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Sample records for analog induce cortisol

  1. Systemic hydrocortisone/cortisol induces allergic skin reactions in presensitized subjects.

    PubMed

    Lauerma, A I; Reitamo, S; Maibach, H I

    1991-02-01

    To determine whether systemic hydrocortisone can elicit allergic skin reactions in patients with contact hypersensitivity to hydrocortisone, we studied four patients with contact hypersensitivity to hydrocortisone and hydrocortisone-17-butyrate and two patients with contact hypersensitivity to hydrocortisone-17-butyrate but not to hydrocortisone. Open oral provocation with 100 or 250 mg hydrocortisone in patients with hydrocortisone contact hypersensitivity elicited cutaneous reactions at sites of previous allergic dermatitis caused by hydrocortisone in two patients and at sites of earlier allergic patch test reactions caused by hydrocortisone in the other two patients. Provocations in two patients with contact hypersensitivity to hydrocortisone-17-butyrate but not to hydrocortisone remained negative. To determine whether the adrenal cortical hormone cortisol, which is identical to hydrocortisone, could induce similar skin reactions, one patient with hydrocortisone contact hypersensitivity underwent adrenocorticotropic hormone stimulation tests; as a control, one hydrocortisone-sensitive patient underwent analogous provocations with placebo. After an 8-hour infusion with the adrenocorticotropic hormone analog tetracosactide, a similar skin reaction to that seen with oral hydrocortisone was observed, whereas provocations with placebo remained negative. We conclude that both oral hydrocortisone and intrinsic cortisol are able to induce allergic skin reactions in presensitized subjects.

  2. Sweat-inducing physiological challenges do not result in acute changes in hair cortisol concentrations.

    PubMed

    Grass, Juliane; Kirschbaum, Clemens; Miller, Robert; Gao, Wei; Steudte-Schmiedgen, Susann; Stalder, Tobias

    2015-03-01

    Hair cortisol concentrations (HCC) are assumed to provide a stable, integrative marker of long-term systemic cortisol secretion. However, contrary to this assumption, some recent observations have raised the possibility that HCC may be subject to acute influences, potentially related to cortisol incorporation from sweat. Here, we provide a first detailed in vivo investigation of this possibility comprising two independent experimental studies: study I (N=42) used a treadmill challenge to induce sweating together with systemic cortisol reactivity while in study II (N=52) a sauna bathing challenge induced sweating without systemic cortisol changes. In both studies, repeated assessments of HCