortisol (p = 0.07). The putative GR blocker RU486 inhibited cortisol-induced increases in salinity tolerance, NKA activity and NKA α1a and α1b transcription, whereas the putative MR blocker spironolactone had no effect. The results provide support that cortisol, and not DOC or aldosterone, is involved in regulating the mineralocorticoid functions of ion uptake and salt secretion in teleost fish.

  9. Analog synthetic biology

    PubMed Central

    Sarpeshkar, R.

    2014-01-01

    We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog–digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA–protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations. PMID:24567476

  10. Analog pulse processor

    DOEpatents

    Wessendorf, Kurt O.; Kemper, Dale A.

    2003-06-03

    A very low power analog pulse processing system implemented as an ASIC useful for processing signals from radiation detectors, among other things. The system incorporates the functions of a charge sensitive amplifier, a shaping amplifier, a peak sample and hold circuit, and, optionally, an analog to digital converter and associated drivers.

  11. Challenges in Using Analogies

    ERIC Educational Resources Information Center

    Lin, Shih-Yin; Singh, Chandralekha

    2011-01-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features. One way to help students learn physics is via analogical reasoning. Students can be taught to make an analogy between situations that are more familiar or easier to understand and another situation where the same…

  12. Hydraulic Capacitor Analogy

    ERIC Educational Resources Information Center

    Baser, Mustafa

    2007-01-01

    Students have difficulties in physics because of the abstract nature of concepts and principles. One of the effective methods for overcoming students' difficulties is the use of analogies to visualize abstract concepts to promote conceptual understanding. According to Iding, analogies are consistent with the tenets of constructivist learning…

  13. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults.

    PubMed

    Hötting, Kirsten; Schickert, Nadine; Kaiser, Jochen; Röder, Brigitte; Schmidt-Kassow, Maren

    2016-01-01

    In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans. PMID:27437149

  14. Stress and selective attention: the interplay of mood, cortisol levels, and emotional information processing.

    PubMed

    Ellenbogen, Mark A; Schwartzman, Alex E; Stewart, Jane; Walker, Claire-Dominique

    2002-11-01

    The effects of a stressful challenge on the processing of emotional words were examined in college students. Stress induction was achieved using a competitive computer task, where the individual either repeatedly lost or won against a confederate. Mood, attention, and cortisol were recorded during the study. There were four findings: (1) Participants in the negative stressor condition were faster to shift attention away from negative words than positive or neutral words; (2) attentional shifts away from negative words were associated with stress-induced mood lowering; (3) participants in the negative stress condition with elevated scores on the Beck Depression Inventory were slow to disengage attention from all stimuli; and (4) elevated depression scores were associated with lower cortisol change from baseline during the experimental phase, and with higher cortisol levels during the recovery phase. These findings point to information-processing strategies as a means to regulate emotion, and to atypical features of cognitive and adrenocortical function that may serve as putative risk markers of depression. PMID:12462500

  15. Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors.

    PubMed

    Goh, Gerald; Scholl, Ute I; Healy, James M; Choi, Murim; Prasad, Manju L; Nelson-Williams, Carol; Kunstman, John W; Kuntsman, John W; Korah, Reju; Suttorp, Anna-Carinna; Dietrich, Dimo; Haase, Matthias; Willenberg, Holger S; Stålberg, Peter; Hellman, Per; Akerström, Göran; Björklund, Peyman; Carling, Tobias; Lifton, Richard P

    2014-06-01

    Adrenal tumors autonomously producing cortisol cause Cushing's syndrome. We performed exome sequencing of 25 tumor-normal pairs and identified 2 subgroups. Eight tumors (including three carcinomas) had many somatic copy number variants (CNVs) with frequent deletion of CDC42 and CDKN2A, amplification of 5q31.2 and protein-altering mutations in TP53 and RB1. Seventeen tumors (all adenomas) had no somatic CNVs or TP53 or RB1 mutations. Six of these had known gain-of-function mutations in CTNNB1 (β-catenin) or GNAS (Gαs). Six others had somatic mutations in PRKACA (protein kinase A (PKA) catalytic subunit) resulting in a p.Leu206Arg substitution. Further sequencing identified this mutation in 13 of 63 tumors (35% of adenomas with overt Cushing's syndrome). PRKACA, GNAS and CTNNB1 mutations were mutually exclusive. Leu206 directly interacts with the regulatory subunit of PKA, PRKAR1A. Leu206Arg PRKACA loses PRKAR1A binding, increasing the phosphorylation of downstream targets. PKA activity induces cortisol production and cell proliferation, providing a mechanism for tumor development. These findings define distinct mechanisms underlying adrenal cortisol-producing tumors. PMID:24747643

  16. The Effects of Acute Physical Exercise on Memory, Peripheral BDNF, and Cortisol in Young Adults

    PubMed Central

    Röder, Brigitte; Schmidt-Kassow, Maren

    2016-01-01

    In animals, physical activity has been shown to induce functional and structural changes especially in the hippocampus and to improve memory, probably by upregulating the release of neurotrophic factors. In humans, results on the effect of acute exercise on memory are inconsistent so far. Therefore, the aim of the present study was to assess the effects of a single bout of physical exercise on memory consolidation and the underlying neuroendocrinological mechanisms in young adults. Participants encoded a list of German-Polish vocabulary before exercising for 30 minutes with either high intensity or low intensity or before a relaxing phase. Retention of the vocabulary was assessed 20 minutes after the intervention as well as 24 hours later. Serum BDNF and salivary cortisol were measured at baseline, after learning, and after the intervention. The high-intensity exercise group showed an increase in BDNF and cortisol after exercising compared to baseline. Exercise after learning did not enhance the absolute number of recalled words. Participants of the high-intensity exercise group, however, forgot less vocabulary than the relaxing group 24 hours after learning. There was no robust relationship between memory scores and the increase in BDNF and cortisol, respectively, suggesting that further parameters have to be taken into account to explain the effects of exercise on memory in humans. PMID:27437149

  17. The novel neurotensin analog NT69L blocks phencyclidine (PCP)-induced increases in locomotor activity and PCP-induced increases in monoamine and amino acids levels in the medial prefrontal cortex.

    PubMed

    Li, Zhimin; Boules, Mona; Williams, Katrina; Peris, Joanna; Richelson, Elliott

    2010-01-22

    Schizophrenia is a life-long, severe, and disabling brain disorder that requires chronic pharmacotherapy. Because current antipsychotic drugs do not provide optimal therapy, we have been developing novel treatments that focus on receptors for the neuropeptide neurotensin (NT). NT69L, an analog of neurotensin(8-13), acts like an atypical antipsychotic drug in several dopamine-based animal models used to study schizophrenia. Another current animal model utilizes non-competitive antagonists of the NMDA/glutamate receptor, such as the psychotomimetic phencyclidine (PCP). In the present study, we investigated the effects of NT69L on PCP-induced behavioral and biochemical changes in the rat. The top of an activity chamber was modified to allow us to perform microdialysis in rat brain, while simultaneously recording the locomotor activity of a rat. PCP injection significantly increased activity as well as the extracellular concentration of norepinephrine (NE), 5-HT, dopamine (DA), and glutamate in the medial prefrontal cortex (mPFC). Pretreating with NT69L blocked the PCP-induced hyperactivity as well as the increase of DA, 5-HT, NE, and glutamate in mPFC. Interestingly and unexpectedly, NT69L markedly increased glycine levels, while PCP was without effect on glycine levels. Thus, NT69L showed antipsychotic-like effects in this glutamate-based animal model for studying schizophrenia. Previous work from our group suggests that NT69L also has antipsychotic-like effects in dopaminergic and serotonergic rodent models. Taken together, these data suggest that NT69L in particular and NT receptor agonists in general, will be useful as broad-spectrum antipsychotic drugs. PMID:19948149

  18. Hair as a retrospective calendar of cortisol production-Increased cortisol incorporation into hair in the third trimester of pregnancy.

    PubMed

    Kirschbaum, Clemens; Tietze, Antje; Skoluda, Nadine; Dettenborn, Lucia

    2009-01-01

    Hair has long been used in toxicology, forensic science, doping control and other fields as a biological specimen for the detection of environmental agents, drugs, or toxins. Most recent evidence suggests that also hormones are incorporated and trapped inside the growing hair. This has led to the hypothesis that cortisol measurement of distinct hair segments could provide a retrospective calendar of cortisol production for the individual. In this first proof-of-concept study in humans, we analyzed cortisol in hair donated by mothers with a neonate child (n-Mothers; N=103), mothers with toddlers 3-9 months of age (t-Mothers; N=19), and control women (N=20). We cut hair strands from each women into at least three 3-cm segments, which, based on an average hair growth rate of 1cm per month, would represent hair grown over the past three, six, and nine months, respectively. Since in the third trimester of pregnancy there is a well-documented increased production of cortisol, we expected to see elevated levels of cortisol in the most proximal hair segment of women who had just given birth to a child (n-Mothers) compared with the control women. Likewise, we expected to see elevated levels in the second, third, or fourth segment of mothers of 3-month olds, 6-months olds, and 9-months olds, respectively. These hair segments, cut at 4-12 cm from the scalp, would represent hair grown throughout the third trimester of pregnancy. Results showed that there was a strong monotonic decline in cortisol concentration from the segment closest to the scalp to the most distal hair segment (p<0.0001). Cortisol levels decreased by 30-40% from one segment to the next for the most recent four hair segments. Segments from hair older than one year had similarly, low levels of cortisol. Comparisons of cortisol levels in hair between n-Mothers and control women yielded the expected results: cortisol levels in the first 3-cm hair segment (i.e., closest to the scalp) of n-Mothers were two

  19. Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in major depressive disorder patients.

    PubMed

    Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Kawano, Aimi; Ando, Tomoko; Okamoto, Shizuko; Kanehisa, Masayuki; Higuma, Haruka; Ninomiya, Taiga; Tsuru, Jusen; Hanada, Hiroaki; Kodama, Kensuke; Isogawa, Koichi; Akiyoshi, Jotaro

    2012-03-30

    Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress. In comparison, psychosocial stress-induced activation of salivary α-amylase (sAA) functions as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in MDD patients. The present study measured sAA and salivary cortisol levels in patients with MDD. The authors determined Profile of Mood State (POMS) and State-Trait anxiety Inventory (STAI) scores, Heart Rate Variability (HRV), and sAA and salivary cortisol levels in 88 patients with MDD and 41 healthy volunteers following the application of electrical stimulation stress. Patients with major depressive disorder were 8 points or more on Hamilton Depression Scale (HAM-D) scores. Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores in patients with major depressive disorder were significantly increased compared to healthy controls. In contrast, Vigor scores in patients with MDD were significantly decreased compared with healthy controls. There was no difference in heart rate variability measures between MDD patients and healthy controls. The threshold of electrical stimulation applied in MDD patients was lower than that in healthy controls. SAA levels in female MDD patients were significantly elevated relative to controls both before and after electrical stimulation. Finally, there were no differences in salivary cortisol levels between major depressive patients and controls. In the present study only three time points were explored. Furthermore, the increased secretion of sAA before and after stimulation could allude to an increased responsiveness of novel and uncontrollable situations in patients with MDD. These preliminary results suggest that sAA might be a useful biological marker of MDD. PMID:22063648

  20. Salivary alpha amylase and salivary cortisol response to fluid consumption in exercising athletes.

    PubMed

    Backes, T P; Horvath, P J; Kazial, K A

    2015-11-01

    The objective of the study was to examine salivary biomarker response to fluid consumption in exercising athletes. Exercise induces stress on the body and salivary alpha amylase (sAA) and salivary cortisol are useful biomarkers for activity in the sympathoadrenal medullary system and the hypothalamic pituitary adrenal axis which are involved in the stress response. Fifteen college students were given 150 ml and 500 ml of water on different days and blinded to fluid condition. The exercise protocol was identical for both fluid conditions using absolute exercise intensities ranging from moderate to high. Saliva was collected prior to exercise, post moderate and post high intensities and analyzed by Salimetrics assays. Exercise was significant for sAA with values different between pre-exercise (85 ± 10 U · ml(-1)) and high intensity (284 ± 30 U · ml(-1)) as well as between moderate intensity (204 ± 32 U · ml(-1)) and high intensity. There was no difference in sAA values between fluid conditions at either intensity. Exercise intensity and fluid condition were each significant for cortisol. Cortisol values were different between pre-exercise (0.30 ± 0.03 ug · dL(-1)) and high intensity (0.45 ± 0.05 ug · dL(-1)) as well as between moderate intensity (0.33 ± 0.04 ug · dL(-1)) and high intensity. Moderate exercise intensity cortisol was lower in the 500 ml condition (0.33 ± 0.03 ug · dL(-1)) compared with the 150 ml condition (0.38 ± 0.03 ug · dL(-1)). This altered physiological response due to fluid consumption could influence sport performance and should be considered. In addition, future sport and exercise studies should control for fluid consumption. PMID:26681828

  1. Salivary alpha amylase and salivary cortisol response to fluid consumption in exercising athletes

    PubMed Central

    Horvath, PJ; Kazial, KA

    2015-01-01

    The objective of the study was to examine salivary biomarker response to fluid consumption in exercising athletes. Exercise induces stress on the body and salivary alpha amylase (sAA) and salivary cortisol are useful biomarkers for activity in the sympathoadrenal medullary system and the hypothalamic pituitary adrenal axis which are involved in the stress response. Fifteen college students were given 150 ml and 500 ml of water on different days and blinded to fluid condition. The exercise protocol was identical for both fluid conditions using absolute exercise intensities ranging from moderate to high. Saliva was collected prior to exercise, post moderate and post high intensities and analyzed by Salimetrics assays. Exercise was significant for sAA with values different between pre-exercise (85 ± 10 U · ml−1) and high intensity (284 ± 30 U · ml−1) as well as between moderate intensity (204 ± 32 U · ml−1) and high intensity. There was no difference in sAA values between fluid conditions at either intensity. Exercise intensity and fluid condition were each significant for cortisol. Cortisol values were different between pre-exercise (0.30 ± 0.03 ug · dL−1) and high intensity (0.45 ± 0.05 ug · dL−1) as well as between moderate intensity (0.33 ± 0.04 ug · dL−1) and high intensity. Moderate exercise intensity cortisol was lower in the 500 ml condition (0.33 ± 0.03 ug · dL−1) compared with the 150 ml condition (0.38 ± 0.03 ug · dL−1). This altered physiological response due to fluid consumption could influence sport performance and should be considered. In addition, future sport and exercise studies should control for fluid consumption. PMID:26681828

  2. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress

    PubMed Central

    Saliba, Flávia G.; Adiwardana, Natanael S.; Uehara, Eliane U.; Silvestre, Renata N.; Leite, Victor V.; Faleiros, Francisca T.V.; Padovani, Flávia H.P.; De Gobbi, Juliana I.F.

    2016-01-01

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  3. Salivary Cortisol Levels: The Importance of Clown Doctors to Reduce Stress.

    PubMed

    Saliba, Flávia G; Adiwardana, Natanael S; Uehara, Eliane U; Silvestre, Renata N; Leite, Victor V; Faleiros, Francisca T V; Padovani, Flávia H P; De Gobbi, Juliana I F

    2016-03-31

    This study was designed to correlate entertainment of clown-doctors (CD) activities on hospitalized children and aphysiological bio-marker. For this purpose we collected saliva samples and verified children satisfaction with these activities by using a visual analog scale (VAS). Children from 6 to 7 years-old, with diagnosis of any acute pathology, interned in the Pediatric Ward of the Botucatu Medical School Hospital (São Paulo, Brazil) were interviewed. Two groups were taken into consideration: lunchCD and dinnerCD. The following protocol was applied in each group (lunch and dinner): collection of the first saliva sample and presentation of VAS prior to CD activities, followed by collection of a second saliva sample and another VAS assessment after CD activities. The salivary cortisol was reduced in both groups comparing the first saliva sample. The satisfaction of the intervention was evident for lunchCD. The CD intervention is effective in decreasing an important physiological biomarker of stress factor, cortisol, in hospitalized children, been effective for the healing process. PMID:27114816

  4. Meat analog: a review.

    PubMed

    Malav, O P; Talukder, S; Gokulakrishnan, P; Chand, S

    2015-01-01

    The health-conscious consumers are in search of nutritious and convenient food item which can be best suited in their busy life. The vegetarianism is the key for the search of such food which resembles the meat in respect of nutrition and sensory characters, but not of animal origin and contains vegetable or its modified form, this is the point when meat analog evolved out and gets shape. The consumers gets full satisfaction by consumption of meat analog due to its typical meaty texture, appearance and the flavor which are being imparted during the skilled production of meat analog. The supplement of protein in vegetarian diet through meat alike food can be fulfilled by incorporating protein-rich vegetative food grade materials in meat analog and by adopting proper technological process which can promote the proper fabrication of meat analog with acceptable meat like texture, appearance, flavor, etc. The easily available vegetables, cereals, and pulses in India have great advantages and prospects to be used in food products and it can improve the nutritional and functional characters of the food items. The various form and functional characters of food items are available world over and attracts the meat technologists and the food processors to bring some innovativeness in meat analog and its presentation and marketability so that the acceptability of meat analog can be overgrown by the consumers. PMID:24915320

  5. Cortisol Function Among Early School-aged Homeless Children

    PubMed Central

    Cutuli, J. J.; Wiik, Kristen L.; Herbers, Janette E.; Gunnar, Megan R.; Masten, Ann S.

    2009-01-01

    SUMMARY Homelessness represents a context of extreme poverty and risk for child development. This study compared the relative influence of two classes of risk in the context of homelessness. Levels of socioeconomic resource-related risk and negative lifetime events were examined with respect to morning cortisol levels and cortisol response to a set of cognitive tasks. Participants were 66 children between the ages of 4 and 7 years staying in an emergency shelter for families. Adversities largely reflecting family level negative life events predicted higher levels of morning cortisol and differences in initial level and change over the course of the session of cognitive tasks. In contrast, a socioeconomic cumulative risk score was not associated with morning or session-related differences in cortisol. PMID:20022181

  6. Intimate partner violence and diurnal cortisol patterns in couples

    PubMed Central

    Kim, Hyoun K.; Tiberio, Stacey S.; Capaldi, Deborah M.; Shortt, Joann Wu; Squires, Erica C.; Snodgrass, J. Josh

    2014-01-01

    Summary This study examined whether physical intimate partner violence (IPV) victimization was associated with diurnal patterns of salivary cortisol in a community sample of 122 couples in their 30s from predominantly lower socioeconomic status backgrounds. Findings indicate that women with higher levels of victimization exhibited flatter patterns of diurnal cortisol characterized by both higher midday levels and more attenuated decreases in cortisol levels across the day, compared to women with lower levels of victimization. However, men's victimization was not associated with their diurnal cortisol levels. This study advances our understanding of the association between physical IPV victimization and dysregulated hypothalamic-pituitary-adrenal (HPA) axis functioning in women, which is likely to have further implications for their subsequent mental and physical health. PMID:25286224

  7. Catecholamine and cortisol levels in Oxford college rowers.

    PubMed Central

    Pearson, R; Ungpakorn, G; Harrison, G A

    1995-01-01

    Urinary catecholamines and cortisol levels in two teams of Oxford college eight oarsmen were compared on three different day types: training days, racing days, and non-rowing days. Adrenaline and cortisol were raised on racing and training days compared to non-racing days. Noradrenaline was raised on training days, reflecting longer periods of physical exercise during training. There was evidence of a progressive lowering of adrenaline output over consecutive race days and that the outcome of the races had an effect on both adrenaline and cortisol. In addition to this there seemed to be differences in cortisol levels between the two teams of rowers on both racing days and non-rowing days. PMID:8800851

  8. Cortisol Response Following Exposure Treatment for PTSD in Rape Victims.

    PubMed

    Gerardi, Maryrose; Rothbaum, Barbara O; Astin, Millie C; Kelley, Mary

    2010-06-01

    This study examined changes in salivary cortisol levels pre-to-post-treatment in adult female rape victims diagnosed with post traumatic stress disorder (PTSD) randomly assigned to be treated with either Prolonged Exposure Therapy or Eye Movement Desensitization and Reprocessing. Salivary cortisol was collected at baseline, session 3, and session 9. A significant decrease in salivary cortisol levels was observed in individuals classified as treatment responders in both treatment conditions. Findings suggest that successful exposure-based treatments for PTSD which result in trauma-related and depressive symptom reduction may impact the action of the hypothalamic-pituitary-adrenal axis as measured by changes in level of salivary cortisol from pre-to-post-treatment. PMID:20526437

  9. [Cortisol and corticosterone plasma levels in different Psittaciformes].

    PubMed

    Hochleithner, M; Nowotny, P

    1992-12-01

    Plasma cortisol and corticosterone levels were measured in macaws, African Grey Parrots, Amazon Parrots and budgerigars using a RIA after preliminary cleaning. As in other avian species, the plasma contains predominantly corticosterone. PMID:1481215

  10. Salivary Cortisol and Cold Pain Sensitivity in Female Twins

    PubMed Central

    Godfrey, Kathryn M; Strachan, Eric; Dansie, Elizabeth; Crofford, Leslie J; Buchwald, Dedra; Goldberg, Jack; Poeschla, Brian; Succop, Annemarie; Noonan, Carolyn; Afari, Niloofar

    2013-01-01

    Background There is a dearth of knowledge about the link between cortisol and pain sensitivity. Purpose We examined the association of salivary cortisol with indices of cold pain sensitivity in 198 female twins and explored the role of familial confounding. Methods Three-day saliva samples were collected for cortisol levels and a cold pressor test was used to collect pain ratings and time to threshold and tolerance. Linear regression modeling with generalized estimating equations examined the overall and within-pair associations. Results Lower diurnal variation of cortisol was associated with higher pain ratings at threshold (p = 0.02) and tolerance (p < 0.01). The relationship of diurnal variation with pain ratings at threshold and tolerance was minimally influenced by familial factors (i.e., genetics and common environment). Conclusions Understanding the genetic and non-genetic mechanisms underlying the link between HPA axis dysregulation and pain sensitivity may help to prevent chronic pain development and maintenance. PMID:23955075

  11. Exogenous cortisol causes a shift from deliberative to intuitive thinking.

    PubMed

    Margittai, Zsofia; Nave, Gideon; Strombach, Tina; van Wingerden, Marijn; Schwabe, Lars; Kalenscher, Tobias

    2016-02-01

    People often rely on intuitive judgments at the expense of deliberate reasoning, but what determines the dominance of intuition over deliberation is not well understood. Here, we employed a psychopharmacological approach to unravel the role of two major endocrine stress mediators, cortisol and noradrenaline, in cognitive reasoning. Healthy participants received placebo, cortisol (hydrocortisone) and/or yohimbine, a drug that increases noradrenergic stimulation, before performing the cognitive reflection test (CRT). We found that cortisol impaired performance in the CRT by biasing responses toward intuitive, but incorrect answers. Elevated stimulation of the noradrenergic system, however, had no effect. We interpret our results in the context of the dual systems theory of judgment and decision making. We propose that cortisol causes a shift from deliberate, reflective cognition toward automatic, reflexive information processing. PMID:26658173

  12. Cortisol, insulin and leptin during space flight and bed rest

    NASA Technical Reports Server (NTRS)

    Stein, T. P.; Schluter, M. D.; Leskiw, M. J.

    1999-01-01

    Most ground based models for studying muscle atrophy and bone loss show reasonable fidelity to the space flight situation. However there are some differences. Investigation of the reasons for these differences can provide useful information about humans during space flight and aid in the refinement of ground based models. This report discusses three such differences, the relationships between: (i) cortisol and the protein loss, (ii) cortisol and ACTH and (iii) leptin, insulin and food intake.

  13. Ambulatory assessed implicit affect is associated with salivary cortisol.

    PubMed

    Mossink, Joram C L; Verkuil, Bart; Burger, Andreas M; Tollenaar, Marieke S; Brosschot, Jos F

    2015-01-01

    One of the presumed pathways linking negative emotions to adverse somatic health is an overactive HPA-axis, usually indicated by elevated cortisol levels. Traditionally, research has focused on consciously reported negative emotions. Yet, given that the majority of information processing occurs without conscious awareness, stress physiology might also be influenced by affective processes that people are not aware of. In a 24-h ambulatory study we examined whether cortisol levels were associated with two implicit measures. Implicit affect was assessed using the Implicit Positive and Negative Affect Test, and implicit negative memory bias was assessed with the word fragment completion tasks. In 55 healthy participants, we measured subjective stress levels, worries, implicit, and explicit affect each hour during waking hours. Also, saliva samples were collected at three fixed times during the day, as well as upon waking and 30 min thereafter (cortisol awakening response). Multilevel analyses of the daytime cortisol levels revealed that the presence of an implicit negative memory bias was associated with increased cortisol levels. Additionally, implicit PA and, unexpectedly, implicit NA were negatively associated with cortisol levels. Finally, participants demonstrating higher levels of implicit sadness during the first measurement day, had a stronger cortisol rise upon awakening at the next day. Contrary to previous research, no associations between explicit affect and cortisol were apparent. The current study was the first to examine the concurrent relation between implicit measures and stress physiology in daily life. The results suggest that the traditional focus on consciously reported feelings and emotions is limited, and that implicit measures can add to our understanding of how stress and emotions contribute to daily physiological activity and, in the long term, health problems. PMID:25713550

  14. Hair cortisol and cognitive performance in healthy older people.

    PubMed

    Pulopulos, Matias M; Hidalgo, Vanesa; Almela, Mercedes; Puig-Perez, Sara; Villada, Carolina; Salvador, Alicia

    2014-06-01

    Worse cognitive performance in older people has been associated with hypothalamic-pituitary-adrenal axis dysregulation (in particular, higher cortisol levels). Analysis of hair cortisol concentrations (HCC) is a novel method to measure long-term cortisol exposure, and its relationship with cognition in healthy older people has not yet been studied. We investigated whether HCC (measured in hair scalp) and diurnal salivary cortisol levels (awakening, 30min after awakening, and evening, across two days) were related to cognitive performance (assessed with the Trail-making Test A and B, Digit Span Forward and Backward, word list-RAVLT and Stories subtest of the Rivermead) in 57 healthy older people (mean age=64.75 years, SD=4.17). Results showed that lower HCC were consistently related to worse working memory, learning, short-term verbal memory (RAVLT first trial and immediate recall) and long-term verbal memory. In contrast, higher mean levels and higher diurnal area under the curve of diurnal salivary cortisol were related to worse attention and short-term verbal memory (immediate story recall), respectively. Interestingly, a higher ratio of mean levels of diurnal salivary cortisol over HCC were related to worse performance on working memory and short-term verbal memory, suggesting that those individuals with lower long-term cortisol exposure might be more vulnerable to the negative effect of HPA-axis dysregulation on these cognitive processes. Our findings suggest that both low long-term cortisol exposure and a possible dysregulation of the diurnal rhythm of the HPA-axis may account, at least in part, for the inter-individual variability in cognitive performance in healthy older people. PMID:24767624

  15. Ambulatory assessed implicit affect is associated with salivary cortisol

    PubMed Central

    Mossink, Joram C. L.; Verkuil, Bart; Burger, Andreas M.; Tollenaar, Marieke S.; Brosschot, Jos F.

    2015-01-01

    One of the presumed pathways linking negative emotions to adverse somatic health is an overactive HPA-axis, usually indicated by elevated cortisol levels. Traditionally, research has focused on consciously reported negative emotions. Yet, given that the majority of information processing occurs without conscious awareness, stress physiology might also be influenced by affective processes that people are not aware of. In a 24-h ambulatory study we examined whether cortisol levels were associated with two implicit measures. Implicit affect was assessed using the Implicit Positive and Negative Affect Test, and implicit negative memory bias was assessed with the word fragment completion tasks. In 55 healthy participants, we measured subjective stress levels, worries, implicit, and explicit affect each hour during waking hours. Also, saliva samples were collected at three fixed times during the day, as well as upon waking and 30 min thereafter (cortisol awakening response). Multilevel analyses of the daytime cortisol levels revealed that the presence of an implicit negative memory bias was associated with increased cortisol levels. Additionally, implicit PA and, unexpectedly, implicit NA were negatively associated with cortisol levels. Finally, participants demonstrating higher levels of implicit sadness during the first measurement day, had a stronger cortisol rise upon awakening at the next day. Contrary to previous research, no associations between explicit affect and cortisol were apparent. The current study was the first to examine the concurrent relation between implicit measures and stress physiology in daily life. The results suggest that the traditional focus on consciously reported feelings and emotions is limited, and that implicit measures can add to our understanding of how stress and emotions contribute to daily physiological activity and, in the long term, health problems. PMID:25713550

  16. Diurnal patterns of salivary alpha-amylase and cortisol secretion in female adolescent tennis players after 16 weeks of training.

    PubMed

    Filaire, Edith; Ferreira, Jose Pedro; Oliveira, Miguel; Massart, Alain

    2013-07-01

    We examined the effects of 16 weeks of training on diurnal pattern of salivary alpha-amylase (sAA), cortisol, and the ratio of sAA over cortisol (AOC) in 12 national adolescent female tennis players. Stress and recovery were also evaluated using the Recovery-Stress-Questionnaire for Athletes-RESTQ-Sport. Data were collected after a 2-week rest (January, W0), and 4 months after W0 (W16). Subjects collected five saliva samples throughout a day. While all participants displayed the previously shown decrease after awakening in adolescents at W0, they showed a rise in the alpha-amylase awakening response and a higher alpha-amylase activity output (p<0.01) at W16 compared to W0. For the daily rhythm of cortisol we found subjects having a low overall output of salivary cortisol (p<0.01) and a blunted response to awakening at W16. Furthermore, an increase in the ratio AOC at W16, and a negative correlation between this ratio and Sport-specific recovery score. Our findings offer support for the hypothesis that increase of training load during the study period induced asymmetry activation between the two stress systems, in relation to psychological alterations and performance decrease. These results provide encouragement to continue exploring the impact of training program using a psychobiological approach among young athletes in order to prevent fatigue and preserve the health of these athletes. PMID:23200107

  17. Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood.

    PubMed

    Buchmann, Arlette F; Holz, Nathalie; Boecker, Regina; Blomeyer, Dorothea; Rietschel, Marcella; Witt, Stephanie H; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Brandeis, Daniel; Zimmermann, Ulrich S; Laucht, Manfred

    2014-06-01

    Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders. The present study aimed to replicate and extend previous evidence indicating that FKBP5 polymorphisms moderate hypothalamus-pituitary-adrenal (HPA) function by examining whether FKBP5 rs1360780 genotype and different measures of childhood adversity interact to predict stress-induced cortisol secretion. At age 19 years, 195 young adults (90 males, 105 females) participating in an epidemiological cohort study completed the Trier Social Stress Test (TSST) to assess cortisol stress responsiveness and were genotyped for the FKBP5 rs1360780. Childhood adversity was assessed using the Childhood Trauma Questionnaire (CTQ) and by a standardized parent interview yielding an index of family adversity. A significant interaction between genotype and childhood adversity on cortisol response to stress was demonstrated for exposure to childhood maltreatment as assessed by retrospective self-report (CTQ), but not for prospectively ascertained objective family adversity. Severity of childhood maltreatment was significantly associated with attenuated cortisol levels among carriers of the rs1360780 CC genotype, while no such effect emerged in carriers of the T allele. These findings point towards the functional involvement of FKBP5 in long-term alterations of neuroendocrine stress regulation related to childhood maltreatment, which have been suggested to represent a premorbid risk or resilience factor in the context of stress-related disorders. PMID:24411633

  18. Cortisol affects tight junction morphology between pavement cells of rainbow trout gills in single-seeded insert culture.

    PubMed

    Sandbichler, Adolf Michael; Farkas, Julia; Salvenmoser, Willi; Pelster, Bernd

    2011-12-01

    A primary culture system of rainbow trout gill pavement cells grown on permeable support (single-seeded insert, SSI) was used to examine histological and physiological changes induced by the addition of the corticosteroid hormone cortisol. Pavement cell epithelia were cultured under symmetrical conditions (L15 apical/L15 basolateral) and developed a high transepithelial resistance (TER, 6.84 ± 1.99 kΩ cm(2), mean ± SEM) with a low phenol red diffusion rate (PRD, 0.15 ± 0.03 μmol l(-1)/day). Addition of cortisol to the basolateral compartment increased TER twofold and reduced PRD threefold over a 5-day period. A similar increase in TER could be seen after 24 h apical freshwater (FW) in control cultures. In cortisol-treated cultures FW exposure did not change TER, but PRD increased significantly. Histochemical staining of the cytoskeleton of cells in SSI culture revealed a morphological partitioning into a single mucosal layer of polarized, polygonal cells featuring cortical F-actin rings which were comparable to F-actin rings of epithelial cells on the lamellar and filamental surface, and several unorganized serosal layers of cells with F-actin stress fibers. Addition of cortisol increased cell density by 18% and in the mucosal layer it led to smaller, less polygonal cells with increased height and increased cell contact area. In transmission electron microscopic images two pairs of cytoplasmatic electron-dense structures confining the zonula occludens apically and basally toward the zonula adhaerens were found. Addition of cortisol increased the distance between those paired structures, hence led to deeper tight junctions. The cortisol-induced increase in barrier properties, therefore, involves a structural fortification of the tight junctions which was not generally modified by a short 24-h apical freshwater stress. These results identify cortisol as a regulator of tight junction morphology between pavement cells of euryhaline fish such as the

  19. Does cortisol influence core executive functions? A meta-analysis of acute cortisol administration effects on working memory, inhibition, and set-shifting.

    PubMed

    Shields, Grant S; Bonner, Joseph C; Moons, Wesley G

    2015-08-01

    The hormone cortisol is often believed to play a pivotal role in the effects of stress on human cognition. This meta-analysis is an attempt to determine the effects of acute cortisol administration on core executive functions. Drawing on both rodent and stress literatures, we hypothesized that acute cortisol administration would impair working memory and set-shifting but enhance inhibition. Additionally, because cortisol is thought to exert different nongenomic (rapid) and genomic (slow) effects, we further hypothesized that the effects of cortisol would differ as a function of the delay between cortisol administration and cognitive testing. Although the overall analyses were nonsignificant, after separating the rapid, nongenomic effects of cortisol from the slower, genomic effects of cortisol, the rapid effects of cortisol enhanced response inhibition, g+ = 0.113, p=.016, but impaired working memory, g+ = -0.315, p=.008, although these effects reversed over time. Contrary to our hypotheses, there was no effect of cortisol administration on set-shifting. Thus, although we did not find support for the idea that increases in cortisol influence set-shifting, we found that acute increases in cortisol exert differential effects on working memory and inhibition over time. PMID:25973565

  20. Effects of different spawning agents on serum levels of reproductive steroid hormones and cortisol level in adult female Barbus sharpeyi (Gunther, 1874).

    PubMed

    Mohammadian, Takavar; Malekpouri, Pedram; Zare, Mojtaba; Zainodini, Mohammad Anwar

    2015-12-01

    The question of whether, as hormone therapies, spawning agents differ from each other to induce physiological pathways of gametogenesis and oocyte maturation in fish remains important, because it could modify undesirable changes, regulated by endocrine systems of individual fish. A series of experimental treatments were applied to investigate the underlying mechanism(s) in which female bunnei (Barbus sharpeyi) fish respond differently to hormone therapies. Female broodstocks were injected twice (with 12 h interval) by three different treatments namely A, B and C. The treatment A received carp pituitary extract (CPE) + luteinizing hormone-releasing hormone analogs (LHRHα2) (0.5 mg CPE kg(-1) BW for first injection and 2 mg CPE kg(-1) BW + 10 µg LHRHα2 kg(-1) for second injection), treatment B received CPE (0.5 and 3.5 mg kg(-1) BW), and treatment C received ovaprim (0.1 and 0.15 ml kg(-1) BW). Blood samples were collected at four different time intervals, including prior to injections, 6 h after first injection, 6 h after second injection and at the time of spawning, and serum steroid hormones, including testosterone, progesterone and estradiol-17β as well as cortisol, were measured. Results showed significant increases in serum estradiol-17β following all treatments, but the most profound response was found in treatments A and B. Testosterone was higher in larger broodfish than in small-sized broodfish (>1.5 vs. <1.5 kg) in all treatments. CPE led to higher concentration of testosterone rather than two other treatments. CPE also increases the progesterone following first injection and approximately remains unchanged till the end of experiment. Change in progesterone level was only significant after second injection of ovaprim as well as after spawning compared with previous time. Linear regression analyses indicated that cortisol had adverse effects on progesterone and testosterone levels of weight group <1.5 kg. These results suggest that among inducing

  1. Estimation of cerebrospinal fluid cortisol level in tuberculous meningitis

    PubMed Central

    Mahale, Rohan R.; Mehta, Anish; Uchil, Sudhir

    2015-01-01

    Background: Central nervous system (CNS) involvement in tuberculosis is around 5–10%. Of the various manifestations of CNS tuberculosis, meningitis is the most common (70–80%). Delay in diagnosis and treatment results in significant morbidity and mortality. Objective: To study the cerebrospinal fluid (CSF) cortisol levels in tubercular meningitis and compare the levels with controls. Methods: Cross-sectional, prospective, observational, hospital-based study done in 20 patients of tubercular meningitis, 20 patients of aseptic meningitis (AM) and 25 control subjects without any preexisting neurological disorders who have undergone lumbar puncture for spinal anesthesia. Results: Cortisol was detected in all 40 CSF samples of patients (100%). Mean CSF cortisol level was 8.82, 3.47 and 1.05 in tubercular meningitis, AM and controls, respectively. Mean CSF cortisol level in tubercular meningitis was significantly higher as compared to AM and controls (P < 0.0001). Conclusion: Cortisol level estimation in CSF is one of the rapid, relatively inexpensive diagnostic markers in early identification of tubercular meningitis along with CSF findings of elevated proteins, hypoglycorrhachia and lymphocytic pleocytosis. This aids in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality. This is the first study on the estimation of CSF cortisol level in tuberculous meningitis. PMID:26752900

  2. Father Contributions to Cortisol Responses in Infancy and Toddlerhood

    PubMed Central

    Mills-Koonce, W. Roger; Garrett-Peters, Patricia; Barnett, Melissa; Granger, Douglas A.; Blair, Clancy; Cox, Martha J.

    2015-01-01

    The current study is one of the first to prospectively examine longitudinal associations between observed father caregiving behaviors and child cortisol reactivity and regulation in response to emotional arousal at 7 and 24 months of child age. Observations of father and mother caregiving behaviors and child cortisol levels in response to challenges at 7 months and 24 months were collected. Analyses were based on a subsample of children from the Family Life Project who lived with both their biological mothers and fathers and for whom there was at least partial cortisol data (7 months: n=717; 24 months n= 579). At 7 months of child age the sample was 49.0% female, 25.8% African American, and 74.2% European American. At 24 months of child age the sample was 49.9% female, 24.7% African American and 75.3% European American. Analyses across assessment points were conducted simultaneously using mixed linear modeling for repeated measures data to test for differential effects of fathering across infancy and toddlerhood. Concurrent measures of father negativity were positively associated with greater increases in child cortisol levels in response to emotion challenge at 7 months (p = .01) and with higher overall levels of cortisol at 24 months (p < .001). However, there was no evidence that father caregiving during infancy independently predicted later cortisol activity during toddlerhood. PMID:21142362

  3. MDMA, cortisol, and heightened stress in recreational ecstasy users.

    PubMed

    Parrott, Andrew C; Montgomery, Cathy; Wetherell, Mark A; Downey, Luke A; Stough, Con; Scholey, Andrew B

    2014-09-01

    Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100-200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress. PMID:25014666

  4. Academic self-concept of ability and cortisol reactivity.

    PubMed

    Minkley, N; Westerholt, D M; Kirchner, W H

    2014-05-01

    The present study aimed to clarify the relationship between a school-specific trait (academic self-concept of ability [ASCA]) and hormonal stress response by using a trait-compatible stressor (test). First, we determined 52 students' ASCA scores for biology and measured their salivary cortisol concentration before and after a biology test (experimental group, n=28) or a free writing task (control group, n=24). For participants who took the test, statistical analysis indicated a significant negative correlation between ASCA score and cortisol response. In contrast, the control group showed a decrease in cortisol concentrations between test times and no correlation between cortisol concentration and ASCA scores were found. These findings indicated an interaction between ASCA scores and hormonal stress response when an academic-related stressor is present. Furthermore, these variables might influence each other adversely: high cortisol concentrations during a test situation may lead to greater feelings of insecurity, resulting in low ASCA scores and awareness of these low scores may lead to a further increase in cortisol, creating a vicious cycle. PMID:24219306

  5. [A critical analysis of cortisol measurements: an update].

    PubMed

    Maidana, Patricia; Bruno, Oscar D; Mesch, Viviana

    2013-01-01

    Serum cortisol measurement is a very useful tool in the biochemical evaluation of adrenocortical function. Since this hormone circulates in blood mainly linked to binding globulins but is also partially free, it can be measured not only in the blood but also in urine, saliva and other biological fluids and tissues. Basal determinations as well as dynamic testing may be performed to evaluate the circadian variations, to estimate the diurnal cortisol secretion and to analyze its relations with other components of the hypothalamic-pituitary-adrenal axis. Measurements of cortisol in blood, saliva and urine may reflect the cortisol secretion at the time of sample collection or during a 24 h span. Recently, it has been proposed the determination of cortisol in tissues such as hair and nails like a means of evaluating the hormonal status during prolonged periods. The aim of this paper is to update the methodology for measuring cortisol and its usefulness for the clinical diagnosis of troubles of the hypothalamic-pituitary-adrenal axis. PMID:24356273

  6. Cortisol levels and anxiety-related behaviors in cattle.

    PubMed

    Bristow, Daniel J; Holmes, David S

    2007-03-16

    This investigation was conducted to examine the relationship between cortisol levels and anxiety-related behavior in nine Angus/Hereford cows. In a non-stressful pasture setting, measures were taken of rumination, distance from another cow, and body position. In a stressful holding pen situation, measures were taken of vocalizations and resistance to entering a squeeze chute. Cortisol was measured in serum samples. Subjects with high levels of cortisol spent less time ruminating (p=0.007) and vocalized more (p=0.07) than subjects with low levels of cortisol. Regardless of statistical significance, all mean differences were in the predicted direction. Cortisol levels were correlated with time spent ruminating (p=0.004) and later entrance to the squeeze chute (p=0.10). All correlations were also in the predicted direction. These findings provide consistent support for the link between cortisol and anxiety-related behavior in beef cattle, and the findings have theoretical and practical implications. PMID:17196624

  7. The Cortisol to Cortisone Ratio during Cardiac Catheterisation in Sows.

    PubMed

    Skarlandtová, Hana; Bičíková, Marie; Neužil, Petr; Mlček, Mikuláš; Hrachovina, Vladimír; Svoboda, Tomáš; Medová, Eva; Kudlička, Jaroslav; Dohnalová, Alena; Havránek, Štěpán; Kazihnítková, Hana; Máčová, Ludmila; Vařejková, Eva; Kittnar, Otomar

    2015-01-01

    A possible effect of mini-invasive heart intervention on a response of hypothalamo-pituitary-adrenal stress axis and conversion of cortisone to cortisol were studied. We have analysed two stress markers levels (cortisol, cortisone) and cortisol/cortisone ratio in 25 sows using minimally invasive heart catheterisation as the stress factor. The values of studied parameters were assessed in four periods of the experiment: (1) the baseline level on the day before intervention, (2) after the introduction of anaesthesia, (3) after conducting tissue stimulation or ablation, and (4) after the end of the catheterisation. For statistical analyses we used the non-parametric Friedman test for four dependent samples (including all four stages of the operation) or three dependent samples (influence of operation only, baseline level was excluded). Statistically significant differences in both Friedman tests were found for cortisol and for cortisone. We have found the highest level of cortisol/cortisone ratio in unstressed conditions, then it decreased to the minimal level at the end of the intervention. We have concluded that cortisol levels are blunted by the influence of anaesthesia after its administration, and therefore decrease back to the baseline at the end of the operation. PMID:26654801

  8. Modeling the Salivary Cortisol Profile in Population Research

    PubMed Central

    Sánchez, Brisa N.; Wu, Meihua; Raghunathan, Trivellore E.; Diez-Roux, Ana V.

    2012-01-01

    In many studies, it has been hypothesized that stress and its biologic consequences may contribute to disparities in rates of cardiovascular disease. However, understanding of the most appropriate statistical methods to analyze biologic markers of stress, such as salivary cortisol, remains limited. The authors explore the utility of various statistical methods in modeling daily cortisol profiles in population-based studies. They demonstrate that the proposed methods allow additional insight into the cortisol profile compared with commonly used summaries of the profiles based on raw data. For instance, one can gain insights regarding the shape of the population average curve, characterize the types of individual-level departures from the average curve, and better understand the relation between covariates and attained cortisol levels or slopes at various points of the day, in addition to drawing inferences regarding common features of the cortisol profile, such as the cortisol awakening response and the area under the curve. The authors compare the inference and interpretations drawn from these methods and use data collected as part of the Multi-Ethnic Study of Atherosclerosis to illustrate them. PMID:23100245

  9. Gene expression in Atlantic salmon skin in response to infection with the parasitic copepod Lepeophtheirus salmonis, cortisol implant, and their combination

    PubMed Central

    2012-01-01

    Background The salmon louse is an ectoparasitic copepod that causes major economic losses in the aquaculture industry of Atlantic salmon. This host displays a high level of susceptibility to lice which can be accounted for by several factors including stress. In addition, the parasite itself acts as a potent stressor of the host, and outcomes of infection can depend on biotic and abiotic factors that stimulate production of cortisol. Consequently, examination of responses to infection with this parasite, in addition to stress hormone regulation in Atlantic salmon, is vital for better understanding of the host pathogen interaction. Results Atlantic salmon post smolts were organised into four experimental groups: lice + cortisol, lice + placebo, no lice + cortisol, no lice + placebo. Infection levels were equal in both treatments upon termination of the experiment. Gene expression changes in skin were assessed with 21 k oligonucleotide microarray and qPCR at the chalimus stage 18 days post infection at 9°C. The transcriptomic effects of hormone treatment were significantly greater than lice-infection induced changes. Cortisol stimulated expression of genes involved in metabolism of steroids and amino acids, chaperones, responses to oxidative stress and eicosanoid metabolism and suppressed genes related to antigen presentation, B and T cells, antiviral and inflammatory responses. Cortisol and lice equally down-regulated a large panel of motor proteins that can be important for wound contraction. Cortisol also suppressed multiple genes involved in wound healing, parts of which were activated by the parasite. Down-regulation of collagens and other structural proteins was in parallel with the induction of proteinases that degrade extracellular matrix (MMP9 and MMP13). Cortisol reduced expression of genes encoding proteins involved in formation of various tissue structures, regulators of cell differentiation and growth factors. Conclusions These results suggest that

  10. Assessing the presence of abnormal regulation of cortisol secretion by membrane hormone receptors: in vivo and in vitro studies in patients with functioning and non-functioning adrenal adenoma.

    PubMed

    Dall'Asta, C; Ballarè, E; Mantovani, G; Ambrosi, B; Spada, A; Barbetta, L; Colombo, P; Travaglini, P; Loli, P; Beck-Peccoz, P

    2004-08-01

    Regulation of cortisol secretion by aberrant hormone receptors may play a role in the pathogenesis of ACTH-independent Cushing's syndrome. In this study, the topic was evaluated by combining in vivo and in vitro approaches. Cortisol responses to various stimuli (standard meal, GnRH + TRH, cisapride, vasopressin, glucagon) were assessed in 6 patients with clinical or subclinical adrenal Cushing's syndrome, and non-functioning adrenal adenoma in two cases. Abnormal responses were observed in three patients with Cushing's syndrome; one patient showed a gastric inhibitory polypeptide (GIP)-dependent cortisol rise after meal, together with responses after GnRH and cisapride; the second patient showed an LH-dependent cortisol response to GnRH, and in the third cortisol rose after cisapride. The pattern of receptor expression performed by RT-PCR showed that while GIP-R was only expressed in tumor from the responsive patient, 5-hydroxytryptamine type 4 receptor and LH-R were also present in normal adrenal tissues and tissues from non-responsive patients. Interestingly, an activating mutation of Gsalpha gene was identified in one of these tumors. Therefore, cortisol responses to agents operating via Gs protein coupled receptors (in one case associated with Gsalpha mutation) were found in Cushing's patients, while these responses were absent in the others. The finding of receptor expression in normal and non-responsive tumors suggests that different mechanisms are probably involved in inducing in vivo cortisol responses. PMID:15326569

  11. Ratio of amniotic fluid cortisol and maternal serum cortisol (AFC/MSC) as an index of fetal lung maturity.

    PubMed

    Varma, K; Heine, M W; Haller, W S; Row, A D; Railsback, K; Varma, S K

    1979-01-01

    Fifty-eight samples of amniotic fluid from pregnant women between the gestation period of 34-42 weeks were analyzed for total cortisol levels. Thirty-four simulatneous maternal serum total cortisol levels were also measured. Amniotic fluid cortisol (AFC), maternal serum cortisol (MSC) and the ratio of AFC/MSC were correlated with L/S ratio. AFC alone and AFC/MSC ratios correlate with L/S ratios (r=0.36, p less than 0.01, and r=0.46, p less than 0.01, respectively). MSC and L/S ratios had no correlation. AFC/MSC had less individual variation as compared to AFC alone. The AFC/MSC could be divided by an arbitrary line at 0.1 and values less than 0.1 signify immature fetal lungs. Values of 0.1 and greater signify mature fetal lungs. PMID:532565

  12. Fatty acid analogs

    DOEpatents

    Elmaleh, David R.; Livni, Eli

    1985-01-01

    In one aspect, a radioactively labeled analog of a fatty acid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fatty acid.

  13. An Analog of Thyrotropin-Releasing Hormone (TRH) is Neuroprotective Against Glutamate-Induced Toxicity In Fetal Rat Hippocampal Neurons In Vitro

    PubMed Central

    Veronesi, Michael C.; Yard, Michael; Jackson, James; Lahiri, Debomoy K.; Kubek, Michael J.

    2007-01-01

    TRH has been found to be efficacious in treating certain neurodegenerative disorders such as epilepsy, Alzheimer’s disease, neurotrauma and depression, however, its mechanism of action is poorly understood. Since Glutamate (Glu) toxicity has been implicated in these disorders, we utilized primary enriched cultures of rat fetal (E 17) hippocampal neurons to test the hypothesis that an analog of TRH, 3-Methyl-Histidine TRH (3Me-H TRH), given concurrently with Glu would protect such neurons against cell damage and cell death. Cell viability was assessed via Trypan Blue exclusion cell counts and neuronal damage was determined by assaying lactic acid dehydrogenase (LDH) released in the conditioned media. Fetal hippocampal neurons were cultured in neurobasal media for 7 days. On day 7, neurons (106/well) were treated with: control media, 10 μM 3Me-H TRH, 500 μM Glu, or 500 μM Glu with either 10, 1, 0.1, 0.01 or 0.001 μM 3Me-H TRH. Both media and neurons were harvested 16 hr after treatment. Prolonged exposure to 10 μM 3Me-H TRH was not toxic to the cells, whereas, neurons exposed to 500 μM Glu resulted in maximal cell death. Notably, 10, 1 and 0.1 μM 3Me-H TRH, when co-treated with 500 μM Glu protected fetal neurons against cell death in a concentration-dependent manner. These results provide support for an important neuroprotective effect of TRH/analogs against glutamate toxicity in primary hippocampal neuronal culture, and implicate a potentially beneficial role of TRH/analogs in neurodegenerative diseases. PMID:17125753

  14. Concerns Regarding Hair Cortisol as a Biomarker of Chronic Stress in Exercise and Sport Science

    PubMed Central

    Gerber, Markus; Brand, Serge; Lindwall, Magnus; Elliot, Catherine; Kalak, Nadeem; Herrmann, Christian; Pühse, Uwe; Jonsdottir, Ingibjörg H.

    2012-01-01

    Hair cortisol has the potential to fill the methodological void of long-term cortisol assessment while becoming a widely accepted measure in biopsychology. This review critically examines the applicability and relevance of hair cortisol measurement specifically within the field of exercise and sport science. Current measures of the HPA axis only cover a brief time period, whereas hair cortisol is a unique, non-invasive means to capture long- term cortisol secretion. Studies have shown that individuals who have elevated cortisol secretion (e.g. due to diseases associated with a disturbed activation of the HPA axis or exposure to stressful life events) reveal increased hair cortisol. By contrast, only weak correlations exist between hair cortisol and perceived stress, and the direction of the relationship between hair cortisol levels and mental disorders is unclear. Acute exercise, however, results in increased levels of cortisol that eventually is reflected in higher levels of cortisol in hair samples and studies have shown that exercise intensity is related to hair cortisol level. Thus, elevated hair cortisol levels found among regular exercisers are not necessarily pathological. Thus, one should practice caution when associating athletes’ elevated hair cortisol with poor mental health or disease. Hair cortisol analysis can contribute to a more complete understanding of how long-term cortisol elevation mediates stress-related effects on the health and performance of recreational exercisers and elite athletes. Nevertheless, it is crucial for exercise and sport scientists to consider whether their research questions can be adequately addressed, given that regular intense exercise results in substantially augmented hair cortisol levels. Key points Hair cortisol is a unique, non-invasive and painless means to capture long-term cortisol secretion. Individuals expected to have elevated cortisol secretion (e.g. due to trauma) have increased hair cortisol. Preliminary

  15. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Takahashi, Kazuyuki

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  16. A new biomarker of hedonic eating? A preliminary investigation of cortisol and nausea responses to acute opioid blockade.

    PubMed

    Daubenmier, Jennifer; Lustig, Robert H; Hecht, Frederick M; Kristeller, Jean; Woolley, Josh; Adam, Tanja; Dallman, Mary; Epel, Elissa

    2014-03-01

    Overweight and obese individuals differ in their degree of hedonic eating. This may reflect adaptations in reward-related neural circuits, regulated in part by opioidergic activity. We examined an indirect, functional measure of central opioidergic activity by assessing cortisol and nausea responses to acute opioid blockade using the opioid antagonist naltrexone in overweight/obese women (mean BMI=31.1±4.8) prior to the start of a mindfulness-based intervention to reduce stress eating. In addition, we assessed indices of hedonic-related eating, including eating behaviors (binge eating, emotional eating, external eating, restraint) and intake of sweets/desserts and carbohydrates (Block Food Frequency); interoceptive awareness (which is associated with dysregulated eating behavior); and level of adiposity at baseline. Naltrexone-induced increases in cortisol were associated with greater emotional and restrained eating and lower interoceptive awareness. Naltrexone-induced nausea was associated with binge eating and higher adiposity. Furthermore, in a small exploratory analysis, naltrexone-induced nausea predicted treatment response to the mindfulness intervention, as participants with more severe nausea at baseline maintained weight whereas those with little or no nausea responses tended to gain weight. These preliminary data suggest that naltrexone-induced cortisol release and nausea may help identify individuals who have greater underlying food reward dependence, which leads to an excessive drive to eat. Future research is needed to confirm this finding and to test if these markers of opioidergic tone might help predict success in certain types of weight management programs. PMID:24291355

  17. Electrical Circuits and Water Analogies

    ERIC Educational Resources Information Center

    Smith, Frederick A.; Wilson, Jerry D.

    1974-01-01

    Briefly describes water analogies for electrical circuits and presents plans for the construction of apparatus to demonstrate these analogies. Demonstrations include series circuits, parallel circuits, and capacitors. (GS)

  18. Validation of a cortisol enzyme immunoassay and characterization of salivary cortisol circadian rhythm in chimpanzees (Pan troglodytes).

    PubMed

    Heintz, Matthew R; Santymire, Rachel M; Parr, Lisa A; Lonsdorf, Elizabeth V

    2011-09-01

    Monitoring concentrations of stress hormones is an important tool for behavioral research and conservation for animals both in the wild and captivity. Glucocorticoids can be measured in mammals as an indicator of stress by analyzing blood, feces, urine, hair, feathers, or saliva. The advantages of using saliva for measuring cortisol concentrations are three-fold: it is minimally invasive, multiple samples can be collected from the same individual in a short timeframe, and cortisol has a relatively short response time in saliva as compared with other materials. The purpose of this study was to: (1) conduct an adrenocorticotropic hormone (ACTH) challenge as a physiological validation for an enzyme immunoassay to measure salivary cortisol in chimpanzees and (2) characterize the circadian rhythm of salivary cortisol in chimpanzees. We determined that salivary cortisol concentrations peaked 45 min following the ACTH challenge, which is similar to humans. Also, salivary cortisol concentrations peaked early in the morning and decreased throughout the day. We recommend that saliva collection may be the most effective method of measuring stress reactivity and has the potential to complement behavioral, cognitive, physiological, and welfare studies. PMID:21538448

  19. Effects of acute stress on aggression and the cortisol response in the African sharptooth catfish Clarias gariepinus: differences between day and night.

    PubMed

    Manuel, R; Boerrigter, J G J; Cloosterman, M; Gorissen, M; Flik, G; van den Bos, R; van de Vis, H

    2016-06-01

    African sharptooth catfish Clarias gariepinus were housed under continuous dim light (1 lx) or 12L:12D (350-0 lx) cycles. The number of skin lesions, as indicator of aggressive acts, and plasma cortisol levels, as indicator of stress-axis activity, were measured at baseline as well as following a stressor (given in the light or dark phase). Results showed that (1) baseline plasma cortisol levels were not different between photoperiods, (2) the number of baseline skin lesions was highest for C. gariepinus housed under continuous dim light, (3) stressor-induced peak levels of plasma cortisol were highest in the light phase and (4) the number of skin lesions following a stressor was highest in the dark phase. The higher number of stressor-related skin lesions in the dark (active) phase suggests increased stressor-induced aggression while in the active phase. In addition, the data suggest that housing under continuous dim light does not result in higher stress-axis activity, as measured by baseline levels of cortisol, but does result in more stressor-induced aggression, as measured by the higher number of skin lesions. The latter may be related to the fact that the continuous dim light photoperiod has twice the number of dark-phase (active) hours in which stressor-induced aggression is stronger compared to the 12L:12D photoperiod, which has a light phase in which stressor-induced aggression is lower. PMID:27125325

  20. Increased cortisol release and transport stress do not influence semen quality and testosterone release in pony stallions.

    PubMed

    Deichsel, Katharina; Pasing, Stephanie; Erber, Regina; Ille, Natascha; Palme, Rupert; Aurich, Jörg; Aurich, Christine

    2015-07-01

    The use of breeding stallions for equestrian competitions requires that fertility is not negatively affected by competition or transport to the competition site. In this study, effects of cortisol release induced by road transport (600 km), adrenocorticotropic hormone (ACTH) administration (3 × 0.5 mg synthetic ACTH) and placebo treatment on semen quality and testosterone release were investigated in Shetland stallions (N = 13) using a crossover design. Saliva for cortisol and blood for testosterone analysis were collected for 10 weeks after treatments. Semen was collected daily for 5 days directly after treatments and twice weekly for another 9 weeks. Total sperm count, sperm morphology, motility, and membrane integrity were analyzed. We hypothesized that elevated cortisol decreases testosterone concentration and semen quality. Cortisol concentrations increased in response to transport and ACTH (P < 0.001) but not control treatments (peak concentration, transport: 7.6 ± 2.4, ACTH: 13.7 ± 1.5, control: 3.8 ± 0.9 ng/mL). No treatment effects on testosterone existed. Total sperm count decreased with daily semen collections in week 1 (P < 0.01) but did not differ between the treatments. The percentage of motile, progressively motile, membrane-intact, and morphologically defective spermatozoa did not change over time from Days 2 to 6, and there existed no differences between the treatments. In conclusion, road transport evoked a stress response which was mimicked by ACTH treatment. Both treatments had no effect on testosterone release and semen quality. Testicular function in stallions is apparently well protected against transiently elevated cortisol concentrations, and stallions can be transported over longer distances without negatively affecting their fertility. PMID:25794840

  1. Effect of Suckling Systems on Serum Oxytocin and Cortisol Concentrations and Behavior to a Novel Object in Beef Calves.

    PubMed

    Chen, Siyu; Tanaka, Shigefumi; Ogura, Shin-Ichiro; Roh, Sanggun; Sato, Shusuke

    2015-11-01

    We investigated differences between effects of natural- and bucket-suckling methods on basal serum oxytocin (OT) and cortisol concentrations, and the effect of OT concentration on affiliative and investigative behavior of calves to a novel object. Ten Japanese Black calves, balanced with birth order, were allocated evenly to natural-suckling (NS) and bucket suckling (BS) groups. Blood samples were collected at the ages of 1 and 2 months (1 week after weaning) calves, and serum OT and cortisol concentrations were measured using enzyme-linked immunosorbent assay and enzymeimmunoassay tests, respectively. Each calf at the age of 2 months (2 weeks after weaning) was released into an open-field with a calf decoy, and its investigative and affiliative behaviors were recorded for 20 minutes. In 1-month-old calves, the basal serum OT concentration (25.5±4.9 [mean±standard deviation, pg/mL]) of NS was significantly higher than that of BS (16.9±6.7) (p<0.05), whereas the basal cortisol concentration (5.8±2.5 [mean±standard deviation, ng/mL]) of NS was significantly lower than that in BS (10.0±2.8) (p<0.05). Additionally, a negative correlation was noted between serum OT and cortisol concentrations in 1-month-old calves (p = 0.06). Further, the higher serum OT concentration the calves had at 1 month old, the more investigative the calves were at 2 months old but not affiliative in the open-field with a calf decoy. Thus, we concluded that the natural suckling method from a dam elevates the basal serum OT concentration in calves, and high serum OT concentrations induce investigative behavior and attenuate cortisol concentrations. PMID:26580289

  2. Effect of Suckling Systems on Serum Oxytocin and Cortisol Concentrations and Behavior to a Novel Object in Beef Calves

    PubMed Central

    Chen, Siyu; Tanaka, Shigefumi; Ogura, Shin-ichiro; Roh, Sanggun; Sato, Shusuke

    2015-01-01

    We investigated differences between effects of natural- and bucket-suckling methods on basal serum oxytocin (OT) and cortisol concentrations, and the effect of OT concentration on affiliative and investigative behavior of calves to a novel object. Ten Japanese Black calves, balanced with birth order, were allocated evenly to natural-suckling (NS) and bucket suckling (BS) groups. Blood samples were collected at the ages of 1 and 2 months (1 week after weaning) calves, and serum OT and cortisol concentrations were measured using enzyme-linked immunosorbent assay and enzymeimmunoassay tests, respectively. Each calf at the age of 2 months (2 weeks after weaning) was released into an open-field with a calf decoy, and its investigative and affiliative behaviors were recorded for 20 minutes. In 1-month-old calves, the basal serum OT concentration (25.5±4.9 [mean±standard deviation, pg/mL]) of NS was significantly higher than that of BS (16.9±6.7) (p<0.05), whereas the basal cortisol concentration (5.8±2.5 [mean±standard deviation, ng/mL]) of NS was significantly lower than that in BS (10.0±2.8) (p<0.05). Additionally, a negative correlation was noted between serum OT and cortisol concentrations in 1-month-old calves (p = 0.06). Further, the higher serum OT concentration the calves had at 1 month old, the more investigative the calves were at 2 months old but not affiliative in the open-field with a calf decoy. Thus, we concluded that the natural suckling method from a dam elevates the basal serum OT concentration in calves, and high serum OT concentrations induce investigative behavior and attenuate cortisol concentrations. PMID:26580289

  3. Effects of electroejaculation and ketamine-HCI on serum cortisol, progesterone, and testosterone in the male cat.

    PubMed

    Carter, K K; Chakraborty, P K; Bush, M; Wildt, D E

    1984-01-01

    The influence of manual restraint, ketamine-hydrochloride anesthesia and electroejaculation under anesthesia on circulating levels of cortisol, progesterone and testosterone was examined in male domestic cats. In the first experiment, cats were anesthetized with ketamine-HCI (17.5 mg/kg of body weight) and serially bled (controls) or serially bled and electroejaculated. These animals showed signs of recovering from anesthesia within 45 to 60 minutes of ketamine-HCI injection. Average serum cortisol concentrations increased (P less than 0.01) over the 84-minute sampling interval in both the electroejaculated and control groups. Cortisol levels reached their maximum concentration in the electrically stimulated males immediately postelectroejaculation (95.1 ng/ml) and were significantly greater (P less than 0.01) than in the controls (36.1 ng/ml) at a comparable time. Maximal mean cortisol concentrations in the control group (62.8 ng/ml) occurred 54 minutes after the first blood sample and occurred together with the onset of anesthesia recovery. Mean testosterone levels did not differ between electroejaculated and control cats, but did decrease (P less than 0.05) between the first and last blood sampling in both groups. In the second experiment, cats were bled on the same time schedule as in Experiment 1, but were bled while awake and manually restrained, or else during a deeper plane of anesthesia induced and maintained with higher doses of ketamine-HCI (initial dose, 23 mg/kg). Mean serum cortisol levels were greater (P less than 0.05) during manual restraint (range, 36.3-41.1 ng/ml) compared to deep anesthesia (range, 16.7-25.8 ng/ml), but did not change over the 84 minute sampling interval in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:6511657

  4. Role of shame and body esteem in cortisol stress responses.

    PubMed

    Lupis, Sarah B; Sabik, Natalie J; Wolf, Jutta M

    2016-04-01

    Studies assessing the role of shame in HPA axis reactivity report mixed findings. Discrepancies may be due to methodological difficulties and inter-individual differences in the propensity to experience shame in a stressful situation. Hence, the current study combined self-report of shame and facial coding of shame expressions and assessed the role of body esteem as a moderator of the shame-stress link. For this, 44 healthy students (24F, age 20.5 ± 2.1 years) were exposed to an acute psychosocial stress paradigm (Trier Social Stress Test: TSST). Salivary cortisol levels were measured throughout the protocol. Trait shame was measured before the stress test, and state shame immediately afterwards. Video recordings of the TSST were coded to determine emotion expressions. State shame was neither associated with cortisol stress responses nor with body esteem (self-report: all ps ≥ .24; expression: all ps ≥ .31). In contrast, higher trait shame was associated with both negative body esteem (p = .049) and stronger cortisol stress responses (p = .013). Lastly, having lower body esteem predicted stronger cortisol stress responses (p = .022); however, it did not significantly moderate the association between shame indices and cortisol stress responses (all ps ≥ .94). These findings suggest that body esteem and trait shame independently contribute to strength of cortisol stress responses. Thus, in addition to trait shame, body esteem emerged as an important predictor of cortisol stress responses and as such, a potential contributor to stress-related negative health outcomes. PMID:26577952

  5. Basal salivary cortisol secretion and susceptibility to upper respiratory infection.

    PubMed

    Janicki-Deverts, Denise; Cohen, Sheldon; Turner, Ronald B; Doyle, William J

    2016-03-01

    The immunosuppressive effects of glucocorticoids (GCs) are well-established. However, whether the net effect of GC-elicited alterations in immune function is sufficient to influence a clinically relevant outcome in healthy adults has yet to be shown. The aim of the present study was to investigate whether inter-individual differences in basal salivary cortisol production are associated with increased risk and severity of infection and subsequent illness following experimental exposure to a virus that causes the common cold. The present analyses combine archival data from three viral-challenge studies. Participants were 608 healthy adults, aged 18 to 55 years (49.2% female; 65.8% white), who each completed a three-day saliva collection protocol; was subsequently exposed to a virus that causes the common cold; and monitored for 5 days for objective signs of infection (presence of challenge virus in nasal secretions) and clinical illness (mucus weight, mucociliary clearance time). Basal cortisol production (operationalized as the calculated area-under-the-curve averaged across the 3 days) showed a graded association with infection risk, with those producing higher levels of cortisol being at greater risk. Cortisol also showed a continuous association with duration of viral shedding, an indicator of viral replication and continuing infection, such that higher cortisol concentrations predicted more days of shedding. Cortisol was not, however, related to severity of objective illness. These findings are the first to demonstrate in healthy adults an association between basal cortisol production and an objectively measured and clinically relevant infectious disease outcome. PMID:26778776

  6. Cortisol levels and suicidal behavior: A meta-analysis.

    PubMed

    O'Connor, Daryl B; Ferguson, Eamonn; Green, Jessica A; O'Carroll, Ronan E; O'Connor, Rory C

    2016-01-01

    Suicide is a major cause of death worldwide, responsible for 1.5% of all mortality. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. This meta-analytic review aimed (i) to estimate the strength and variability of the association between naturally fluctuating cortisol levels and suicidal behavior and (ii) to identify moderators of this relationship. A systematic literature search identified 27 studies (N=2226; 779 suicide attempters and 1447 non-attempters) that met the study eligibility criteria from a total of 417 unique records initially examined. Estimates of effect sizes (r) obtained from these studies were analysed using Comprehensive Meta-Analysis. In these analyses, we compared participants identified as having a past history of suicide attempt(s) to those with no such history. Study quality, mean age of sample and percentage of male participants were examined as potential moderators. Overall, there was no significant effect of suicide group on cortisol. However, significant associations between cortisol and suicide attempts were observed as a function of age. In studies where the mean age of the sample was below 40 years the association was positive (i.e., higher cortisol was associated with suicide attempts; r=.234, p<.001), and where the mean age was 40 or above the association was negative (i.e., lower cortisol was associated with suicide attempts; r=-.129, p<.001). These findings confirm that HPA axis activity, as indicated by age-dependent variations in cortisol levels, is associated with suicidal behavior. The challenge for theory and clinical practice is to explain the complete reversal of the association with age and to identify its clinical implications. PMID:26555430

  7. The effects of social stress and cortisol responses on the preconscious selective attention to social threat.

    PubMed

    Roelofs, Karin; Bakvis, Patricia; Hermans, Erno J; van Pelt, Johannes; van Honk, Jack

    2007-04-01

    The purpose of the present study was to investigate the effects of social stress and stress-induced cortisol on the preconscious selective attention to social threat. Twenty healthy participants were administered a masked emotional Stroop task (comparing color-naming latencies for angry, neutral and happy faces) in conditions of rest and social stress. Stress was induced by means of the Trier social stress test. Based on the stress-induced increase in cortisol levels, participants were allocated post hoc (median-split) to a high and low responders group. In contrast to low responders, high responders showed a negative or avoidant attentional bias to threat (i.e. shorter latencies for angry than neutral faces) in the rest condition. Most importantly, although low responders became avoidant, the high responders became vigilant to the angry faces after stress induction. There were no such effects for happy faces. Our findings are in line with previous studies in both animals and humans, that associate high glucocorticoid stress-responsiveness with diminished avoidance and prolonged freezing reactions during stress. PMID:17030399

  8. Environmental Influences in Family Similarity in Afternoon Cortisol Levels: A Parent-Offspring Design

    PubMed Central

    Schreiber, Jane E.; Shirtcliff, Elizabeth; Van Hulle, Carol; Lemery-Chalfant, Kathryn; Klein, Marjorie H.; Kalin, Ned H.; Essex, Marilyn J.; Goldsmith, H. Hill

    2009-01-01

    Summary Modest genetic effects on morning, but not late-day, cortisol levels have been established. Environmental demands may influence basal cortisol levels later in the day. Thus, we anticipated that individuals in the same family would have similar afternoon cortisol levels to the extent that they share aspects of their environment. We examined afternoon basal cortisol levels measured across three consecutive days in mothers and fathers and in multiple offspring in two separate large, longitudinal studies. Study I involved 321 families with singletons while study II involved 233 families with twins. Modest family similarity was apparent for afternoon basal cortisol levels in both studies. Spouses’ cortisol levels were also correlated. Data from Study II demonstrated that family resemblance in afternoon cortisol was accounted for by underlying shared environmental factors but not underlying genetic factors. Shared environment accounted for 62% of the variation in twin afternoon basal cortisol levels and 14% of the variation in parent afternoon basal cortisol levels. We used pooled data from the two studies to examine whether parental depression, socioeconomic status (SES), and offspring sex and age impacted cortisol levels. Female offspring had higher cortisol levels than males, and cortisol decreased with age until about nine years of age, after which cortisol increased with age. Family similarity persisted after accounting for parental depression, SES, time of day, and offspring sex and age, which suggests that the shared family environment influences parent and offspring stress hormone levels throughout the childhood years. PMID:16997489

  9. Plasma cortisol and noradrenalin concentrations in pigs: automated sampling of freely moving pigs housed in PigTurn versus manually sampled and restrained pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Minimizing the effects of restraint and human interaction on the endocrine physiology of animals is essential for collection of accurate physiological measurements. Our objective was to compare stress-induced cortisol (CORT) and noradrenalin (NorA) responses in automated versus manual blood sampling...

  10. Plasma cortisol and norepinephrine concentrations in pigs: automated sampling of freely moving pigs housed in the PigTurn versus manually sampled and restrained pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Minimizing effects of restraint and human interaction on the endocrine physiology of animals is essential for collection of accurate physiological measurements. Our objective was to compare stress-induced cortisol (CORT) and norepinephrine (NE) responses in automated versus manual blood sampling. A ...

  11. Digital and analog communication systems

    NASA Technical Reports Server (NTRS)

    Shanmugam, K. S.

    1979-01-01

    The book presents an introductory treatment of digital and analog communication systems with emphasis on digital systems. Attention is given to the following topics: systems and signal analysis, random signal theory, information and channel capacity, baseband data transmission, analog signal transmission, noise in analog communication systems, digital carrier modulation schemes, error control coding, and the digital transmission of analog signals.

  12. Analogical Reasoning in Geometry Education

    ERIC Educational Resources Information Center

    Magdas, Ioana

    2015-01-01

    The analogical reasoning isn't used only in mathematics but also in everyday life. In this article we approach the analogical reasoning in Geometry Education. The novelty of this article is a classification of geometrical analogies by reasoning type and their exemplification. Our classification includes: analogies for understanding and setting a…

  13. Electrical analogous in viscoelasticity

    NASA Astrophysics Data System (ADS)

    Ala, Guido; Di Paola, Mario; Francomano, Elisa; Li, Yan; Pinnola, Francesco P.

    2014-07-01

    In this paper, electrical analogous models of fractional hereditary materials are introduced. Based on recent works by the authors, mechanical models of materials viscoelasticity behavior are firstly approached by using fractional mathematical operators. Viscoelastic models have elastic and viscous components which are obtained by combining springs and dashpots. Various arrangements of these elements can be used, and all of these viscoelastic models can be equivalently modeled as electrical circuits, where the spring and dashpot are analogous to the capacitance and resistance, respectively. The proposed models are validated by using modal analysis. Moreover, a comparison with numerical experiments based on finite difference time domain method shows that, for long time simulations, the correct time behavior can be obtained only with modal analysis. The use of electrical analogous in viscoelasticity can better reveal the real behavior of fractional hereditary materials.

  14. Serotonin directly stimulates cortisol secretion from the interrenals in goldfish.

    PubMed

    Lim, Jan E; Porteus, Cosima S; Bernier, Nicholas J

    2013-10-01

    While serotonin (5-HT) can stimulate the hypothalamic-pituitary-interrenal stress axis in fish, the specific site(s) of 5-HT action are poorly understood. In this study, goldfish (Carassius auratus) were injected intraperitoneally with either saline or the 5-HT1A/7 receptor agonist 8-OH-DPAT at a dose of 100 or 400 μg/kg body weight and sampled 1.5 and 8 h post-injection. Relative to unhandled controls, the saline and 100 μg/kg 8-OH-DPAT treatments elicited similar transient 5- to 7-fold increases in plasma cortisol and the 400 μg/kg 8-OH-DPAT dosage resulted in a sustained 16-fold increase in cortisol levels. Although the 5-HT1A receptor is expressed in the brain preoptic area (POA), the pituitary and the head kidney, neither the saline nor the 8-OH-DPAT treatments affected the mRNA abundance of POA corticotropin-releasing factor and pituitary pro-opiomelanocortin or plasma adrenocorticotropic hormone (ACTH) levels. To assess the direct actions of 5-HT on cortisol secretion relative to those of ACTH, head kidney tissue were superfused with 10(-7)M 5-HT, ACTH or a combined 5-HT/ACTH treatment. Overall, the ACTH and 5-HT/ACTH treatments resulted in higher peak cortisol and total cortisol release than in the 5-HT treatment but the response time to peak cortisol release was shorter in the combined treatment than in either the 5-HT or ACTH alone treatments. Both 8-OH-DPAT and cisapride, a 5-HT4 receptor agonist, also stimulated cortisol release in vitro and their actions were reversed by selective 5-HT1A and 5-HT4 receptor antagonists, respectively. Finally, double-labeling with anti-tyrosine hydroxylase and anti-5-HT revealed that the chromaffin cells of the head kidney contain 5-HT. Thus, in goldfish, 5-HT can directly stimulate cortisol secretion from the interrenals via multiple 5-HT receptor subtypes and the chromaffin cells may be involved in the paracrine regulation of cortisol secretion via 5-HT. PMID:24013027

  15. Plasma-cortisol levels in experimental heatstroke in dogs

    NASA Astrophysics Data System (ADS)

    Assia, Ehud; Epstein, Yoram; Magazanik, Avraham; Shapiro, Yair; Sohar, Ezra

    1989-06-01

    The effect of external heat-load, exercise and dehydration on dynamic changes in plasma cortisol during the development of heatstroke was investigated. Thirty-three unanesthetized dogs were tested under two sets of climatic conditions: comfort conditions and hot-dry climatic conditions, half of them while exercising. Half of the dogs in each group were rehydrated. None of the dogs that were investigated at room temperature suffered heatstroke. Of the dogs exposed to high ambient temperature, all of the exercising, as well as five out of six non-hydrated dogs and one rehydrated non-exercising dog suffered heatstroke. Significant dehydration (6% 7% of body weight), occurred only under hgh ambient temperature. Plasma cortisol levels of all dogs that suffered heatstroke rose conspicuously for at least 5 h and returned to normal levels 24 h later. Cortisol levels of dogs who did not experience heatstroke remained within the normal range. Cortisol levels correlated with the severity of the stress leading to heatstroke. High and rising levels of cortisol, several hours after body temperature returns to normal, may support the diagnosis of heatstroke.

  16. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently

    PubMed Central

    Lee, Seung-Eun; Lee, You-Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung-Han; Oh, Young Lyun

    2015-01-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  17. Perceived Partner Responsiveness Predicts Diurnal Cortisol Profiles 10 Years Later

    PubMed Central

    Slatcher, Richard B.; Selcuk, Emre; Ong, Anthony D.

    2015-01-01

    Several decades of research have demonstrated that marital relationships have a powerful influence on physical health. However, surprisingly little is known about how marriage affects health—both in terms of psychological processes and biological ones. We investigated the associations between perceived partner responsiveness—the extent to which people feel understood, cared for and appreciated by their romantic partner—and diurnal cortisol over a 10-year period in a large sample of married and cohabitating couples in the U.S. Partner responsiveness predicted higher wakeup cortisol values and steeper (“healthier”) cortisol slopes at the 10-year follow-up, and these associations remained strong after controlling for demographic factors, depressive symptoms, agreeableness, and other positive and negative relationship factors. Further, declines in negative affect over the 10-year period mediated the prospective association between responsiveness and cortisol slope. These findings suggest that diurnal cortisol may be a key biological pathway through which social relationships impact long-term health. PMID:26015413

  18. Bilateral Adrenocortical Masses Producing Aldosterone and Cortisol Independently.

    PubMed

    Lee, Seung Eun; Kim, Jae Hyeon; Lee, You Bin; Seok, Hyeri; Shin, In Seub; Eun, Yeong Hee; Kim, Jung Han; Oh, Young Lyun

    2015-12-01

    A 31-year-old woman was referred to our hospital with symptoms of hypertension and bilateral adrenocortical masses with no feature of Cushing syndrome. The serum aldosterone/renin ratio was elevated and the saline loading test showed no suppression of the plasma aldosterone level, consistent with a diagnosis of primary hyperaldosteronism. Overnight and low-dose dexamethasone suppression tests showed no suppression of serum cortisol, indicating a secondary diagnosis of subclinical Cushing syndrome. Adrenal vein sampling during the low-dose dexamethasone suppression test demonstrated excess secretion of cortisol from the left adrenal mass. A partial right adrenalectomy was performed, resulting in normalization of blood pressure, hypokalemia, and high aldosterone level, implying that the right adrenal mass was the main cause of the hyperaldosteronism. A total adrenalectomy for the left adrenal mass was later performed, resulting in a normalization of cortisol level. The final diagnosis was bilateral adrenocortical adenomas, which were secreting aldosterone and cortisol independently. This case is the first report of a concurrent cortisol-producing left adrenal adenoma and an aldosterone-producing right adrenal adenoma in Korea, as demonstrated by adrenal vein sampling and sequential removal of adrenal masses. PMID:26248855

  19. Latent trait cortisol (LTC) levels: reliability, validity, and stability.

    PubMed

    Doane, Leah D; Chen, Frances R; Sladek, Michael R; Van Lenten, Scott A; Granger, Douglas A

    2015-05-01

    The regulation of the hypothalamic pituitary adrenal (HPA) axis has received empirical attention as a mechanism contributing to individual differences in health and human development. A variety of sampling tactics and strategies index daily HPA axis functioning including the cortisol awakening response (CAR), the diurnal slope, and the area under the curve (AUGg). In an ethnically diverse sample (54% European-American, 23% Latino) of 82 adolescents (24% male, M age=18.05 years), we assessed salivary cortisol 45 times over the transition to college: 5 times per day, over 3 sequential days, across 3 waves (initially, 5, and 9 months later). Samples were collected at waking; 30 min, 3, and 8h post waking; and bedtime. Latent state-trait modeling indicated that the waking and 30 min post waking samples contributed to indices of within and across wave latent trait cortisol (LTC) levels. As such, a latent trait factor of cortisol was derived to reflect both within- and across-wave trait components of the variance in cortisol. LTC was distinct from the CAR, differentially predicted components of the diurnal profile across the day, and was highly stable across assessment waves (months). As preliminary evidence for convergent validity of LTC levels, childhood trauma was positively associated with LTC. Findings document the reliability, divergent and convergent validity, and stability of a latent trait factor of individual differences in HPA axis activity that may provide a cost efficient alternative to existing strategies and minimize participant burden. PMID:25705799

  20. Serum cortisol levels in patients with uncomplicated and cerebral malaria.

    PubMed

    Shwe, T; Khin, M; Min, H; Hla, K K; Win, Y Y; Htwe, K; Thu, T M

    1998-03-01

    Ten patients with uncomplicated malaria, ten with cerebral malaria and 37 controls (blood donors from blood bank) were included in the study. The serum cortisol levels of the patients were determined daily for 7 days while they were at the hospital. A radio-immunoassay method was used for quantitative measurement of cortisol in human serum. The mean serum cortisol level of patients with uncomplicated malaria was 528.2 +/- 123.9 nmol/l, with cerebral malaria was 516.0 +/- 80.5 nmol/l, and in controls was 393.8 +/- 141.0 nmol/l. There was a significant rise of serum cortisol levels in patients with malaria when compared to controls at the day of admission to hospital. There was no significant difference between uncomplicated malaria patients and those with cerebral malaria. There was also no significant difference between the different days of treatment up till day 7. We found no cortisol insufficiency in cases with falciparum malaria during acute and convalescent stages of illness. PMID:9740267

  1. Cortisol disrupts the neural correlates of extinction recall.

    PubMed

    Kinner, Valerie L; Merz, Christian J; Lissek, Silke; Wolf, Oliver T

    2016-06-01

    The renewal effect describes the recovery of extinguished responses that may occur after a change in context and indicates that extinction memory retrieval is sometimes prone to failure. Stress hormones have been implicated to modulate extinction processes, with mostly impairing effects on extinction retrieval. However, the neurobiological mechanisms mediating stress effects on extinction memory remain elusive. In this functional magnetic resonance imaging study, we investigated the effects of cortisol administration on the neural correlates of extinction memory retrieval in a predictive learning task. In this task, participants were required to predict whether certain food stimuli were associated with stomach trouble when presented in two different contexts. A two-day renewal paradigm was applied in which an association was acquired in context A and subsequently extinguished in context B. On the following day, participants received either cortisol or placebo 40min before extinction memory retrieval was tested in both contexts. Behaviorally, cortisol impaired the retrieval of extinguished associations when presented in the extinction context. On the neural level, this effect was characterized by a reduced context differentiation for the extinguished stimulus in the ventromedial prefrontal cortex, but only in men. In the placebo group, ventromedial prefrontal cortex was functionally connected to the left cerebellum, the anterior cingulate and the right anterior parahippocampal gyrus to express extinction memory. This functional crosstalk was reduced under cortisol. These findings illustrate that the stress hormone cortisol disrupts ventromedial prefrontal cortex functioning and its communication with other brain regions implicated in extinction memory. PMID:26973167

  2. A quantitative approach to analysing cortisol response in the horse.

    PubMed

    Ekstrand, C; Ingvast-Larsson, C; Olsén, L; Hedeland, M; Bondesson, U; Gabrielsson, J

    2016-06-01

    The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 μg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57 μg/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24 μg/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65 ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test. PMID:26542753

  3. Co-administration of α-GalCer analog and TLR4 agonist induces robust CD8(+) T-cell responses to PyCS protein and WT-1 antigen and activates memory-like effector NKT cells.

    PubMed

    Coelho-Dos-Reis, Jordana G; Huang, Jing; Tsao, Tiffany; Pereira, Felipe V; Funakoshi, Ryota; Nakajima, Hiroko; Sugiyama, Haruo; Tsuji, Moriya

    2016-07-01

    In the present study, the combined adjuvant effect of 7DW8-5, a potent α-GalCer-analog, and monophosphoryl lipid A (MPLA), a TLR4 agonist, on the induction of vaccine-induced CD8(+) T-cell responses and protective immunity was evaluated. Mice were immunized with peptides corresponding to the CD8(+) T-cell epitopes of a malaria antigen, a circumsporozoite protein of Plasmodium yoelii, and a tumor antigen, a Wilms Tumor antigen-1 (WT-1), together with 7DW8-5 and MPLA, as an adjuvant. These immunization regimens were able to induce higher levels of CD8(+) T-cell responses and, ultimately, enhanced levels of protection against malaria and tumor challenges compared to the levels induced by immunization with peptides mixed with 7DW8-5 or MPLA alone. Co-administration of 7DW8-5 and MPLA induces activation of memory-like effector natural killer T (NKT) cells, i.e. CD44(+)CD62L(-)NKT cells. Our study indicates that 7DW8-5 greatly enhances important synergistic pathways associated to memory immune responses when co-administered with MPLA, thus rendering this combination of adjuvants a novel vaccine adjuvant formulation. PMID:27132023

  4. Co-administration of α-GalCer analog and TLR4 agonist induces robust CD8+ T-cell responses to PyCS protein and WT-1 antigen and activates memory-like effector NKT cells

    PubMed Central

    Coelho-dos-Reis, Jordana G.; Huang, Jing; Tsao, Tiffany; Pereira, Felipe V.; Funakoshi, Ryota; Nakajima, Hiroko; Sugiyama, Haruo; Tsuji, Moriya

    2016-01-01

    In the present study, the combined adjuvant effect of 7DW8-5, a potent α-GalCer-analog, and monophosphoryl lipid A (MPLA), a TLR4 agonist, on the induction of vaccine-induced CD8+ T-cell responses and protective immunity was evaluated. Mice were immunized with peptides corresponding to the CD8+ T-cell epitopes of a malaria antigen, a circumsporozoite protein of Plasmodium yoelii, and a tumor antigen, a Wilms Tumor antigen-1 (WT-1), together with 7DW8-5 and MPLA, as an adjuvant. These immunization regimens were able to induce higher levels of CD8+ T-cell responses and, ultimately, enhanced levels of protection against malaria and tumor challenges compared to the levels induced by immunization with peptides mixed with 7DW8-5 or MPLA alone. Co-administration of 7DW8-5 and MPLA induces activation of memory-like effector natural killer T (NKT) cells, i.e. CD44+CD62L−NKT cells. Our study indicates that 7DW8-5 greatly enhances important synergistic pathways associated to memory immune responses when co-administered with MPLA, thus rendering this combination of adjuvants a novel vaccine adjuvant formulation. PMID:27132023

  5. Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE-19 cell toxicity

    SciTech Connect

    Li, Yuan; Zou, Xuan; Cao, Ke; Xu, Jie; Yue, Tingting; Dai, Fang; Zhou, Bo; Lu, Wuyuan; Feng, Zhihui; Liu, Jiankang

    2013-11-01

    Curcumin, a phytochemical agent in the spice turmeric, has received increasing attention for its anticancer, anti-inflammatory and antioxidant properties. However, application of curcumin has been limited due to its insolubility in water and poor bioavailability both clinically and experimentally. In addition, the protective effects and mechanisms of curcumin in eye diseases have been poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved protective effect against acrolein-induced toxicity in a human retinal pigment epithelial cell line (ARPE-19). At 5 μM, curcumin completely protected against acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial function. Surprisingly, C3 displayed a complete protective effect at 0.5 μM, which was much more efficient than curcumin. Both 0.5 μM C3 and 5 μM curcumin induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly. Experiments using Nrf2 siRNA showed that the protective effects of curcumin and C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3 activated the PI3/Akt pathway, however, Nrf2 activation was independent of this pathway, and therefore, we hypothesized that both curcumin and C3 activated phase II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as a model of smoking and age-related macular degeneration (AMD), we concluded that the curcumin analog, C3, may be a more promising drug candidate for its potential application for the prevention and treatment of eye diseases, such as AMD. - Highlights: • We examine toxicity effects of cigarette smoking component acrolein in retina cells. • We report a more efficient curcumin analog (C3) protecting cellular function. • Mitochondrial function and phase II enzyme activation are the major

  6. Ontogeny of the cortisol stress response in channel catfish (Ictalurus punctatus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cortisol is a glucocorticoid hormone which is an endocrine signaling molecule in all vertebrates and acts through intracellular glucocorticoid receptors (GR). Cortisol affects many biological functions including immunity, stress, growth, ion homeostasis, and reproduction. The objective of this stu...

  7. The pro-social neurohormone oxytocin reverses the actions of the stress hormone cortisol in human ovarian carcinoma cells in vitro.

    PubMed

    Mankarious, Amanda; Dave, Foram; Pados, George; Tsolakidis, Dimitris; Gidron, Yori; Pang, Yefei; Thomas, Peter; Hall, Marcia; Karteris, Emmanouil

    2016-05-01

    The journey patients with ovarian cancer travel from non-specific symptoms causing delayed diagnosis through surgery and chemotherapy, culminating in a 5-year survival rate of 43%, must have a profound and detrimental psychological impact on patients. Emerging studies link higher levels of oxytocin (OT) and increased social support, an independent prognostic factor in cancer, with a moderating effect on stress. In contrast, there is a known association of tumour cell proliferation with elevated cortisol (stress hormone) levels. We hypothesise therefore that there is cross-talk between cortisol and oxytocin at a molecular level. Three ovarian cancer cell lines, used as in vitro models, were treated with cortisol at concentrations mimicking physiological stress in vivo in the presence or absence of OT. OT reduced cell proliferation and migration, induced apoptosis and autophagy for all three cell lines, partially reversing the effects of cortisol. Quantitative RT-PCR of tissue taken from ovarian cancer patients revealed that the glucocorticoid receptor (splice variant GR-P) and OT receptor (OTR) were significantly upregulated compared to controls. Tissue microarray revealed that the expression of GRα was lower in the ovarian cancer samples compared to normal tissue. OT is also shown to drive alternative splicing of the GR gene and cortisol-induced OTR expression. OT was able to transactivate GR in the presence of cortisol, thus providing further evidence of cross-talk in vitro. These data provide explanations for why social support might help distressed ovarian cancer patients and help define novel hypotheses regarding potential therapeutic interventions in socially isolated patients. PMID:26935408

  8. The pro-social neurohormone oxytocin reverses the actions of the stress hormone cortisol in human ovarian carcinoma cells in vitro

    PubMed Central

    MANKARIOUS, AMANDA; DAVE, FORAM; PADOS, GEORGE; TSOLAKIDIS, DIMITRIS; GIDRON, YORI; PANG, YEFEI; THOMAS, PETER; HALL, MARCIA; KARTERIS, EMMANOUIL

    2016-01-01

    The journey patients with ovarian cancer travel from non-specific symptoms causing delayed diagnosis through surgery and chemotherapy, culminating in a 5-year survival rate of 43%, must have a profound and detrimental psychological impact on patients. Emerging studies link higher levels of oxytocin (OT) and increased social support, an independent prognostic factor in cancer, with a moderating effect on stress. In contrast, there is a known association of tumour cell proliferation with elevated cortisol (stress hormone) levels. We hypothesise therefore that there is cross-talk between cortisol and oxytocin at a molecular level. Three ovarian cancer cell lines, used as in vitro models, were treated with cortisol at concentrations mimicking physiological stress in vivo in the presence or absence of OT. OT reduced cell proliferation and migration, induced apoptosis and autophagy for all three cell lines, partially reversing the effects of cortisol. Quantitative RT-PCR of tissue taken from ovarian cancer patients revealed that the glucocorticoid receptor (splice variant GR-P) and OT receptor (OTR) were significantly upregulated compared to controls. Tissue microarray revealed that the expression of GRα was lower in the ovarian cancer samples compared to normal tissue. OT is also shown to drive alternative splicing of the GR gene and cortisol-induced OTR expression. OT was able to transactivate GR in the presence of cortisol, thus providing further evidence of cross-talk in vitro. These data provide explanations for why social support might help distressed ovarian cancer patients and help define novel hypotheses regarding potential therapeutic interventions in socially isolated patients. PMID:26935408

  9. BJ-1108, a 6-Amino-2,4,5-Trimethylpyridin-3-ol Analog, Inhibits Serotonin-Induced Angiogenesis and Tumor Growth through PI3K/NOX Pathway

    PubMed Central

    Banskota, Suhrid; Gautam, Jaya; Regmi, Sushil C.; Gurung, Pallavi; Park, Myo-Hyeon; Kim, Seung Joo; Nam, Tae-gyu; Jeong, Byeong-Seon; Kim, Jung-Ae

    2016-01-01

    5-Hydroxytryptamine (5-HT) induces proliferation of cancer cells and vascular cells. In addition to 5-HT production by several cancer cells including gastrointestinal and breast cancer, a significant level of 5-HT is released from activated platelets in the thrombotic environment of tumors, suggesting that inhibition of 5-HT signaling may constitute a new target for antiangiogenic anticancer drug discovery. In the current study we clearly demonstrate that 5-HT-induced angiogenesis was mediated through the 5-HT1 receptor-linked Gβγ/Src/PI3K pathway, but not through the MAPK/ERK/p38 pathway. In addition, 5-HT induced production of NADPH oxidase (NOX)-derived reactive oxygen species (ROS). In an effort to develop new molecularly targeted anticancer agents against 5-HT action in tumor growth, we demonstrate that BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, significantly inhibited 5-HT-induced angiogenesis. In addition, BJ-1108 induced a significant reduction in the size and weight of excised tumors in breast cancer cell-inoculated CAM assay, showing proportionate suppression of tumor growth along with inhibition of angiogenesis. In human umbilical vein endothelial cells (HUVECs), BJ-1108 significantly suppressed 5-HT-induced ROS generation and phosphorylation of PI3K/Akt but not of Src. Unlike NOX inhibitors, BJ-1108, which showed better antioxidant activity than vitamin C, barely suppressed superoxide anion induced by mevalonate or geranylgeranyl pyrophosphate which directly activates NOX without help from other signaling molecules in HUVECs, implying that the anti-angiogenic action of BJ-1108 was not mediated through direct action on NOX activation, or free radical scavenging activity. In conclusion, BJ-1108 inhibited 5-HT-induced angiogenesis through PI3K/NOX signaling but not through Src, ERK, or p38. PMID:26824764

  10. Memory performance is related to the cortisol awakening response in older people, but not to the diurnal cortisol slope.

    PubMed

    Hidalgo, Vanesa; Almela, Mercedes; Pulopulos, Matias M; Salvador, Alicia

    2016-09-01

    There are large individual differences in age-related cognitive decline. Hypothalamic-pituitary-adrenal axis (HPA-axis) functioning has been suggested as one of the mechanisms underlying these differences. This study aimed to investigate the relationships between the diurnal cortisol cycle, measured as the cortisol awakening response (CAR), and the diurnal cortisol slope (DCS) and the memory performance of healthy older people. To do so, we assessed the verbal, visual, and working memory performance of 64 participants (32 men) from 57 to 76 years old who also provided 14 saliva samples on two consecutive weekdays to determine their diurnal cortisol cycle. The CAR was linearly and negatively associated with verbal (significantly) and visual (marginally) memory domains, but not with working memory. Sex did not moderate these relationships. Furthermore, no associations were found between the DCS and any of the three memory domains assessed. Our results indicate that the two components of the diurnal cortisol cycle have different relationships with memory performance, with the CAR being more relevant than DCS in understanding the link from HPA-axis activity and regulation to different types of memory. These results suggest that the CAR is related to memory domains dependent on hippocampal functioning (i.e., declarative memory), but not to those that are more dependent on prefrontal cortex functioning (i.e., working memory). PMID:27266967

  11. Circulating angiogenic cell function is inhibited by cortisol in vitro and associated with psychological stress and cortisol in vivo.

    PubMed

    Aschbacher, Kirstin; Derakhshandeh, Ronak; Flores, Abdiel J; Narayan, Shilpa; Mendes, Wendy Berry; Springer, Matthew L

    2016-05-01

    Psychological stress and glucocorticoids are associated with heightened cardiovascular disease risk. We investigated whether stress or cortisol would be associated with reduced circulating angiogenic cell (CAC) function, an index of impaired vascular repair. We hypothesized that minority-race individuals who experience threat in interracial interactions would exhibit reduced CAC function, and that this link might be explained by cortisol. To test this experimentally, we recruited 106 African American participants for a laboratory interracial interaction task, in which they received socially evaluative feedback from Caucasian confederates. On a separate day, a subset of 32 participants (mean age=26years, 47% female) enrolled in a separate biological substudy and provided blood samples for CAC isolation and salivary samples to quantify the morning peak in cortisol (the cortisol awakening response, CAR). CAC function was quantified using cell culture assays of migration to vascular endothelial growth factor (VEGF) and secretion of VEGF into the culture medium. Heightened threat in response to an interracial interaction and trait anxiety in vivo were both associated with poorer CAC migratory function in vitro. Further, threat and poorer sustained attention during the interracial interaction were associated with a higher CAR, which in turn, was related to lower CAC sensitivity to glucocorticoids. In vitro, higher doses of cortisol impaired CAC migratory function and VEGF protein secretion. The glucocorticoid receptor antagonist RU486 reversed this functional impairment. These data identify a novel, neuroendocrine pathway by which psychological stress may reduce CAC function, with potential implications for cardiovascular health. PMID:26925833

  12. Reasoning through Instructional Analogies

    ERIC Educational Resources Information Center

    Kapon, Shulamit; diSessa, Andrea A.

    2012-01-01

    This article aims to account for students' assessments of the plausibility and applicability of analogical explanations, and individual differences in these assessments, by analyzing properties of students' underlying knowledge systems. We developed a model of explanation and change in explanation focusing on knowledge elements that provide a…

  13. Quantum Analog Computing

    NASA Technical Reports Server (NTRS)

    Zak, M.

    1998-01-01

    Quantum analog computing is based upon similarity between mathematical formalism of quantum mechanics and phenomena to be computed. It exploits a dynamical convergence of several competing phenomena to an attractor which can represent an externum of a function, an image, a solution to a system of ODE, or a stochastic process.

  14. Learning by Analogical Bootstrapping.

    ERIC Educational Resources Information Center

    Miao, Chun-Hui; Kurtz, Kenneth J.; Gentner, Dedre

    2001-01-01

    Reports on research into whether mutual alignment of partially known situations can be an effective strategy when compared to the common procedure of drawing analogies from a well understood situation to one that is poorly understood. Results suggest that such mutual alignment is an effective means of promoting insight. (MM)

  15. Analogy, explanation, and proof

    PubMed Central

    Hummel, John E.; Licato, John; Bringsjord, Selmer

    2014-01-01

    People are habitual explanation generators. At its most mundane, our propensity to explain allows us to infer that we should not drink milk that smells sour; at the other extreme, it allows us to establish facts (e.g., theorems in mathematical logic) whose truth was not even known prior to the existence of the explanation (proof). What do the cognitive operations underlying the inference that the milk is sour have in common with the proof that, say, the square root of two is irrational? Our ability to generate explanations bears striking similarities to our ability to make analogies. Both reflect a capacity to generate inferences and generalizations that go beyond the featural similarities between a novel problem and familiar problems in terms of which the novel problem may be understood. However, a notable difference between analogy-making and explanation-generation is that the former is a process in which a single source situation is used to reason about a single target, whereas the latter often requires the reasoner to integrate multiple sources of knowledge. This seemingly small difference poses a challenge to the task of marshaling our understanding of analogical reasoning to understanding explanation. We describe a model of explanation, derived from a model of analogy, adapted to permit systematic violations of this one-to-one mapping constraint. Simulation results demonstrate that the resulting model can generate explanations for novel explananda and that, like the explanations generated by human reasoners, these explanations vary in their coherence. PMID:25414655

  16. An Interesting Analogy

    ERIC Educational Resources Information Center

    Pacheco, Jose M.; Fernandez, Isabel

    2002-01-01

    The aim of this note is to give some insight into the formal unity of a very applicable area of mathematics by showing an interesting analogy between the weak part of the Rouche-Frobenius theorem and the existence result for the initial value problem for the general first-order linear two-dimensional PDE.

  17. How Analogy Drives Physics

    SciTech Connect

    Hofstadter, Doug

    2004-05-05

    Many new ideas in theoretical physics come from analogies to older ideas in physics. For instance, the abstract notion of 'isospin' (or isotopic spin) originated in the prior concept of 'spin' (quantized angular momentum); likewise, the concept of 'phonon' (quantum of sound, or quantized collective excitation of a crystal) was based on the prior concept of 'photon' (quantum of light, or quantized element of the electromagnetic field). But these two examples, far from being exceptions, in fact represent the bread and butter of inventive thinking in physics. In a nutshell, intraphysics analogy-making -- borrowing by analogy with something already known in another area of physics -- is central to the progress of physics. The aim of this talk is to reveal the pervasiveness -- indeed, the indispensability -- of this kind of semi-irrational, wholly intuitive type of thinking (as opposed to more deductive mathematical inference) in the mental activity known as 'doing physics'. Speculations as to why wild analogical leaps are so crucial to the act of discovery in physics (as opposed to other disciplines) will be offered.

  18. Arterial Pressure Analog.

    ERIC Educational Resources Information Center

    Heusner, A. A.; Tracy, M. L.

    1980-01-01

    Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…

  19. A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway

    SciTech Connect

    Zhang, Xuenong; Wei, Han; Liu, Ziwei; Yuan, Qianying; Wei, Anhua; Shi, Du; Yang, Xian; Ruan, Jinlan

    2013-07-15

    Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent. - Highlights: • We showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. • Autophagy induced by RY10-4 played as a promotion mechanism for cell death. • RY10-4 induced autophagy in MCF-7 cell through the Akt/mTOR pathway. • We provided new insights for the mechanism of RY10-4 induced cell death.

  20. The hypothalamic-pituitary response in SLE. Regulation of prolactin, growth hormone and cortisol release.

    PubMed

    Rovenský, J; Blazícková, S; Rauová, L; Jezová, D; Koska, J; Lukác, J; Vigas, M

    1998-01-01

    It has been suggested that neuroendocrine regulation plays an important role in the pathogenesis and activation of autoimmune diseases. The aim of this investigation was to clarify the hypothalamic-pituitary response to a well-defined stimulus under standardised conditions in patients with SLE. Plasma concentrations of prolactin (PRL), growth hormone (GH) and cortisol were determined in venous blood drawn through an indwelling cannula during insulin-induced hypoglycaemia (0.1 U/kg b.w., i.v.) in ten patients and in 12 age-, gender- and weight-matched healthy subjects. Basal PRL concentrations were higher in patients vs healthy controls (12 vs 6 ng/ml, P < 0.01), though still within the physiological range. Insulin-induced plasma PRL and GH were significantly increased both in patients and healthy subjects; however, the increments or areas under the curves were not different in the two groups. Plasma cortisol response showed moderate attenuation in patients. Sensitivity of pituitary lactotrothrops to thyrotropin-releasing hormone (TRH) administration (200 microg, i.v.) was the same in patients and control subjects. In SLE patients with low activity of the disease the sensitivity of pituitary PRL release to TRH administration remained unchanged. The hypothalamic response to stress stimulus (hypoglycaemia) was comparable in patients and healthy subjects. PMID:9736325

  1. Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.

    PubMed

    Zhu, Heping; Xu, Tingting; Qiu, Chenyu; Wu, Beibei; Zhang, Yali; Chen, Lingfeng; Xia, Qinqin; Li, Chenglong; Zhou, Bin; Liu, Zhiguo; Liang, Guang

    2016-10-01

    A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI). PMID:27240273

  2. Cortisol Awakening Response and Walking Speed in Older People.

    PubMed

    Pulopulos, Matias M; Puig-Perez, Sara; Hidalgo, Vanesa; Villada, Carolina; Salvador, Alicia

    2016-01-01

    In older people, less diurnal variability in cortisol levels has been consistently related to worse physical performance, especially to slower walking speed (WS). The cortisol awakening response (CAR) is a discrete component of the hypothalamic-pituitary-adrenal axis that has been related to several health problems, such as cardiovascular disease and/or worse performance on executive function and memory. The relationship between the CAR and physical performance in older people is poorly understood. In this study, in 86 older people (mean age = 64.42, SD = 3.93), we investigated the relationship between the CAR and WS, a commonly used measure of physical performance in the older population that has also been related to health problems, such as cardiovascular disease and executive function performance in older people. Additionally, we studied whether the relationship between the CAR and WS was independent from cortisol levels on awakening and several possible confounders. Results showed that a CAR of reduced magnitude (measured with 3 samples each day, for two consecutive days, and calculated as the area under the curve with respect to the increase), but not cortisol levels on awakening, was related to slower WS. In addition, this relationship was independent from cortisol levels on awakening. It is possible that a CAR of reduced magnitude would contribute to less diurnal cortisol variability, affecting physical performance. Additionally, it is possible that a CAR of reduced magnitude affects WS through a possible negative effect on executive function, or that the association between the CAR and WS is due to the fact that both are related to similar health problems and to changes in cognitive performance in older people. PMID:27191847

  3. Cortisol Awakening Response and Walking Speed in Older People

    PubMed Central

    Pulopulos, Matias M.; Puig-Perez, Sara; Hidalgo, Vanesa; Villada, Carolina; Salvador, Alicia

    2016-01-01

    In older people, less diurnal variability in cortisol levels has been consistently related to worse physical performance, especially to slower walking speed (WS). The cortisol awakening response (CAR) is a discrete component of the hypothalamic-pituitary-adrenal axis that has been related to several health problems, such as cardiovascular disease and/or worse performance on executive function and memory. The relationship between the CAR and physical performance in older people is poorly understood. In this study, in 86 older people (mean age = 64.42, SD = 3.93), we investigated the relationship between the CAR and WS, a commonly used measure of physical performance in the older population that has also been related to health problems, such as cardiovascular disease and executive function performance in older people. Additionally, we studied whether the relationship between the CAR and WS was independent from cortisol levels on awakening and several possible confounders. Results showed that a CAR of reduced magnitude (measured with 3 samples each day, for two consecutive days, and calculated as the area under the curve with respect to the increase), but not cortisol levels on awakening, was related to slower WS. In addition, this relationship was independent from cortisol levels on awakening. It is possible that a CAR of reduced magnitude would contribute to less diurnal cortisol variability, affecting physical performance. Additionally, it is possible that a CAR of reduced magnitude affects WS through a possible negative effect on executive function, or that the association between the CAR and WS is due to the fact that both are related to similar health problems and to changes in cognitive performance in older people. PMID:27191847

  4. Cortisol levels in central adrenal insufficiency: light and shade.

    PubMed

    De Sanctis, Vincenzo; Soliman, Ashraf; Yassin, Mohamed; Garofalo, Piernicola

    2015-03-01

    Evaluating children or adolescents with central adrenal insufficiency (CAI) is a difficult task in clinical practice, especially in subjects with hypothalamic-pituitary diseases and partial ACTH deficiency, or in those with recent pituitary surgery or brain irradiation when the adrenal cortex may still be responsive to stress. In 2008, a meta-analysis reported a three-step approach for evaluating patients at risk for CAI with no acute illness. In particular, the authors recommended the evaluation of morning cortisol, a low dose ACTH test (LDST) and the "gold standard" insulin tolerance test or metyrapone test if the low LDCT was not diagnostic. Cortisol and ACTH secretion exhibit significant fluctuation throughout the day. The reference ranges supplied by labs are so wide that they only flag up extremely low cortisol levels. Interpreting the results correctly can be difficult for a physician without an experience in adrenal dysfunctions. The lack of uniformity in these cut-off levels could in part be attributed to differences in study populations, variability of dynainic tests, the use of different serum cortisol assays and dissimilar cut-off peak serum cortisol response indicative of a normal axis response and the difference in the clinical context in which the studies were done. Therefore, Laboratories have to advertise the need to establish reference values for given populations, both for basal or stimulated hormone levels. Failure to apply this rule may elicit false-positive and more critically, false-negative results. LDST (1 pg synthetic ACTH as iv bolus with measurement of serum cortisol) has been proposed as a sensitive test for the diagnosis of CAl. However, the advantage of LDST compared with the high dose test may be offset by the technical difficulties inherent to dilution of 250 pg ampoules. Clinical judgment remains imperative especially regarding the use of glucocorticoid supplementation during extreme stress. PMID:25962205

  5. Children's Cortisol Patterns and the Quality of the Early Learning Environment

    ERIC Educational Resources Information Center

    Sajaniemi, Nina; Suhonen, Eira; Kontu, Elina; Rantanen, Pekka; Lindholm, Harri; Hyttinen, Sirpa; Hirvonen, Ari

    2011-01-01

    The aim of this study was to evaluate the influence of early educational quality on children's cortisol levels. It was hypothesised that the environmental stressors might load children's immature stress regulative systems thus affecting their diurnal cortisol levels. The study sample consisted of 146 preschool-aged children. Cortisol was measured…

  6. Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women

    PubMed Central

    Lovallo, William R.; Farag, Noha H.; Vincent, Andrea S.; Thomas, Terrie L.; Wilson, Michael F.

    2008-01-01

    Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg × 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (ps<.05). After a postexercise meal, the women had a larger cortisol response than the men, and this effect was greater after caffeine (p<.01). Cortisol release in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women. PMID:16631247

  7. Exposure to Maternal Distress in Childhood and Cortisol Activity in Young Adulthood

    ERIC Educational Resources Information Center

    Mahrer, Nicole E.; Luecken, Linda J.; Wolchik, Sharlene A.; Tein, Jenn-Yun; Sandler, Irwin N.

    2014-01-01

    Dysregulated cortisol is a risk factor for poor health outcomes. Children of distressed mothers exhibit dysregulated cortisol, yet it is unclear whether maternal distress predicts cortisol activity in later developmental stages. This longitudinal study examined the prospective relation between maternal distress during late childhood (9-12 years)…

  8. Cortisol Reactivity and Regulation Associated with Shame Responding in Early Childhood

    ERIC Educational Resources Information Center

    Mills, Rosemary S. L.; Imm, Gorette P.; Walling, Bobbi R.; Weiler, Hope A.

    2008-01-01

    The purpose of this study was to characterize cortisol response and regulation associated with shame responding in early childhood and to examine how general the relation between shame and cortisol is. It was predicted that children responding to task failure with shame would show a larger and more prolonged cortisol response than other children.…

  9. Endogenous Cortisol: Acute Modulation of Cytokine Gene Expression in Bovine PBMCs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar, Neuroimmunomod 2009;16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expres...

  10. Cortisol Reactivity is Positively Related to Executive Function in Preschool Children Attending Head Start

    ERIC Educational Resources Information Center

    Blair, Clancy; Granger, Douglas; Razza, Rachel Peters

    2005-01-01

    This study examined relations among cortisol reactivity and measures of cognitive function and social behavior in 4- to 5-year-old children (N=169) attending Head Start. Saliva samples for the assay of cortisol were collected at the beginning, middle, and end of an approximately 45-min testing session. Moderate increase in cortisol followed by…

  11. Whole-body cortisol response of zebrafish to acute net handling stress

    USGS Publications Warehouse

    Ramsay, J.M.; Feist, G.W.; Varga, Z.M.; Westerfield, M.; Kent, M.L.; Schreck, C.B.

    2009-01-01

    Zebrafish, Danio rerio, are frequently handled during husbandry and experimental procedures in the laboratory, yet little is known about the physiological responses to such stressors. We measured the whole-body cortisol levels of adult zebrafish subjected to net stress and air exposure at intervals over a 24 h period; cortisol recovered to near control levels by about 1 h post-net-stress (PNS). We then measured cortisol at frequent intervals over a 1 h period. Cortisol levels were more than 2-fold higher in net stressed fish at 3 min PNS and continued to increase peaking at 15 min PNS, when cortisol levels were 6-fold greater than the control cortisol. Mean cortisol declined from 15 to 60 min PNS, and at 60 min, net-stressed cortisol was similar to control cortisol. Because the age of fish differed between studies, we examined resting cortisol levels of fish of different ages (3, 7, 13, and 19 months). The resting cortisol values among tanks with the same age fish differed significantly but there was no clear effect of age. Our study is the first to report the response and recovery of cortisol after net handling for laboratory-reared zebrafish. ?? 2009 Elsevier B.V.

  12. Acute modulation of cytokine gene expression in bovine peripheral blood mononuclear cells (PBMCs) by endogenous cortisol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar. 2009. Neuroimmunomod. 16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expr...

  13. Acute modulation of cytokine gene expression in bovine PBMCs by endogenous cortisol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cortisol suppresses many aspects of immune function. However, recent publications suggest acute cortisol exposure may actually enhance immune function (Dhabhar, Neuroimmunomod 2009;16:300). The objective of this study was to determine the influence of acute increases in endogenous cortisol on expres...

  14. Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Ortiz, R. M.

    1997-01-01

    Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

  15. BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro.

    PubMed

    Matthews, Lynn; Chapman, Sherita; Ramchandani, Meena S; Lane, H Clifford; Davey, Richard T; Sereti, Irini

    2004-12-01

    Interleukin-2 administration induces CD4 T cell expansion in HIV-infected patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2 analog with >1000-fold specificity for the high-affinity IL-2 receptor. The effects of this compound on unstimulated human PBMC were evaluated. PBMC from HIV(-) and HIV(+) donors were cultured in vitro with incremental doses of BAY 50-4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50-4798 induced dose-dependent increases in CD25 expression and proliferation of T cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25. Induction of pro-inflammatory cytokines was also dose-dependent and was observed at the concentrations of BAY 50-4798 with the highest biologic activity. These data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells but loss of T cell selectivity and induction of pro-inflammatory cytokines occur at concentrations exerting the highest biologic activity. PMID:15507389

  16. Approaches to synthetic platelet analogs.

    PubMed

    Modery-Pawlowski, Christa L; Tian, Lewis L; Pan, Victor; McCrae, Keith R; Mitragotri, Samir; Sen Gupta, Anirban

    2013-01-01

    Platelet transfusion is routinely used for treating bleeding complications in patients with hematologic or oncologic clotting disorders, chemo/radiotherapy-induced myelosuppression, trauma and surgery. Currently, these transfusions mostly use allogeneic platelet concentrates, while products like lyophilized platelets, cold-stored platelets and infusible platelet membranes are under investigation. These natural platelet-based products pose considerable risks of contamination, resulting in short shelf-life (3-5 days). Recent advances in pathogen reduction technologies have increased shelf-life to ~7 days. Furthermore, natural platelets are short in supply and also cause several biological side effects. Hence, there is significant clinical interest in platelet-mimetic synthetic analogs that can allow long storage-life and minimum side effects. Accordingly, several designs have been studied which decorate synthetic particles with motifs that promote platelet-mimetic adhesion or aggregation. Recent refinement in this design involves combining the adhesion and aggregation functionalities on a single particle platform. Further refinement is being focused on constructing particles that also mimic natural platelet's shape, size and elasticity, to influence margination and wall-interaction. The optimum design of a synthetic platelet analog would require efficient integration of platelet's physico-mechanical properties and biological functionalities. We present a comprehensive review of these approaches and provide our opinion regarding the future directions of this research. PMID:23092864

  17. The carbocyclic analog of 2'-deoxyguanosine induces a prolonged inhibition of duck hepatitis B virus DNA synthesis in primary hepatocyte cultures and in the liver.

    PubMed Central

    Fourel, I; Saputelli, J; Schaffer, P; Mason, W S

    1994-01-01

    The carbocyclic analog of 2'-deoxyguanosine (2'-CDG) is a strong inhibitor of hepatitis B virus (HBV) DNA synthesis in HepG2 cells (P.M. Price, R. Banerjee, and G. Acs, Proc. Natl. Acad. USA 86:8543-8544, 1989). We now report that 2'-CDG inhibited duck hepatitis B virus (DHBV) DNA synthesis in primary cultures of duck hepatocytes and in experimentally infected ducks. Like foscarnet (phosphonoformic acid [PFA]) and 2'-,3'-dideoxycytidine (ddC), 2'-CDG blocked viral DNA replication in primary hepatocyte cultures when present during an infection but failed to inhibit the DNA repair reaction that occurs during the initiation of infection to convert virion relaxed circular DNA to covalently closed circular DNA, the template for viral mRNA transcription. Moreover, as for PFA and ddC, viral RNA synthesis was detected when infection was initiated in the presence 2'-CDG. In another respect, however, 2'-CDG exhibited antiviral activity unlike that of ddC or PFA: a single 1-day treatment of hepatocytes with 2'-CDG blocked initiation of viral DNA synthesis for at least 8 days, irrespective of whether DHBV infection was carried out at the time of drug treatment or several days later. Furthermore, orally administered 2'-CDG was long-acting against DHBV in experimentally infected ducklings. Virus replication was delayed by up to 4 days in ducklings infected after administration of 2'-CDG. These observations of long-lasting efficacy in vitro and in vivo even after oral administration suggest that this inhibitor or a nucleoside with similar pharmacological properties may be ideal for reducing virus replication in patients with chronic HBV infection. Images PMID:8289335

  18. The small molecule curcumin analog FLLL32 induces apoptosis in melanoma cells via STAT3 inhibition and retains the cellular response to cytokines with anti-tumor activity

    PubMed Central

    2010-01-01

    Background We characterized the biologic effects of a novel small molecule STAT3 pathway inhibitor that is derived from the natural product curcumin. We hypothesized this lead compound would specifically inhibit the STAT3 signaling pathway to induce apoptosis in melanoma cells. Results FLLL32 specifically reduced STAT3 phosphorylation at Tyr705 (pSTAT3) and induced apoptosis at micromolar amounts in human melanoma cell lines and primary melanoma cultures as determined by annexin V/propidium iodide staining and immunoblot analysis. FLLL32 treatment reduced expression of STAT3-target genes, induced caspase-dependent apoptosis, and reduced mitochondrial membrane potential. FLLL32 displayed specificity for STAT3 over other homologous STAT proteins. In contrast to other STAT3 pathway inhibitors (WP1066, JSI-124, Stattic), FLLL32 did not abrogate IFN-γ-induced pSTAT1 or downstream STAT1-mediated gene expression as determined by Real Time PCR. In addition, FLLL32 did not adversely affect the function or viability of immune cells from normal donors. In peripheral blood mononuclear cells (PBMCs), FLLL32 inhibited IL-6-induced pSTAT3 but did not reduce signaling in response to immunostimulatory cytokines (IFN-γ, IL 2). Treatment of PBMCs or natural killer (NK) cells with FLLL32 also did not decrease viability or granzyme b and IFN-γ production when cultured with K562 targets as compared to vehicle (DMSO). Conclusions These data suggest that FLLL32 represents a lead compound that could serve as a platform for further optimization to develop improved STAT3 specific inhibitors for melanoma therapy. PMID:20576164

  19. 3,3′-Diindolylmethane (DIM) and its ring-substituted halogenated analogs (ring-DIMs) induce differential mechanisms of survival and death in androgen-dependent and –independent prostate cancer cells

    PubMed Central

    Montes-Grajales, Diana; Olivero-Verbél, Jesus; Safe, Stephen H.; Sanderson, J. Thomas

    2015-01-01

    We recently reported that novel ring-substituted analogs of 3,3′-diindolylmethane (ring-DIMs) induce apoptosis and necrosis in androgen-dependent and –independent prostate cancer cells. In this paper, we have focused on the mechanism(s) associated with ring-DIM-mediated cell death, and on identifying the specific intracellular target(s) of these compounds. The 4,4′- and 7,7′-dichloroDIMs and 4,4′- and 7,7′-dibromoDIMs induced the death of LNCaP, C42B and DU145 prostate cancer cells, but not that of immortalized normal human prostate epithelial (RWPE-1) cells. Ring-DIMs caused the early loss of mitochondrial membrane potential (MMP) and decreased mitochondrial ATP generation in prostate cancer cells. Cyclosporin A, an inhibitor of the mitochondrial permeability transition pore, inhibited ring-DIM-mediated cell death, and salubrinal, an inhibitor of ER stress, inhibited cell death mediated only by 4,4′-dihaloDIMs. We found that although salubrinal did not inhibit the onset of ER stress, it prevented 4,4′-dibromoDIM mediated loss of MMP. Salubrinal potentiated cell death in response to 7,7′-dihaloDIMs and DIM, and this effect concurred with increased loss of MMP. Using in silico 3-D docking affinity analysis, we identified Ca2+/calmodulin-dependent kinase II (CaMKII) as a potential direct target for the most toxic ring-DIM, 4,4′-dibromoDIM. An inhibitor of CaMKII, KN93, but not its inactive analog KN92, abrogated cell death mediated by 4,4′-dibromoDIM. The ring-DIMs induced ER stress and autophagy, but these processes were not necessary for ring-DIM-mediated cell death. Inhibition of autophagy with bafilomycin A1, 3-methyladenine or by LC3B gene silencing sensitized LNCaP and C42B, but not ATG5-deficient DU145 cells to ring-DIM- and DIM-mediated cell death. We propose that autophagy induced by the ring-DIMs and DIM has a cytoprotective function in prostate cancer cells. PMID:26124925

  20. Cortisol awakening response and diurnal cortisol among children at elevated risk for schizophrenia: Relationship to psychosocial stress and cognition

    PubMed Central

    Cullen, Alexis E.; Zunszain, Patricia A.; Dickson, Hannah; Roberts, Ruth E.; Fisher, Helen L.; Pariante, Carmine M.; Laurens, Kristin R.

    2014-01-01

    Summary Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9–12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11–14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size = −0.73, p = 0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness

  1. Cortisol awakening response and diurnal cortisol among children at elevated risk for schizophrenia: relationship to psychosocial stress and cognition.

    PubMed

    Cullen, Alexis E; Zunszain, Patricia A; Dickson, Hannah; Roberts, Ruth E; Fisher, Helen L; Pariante, Carmine M; Laurens, Kristin R

    2014-08-01

    Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9-12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11-14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size=-0.73, p=0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than

  2. Terrestrial Spaceflight Analogs: Antarctica

    NASA Technical Reports Server (NTRS)

    Crucian, Brian

    2013-01-01

    Alterations in immune cell distribution and function, circadian misalignment, stress and latent viral reactivation appear to persist during Antarctic winterover at Concordia Station. Some of these changes are similar to those observed in Astronauts, either during or immediately following spaceflight. Others are unique to the Concordia analog. Based on some initial immune data and environmental conditions, Concordia winterover may be an appropriate analog for some flight-associated immune system changes and mission stress effects. An ongoing smaller control study at Neumayer III will address the influence of the hypoxic variable. Changes were observed in the peripheral blood leukocyte distribution consistent with immune mobilization, and similar to those observed during spaceflight. Alterations in cytokine production profiles were observed during winterover that are distinct from those observed during spaceflight, but potentially consistent with those observed during persistent hypobaric hypoxia. The reactivation of latent herpesviruses was observed during overwinter/isolation, that is consistently associated with dysregulation in immune function.

  3. Analogy Construction versus Analogy Solution, and Their Influence on Transfer

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo; Ben-Amram, Einat

    2006-01-01

    This study compares transfer performed by subjects trained to solve verbal analogies, with transfer by subjects trained to construct them. The first group (n = 57) received instruction in a strategy to solve verbal analogies and the second group (n = 66) was trained in strategies for constructing such analogies. Before and after intervention, all…

  4. Analog storage integrated circuit

    DOEpatents

    Walker, J.T.; Larsen, R.S.; Shapiro, S.L.

    1989-03-07

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks. 6 figs.

  5. Antarctic analogs for Enceladus

    NASA Astrophysics Data System (ADS)

    Murray, A. E.; Andersen, D. T.; McKay, C. P.

    2014-12-01

    Enceladus is a new world for Astrobiology. The Cassini discovery of the icy plume emanating from the South Polar region indicates an active world, where detection of water, organics, sodium, and nano-particle silica in the plume strongly suggests that the source is a subsurface salty ocean reservoir. Recent gravity data from Cassini confirms the presence of a regional sea extending north to 50°S. An ocean habitat under a thick ice cover is perhaps a recurring theme in the Outer Solar System, but what makes Enceladus unique is that the plume jetting out into space is carrying samples of this ocean. Therefore, through the study of Enceladus' plumes we can gain new insights not only of a possible habitable world in the Solar Systems, but also about the formation and evolution of other icy-satellites. Cassini has been able to fly through this plume - effectively sampling the ocean. It is time to plan for future missions that do more detailed analyses, possibly return samples back to Earth and search for evidence of life. To help prepare for such missions, the need for earth-based analog environments is essential for logistical, methodological (life detection) and theoretical development. We have undertaken studies of two terrestrial environments that are close analogs to Enceladus' ocean: Lake Vida and Lake Untersee - two ice-sealed Antarctic lakes that represent physical, chemical and possibly biological analogs for Enceladus. By studying the diverse biology and physical and chemical constraints to life in these two unique lakes we will begin to understand the potential habitability of Enceladus and other icy moons, including possible sources of nutrients and energy, which together with liquid water are the key ingredients for life. Analog research such as this will also enable us to develop and test new strategies to search for evidence of life on Enceladus.

  6. Analog storage integrated circuit

    DOEpatents

    Walker, J. T.; Larsen, R. S.; Shapiro, S. L.

    1989-01-01

    A high speed data storage array is defined utilizing a unique cell design for high speed sampling of a rapidly changing signal. Each cell of the array includes two input gates between the signal input and a storage capacitor. The gates are controlled by a high speed row clock and low speed column clock so that the instantaneous analog value of the signal is only sampled and stored by each cell on coincidence of the two clocks.

  7. A modified and cost-effective method for hair cortisol analysis.

    PubMed

    Xiang, Lianbin; Sunesara, Imran; Rehm, Kristina E; Marshall, Gailen D

    2016-05-01

    Hair cortisol may hold potential as a biomarker for assessment of chronic psychological stress. We report a modified and cost-effective method to prepare hair samples for cortisol assay. Hair samples were ground using an inexpensive ball grinder - ULTRA-TURRAX tube drive. Cortisol was extracted from the powder under various defined conditions. The data showed that the optimal conditions for this method include cortisol extraction at room temperature and evaporation using a stream of room air. These findings should allow more widespread research using economical technology to validate the utility of hair cortisol as a biomarker for assessing chronic stress status. PMID:26767335

  8. Association of copeptin and cortisol in newly diagnosed multiple sclerosis patients.

    PubMed

    Baranowska-Bik, Agnieszka; Kochanowski, Jan; Uchman, Dorota; Litwiniuk, Anna; Kalisz, Malgorzata; Martynska, Lidia; Wolinska-Witort, Ewa; Baranowska, Boguslawa; Bik, Wojciech

    2015-05-15

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Obesity may increase the risk of developing MS. The aim of this study was to evaluate copeptin and cortisol plasma levels in newly diagnosed untreated MS patients and to determine whether copeptin and cortisol are related to the patients' clinical statuses. We report that copeptin and cortisol were higher in overweight/obese MS patients. Positive correlations were observed between the two parameters. We conclude that alterations of copeptin and cortisol levels in multiple sclerosis patients may be related to adiposity. An increase in cortisol may also be associated with copeptin secretion. PMID:25903724

  9. A Transiting Jupiter Analog

    NASA Astrophysics Data System (ADS)

    Kipping, D. M.; Torres, G.; Henze, C.; Teachey, A.; Isaacson, H.; Petigura, E.; Marcy, G. W.; Buchhave, L. A.; Chen, J.; Bryson, S. T.; Sandford, E.

    2016-04-01

    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of (0.91+/- 0.02) {R}{{J}}, a low orbital eccentricity ({0.06}-0.04+0.10), and an equilibrium temperature of (131+/- 3) K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323 ± 0.0006d), paving the way for follow-up of this K = 11.8 mag target.

  10. The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines

    PubMed Central

    2011-01-01

    analog FLLL32 has biologic activity against OSA cell lines through inhibition of STAT3 function and expression. Future work with FLLL32 will define the therapeutic potential of this compound in vivo. PMID:21443800

  11. Reduction of radiation-induced vascular nitrosative stress by the vitamin E analog, γ-tocotrienol: evidence of a role for tetrahydrobiopterin

    PubMed Central

    Berbee, Maaike; Fu, Qiang; Boerma, Marjan; Pathak, Rupak; Zhou, Daohong; Kumar, K. Sree; Hauer-Jensen, Martin

    2010-01-01

    Purpose The vitamin E analog γ-tocotrienol (GT3) is a powerful radioprotector. GT3 reduces post-radiation vascular peroxynitrite production, an effect dependent on inhibition of hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase. HMG-CoA reductase inhibitors mediate their pleiotropic effects via eNOS that requires the co-factor tetrahydrobiopterin (BH4). This study investigated the effects of radiation on BH4 bioavailability and of GT3 on BH4 metabolism. Methods and Materials Mice were exposed to 8.5 Gy total body irradiation (TBI). Lung BH4 and total biopterin concentrations were measured 0, 3.5, 7, 14 and 21 days after TBI using differential oxidation followed by HPLC. The effect of exogenous GT3 and BH4 treatment on post-radiation vascular oxidative stress and bone marrow colony-forming units (BM-CFU) were assessed in vivo. The effect of GT3 on endothelial cell apoptosis and endothelial expression of GTP cyclohydrolase 1 (GTPCH), GTPCH regulatory protein (GFRP), GFRP transcription, GFRP protein levels, and GFRP-CTPCH protein binding were determined in vitro. Results Compared to baseline levels, lung BH4 concentrations decreased by 24% at 3.5 days after TBI, an effect that was reversed by GT3. At 14 and 21 days after TBI, compensatory increases in BH4 (58% and 80%, respectively) were observed. Relative to vehicle-treated controls, both GT3 and BH4 supplementation reduced post-irradiation vascular peroxynitrite production at 3.5 days (by 66% and 33%, respectively), and BH4 resulted in a 68% increase in BM-CFU. GT3 ameliorated endothelial cell apoptosis and reduced endothelial GFRP protein levels and GFRP-GTPCH binding by decreasing transcription of the GFRP gene. Conclusions BH4 bioavailability is reduced in the early post-radiation phase. Exogenous administration of BH4 reduces post-irradiation vascular oxidative stress. GT3 potently reduces the expression of GFRP, one of the key regulatory proteins in the BH4 pathway, and may thus exert some of its

  12. Reduction of Radiation-Induced Vascular Nitrosative Stress by the Vitamin E Analog {gamma}-Tocotrienol: Evidence of a Role for Tetrahydrobiopterin

    SciTech Connect

    Berbee, Maaike; Fu Qiang; Boerma, Marjan; Pathak, Rupak; Zhou Daohong; Kumar, K. Sree; Hauer-Jensen, Martin

    2011-03-01

    Purpose: The vitamin E analog {gamma}-tocotrienol (GT3) is a powerful radioprotector. GT3 reduces postradiation vascular peroxynitrite production, an effect dependent on inhibition of hydroxy-methylglutaryl-coenzyme A reductase. Hydroxy-methylglutaryl-coenzyme A reductase inhibitors mediate their pleiotropic effects via endothelial nitric oxide synthase that requires the cofactor tetrahydrobiopterin (BH4). This study investigated the effects of radiation on BH4 bioavailability and of GT3 on BH4 metabolism. Methods and Materials: Mice were exposed to 8.5 Gy of total body irradiation (TBI). Lung BH4 and total biopterin concentrations were measured 0, 3.5, 7, 14, and 21 days after TBI by use of differential oxidation followed by high-performance liquid chromatography. The effect of exogenous GT3 and BH4 treatment on postradiation vascular oxidative stress and bone marrow colony-forming units were assessed in vivo. The effect of GT3 on endothelial cell apoptosis and endothelial expression of guanosine triphosphate (GTP) cyclohydrolase 1 (GTPCH), GTPCH feedback regulatory protein (GFRP), GFRP transcription, GFRP protein levels, and GFRP-GTPCH protein binding was determined in vitro. Results: Compared with baseline levels, lung BH4 concentrations decreased by 24% at 3.5 days after TBI, an effect that was reversed by GT3. At 14 and 21 days after TBI, compensatory increases in BH4 (58% and 80%, respectively) were observed. Relative to vehicle-treated controls, both GT3 and BH4 supplementation reduced postirradiation vascular peroxynitrite production at 3.5 days (by 66% and 33%, respectively), and BH4 resulted in a 68% increase in bone marrow colony-forming units. GT3 ameliorated endothelial cell apoptosis and reduced endothelial GFRP protein levels and GFRP-GTPCH binding by decreasing transcription of the GFRP gene. Conclusions: BH4 bioavailability is reduced in the early postradiation phase. Exogenous administration of BH4 reduces postirradiation vascular oxidative stress

  13. NaturAnalogs for the Unsaturated Zone

    SciTech Connect

    A. Simmons; A. Unger; M. Murrell

    2000-03-08

    The purpose of this Analysis/Model Report (AMR) is to document natural and anthropogenic (human-induced) analog sites and processes that are applicable to flow and transport processes expected to occur at the potential Yucca Mountain repository in order to build increased confidence in modeling processes of Unsaturated Zone (UZ) flow and transport. This AMR was prepared in accordance with ''AMR Development Plan for U0135, Natural Analogs for the UZ'' (CRWMS 1999a). Knowledge from analog sites and processes is used as corroborating information to test and build confidence in flow and transport models of Yucca Mountain, Nevada. This AMR supports the Unsaturated Zone (UZ) Flow and Transport Process Model Report (PMR) and the Yucca Mountain Site Description. The objectives of this AMR are to test and build confidence in the representation of UZ processes in numerical models utilized in the UZ Flow and Transport Model. This is accomplished by: (1) applying data from Boxy Canyon, Idaho in simulations of UZ flow using the same methodologies incorporated in the Yucca Mountain UZ Flow and Transport Model to assess the fracture-matrix interaction conceptual model; (2) Providing a preliminary basis for analysis of radionuclide transport at Pena Blanca, Mexico as an analog of radionuclide transport at Yucca Mountain; and (3) Synthesizing existing information from natural analog studies to provide corroborating evidence for representation of ambient and thermally coupled UZ flow and transport processes in the UZ Model.

  14. Free cortisol awakening responses are influenced by awakening time.

    PubMed

    Federenko, Ilona; Wüst, Stefan; Hellhammer, Dirk H; Dechoux, Ralph; Kumsta, Robert; Kirschbaum, Clemens

    2004-02-01

    Psychobiological investigations on the hypothalamus-pituitary-adrenal (HPA) axis depend on markers that adequately describe the activity of this system. There is evidence that the free cortisol response to awakening, proposed as a marker for the HPA axis, can be influenced by time of awakening. To further investigate this possible confounder, 24 shift working nurses and 31 female students on a regular sleep-wake cycle collected saliva samples 0, 30, 45 and 60 minutes after awakening. Nurses were investigated on the first and second day of their early (awakening: 04:00-05:30 h), late (awakening: 06:00-09:00 h), and night shift (awakening: 11:00-14:00 h), respectively. Students were studied after taking a short nap on two consecutive weekdays (awakening: 18:45-20:30 h). Mean cortisol levels after awakening increased significantly under all three shift conditions (p<0.01), but decreased in the student sample (p<.05). Within the three shift conditions, cortisol responses following waking in the early shift were more pronounced than in late (p<.01) and night shift (p<.05). The present study shows that in a sample with a large range of awakening times, an impact of this variable on the cortisol awakening response can be observed. The data furthermore strongly suggest that waking up per se is insufficient for adrenocortical stimulation. PMID:14604599

  15. Infant Emotional and Cortisol Responses to Goal Blockage

    ERIC Educational Resources Information Center

    Lewis, Michael; Ramsay, Douglas

    2005-01-01

    This study examined the relation of infant emotional responses of anger and sadness to cortisol response in 2 goal blockage situations. One goal blockage with 4-month-old infants (N=56) involved a contingency learning procedure where infants' learned response was no longer effective in reinstating an event. The other goal blockage with 6-month-old…

  16. Contextual control over expression of fear is affected by cortisol

    PubMed Central

    van Ast, Vanessa A.; Vervliet, Bram; Kindt, Merel

    2012-01-01

    At the core of anxiety disorders is the inability to use contextual information to modulate behavioral responses to potentially threatening events. Models of the pathogenesis of anxiety disorders incorporate stress and concomitant stress hormones as important vulnerability factors, while others emphasize sex as an important factor. However, translational basic research has not yet investigated the effects of stress hormones and sex on the ability to use contextual information to modulate responses to threat. Therefore, the purpose of the present study was threefold: first, we aimed at developing an experimental paradigm specifically capable of capturing contextual modulation of the expression of fear. Second, we tested whether cortisol would alter the contextualization of fear expression. Third, we aimed at assessing whether alterations in contextualization due to cortisol were different for men and women. Healthy participants (n = 42) received placebo or hydrocortisone (20 mg) prior to undergoing a newly developed differential contextual fear-conditioning paradigm. The results indicated that people rapidly acquire differential contextual modulation of the expression of fear, as measured by fear potentiated startle (FPS) and skin conductance responses (SCR). In addition, cortisol impaired the contextualization of fear expression leading to increased fear generalization on FPS data in women. The opposite pattern was found in men. Finally, as assessed by SCR, cortisol impaired differential conditioning in men. The results are in line with models suggesting heightened vulnerability in women for developing anxiety disorders after stressful events. PMID:23087629

  17. Intimate Partner Violence Exposure, Salivary Cortisol, and Childhood Asthma

    ERIC Educational Resources Information Center

    Bair-Merritt, Megan H.; Johnson, Sara B.; Okelo, Sande; Page, Gayle

    2012-01-01

    Parents were given supplies to collect 3 child salivary cortisol samples (awakening, 30-min after awakening, bedtime) at home on a typical day, and return them via mail. Medical records also were abstracted. Results: Fifty-three percent (n = 29) returned child salivary samples. Families who returned samples typically returned them within 2 weeks,…

  18. The Cortisol Awakening Response and Resilience in Elite Swimmers.

    PubMed

    Meggs, J; Golby, J; Mallett, C J; Gucciardi, D F; Polman, R C J

    2016-02-01

    The sports environment is stress-eliciting in that it encapsulates perceived uncontrollability, unpredictability and requires ego-involvement. The HPA axis has been shown (indicated by cortisol release) to respond to anticipated sports competition up to a week prior to the event. Research also alludes to the importance of individual differences, such as optimism and trait perfectionism, in moderating the impact of cortisol upon performance. In total, 41 (male n=27) national (n=38) and international (n=3) swimmers were recruited from northeast England and Australia. Swimmers completed a measure of resilience and also provided buccal saliva swabs, from which total cortisol release prior to and during the event was calculated. Findings revealed that resilience significantly predicted performance and the influence of AUC (cortisol release) upon performance was moderated by resilience. These findings suggest that resilience can influence athletic performance either directly or indirectly, through appraisal (i. e., interpretation of the stressor to be facilitative and non-threatening). PMID:26509364

  19. The cortisol awakening response (CAR): facts and future directions.

    PubMed

    Fries, Eva; Dettenborn, Lucia; Kirschbaum, Clemens

    2009-04-01

    In humans, the secretion of cortisol from the adrenal glands follows a diurnal cycle with a profound increase after awakening. This increase after awakening, a phenomenon termed the cortisol awakening response (CAR), appears to be a distinct feature of the hypothalamus-pituitary-adrenal (HPA) axis, superimposing the circadian rhythmicity of cortisol secretion. Several studies point towards an important role of the hippocampus and, additionally, other brain structures (e. g. amygdala, prefrontal cortex, suprachiasmatic nucleus) in the regulation of the CAR. There is increasing knowledge that the CAR is influenced by a variety of factors such as gender, health status, and health behavior or stress perception. However, the exact function of the profound cortisol increase after awakening is still not clarified. We hypothesize that the anticipation of the upcoming day is of major relevance for the magnitude of the CAR. The present paper reviews the current knowledge on the neural regulation of the CAR and factors influencing this phenomenon and considerations are addressed concerning the exact function of the CAR. PMID:18854200

  20. Decreased Cortisol and Pain in Breast Cancer: Biofield Therapy Potential

    PubMed Central

    Running, Alice

    2015-01-01

    Breast cancer is one of the leading causes of cancer death among women of all races. Pain is a common symptom associated with cancer; 75–90% of cancer patients experience pain during their illness and up to 50% of that pain is undertreated. Unrelieved pain leads to increased levels of the stress hormone cortisol. The purpose of this study was to examine the impact of bioenergy on fecal cortisol levels for mice injected with murine mammary carcinoma 4T1 in two separate pilot studies. Using a multiple experimental group design, six to eight week old female BALB/c mice were injected with tumor and randomly assigned, in groups of 10, to daily treatment, every other day treatment, and no treatment groups. Five days after tumor cell injection, bioenergy interventions were begun for a period of ten consecutive days. Fecal samples were collected for each study and ELISA analysis was conducted at the end of both studies. For both studies, cortisol levels were decreased in the every other day treatment groups but remained high in the no treatment groups. Future studies utilizing bioenergy therapies on cortisol levels in a murine breast cancer model can begin to describe pain outcomes and therapeutic dose. PMID:26170887

  1. Cortisol modifies extinction learning of recently acquired fear in men.

    PubMed

    Merz, Christian Josef; Hermann, Andrea; Stark, Rudolf; Wolf, Oliver Tobias

    2014-09-01

    Exposure therapy builds on the mechanism of fear extinction leading to decreased fear responses. How the stress hormone cortisol affects brain regions involved in fear extinction in humans is unknown. For this reason, we tested 32 men randomly assigned to receive either 30 mg hydrocortisone or placebo 45 min before fear extinction. In fear acquisition, a picture of a geometrical figure was either partially paired (conditioned stimulus; CS+) or not paired (CS-) with an electrical stimulation (unconditioned stimulus; UCS). In fear extinction, each CS was presented again, but no UCS occurred. Cortisol increased conditioned skin conductance responses in early and late extinction. In early extinction, higher activation towards the CS- than to the CS+ was found in the amygdala, hippocampus and posterior parahippocampal gyrus. This pattern might be associated with the establishment of a new memory trace. In late extinction, the placebo compared with the cortisol group displayed enhanced CS+/CS- differentiation in the amygdala, medial frontal cortex and nucleus accumbens. A change from early deactivation to late activation of the extinction circuit as seen in the placebo group seems to be needed to enhance extinction and to reduce fear. Cortisol appears to interfere with this process thereby impairing extinction of recently acquired conditioned fear. PMID:23945999

  2. Salivary Cortisol, Salivary Alpha Amylase, and the Dental Anxiety Scale

    PubMed Central

    Sadi, Hana; Finkelman, Matthew; Rosenberg, Morton

    2013-01-01

    The aim of this study was to investigate the correlation between dental anxiety, salivary cortisol, and salivary alpha amylase (sAA) levels. Furthermore, the aim was to look into individual differences such as age, race, gender, any existing pain, or traumatic dental experience and their effect on dental anxiety. This study followed a cross-sectional design and included a convenience sample of 46. Every patient was asked to complete the Dental Anxiety Scale (DAS) and a basic demographic/dental history questionnaire. A saliva sample, utilizing the method of passive drooling, was then collected in 2-mL cryovials. Samples were analyzed for salivary cortisol and sAA levels by Salimetrics. Significant associations were observed between DAS scores and presence of pain and history of traumatic dental experience. However, no significant correlations were observed between DAS, cortisol, and sAA levels. Our study reconfirms that dental anxiety is associated with presence of pain and a history of traumatic dental experience. On the other hand, our study was the first to our knowledge to test the correlation between the DAS and sAA; nevertheless, our results failed to show any significant correlation between dental anxiety, cortisol, and sAA levels. PMID:23763559

  3. Cortisol Levels and Children's Orientation in Day Care

    ERIC Educational Resources Information Center

    Reunamo, Jyrki; Sajaniemi, Nina; Suhonen, Eira; Kontu, Elina

    2012-01-01

    Children's stress in day care is related to the stressful qualities of the environment and to children's orientations in that environment. The study involved 55 children in five day centres in Finland. Baseline saliva samples for measuring cortisol (stress) levels were collected five times during the day. Children were interviewed to measure their…

  4. Colloidal gold probe based rapid immunochromatographic strip assay for cortisol.

    PubMed

    Nara, Seema; Tripathi, Vinay; Singh, Harpal; Shrivastav, Tulsidas G

    2010-12-01

    A rapid and semi-quantitative immunochromatographic strip (ICS) test for cortisol analysis in serum was developed. The test strip was based on a competitive assay format. Colloidal gold nanoparticles were synthesized and coupled with cortisol-3-carboxymethyloxime-adipic acid dihydrazide-bovine serum albumin (F-3-CMO-ADH-BSA) antigen to directly compete with cortisol in human serum samples. F-3-CMO-ADH-BSA-gold label and uncoupled colloidal gold nanoparticles were appropriately characterized using UV-vis spectroscopy, transmission electron microscopy and atomic force microscopy. Anticortisol antibody raised against F-3-CMO-BSA immunogen in New Zealand white rabbits was coated on the NC membrane as test line. Anti-BSA antibody was used as control line. The lower detection limit of the ICS test was 30 ngmL(-1) with visual detection and was completed in 10 min. About 30 human serum samples were also analyzed by the developed strip test and their range of cortisol concentration was established. The developed ICS test is rapid, economic and user friendly. PMID:21056716

  5. Decreased Cortisol and Pain in Breast Cancer: Biofield Therapy Potential.

    PubMed

    Running, Alice

    2015-01-01

    Breast cancer is one of the leading causes of cancer death among women of all races. Pain is a common symptom associated with cancer; 75-90% of cancer patients experience pain during their illness and up to 50% of that pain is undertreated. Unrelieved pain leads to increased levels of the stress hormone cortisol. The purpose of this study was to examine the impact of bioenergy on fecal cortisol levels for mice injected with murine mammary carcinoma 4T1 in two separate pilot studies. Using a multiple experimental group design, six to eight week old female BALB/c mice were injected with tumor and randomly assigned, in groups of 10, to daily treatment, every other day treatment, and no treatment groups. Five days after tumor cell injection, bioenergy interventions were begun for a period of ten consecutive days. Fecal samples were collected for each study and ELISA analysis was conducted at the end of both studies. For both studies, cortisol levels were decreased in the every other day treatment groups but remained high in the no treatment groups. Future studies utilizing bioenergy therapies on cortisol levels in a murine breast cancer model can begin to describe pain outcomes and therapeutic dose. PMID:26170887

  6. Evaluation of hair cortisol in beef cattle of divergent temperaments

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this research project was to evaluate the relationships among hair and serum cortisol concentrations and cattle disposition. Spring born (n = 101) crossbred beef heifers (7 to 8 mo. of age) were evaluated for temperament preweaning and at weaning by pen score (PS; 1 = calm and 5 = e...

  7. Sleep problems predict cortisol reactivity to stress in urban adolescents.

    PubMed

    Mrug, Sylvie; Tyson, Anna; Turan, Bulent; Granger, Douglas A

    2016-03-01

    This study examined the role of sleep problems and sleep duration on stress-related HPA axis reactivity among urban, low income adolescents. A total of 84 adolescents (M age 13.36 years; 50% male; 95% African American) and their parents provided information on adolescents' sleep problems and sleep quantity. Adolescents completed a standardized social stress test in the laboratory (the Trier Social Stress Test; TSST). Saliva samples collected before and after the TSST yielded measures of cortisol pre-test, 15 min post-test, and 55 min post-test, as well as overall cortisol secretion and its increase (AUCG and AUCI). More sleep problems and longer sleep duration predicted higher cortisol reactivity to the TSST, particularly among females. Self-reports of sleep were more consistently related to stress-related cortisol reactivity than parent reports. Sleep problems and longer sleep duration may place adolescents at risk for HPA axis hyper-reactivity to stress, contributing to academic, behavioral and health problems. PMID:26679739

  8. A stochastic differential equation model of diurnal cortisol patterns

    NASA Technical Reports Server (NTRS)

    Brown, E. N.; Meehan, P. M.; Dempster, A. P.

    2001-01-01

    Circadian modulation of episodic bursts is recognized as the normal physiological pattern of diurnal variation in plasma cortisol levels. The primary physiological factors underlying these diurnal patterns are the ultradian timing of secretory events, circadian modulation of the amplitude of secretory events, infusion of the hormone from the adrenal gland into the plasma, and clearance of the hormone from the plasma by the liver. Each measured plasma cortisol level has an error arising from the cortisol immunoassay. We demonstrate that all of these three physiological principles can be succinctly summarized in a single stochastic differential equation plus measurement error model and show that physiologically consistent ranges of the model parameters can be determined from published reports. We summarize the model parameters in terms of the multivariate Gaussian probability density and establish the plausibility of the model with a series of simulation studies. Our framework makes possible a sensitivity analysis in which all model parameters are allowed to vary simultaneously. The model offers an approach for simultaneously representing cortisol's ultradian, circadian, and kinetic properties. Our modeling paradigm provides a framework for simulation studies and data analysis that should be readily adaptable to the analysis of other endocrine hormone systems.

  9. Development of a specific radioimmunoassay for cortisol 17-butyrate

    SciTech Connect

    Smith, G.N.; Lee, Y.F.; Bu'Lock, D.E.; August, P.; Anderson, D.C.

    1983-07-01

    We describe the development and validation of an assay for cortisol 17-butyrate in blood in which there is no significant cross reaction with endogenous corticosteroids at levels encountered normally in man. Preliminary data on blood levels of the drug in absorption studies are presented.

  10. Cortisol decreases and serotonin and dopamine increase following massage therapy.

    PubMed

    Field, Tiffany; Hernandez-Reif, Maria; Diego, Miguel; Schanberg, Saul; Kuhn, Cynthia

    2005-10-01

    In this article the positive effects of massage therapy on biochemistry are reviewed including decreased levels of cortisol and increased levels of serotonin and dopamine. The research reviewed includes studies on depression (including sex abuse and eating disorder studies), pain syndrome studies, research on auto-immune conditions (including asthma and chronic fatigue), immune studies (including HIV and breast cancer), and studies on the reduction of stress on the job, the stress of aging, and pregnancy stress. In studies in which cortisol was assayed either in saliva or in urine, significant decreases were noted in cortisol levels (averaging decreases 31%). In studies in which the activating neurotransmitters (serotonin and dopamine) were assayed in urine, an average increase of 28% was noted for serotonin and an average increase of 31% was noted for dopamine. These studies combined suggest the stress-alleviating effects (decreased cortisol) and the activating effects (increased serotonin and dopamine) of massage therapy on a variety of medical conditions and stressful experiences. PMID:16162447

  11. A stochastic differential equation model of diurnal cortisol patterns.

    PubMed

    Brown, E N; Meehan, P M; Dempster, A P

    2001-03-01

    Circadian modulation of episodic bursts is recognized as the normal physiological pattern of diurnal variation in plasma cortisol levels. The primary physiological factors underlying these diurnal patterns are the ultradian timing of secretory events, circadian modulation of the amplitude of secretory events, infusion of the hormone from the adrenal gland into the plasma, and clearance of the hormone from the plasma by the liver. Each measured plasma cortisol level has an error arising from the cortisol immunoassay. We demonstrate that all of these three physiological principles can be succinctly summarized in a single stochastic differential equation plus measurement error model and show that physiologically consistent ranges of the model parameters can be determined from published reports. We summarize the model parameters in terms of the multivariate Gaussian probability density and establish the plausibility of the model with a series of simulation studies. Our framework makes possible a sensitivity analysis in which all model parameters are allowed to vary simultaneously. The model offers an approach for simultaneously representing cortisol's ultradian, circadian, and kinetic properties. Our modeling paradigm provides a framework for simulation studies and data analysis that should be readily adaptable to the analysis of other endocrine hormone systems. PMID:11171600

  12. Shiftwork and Diurnal Salivary Cortisol Patterns Among Police Officers

    PubMed Central

    Charles, Luenda E.; Fekedulegn, Desta; Burchfiel, Cecil M.; Hartley, Tara A.; Andrew, Michael E.; Violanti, John M.; Miller, Diane B.

    2016-01-01

    Objective To investigate associations between shiftwork and diurnal salivary cortisol among 319 police officers (77.7% men) Methods Information on shiftwork was obtained from the City of Buffalo, NY electronic payroll records. Saliva was collected using Salivettes at seven time points and analyzed for free cortisol concentrations (nmol/L) using a chemiluminescence immunoassay. Mean slopes and areas under the curve were compared across shift schedule using analysis of variance (ANOVA)/analysis of covariance (ANCOVA). Results Officers working primarily on the night shift had a significantly shallower slope. Mean slope (nmol/L/minutes) of the cortisol curve varied significantly across shifts (day: −0.00332 ± 0.00017, afternoon: −0.00313 ± 0.00018, night: −0.00257 ± 0.0002); adjusted P = 0.023. Conclusions Our results suggest that night shiftwork is a work-place factor that may alter the response of the hypothalamic–pituitary–adrenal (HPA) axis to the circadian cues responsible for the pattern of the diurnal cortisol curve. PMID:27129020

  13. The Cortisol Paradox of Trauma-Related Disorders: Lower Phasic Responses but Higher Tonic Levels of Cortisol Are Associated with Sexual Abuse in Childhood

    PubMed Central

    Schalinski, Inga; Elbert, Thomas; Steudte-Schmiedgen, Susann; Kirschbaum, Clemens

    2015-01-01

    Objectives Inconsistent findings exist for the activity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with stress related disorders. Recent studies point towards early life stress as a potential modulator. Methods We investigated the impact of childhood sexual abuse on phasic (saliva cortisol reactivity) and tonic (hair cortisol) regulation. Furthermore, we assessed predictors on cortisol accumulation in hair. Women (N = 43) with stress-related disorders underwent a standardized assessment of idiographic adverse and traumatic experiences and psychopathology, while measuring salivary cortisol and, heart rate and blood pressure. Results Comparing women with and without childhood sexual abuse revealed lower rates of responders and distinct levels of salivary cortisol to the interview in conjunction with a lower heart rate for the abused group. Childhood adversities, traumatic experiences, and depression contributed to higher hair cortisol levels. Conclusions Our finding of lower response rate and distinct salivary cortisol pattern in individuals with childhood sexual abuse compared to individuals without early sexual abuse supports the role of environmental programming for the HPA axis. Both, childhood adversities and traumatic stress emerge as crucial factors for long-term cortisol secretion. Lower or suppressed phasic cortisol responses to trauma-related stimuli may therefore be associated with higher tonic values. Thus, early exposure to adversities may result in a biological distinct phenotype in adult patients with stress-related disorders. PMID:26317554

  14. Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress.

    PubMed

    Wosu, Adaeze C; Valdimarsdóttir, Unnur; Shields, Alexandra E; Williams, David R; Williams, Michelle A

    2013-12-01

    Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis, and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, "cortisol," "hair," "confounders," "chronic," "stress," and "correlates." Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., post-traumatic stress disorder), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome), and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear not to be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies. PMID:24184029

  15. Concordance of mother-daughter diurnal cortisol production: Understanding the intergenerational transmission of risk for depression.

    PubMed

    LeMoult, Joelle; Chen, Michael C; Foland-Ross, Lara C; Burley, Hannah W; Gotlib, Ian H

    2015-05-01

    A growing body of research is demonstrating concordance between mother and child diurnal cortisol production. In the context of maternal history of depression, intergenerational concordance of cortisol production could contribute to hypercortisolemia in children of depressed mothers, which has been shown to increase risk for MDD. The current study is the first to examine concordance in diurnal cortisol production between mothers with a history of depression and their never-depressed, but high-risk, children. We collected salivary cortisol across 2 days from mothers with (remitted; RMD) and without (CTL) a history of recurrent episodes of depression and their never-depressed daughters. As expected, RMD mothers and their daughters both exhibited higher cortisol production than did their CTL counterparts. Moreover, both across and within groups, mothers' and daughters' cortisol production were directly coupled. These findings suggest that there is an intergenerational concordance in cortisol dysregulation that may contribute to hypercortisolemia in girls at familial risk for depression. PMID:25862380

  16. Concordance of Mother-Daughter Diurnal Cortisol Production: Understanding the Intergenerational Transmission of Risk for Depression

    PubMed Central

    LeMoult, Joelle; Chen, Michael C.; Foland-Ross, Lara C.; Burley, Hannah W.; Gotlib, Ian H.

    2015-01-01

    A growing body of research is demonstrating concordance between mother and child diurnal cortisol production. In the context of maternal history of depression, intergenerational concordance of cortisol production could contribute to hypercortisolemia in children of depressed mothers, which has been shown to increase risk for MDD. The current study is the first to examine concordance in diurnal cortisol production between mothers with a history of depression and their never-depressed, but high-risk, children. We collected salivary cortisol across two days from mothers with (remitted; RMD) and without (CTL) a history of recurrent episodes of depression and their never-depressed daughters. As expected, RMD mothers and their daughters both exhibited higher cortisol production than did their CTL counterparts. Moreover, both across and within groups, mothers’ and daughters’ cortisol production was directly coupled. These findings suggest that there is an intergenerational concordance in cortisol dysregulation that may contribute to hypercortisolemia in girls at familial risk for depression. PMID:25862380

  17. Social Stress Increases Cortisol and Hampers Attention in Adolescents with Excess Weight

    PubMed Central

    Verdejo-Garcia, Antonio; Moreno-Padilla, Maria; Garcia-Rios, M. Carmen; Lopez-Torrecillas, Francisca; Delgado-Rico, Elena; Schmidt-Rio-Valle, Jacqueline; Fernandez-Serrano, Maria J.

    2015-01-01

    Objective To experimentally examine if adolescents with excess weight are more sensitive to social stress and hence more sensitive to harmful effects of stress in cognition. Design and Methods We conducted an experimental study in 84 adolescents aged 12 to 18 years old classified in two groups based on age adjusted Body Mass Index percentile: Normal weight (n=42) and Excess weight (n=42). Both groups were exposed to social stress as induced by the virtual reality version of the Trier Social Stress Task --participants were requested to give a public speech about positive and negative aspects of their personalities in front of a virtual audience. The outcome measures were salivary cortisol levels and performance in cognitive tests before and after the social stressor. Cognitive tests included the CANTAB Rapid Visual Processing Test (measuring attention response latency and discriminability) and the Iowa Gambling Task (measuring decision-making). Results Adolescents with excess weight compared to healthy weight controls displayed increased cortisol response and less improvement of attentional performance after the social stressor. Decision-making performance decreased after the social stressor in both groups. Conclusion Adolescents who are overweight or obese have increased sensitivity to social stress, which detrimentally impacts attentional skills. PMID:25898204

  18. Effects of Butafosfan on salivary cortisol and behavioral response to social stress in piglets.

    PubMed

    Van Der Staay, F J; De Groot, J; Van Reenen, C G; Hoving-Bolink, A H; Schuurman, T; Schmidt, B H

    2007-10-01

    We assessed the efficacy of Butafosfan, a component of Catosal, in the metaphylactic treatment of stress in pigs. Four 6-week-old female littermates were taken from 12 litters. They were confronted with a pig from a different litter for 2 h. There were 24 pairs, each consisting of confronting two unfamiliar pigs in a new pen. This housing of unfamiliar pigs provides a good, but simple, model of the psychosocial stress that pigs experience when housed in large groups on pig farms. Immediately before being housed with an unfamiliar pig, 12 pairs of pigs were injected subcutaneously with Catosal at a dose equivalent to 20 mg Butafosfan per kg body weight; the other 12 pairs received the control solution containing all ingredients of Catosal except Butafosfan. The frequency and duration of aggressive behavior and the salivary cortisol response were measured during the first 2 h of the encounter. No adverse effects associated with Catosal were observed. Subcutaneous injection of Catosal reduced the stress-induced salivary cortisol response and the frequency of aggressive behavior evoked by the social stress of housing two unfamiliar pigs together. PMID:17803732

  19. A vitamin D3 analog induces a G1-phase arrest in CaCo-2 cells by inhibiting cdk2 and cdk6: roles of cyclin E, p21Waf1, and p27Kip1.

    PubMed

    Scaglione-Sewell, B A; Bissonnette, M; Skarosi, S; Abraham, C; Brasitus, T A

    2000-11-01

    Previous studies by our laboratory have shown that a noncalcemic fluorinated analog of 1alpha,25-dihydroxyvitamin D3, 1alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholcal ciferol (F6-D3), significantly reduced the frequency of colonic adenomas and completely abolished the development of colonic adenocarcinomas in rats treated with azoxymethane. The mechanisms involved in this analog's chemopreventive actions, however, remain unclear. In the present study, we now show that although both 1alpha,25-dihydroxyvitamin D3 and F6-D3 inhibited the proliferation of CaCo-2 cells, a human colonic adenocarcinoma cell line, by increasing their doubling times, only F6-D3 caused an arrest of these cells in the G1 phase of their cell cycle. This arrest was accompanied by an increase in the expression of the cyclin-dependent kinase (cdk) inhibitor proteins, p2Waf1 and p27Kip1, which served to decrease the activity of cyclin-dependent kinase 2 and cyclin-dependent kinase 6, whereas the expression and phosphorylation of pRB were unchanged. In contrast to the increased expression of these cdk inhibitors, the expression of cyclin E was decreased, which further inhibited the activity of cyclin-dependent kinase 2. Collectively, the inhibition of these cyclin-dependent kinases served to arrest the CaCo-2 cells, independent of changes in pRB. Furthermore, antibody neutralization studies suggest that transforming growth factor-beta may mediate the coassociations between cdk2 and p27Kip1 and cyclin E induced by F6-D3. These data indicate that cell cycle arrest may, at least in part, underlie the chemopreventive actions of F6-D3 observed in the azoxymethane model of colon cancer. Furthermore, if the antiproliferative action observed in CaCo-2 cells also occurs in human colonic epithelium, F6-D3 may have chemopreventive potential against human colon cancer, as well. PMID:11089522

  20. Mercury and cortisol in Western Hudson Bay polar bear hair.

    PubMed

    Bechshoft, T; Derocher, A E; Richardson, E; Mislan, P; Lunn, N J; Sonne, C; Dietz, R; Janz, D M; St Louis, V L

    2015-08-01

    Non-invasive methods of assessing animal health and life history are becoming increasingly popular in wildlife research; hair samples from polar bears (Ursus maritimus), are being used to study an ever broader range of anthropogenic and endocrine compounds. A number of contaminants are known to disrupt endocrine function in polar bears. However, the relationship between mercury and cortisol remains unknown, although mercury is an endocrine disruptor in other species. Here, we examine the relationship between concentrations of cortisol and total mercury (THg) analyzed in guard hair from 378 polar bears (184 females, 194 males) sampled in Western Hudson Bay, 2004-2012. The difference in mean cortisol concentration between female (0.8 ± 0.6 pg/mg) and male (0.7 ± 0.5 pg/mg) polar bears bordered on significance (p = 0.054). However, mean mercury concentration was significantly greater (p = 0.009) in females (4.7 ± 1.4 μg/g) than males (4.3 ± 1.2 μg/g). Hair cortisol in males was significantly influenced by mercury, age, and fatness, as well as interactions between mercury and year, mercury and fatness, and year and fatness (all: p < 0.03) (multiple regression analysis, whole model: r(2) = 0.14, F(7,185) = 4.43, p = 0.0001). Fatness was the only significant variable in the multiple regression analysis for females (r(2) = 0.06, F(1,182) = 13.0, p = 0.0004). In conclusion, a significant, but complex, relationship was found between mercury and cortisol concentrations in hair from male, but not female, polar bears. PMID:26044932

  1. Determinants of cortisol awakening responses to naps and nighttime sleep.

    PubMed

    Devine, Jaime K; Wolf, Jutta M

    2016-01-01

    The cortisol awakening response (CAR) is a phenomenon describing the sharp increase in basal cortisol levels shortly after waking from sleep. While extensively studied, little is known about the role of sleep architecture contributing to CAR. Furthermore, the potential for CAR after a shorter bout of sleep--a nap--has not been directly investigated. The current studies thus aimed at assessed sleep duration, time of day, and sleep architecture as potential determinants of the cortisol awakening response. Saliva samples were collected during the first hour (0, 30, 45, 60 min) following several EEG-monitored laboratory sleep conditions. Those included afternoon naps wherein 17 participants (4 men; ages 18-26) napped for 50 min and 24 participants (11 men; ages 18-24) napped for 90 min. Furthermore, 20 participants (10 men; ages 18-35) visited the lab twice and in addition to staying overnight, napped 90 min in the morning either under placebo conditions or pharmacologically-manipulated sleep conditions (5mg Zolpidem). Cortisol increases were observed in response to each sleep condition except to 50-min afternoon naps. Furthermore, CARs were predicted by Stage 2 sleep when following nighttime sleep (r=.46, p=.04) and by Stage 1 sleep when following placebo morning naps (r=.54, p=.01). The current study established cortisol awakening responses to naps and implicates sleep duration and architecture in the generation of CAR to both napping and nighttime sleep. Assessing CAR in conjunction with the specific type of sleep may thus contribute to our understanding of mechanisms underlying positive and negative health effects of napping. PMID:26441231

  2. High levels of plasma cortisol and impaired hypoosmoregulation in a mutant medaka deficient in P450c17I.

    PubMed

    Takahashi, Hideya; Sato, Tadashi; Ikeuchi, Toshitaka; Saito, Kazuhiro; Sakaizumi, Mitsuru; Sakamoto, Tatsuya

    2016-07-15

    scl is a spontaneous medaka mutant deficient in P450c17I, which is required for production of sex steroids, but not of cortisol, the major role of which is osmoregulation in teleost fish. The scl mutant provides a new model to study the functions of these hormones. We first found that fish homozygous for this mutation have plasma cortisol constitutively at a high physiological level (1000 nM). Since we previously showed that this level reversed the seawater-type differentiation of the medaka gastrointestinal tract, hypoosmoregulation of the scl mutant was analyzed. Muscle water contents in freshwater were normal in scl homozygotes, but the contents were lower than those of the wild type (WT) after seawater transfer. There were no differences in gill mRNA levels of corticosteroid receptors or ion transporters between scl homozygotes and WT. In the intestine, expression of glucocorticoid receptors and Na(+)/K(+)/2Cl(-) cotransporter were induced in WT during seawater acclimation, but not in scl homozygotes. The high plasma cortisol may prevent hypoosmoregulation by inhibition of increased intestinal water absorption, essentially by the Na(+)/K(+)/2Cl(-) cotransporter, in seawater. PMID:27107936

  3. Effects of xylazine-ketamine anesthesia on plasma levels of cortisol and vital signs during laparotomy in dogs

    PubMed Central

    Naddaf, H.; Varzi, H. Najafzade; Sabiza, S.; Falah, H.

    2014-01-01

    This study was designed to evaluate effects of xylazine-ketamine anesthesia on plasma levels of cortisol and vital signs during and after laparotomy in dogs. Eight clinically healthy, adult male dogs, weighing 20 kg were used. All dogs were initially sedated by acepromazine. Thirty minutes later, ketamine plus xylazine was used to induce anesthesia. Surgical incision of laparotomy was done. After a 5 min manipulation of the abdominal organs, the incision was sutured. Vital signs including heart rate, respiratory rate and rectal temperature (RT) were recorded at the times of -30: premedication, 0: induction and Surgical incision, 30: End of surgery, 60, 90 and 120 min. Blood was sampled at the above mentioned times and analyzed using a commercial ELISA kit for cortisol. A significant decreasing trend in RT was observed during the studied times. No significant changes were observed in heart rate and respiratory rate (p>0.05), except at the time of 60 respiratory rate significantly decreased when compared to the time of 90 (p=0.026) and 120 (p=0.041). A non-significant but increasing trend in plasma levels of cortisol was observed. PMID:26623345

  4. Wool cortisol is a better indicator of stress than blood cortisol in ewes exposed to heat stress and water restriction.

    PubMed

    Ghassemi Nejad, J; Lohakare, J D; Son, J K; Kwon, E G; West, J W; Sung, K I

    2014-01-01

    This study investigated the effect of water restriction on wool and blood cortisol concentrations and water consumption patterns in heat-stressed sheep. Nine Corriedale female sheep (average BW=43±6.5 kg) were individually fed diets based on maintenance requirement in metabolic crates. They were assigned to three treatments according to a Latin square design (3×3) for three periods with a 21-day duration for each period (nine sheep per treatment). Treatments included free access to water (FAW), 2 h water restriction (2hWR) and 3 h water restriction (3hWR) after feeding. Average temperature-humidity index in the experimental room was 27.9 throughout the experiment that defines heat stress conditions. Wool samples were taken at the end of each period on day 21. No differences were found in cortisol concentration in each fragment (dried, washed and residual extract) of wool (P<0.05). Total wool cortisol concentration was higher in the 3hWR group than the other treatments (P<0.05). Blood cortisol was not different among the treatments (P>0.05) and resulted in higher variable data compared with wool cortisol. Blood neutrophils and neutrophil/lymphocyte ratio suppressed in FAW and 3hWR groups compared with the 2hWR group (P<0.05). The duration of water consumption recorded after feeding in the 3hWR group was higher than in the 2hWR group when recorded in the afternoon (P<0.01). Water consumption rate was higher in the 3hWR group than in the 2hWR group (P<0.01). However, total water consumed was lower in the 3hWR group compared with other treatments (P>0.05). It can be concluded that wool cortisol provides more precise and accurate data than blood cortisol during heat stress conditions. Water restriction for 3 h after feeding can act as a stressor and is critical for sheep during heat stress as the consumption of water decreases with restriction. PMID:24182313

  5. Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms

    PubMed Central

    Ruijters, Erik J. B.; Haenen, Guido R. M. M.; Willemsen, Mathijs; Weseler, Antje R.; Bast, Aalt

    2016-01-01

    In chronic inflammatory diseases the anti-inflammatory effect of glucocorticoids (GCs) is often decreased, leading to GC resistance. Inflammation is related with increased levels of reactive oxygen species (ROS), leading to oxidative stress which is thought to contribute to the development of GC resistance. Plant-derived compounds such as flavonoids are known for their ability to protect against ROS. In this exploratory study we screened a broad range of food-derived bioactives for their antioxidant and anti-inflammatory effects in order to investigate whether their antioxidant effects are associated with the ability to preserve the anti-inflammatory effects of cortisol. The anti-inflammatory potency of the tested compounds was assessed by measuring the oxidative stress–induced GC resistance in human macrophage-like cells. Cells were pre-treated with H2O2 (800 µM) with and without bioactives and then exposed to lipopolysaccharides (LPS) (10 ng/mL) and cortisol (100 nM). The level of inflammation was deducted from the concentration of interleukin-8 (IL-8) in the medium. Intracellular oxidative stress was measured using the fluorescent probe 2′,7′-dichlorofluorescein (DCFH). We found that most of the dietary bioactives display antioxidant and anti-inflammatory action through the protection of the cortisol response. All compounds, except for quercetin, revealing antioxidant activity also protect the cortisol response. This indicates that the antioxidant activity of compounds plays an important role in the protection of the GC response. However, next to the antioxidant activity of the bioactives, other mechanisms also seem to be involved in this protective, anti-inflammatory effect. PMID:26891295

  6. Reduced Cingulate Gyrus Volume Associated with Enhanced Cortisol Awakening Response in Young Healthy Adults Reporting Childhood Trauma

    PubMed Central

    Wei, Zhaoguo; Wu, Weiwei; Liao, Mei; Ding, Yuqiang; Zhang, Zhijun; Li, Lingjiang

    2013-01-01

    Background Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA) axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures. Methods Twenty four healthy adults with childhood trauma and 24 age- and gender-matched individuals without childhood trauma were recruited. Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of cortisol awakening response (CAR). The 3D T1-weighted magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner. Voxel-based morphometry analyses were conducted to compare the gray matter volume between two groups. Correlations of gray matter volume changes with severity of childhood trauma and CAR data were further analyzed. Results Adults with self-reported childhood trauma showed an enhanced CAR and decreased gray matter volume in the right middle cingulate gyrus. Moreover, a significant association was observed between salivary cortisol secretions after awaking and the right middle cingulate gyrus volume reduction in subjects with childhood trauma. Conclusions The present research outcomes suggest that childhood trauma is associated with hyperactivity of the HPA axis and decreased gray matter volume in the right middle cingulate gyrus, which may represent the vulnerability for developing psychosis after childhood trauma experiences. In addition, this study demonstrates that gray matter loss in the cingulate gyrus is related to increased cortisol levels. PMID:23894454

  7. Food-Derived Bioactives Can Protect the Anti-Inflammatory Activity of Cortisol with Antioxidant-Dependent and -Independent Mechanisms.

    PubMed

    Ruijters, Erik J B; Haenen, Guido R M M; Willemsen, Mathijs; Weseler, Antje R; Bast, Aalt

    2016-01-01

    In chronic inflammatory diseases the anti-inflammatory effect of glucocorticoids (GCs) is often decreased, leading to GC resistance. Inflammation is related with increased levels of reactive oxygen species (ROS), leading to oxidative stress which is thought to contribute to the development of GC resistance. Plant-derived compounds such as flavonoids are known for their ability to protect against ROS. In this exploratory study we screened a broad range of food-derived bioactives for their antioxidant and anti-inflammatory effects in order to investigate whether their antioxidant effects are associated with the ability to preserve the anti-inflammatory effects of cortisol. The anti-inflammatory potency of the tested compounds was assessed by measuring the oxidative stress-induced GC resistance in human macrophage-like cells. Cells were pre-treated with H₂O₂ (800 µM) with and without bioactives and then exposed to lipopolysaccharides (LPS) (10 ng/mL) and cortisol (100 nM). The level of inflammation was deducted from the concentration of interleukin-8 (IL-8) in the medium. Intracellular oxidative stress was measured using the fluorescent probe 2',7'-dichlorofluorescein (DCFH). We found that most of the dietary bioactives display antioxidant and anti-inflammatory action through the protection of the cortisol response. All compounds, except for quercetin, revealing antioxidant activity also protect the cortisol response. This indicates that the antioxidant activity of compounds plays an important role in the protection of the GC response. However, next to the antioxidant activity of the bioactives, other mechanisms also seem to be involved in this protective, anti-inflammatory effect. PMID:26891295

  8. Effects of dermal dexamethasone application on ACTH and both basal and ACTH-stimulated cortisol concentration in normal horses.

    PubMed

    Abraham, G; Allersmeier, M; Gottschalk, J; Schusser, G F; Hoppen, H-O; Ungemach, F R

    2009-08-01

    There are no data available regarding the systemic (adverse) effects which might be induced by topical/dermal glucocorticoids (GCs) application in the horse. Besides their widespread use for the treatment of a variety of peripheral inflammatory disorders such as atopic dermatitis, eczemas or arthritis in the horse, their surreptitious application has become a concern in doping cases in competition/performance horses. Assessing both basal and ACTH-stimulated plasma cortisol as well as basal ACTH concentrations following application of dexamethsone-containing dermal ointment is necessary to determine influences on hypothalamus-pituitary-adrenal (HPA) axis. Ten clinically healthy adult standardbred horses (6 mares, 4 geldings) were rubbed twice daily each with 50 g dexamethasone-containing ointment on a defined skin area (30 x 50 cm) for 10 days. RIA and chemiluminescent enzyme immuno-metric assay were used to determine resting and ACTH-stimulated plasma cortisol and basal ACTH concentrations, respectively. HPA feedback sensitivity and adrenal function were measured by a standard ACTH stimulation test. Dermal dexamethasone suppressed significantly the resting plasma cortisol level (to 75-98%) below baseline (P < 0.001) within the first 2 days and decreased further until day 10. ACTH stimulation test showed a markedly reduced rise in plasma cortisol concentrations (P < 0.001 vs. baseline). Plasma ACTH level decreased also during topical dexamethasone application. The number of total lymphocytes and eosinophil granulocytes was reduced, whereas the number of neutrophils increased. No significant change of serum biochemical parameters was noted. Dermal dexamethasone application has the potential to cause an almost complete and transient HPA axis suppression and altered leukocyte distribution in normal horses. The effects on HPA axis function should be considered in relation to the inability of animals to resist stress situations. The data further implicate that

  9. Neural Analog Information Processing

    NASA Astrophysics Data System (ADS)

    Hecht-Nielsen, Robert

    1982-07-01

    Neural Analog Information Processing (NAIP) is an effort to develop general purpose pattern classification architectures based upon biological information processing principles. This paper gives an overview of NAIP and its relationship to the previous work in neural modeling from which its fundamental principles are derived. It also presents a theorem concerning the stability of response of a slab (a two dimensional array of identical simple processing units) to time-invariant (spatial) patterns. An experiment (via computer emulation) demonstrating classification of a spatial pattern by a simple, but complete NAIP architecture is described. A concept for hardware implementation of NAIP architectures is briefly discussed.

  10. Anti-tumor activity of the novel hexahydrocannabinol analog LYR-8 in Human colorectal tumor xenograft is mediated through the inhibition of Akt and hypoxia-inducible factor-1α activation.

    PubMed

    Thapa, Dinesh; Kang, Youra; Park, Pil-Hoon; Noh, Seok Kyun; Lee, Yong Rok; Han, Sung Soo; Ku, Sae Kwang; Jung, Yunjin; Kim, Jung-Ae

    2012-01-01

    Cannabinoid compounds have been shown to exert anti-tumor effects by affecting angiogenesis, invasion, and metastasis. In the present study, we examined the action mechanism by which LYR-8, a novel hexahydrocannabinol analog, exerts anti-angiogenic and anti-tumor activity in human cancer xenografts. In the xenografted tumor tissues, LYR-8 significantly reduced the expression of hypoxia-inducible factor-1 alpha (HIF-1α), a transcription factor responsible for induction of angiogenesis-promoting factors, and its target genes, vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2). In HT-29 human colon cancer cells treated with a hypoxia-inducing agent (CoCl(2)), LYR-8 dose-dependently suppressed the induction of HIF-1α and subsequently its targets, VEGF and COX-2. In addition, highly elevated prostaglandin E(2) (PGE(2)) concentrations in CoCl(2)-treated HT-29 cells were also significantly suppressed by LYR-8. However, LYR-8 alone in the absence of CoCl(2) did not alter the basal expression of VEGF and COX-2, or PGE(2) production. Furthermore, LYR-8 effectively suppressed Akt signaling, which corresponded to the suppression of CoCl(2)-induced HIF-1α accumulation. Taken together, LYR-8 exerts anti-tumor effects through the inhibition of Akt and HIF-1α activation, and subsequently suppressing factors regulating tumor microenvironment, such as VEGF and COX-2. These results indicate a novel function of cannabinoid-like compound LYR-8 as an anti-tumor agent with a HIF-1α inhibitory activity. PMID:22687485

  11. Antarctic Space Analog Program

    NASA Technical Reports Server (NTRS)

    Palinkas, Lawrence A; Gunderson, E. K. Eric; Johnson, Jeffrey C.; Holland, Albert W.

    1998-01-01

    The primary aim of this project was to examine group dynamics and individual performance in extreme, isolated environments and identify human factors requirements for long-duration space missions using data collected in an analog environment. Specifically, we wished to determine: 1) the characteristics of social relations in small groups of individuals living and working together in extreme, isolated environments, and 2) the environmental, social and psychological determinants of performance effectiveness in such groups. These two issues were examined in six interrelated studies using data collected in small, isolated research stations in Antarctica from 1963 to the present. Results from these six studies indicated that behavior and performance on long-duration space flights is likely to be seasonal or cyclical, situational, social, and salutogenic in nature. The project responded to two NASA program emphases for FY 1997 as described in the NRA: 1) the primary emphasis of the Behavior and Performance Program on determining long-term individual and group performance responses to space, identifying critical factors affecting those responses and understanding underlying mechanisms involved in behavior and performance, and developing and using ground-based models and analogs for studying space-related behavior and performance; and 2) the emphasis of the Data Analysis Program on extended data analysis. Results from the study were used to develop recommendations for the design and development of pre-flight crew training and in-flight psychological countermeasures for long-duration manned space missions.

  12. Prostaglandin analogous and antioxidant activity mediated gastroprotective action of Tabernaemontana divaricata (L.) R. Br. flower methanolic extract against chemically induced gastric ulcers in rats.

    PubMed

    Ali Khan, Mohammed Safwan; Mat Jais, Abdul Manan; Afreen, Adiba

    2013-01-01

    The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses--125, 250, and 500 mg/kg--orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization--high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous. PMID:24350249

  13. Prostaglandin Analogous and Antioxidant Activity Mediated Gastroprotective Action of Tabernaemontana divaricata (L.) R. Br. Flower Methanolic Extract against Chemically Induced Gastric Ulcers in Rats

    PubMed Central

    Mat Jais, Abdul Manan; Afreen, Adiba

    2013-01-01

    The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses—125, 250, and 500 mg/kg—orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization—high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous. PMID:24350249

  14. Carbon Isotopic Composition of CO2, Evolved During Perchlorate-Induced Reactions in Mars Analog Materials: Interpreting SAM/MSL Rocknest Data

    NASA Technical Reports Server (NTRS)

    Stern, J. C.; McAdam, A. C.; Archer, P. D., Jr.; Bower, H.; Buch, A.; Eigenbrode, J.; Freissinet, C.; Franz, H. B.; Glavin, D.; Jones, J. H.; Mahaffy, P. R.; Ming, D. W.; Niles, P. B.; Steele, A.; Sutter, B.

    2013-01-01

    The Sample Analysis at Mars (SAM) Instrument Suite on the Mars Science Laboratory (MSL) Rover Curiosity made its first solid sample evolved gas analysis of unconsolidated material at aeolian bedform Rocknest in Gale Crater. The magnitude of O2 evolved in each run as well as the chlorinated hydrocarbons detected by SAM gas chromatograph/ mass spectrometer (GCMS) [1] suggest a chlorinated oxidant such as perchlorate in Rocknest materials [2]. Perchlorate induced combustion of organics present in the sample would contribute to the CO2 volatile inventory, possibly overlapping with CO2 from inorganic sources. The resulting carbon and oxygen isotopic composition of CO2 sent to the Tunable Laser Spectrometer (TLS) for analysis would represent mixed sources. This work was undertaken to better understand a) how well the carbon isotopic composition ( 13C) of CO2 from partially combusted products represents their source and b) how the 13C of combusted products can be deconvolved from other carbon sources such as thermal decomposition of carbonate.

  15. Correlates of Cortisol in Human Hair: Implications for Epidemiologic Studies on Health Effects of Chronic Stress

    PubMed Central

    Wosu, Adaeze C.; Valdimarsdóttir, Unnur; Shields, Alexandra E.; Williams, David R.; Williams, Michelle A.

    2013-01-01

    Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, “cortisol” “hair” “confounders” “chronic” “stress” and “correlates.” Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., PTSD), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing´s syndrome) and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear to not be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies. PMID:24184029

  16. Effects of major depression diagnosis and cortisol levels on indices of neurocognitive function.

    PubMed

    Gomez, Rowena G; Posener, Joel A; Keller, Jennifer; DeBattista, Charles; Solvason, Brent; Schatzberg, Alan F

    2009-08-01

    Although many studies have examined separately the effects of depression and cortisol on cognition, no study has examined their relative or potentially additive effects. Our study simultaneously investigated the contributions of clinical status [major depression (MD) versus psychiatrically healthy controls (HC)] and cortisol on a hippocampal/mediotemporal mediated verbal memory task (Paragraph Recall) and a prefrontal cortex/cingulate mediated executive functioning task (Stroop). Thirty-seven unmedicated nondelusional MDs and 18 HCs underwent psychiatric ratings, hourly assessments of cortisol activity over 24 h, and neuropsychological assessments. Hierarchical multiple regressions indicated a significant effect of cortisol but not of diagnosis on verbal memory. Greater cortisol levels were related to poorer memory performance independent of group. In contrast, a significant interaction between cortisol and diagnosis was found for a color-word index of response inhibition. This interaction suggests that the detrimental effect of elevated cortisol level on this type of executive functioning exists only in the healthy control group but not in MDs. On an Interference score, another measure of response inhibition, cortisol had a significant independent effect, but neither the effects of diagnosis and the interaction attained full significance. Our study suggests that cortisol has an independent effect on verbal memory. Also, our study produced evidence of an interaction between diagnosis and cortisol on response inhibition. PMID:19261389

  17. Correspondence of plasma and salivary cortisol patterns in women with breast cancer

    PubMed Central

    Zeitzer, Jamie M.; Nouriani, Bita; Neri, Eric; Spiegel, David

    2014-01-01

    Introduction The ‘diurnal slope’ of salivary cortisol has been used as a measure of stress and circadian function in a variety of reports with several detailing its association with cancer progression. The relationship of this slope, typically a negative value from high morning concentrations to low evening concentrations, to the underlying daily variation in total plasma cortisol throughout the 24-hour cycle, however, has never been reported. Methods To examine the relationship between diurnal salivary cortisol slope and the underlying pattern of plasma cortisol in individuals with cancer, we examined a cohort of women with advanced breast cancer (n=97) who had saliva and plasma collected during a modified 24-hour, constant posture protocol. Results We found that steepness of the diurnal slope of salivary cortisol was correlated with the amplitude of plasma cortisol rhythm when the slope was calculated from samples taken at wake+30 minutes and 9PM (r=−0.29, p>0.05). Other variants of salivary slope calculations were not significantly correlated with the amplitude of the plasma cortisol rhythm. Diurnal salivary cortisol slope steepness was not correlated with the time between habitual waking and the computed circadian peak of cortisol, but there was a correlation between diurnal slope steepness and the time between habitual waking and the time of the awakening spike of morning cortisol (r’s<−0.23, p’s<0.05). Conclusion It therefore appears that in women with advanced breast cancer, diurnal salivary cortisol slope primarily represents aspects of the cortisol awakening response in relation to evening levels more than the circadian rhythm of total plasma cortisol. PMID:25228297

  18. Temporal relationships between plasma cortisol, corticosteriod-binding globulin (CBG), and the free cortisol index (FCI) in pigs in response to adrenal stimulation or suppression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In swine, more than 60% of cortisol in circulation is bound to its carrier glycoprotein, porcine corticosteroid-binding globulin (pCBG), and is considered biologically inactive. Limitations exist when only total plasma cortisol levels are used to assess the stress response in swine in situations whe...

  19. Eye Tracking, Cortisol, and a Sleep vs. Wake Consolidation Delay: Combining Methods to Uncover an Interactive Effect of Sleep and Cortisol on Memory

    PubMed Central

    Bennion, Kelly A.; Mickley Steinmetz, Katherine R.; Kensinger, Elizabeth A.; Payne, Jessica D.

    2014-01-01

    Although rises in cortisol can benefit memory consolidation, as can sleep soon after encoding, there is currently a paucity of literature as to how these two factors may interact to influence consolidation. Here we present a protocol to examine the interactive influence of cortisol and sleep on memory consolidation, by combining three methods: eye tracking, salivary cortisol analysis, and behavioral memory testing across sleep and wake delays. To assess resting cortisol levels, participants gave a saliva sample before viewing negative and neutral objects within scenes. To measure overt attention, participants’ eye gaze was tracked during encoding. To manipulate whether sleep occurred during the consolidation window, participants either encoded scenes in the evening, slept overnight, and took a recognition test the next morning, or encoded scenes in the morning and remained awake during a comparably long retention interval. Additional control groups were tested after a 20 min delay in the morning or evening, to control for time-of-day effects. Together, results showed that there is a direct relation between resting cortisol at encoding and subsequent memory, only following a period of sleep. Through eye tracking, it was further determined that for negative stimuli, this beneficial effect of cortisol on subsequent memory may be due to cortisol strengthening the relation between where participants look during encoding and what they are later able to remember. Overall, results obtained by a combination of these methods uncovered an interactive effect of sleep and cortisol on memory consolidation. PMID:24962611

  20. Maternal Disrupted Communication During Face-to-Face Interaction at 4 months: Relation to Maternal and Infant Cortisol Among at-Risk Families

    PubMed Central

    Crockett, Erin E.; Holmes, Bjarne M.; Granger, Douglas A.; Lyons-Ruth, Karlen

    2014-01-01

    The study evaluated the association between maternal disrupted communication and the reactivity and regulation of the psychobiology of the stress response in infancy. Mothers and infants were recruited via the National Health Service from the 20% most economically impoverished data zones in a suburban region of Scotland. Mothers (N = 63; M age = 25.9) and their 4-month-old infants (35 boys, 28 girls) were videotaped interacting for 8 min, including a still-face procedure as a stress inducer and a 5-min coded recovery period. Saliva samples were collected from the dyads prior to, during, and after the still-face procedure and later assayed for cortisol. Level of disruption in maternal communication with the infant was coded from the 5-min videotaped interaction during the recovery period which followed the still-face procedure. Severely disrupted maternal communication was associated with lower levels of maternal cortisol and a greater divergence between mothers’ and infants’ cortisol levels. Results point to low maternal cortisol as a possible mechanism contributing to the mother’s difficulty in sensitively attuning to her infant’s cues, which in turn has implications for the infant’s reactivity to and recovery from a mild stressor in early infancy. PMID:25506272

  1. Changes in Men’s Salivary Testosterone and Cortisol Levels, and in Sexual Desire after Smelling Female Axillary and Vulvar Scents

    PubMed Central

    Cerda-Molina, Ana Lilia; Hernández-López, Leonor; de la O, Claudio E.; Chavira-Ramírez, Roberto; Mondragón-Ceballos, Ricardo

    2013-01-01

    Several studies have shown that a woman’s vaginal or axillary odors convey information on her attractivity. Yet, whether such scents induce psychoneuroendocrinological changes in perceivers is still controversial. We studied if smelling axillary and vulvar odors collected in the periovulatory and late luteal phases of young women modify salivary testosterone and cortisol levels, as well as sexual desire in men. Forty-five women and 115 men, all of them college students and unacquainted with each other, participated in the study. Female odors were collected on pads affixed to the axilla and on panty protectors both worn the entire night before experiments. Men provided five saliva samples, a basal one before the smelling procedure, and four more 15, 30, 60, and 75 min after exposure to odors. Immediately after smelling the odor source, men answered a questionnaire rating hedonic qualities of scents, and after providing the last saliva sample they answered questionnaire on sexual desire. We found that periovulatory axillary and vulvar odors increased testosterone and cortisol levels, with vulvar scents producing a more prolonged effect. Luteal axilla odors decreased testosterone and cortisol levels, while luteal vulva odors increased cortisol. Periovulatory axilla and vulva scents accounted for a general increase of interest in sex. These odors were also rated as more pleasant and familiar, while luteal vulvar odors were perceived as intense and unpleasant. PMID:24194730

  2. The influence of crystallinity degree on the glycine decomposition induced by 1 MeV proton bombardment in space analog conditions.

    PubMed

    Pilling, Sergio; Mendes, Luiz A V; Bordalo, Vinicius; Guaman, Christian F M; Ponciano, Cássia R; da Silveira, Enio F

    2013-01-01

    Glycine is the simplest proteinaceous amino acid and is present in all life-forms on Earth. In aqueous solutions, it appears mainly as zwitterion glycine (+NH3CH2COO-); however, in solid phase, it may be found in amorphous or crystalline (α, β, and γ) forms. The crystalline forms differ from each other by the packing of zwitterions in the unitary cells and by the number of intermolecular hydrogen bonds. This molecular species has been extensively detected in carbonaceous meteorites and was recently observed in the cometary samples returned to Earth by NASA's Stardust spacecraft. In space, glycine is exposed to several radiation fields at different temperatures. We present an experimental study on the destruction of zwitterionic glycine crystals at room temperature by 1 MeV protons, in which the dependence of the destruction rates of the α-glycine and β-glycine crystals on bombardment fluence is investigated. The samples were analyzed in situ by Fourier transform infrared spectrometry at different proton fluences. The experiments occurred under ultrahigh vacuum conditions at the Van de Graaff accelerator lab at the Pontifical Catholic University at Rio de Janeiro (PUC-Rio), Brazil. For low fluences, the dissociation cross section of α-glycine was observed to be 2.5×10(-14) cm2, a value roughly 5 times higher than the dissociation cross section found for β-glycine. The estimated half-lives of α-glycine and β-glycine zwitterionic forms extrapolated to the Earth orbit environment are 9×10(5) and 4×10(6) years, respectively. In the diffuse interstellar medium the estimated values are 1 order of magnitude lower. These results suggest that pristine interstellar β-glycine is the one most likely to survive the hostile environments of space radiation. A small feature around 1650-1700 cm(-1), tentatively attributed to an amide functional group, was observed in the IR spectra of irradiated samples, suggesting that cosmic rays may induce peptide bond synthesis in

  3. Vorticity in analog gravity

    NASA Astrophysics Data System (ADS)

    Cropp, Bethan; Liberati, Stefano; Turcati, Rodrigo

    2016-06-01

    In the analog gravity framework, the acoustic disturbances in a moving fluid can be described by an equation of motion identical to a relativistic scalar massless field propagating in curved space-time. This description is possible only when the fluid under consideration is barotropic, inviscid, and irrotational. In this case, the propagation of the perturbations is governed by an acoustic metric that depends algebrically on the local speed of sound, density, and the background flow velocity, the latter assumed to be vorticity-free. In this work we provide a straightforward extension in order to go beyond the irrotational constraint. Using a charged—relativistic and nonrelativistic—Bose–Einstein condensate as a physical system, we show that in the low-momentum limit and performing the eikonal approximation we can derive a d’Alembertian equation of motion for the charged phonons where the emergent acoustic metric depends on flow velocity in the presence of vorticity.

  4. JKA97, a Novel Benzylidene Analog of Harmine, Exerts Anti-Cancer Effects by Inducing G1 Arrest, Apoptosis, and p53-Independent Up-Regulation of p21

    PubMed Central

    Qin, Jiang-Jiang; Wang, Ming-Hai; Sharma, Horrick; Buolamwini, John K.; Wang, Hui; Zhang, Ruiwen

    2012-01-01

    JKA97, a benzylidene analog of harmine, has been found to be a promising drug candidate for human cancer therapy, although the underlying molecular mechanisms have not been fully demonstrated. In this study, we evaluated the effects of JKA97 on human breast cancer cells in vitro and in vivo. JKA97 inhibited the growth and proliferation of MCF7 (p53 wild-type), MCF7 (p53 knockdown), and MDA-MB-468 (p53 mutant) cells in a dose-dependent manner. Treatment with JKA97 arrested breast cancer cells in G1 phase and induced apoptosis. JKA97 also significantly suppressed the growth of MCF7 and MDA-MB-468 xenograft tumors. It regulated the expression levels of G1 phase regulators, such as p21, p27, cyclinE, and cylinD1. JKA97 activated p21 transcription, independent of p53, but had little effect on p21 protein stability/degradation. In summary, our results suggest that JKA97 inhibits human breast cancer cell growth through activating p21, independent of p53, which provides a basis for developing this compound as a novel drug for human breast cancer therapy. PMID:22558087

  5. Elevated hair cortisol levels in chronically stressed dementia caregivers.

    PubMed

    Stalder, Tobias; Tietze, Antje; Steudte, Susann; Alexander, Nina; Dettenborn, Lucia; Kirschbaum, Clemens

    2014-09-01

    Hair cortisol concentrations (HCC) are assumed to reflect integrated long-term cortisol levels and have been proposed as a promising endocrine marker of chronic psychological stress. The current study examined HCC in relation to caregiving burden, a well-established naturalistic model of chronic stress in humans. HCC and relevant psychosocial data were examined in 20 caregivers of relatives with dementia and 20 non-caregiver controls matched for age and sex. Results revealed elevated HCC in dementia caregivers compared to non-caregiver controls (F(1,38)=4.4, p=.04, ηp2=.10). Further, within caregivers, a trend for a positive association of HCC with self-reported caregiving burden (r=.43, p=.058) and a positive association with depressiveness (r=.48, p=.045) were observed. No other associations between HCC and subjective measures were seen. These findings concur with the notion that HCC sensitively capture endocrine aberrations in stress-exposed groups. PMID:25001953

  6. Phagocytic function in cyclists: correlation with catecholamines and cortisol.

    PubMed

    Ortega Rincón, E; Marchena, J M; García, J J; Schmidt, A; Schulz, T; Malpica, I; Rodríguez, A B; Barriga, C; Michna, H; Lötzerich, H

    2001-09-01

    Flow cytometer measurements were made of the basal variations in peripheral blood functional monocytes and granulocytes over the course of a training season (January to November) of a cycling team. Parallel determinations were made of plasma concentration of catecholamines (chromatography) and cortisol (RIA) in a search for neuroendocrine markers. The results showed the greatest phagocytic capacity to occur in the central months (March, May, and July), coinciding with the greatest number and highest level of competitive events with good correlation with a peak in epinephrine during these months (r(2) = 0.998 for monocytes and r(2) = 0.674 for granulocytes). No good correlations were found between phagocytosis and norepinephrine or cortisol. The highest values for phagocytosis and epinephrine concentration were found in May. These results suggest that blood epinephrine concentration could be a good neuroendocrine marker of sportspeople's phagocytic response. PMID:11509500

  7. Use of hair cortisol analysis to detect hypercortisolism during active drinking phases in alcohol-dependent individuals.

    PubMed

    Stalder, Tobias; Kirschbaum, Clemens; Heinze, Kareen; Steudte, Susann; Foley, Paul; Tietze, Antje; Dettenborn, Lucia

    2010-12-01

    The assessment of cortisol levels in human hair has recently been suggested to provide a retrospective index of cumulative cortisol exposure over periods of up to 6 months. The current study examined the utility of hair cortisol analysis to retrospectively detect hypercortisolism during active drinking phases in alcoholics in acute withdrawal (n=23), the normalisation of cortisol output in abstinent alcoholics (n=25) and cortisol levels in age- and gender-matched controls (n=20). Scalp-near 3-cm hair segments were sampled and analysed for cortisol content. Results showed three to fourfold higher cortisol levels in hair samples of alcoholics in acute withdrawal than in those of abstinent alcoholics (p<.001) or controls (p<.001), with no differences between the latter two groups. The current hair cortisol findings closely mirror results of previous research using well-established measures of systemic cortisol secretion and thus provide further validation of this novel method. PMID:20727937

  8. Effect of weaning age on cortisol release in piglets.

    PubMed

    Li, L A; Yang, J J; Li, Y; Lv, L; Xie, J J; Du, G M; Jin, T M; Qin, S Y; Jiao, X L

    2016-01-01

    The effect of weaning age on the adrenal cortex, which plays a vital role in the stress response, is currently unknown. Therefore, plasma adrenocorticotropic hormone (ACTH) and cortisol levels, weights and relative weights of adrenal glands, and steroidogenesis-related protein and enzyme expression levels in piglets weaned on different days were determined. Piglets weaned at 35 days had significantly lower ACTH levels than those weaned at 14 or 21 days, and cortisol levels of piglets weaned at 21, 28, and 35 days were significantly lower than those of piglets weaned on day 14. Adrenal gland weights of piglets weaned at 28 and 35 days and relative adrenal gland weights of piglets weaned at 35 days were significantly lower than those of piglets weaned at 14 days. However, no significant difference was detected in the expression of melanocortin-type 2 receptor mRNA, which is associated with weaning age. Steroidogenic acute-regulatory (StAR) mRNA and cholesterol side-chain cleavage cytochrome P450 mRNA expression levels in piglets weaned at 28 and 35 days were significantly lower than in those weaned at 14 or 21 days, and P450 11β mRNA expression levels in piglets weaned at 28 and 35 days were significantly lower than in those weaned at 14 days. Therefore, early-weaned piglets exhibited increased adrenal gland weights and StAR and steroidogenic enzyme expression, all of which contributed to high cortisol levels. The high plasma ACTH and cortisol levels in early-weaned piglets indicate that these animals would be greatly affected by stress. PMID:27173313

  9. Predictors of hair cortisol concentrations in older adults.

    PubMed

    Feller, Silke; Vigl, Matthaeus; Bergmann, Manuela M; Boeing, Heiner; Kirschbaum, Clemens; Stalder, Tobias

    2014-01-01

    People at older ages are at increased risk for developing stress-related diseases associated with chronically elevated cortisol secretion. However, the main factors contributing to such endocrine alterations in this age group are still largely unknown. This cross-sectional study examined patterns of long-term integrated cortisol secretion, as assessed in hair, in a sample of 654 participants in middle and old adulthood (mean age: 65.8 years; range: 47-82 years) from the German cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC) study in Potsdam. Hair cortisol concentrations (HCC) were determined from the first scalp-near 3 cm hair segment and several sociodemographic, lifestyle, anthropometric, disease-related, and psychological parameters were assessed. In simple linear regressions, HCC were found to increase with participants' age and to be higher in men compared to women. HCC also showed positive associations with waist-to-hip ratio, waist circumference, smoking, prevalent type 2 diabetes mellitus, mental health, daytime sleeping, and being unemployed or retired--as well as a negative association with diastolic blood pressure. After full mutual adjustment, only age and smoking remained independent predictors of HCC. The association between prevalent type 2 diabetes mellitus and HCC was attenuated but still persisted independently in women. Similar, a positive relationship between HCC and alcohol consumption was found in women. The current results confirm previous evidence of positive associations of HCC with age, sex, alcohol consumption, and type 2 diabetes mellitus and add new knowledge on factors--such as smoking--that may contribute to elevated cortisol levels in people at older ages. PMID:24275012

  10. Analog and digital signal processing

    NASA Astrophysics Data System (ADS)

    Baher, H.

    The techniques of signal processing in both the analog and digital domains are addressed in a fashion suitable for undergraduate courses in modern electrical engineering. The topics considered include: spectral analysis of continuous and discrete signals, analysis of continuous and discrete systems and networks using transform methods, design of analog and digital filters, digitization of analog signals, power spectrum estimation of stochastic signals, FFT algorithms, finite word-length effects in digital signal processes, linear estimation, and adaptive filtering.

  11. Cortisol as a Biomarker of Stress in Term Human Labor: Physiological and Methodological Issues

    PubMed Central

    Newton, Edward R.; Tanner, Charles J.; Heitkemper, Margaret M.

    2013-01-01

    Literature on the use of plasma cortisol to quantify psychophysiological stress in humans is extensive. However, in parturition at term gestation the use of cortisol as a biomarker of stress is particularly complex. Plasma cortisol levels increase as labor progresses. This increase seems to be important for maintenance of maternal/fetal wellbeing and facilitation of normal labor progress. Unique physiological and methodological issues involved in the use of cortisol as a biomarker of stress in labor present challenges for researchers. This review examines these issues, suggests mixed methods and within-subject repeated measures designs, and offers recommendations for assay procedures for parturient sampling. Documentation of clinical interventions and delivery outcomes may elucidate relationships among psychophysiological stressors, cortisol and normal labor progress. With attention to these methodological issues, analysis of plasma cortisol may lead to clinical interventions that support normal labor physiology. PMID:23338011

  12. Cortisol Response to Challenge Involving Low Controllability: The Role of Control Beliefs and Age

    PubMed Central

    Agrigoroaei, Stefan; Polito, Michael; Lee, Angela; Kranz-Graham, Eileen; Seeman, Teresa; Lachman, Margie E.

    2013-01-01

    Cortisol responses are typically more pronounced under low controllability conditions, yet little is known about the role of individual differences. This study examined whether cortisol response to a situation with low controllability differs as a function of preexisting control beliefs and age. We manipulated level of controllability using a driving simulator. Control beliefs were assessed prior to the lab session. Salivary cortisol was measured before and after the driving simulation. Participants were 152 adults aged 22-84 from a Boston area sample. In comparison to the normal controllability condition, those in the low controllability condition reported less perceived control over driving, supporting the effectiveness of the manipulation. In the low controllability condition those with higher control beliefs showed a greater cortisol response than those with low control beliefs. Older adults showed a greater cortisol response than younger adults during the challenge. Implications of acute cortisol responses for performance outcomes are discussed. PMID:23348557

  13. Towards a Biopsychological Understanding of Costly Punishment: The Role of Basal Cortisol

    PubMed Central

    Pfattheicher, Stefan; Keller, Johannes

    2014-01-01

    Recent findings have documented a negative relation of basal endogenous cortisol and aggression after a provocation (i.e., reactive aggression) in humans. We build on these findings and investigated the relation of endogenous cortisol and reactive aggression in a social dilemma situation, that is, costly punishment of individuals who did not appropriately contribute to a common group project. Specifically, we predicted that basal cortisol is negatively related to costly punishment of uncooperative individuals. In the present study, basal cortisol was assessed prior to a public goods game with the option to punish other group members. In line with previous research on reactive aggression and basal cortisol, we found that basal cortisol was indeed negatively related to costly punishment. The findings are important for understanding costly punishment because this tendency has been documented as a possible basis for the evolution of cooperation. PMID:24416441

  14. Hair Cortisol Analysis: A Promising Biomarker of HPA Activation in Older Adults

    PubMed Central

    Wright, Kathy D.; Hickman, Ronald; Laudenslager, Mark L.

    2015-01-01

    Prolonged stress is a potentially harmful and often undetected risk factor for chronic illness in older adults. Cortisol, one indicator of the body’s hormonal responses to stress, is regulated by the hypothalamic-pituitary-adrenal (HPA) axis and is commonly measured in saliva, urine, or blood samples. Cortisol possesses a diurnal pattern and thus collection timing is critical. Hair cortisol is a proxy measure to the total retrospective activity of the HPA axis over the preceding months, much like hemoglobin A1c is a proxy measure of glucose control over the past 3 months. The aim of this review is to examine a novel biomarker, hair cortisol, as a practical measure of long-term retrospective cortisol activity associated with chronic stress in older adults. Hair cortisol analysis advances the science of aging by better characterizing chronic stress as a risk factor for chronic illness progression and as a biomarker of the effectiveness of stress reduction interventions. PMID:26055775

  15. Successful hunting increases testosterone and cortisol in a subsistence population

    PubMed Central

    Trumble, Benjamin C.; Smith, Eric A.; O'Connor, Kathleen A.; Kaplan, Hillard S.; Gurven, Michael D.

    2014-01-01

    Controversy over the adaptive significance of male hunting in subsistence societies hinges on the relative importance of familial provisioning and mate-quality signalling. This paper examines the proximate and ultimate motivations of hunting behaviour from a neuroendocrine perspective, using salivary testosterone and cortisol data collected before, during and after hunting focal follows from 31 Tsimane hunters aged 18–82 years. Despite circadian declines in hormone levels, testosterone and cortisol of Tsimane hunters increased at the time of a kill, and remained high as successful hunters returned home. Previous studies of hormonal changes during competitions find that high-stakes and success in the presence of relevant audiences result in increased neuroendocrine arousal. If men hunt primarily to provision their families, then an additional audience would not be expected to impact testosterone or cortisol, nor would the size of the animal killed. However, if signalling male quality by ‘showing off’ was a larger relative driver of men's hunting behaviour, one would expect greater hormonal response in cases where men returned with large sharable kills, especially in the presence of community members. Consistent with provisioning models of male hunting motivation, neither kill size nor encountering an audience of villagers while returning from hunting was associated with hormonal changes for successful hunters. PMID:24335989

  16. Adolescence, Stress and Cortisol in Autism Spectrum Disorders.

    PubMed

    Corbett, Blythe A; Simon, David

    2014-02-01

    Adolescence, the transition between childhood and adulthood, is a period of remarkable physiological, psychological and social change. A variety of physiological changes coincide with the dynamic transition, which is evident in the regulation and responsivity of the Limbic-Hypothalamic-Pituitary-Adrenocortical (LHPA) axis. Specifically, elevations in diurnal basal cortisol levels have been reported, as well as higher cortisol in response to perceived stressors. While this enhanced responsivity may help prepare the individual to adapt to increased demands and new challenges, it may also mark a time of increased vulnerability in populations already prone to enhanced physiological arousal and poor adaption to change, such as autism. To date most studies investigating the integrity of the LHPA axis in children with autism spectrum disorders (ASD) have shown more variable diurnal regulation and a pattern of enhanced responsivity to stress. There is also evidence of more marked reactivity over development suggesting that adolescence may be a time of increased risk for enhanced physiological arousal and social stress. The following review briefly summarizes the literature to date on autism, adolescence and salivary cortisol. The current summary suggests that enhanced study of the interplay between social functioning and stress during the adolescent period in ASD is warranted. PMID:24665363

  17. The cortisol response to social stress in social anxiety disorder.

    PubMed

    Vaccarino, Oriana; Levitan, Robert; Ravindran, Arun

    2015-04-01

    This study evaluated the cortisol stress response (CSR) following the Trier Social Stress Test in Social Anxiety Disorder (SAD) and control participants, to determine whether individual differences in CSR associate more with SAD diagnosis or dimensional characteristics [i.e. childhood trauma (CT)]. Twenty-one participants (11 with SAD) had full data available for both CT-scores and cortisol area-under-the-curve (AUC). Linear regression produced significant results: predicting AUCG with study group, emotional abuse (EA) scores and their interaction (F=3.14, df=5,15; p=.039); of note, the study group by EA interaction was significant at p=.015, driven by a strong positive association between EA and cortisol AUCG in the control group, and a negative association between these variables in the SAD group (standardized-beta=1.56, t=2.75, p=.015). This suggests that EA in SAD patients is associated with altered CSR, highlighting need to measure dimensional characteristics. PMID:25864645

  18. The acute testosterone, growth hormone, cortisol and interleukin-6 response to 164-km road cycling in a hot environment.

    PubMed

    Vingren, Jakob L; Budnar, Ronald G; McKenzie, Amy L; Duplanty, Anthony A; Luk, Hui-Ying; Levitt, Danielle E; Armstrong, Lawrence E

    2016-01-01

    This study investigated the acute endocrine responses to a 164-km road cycling event in a hot environment. Thirty-four male experienced cyclists (49.1 ± 8.3 years, 86.8 ± 12.5 kg, 178.1 ± 5.1 cm) participating in a 164-km road cycling event were recruited. Blood samples were collected within 0.3-2.0 h before the start (PRE: ~0500-0700 h) and immediately following the ride (POST). Samples were analysed for testosterone, growth hormone (GH), cortisol and interleukin-6 (IL-6). The temperature and humidity during the event were 35.3 ± 4.9°C and 47.2 ± 14.0%, respectively. Based on the finishing time, results for the fastest (FAST, 305 ± 10 min) and the slowest (SLOW, 467 ± 31 min) quartiles were compared. At POST, testosterone concentration was significantly (P < 0.05) lower (PRE, 20.8 ± 8.6; POST, 18.2 ± 6.7 nmol · L(-1)), while GH (PRE, 0.3 ± 0.1; POST, 2.3 ± 0.3 µg · L(-1)), cortisol (PRE, 661 ± 165; POST, 1073 ± 260 nmol · L(-1)) and IL-6 (PRE, 4.0 ± 3.4; POST, 22.4 ± 15.2 pg · mL(-1)) concentrations were significantly higher than those at PRE. At POST, GH and cortisol were significantly higher for the FAST group than for the SLOW group (GH, 3.6 ± 2.0 and 1.0 ± 0.8 µg · L(-1); cortisol, 1187 ± 209 and 867 ± 215 nmol · L(-1)). Participation in an ultra-endurance road cycling event in a hot environment induced significant acute changes in concentrations of circulating hormones, with a greater augmentation of GH and cortisol in those completing the ride fastest. PMID:26199143

  19. Salivary cortisol day curves in Addison's disease in patients on hydrocortisone replacement.

    PubMed

    Ross, I L; Levitt, N S; Van der Walt, J S; Schatz, D A; Johannsson, G; Haarburger, D H; Pillay, T S

    2013-01-01

    Using salivary cortisol (SC) measurements, cortisol exposure in Addison's disease patients on hydrocortisone replacement was determined and compared with healthy controls. Cortisol pharmacokinetics was assessed in 31 patients with Addison's disease on replacement hydrocortisone doses (median daily dose 20 mg; range 5-50 mg) and 30 healthy control subjects. Saliva samples (n=16) were collected between 08:00 and 00:00 h in 1 day, using a passive drool technique. Cortisol exposure was evaluated by noncompartmental approach. In the patients, cortisol exposure was significantly higher than in controls: median inter-quartile range (IQR) peak cortisol (C(max)) 174.5 (59.3-837.0) vs. 6.50 (4.7-19.3) nmol/l, p=0.0001; area under the curve (AUC) 390.1 (177.1-928.9) vs. 21.4 (14.6-28.4) minutes*nmol/l, p=0.0001, trough cortisol level (C(min)) 0.49 (0.49-0.96) vs. 0.49 (0.49-0.49) nmol/l, p=0.02, occurring at 480.0 (0.1-660.0) vs. 405.0 (180.0-570.0) min, p=0.56. First peak cortisol was 174.5 (53.0-754.7) vs. 6.27 (3.90-8.47) nmol/l, p=0.0001 and second peak cortisol 18.90 (5.22-76.9) vs. 3.12 (1.76-4.79) nmol/l, p=0.0001. The time to first peak cortisol differed between the 2 groups, 30 (30-75) vs. 0.1 (0.1-30) minutes; p=0.0001. At doses studied, hydrocortisone replacement therapy results in cortisol pharmacokinetics being markedly different from endogenous cortisol profiles in healthy control subjects. Addison's disease patients had significantly higher SC levels compared to healthy control subjects. PMID:22893258

  20. Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy.

    PubMed

    Keller-Wood, Maureen; Feng, Xiaodi; Wood, Charles E; Richards, Elaine; Anthony, Russell V; Dahl, Geoffrey E; Tao, Sha

    2014-08-15

    In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg(-1)·day(-1)) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), β-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes. PMID:24920731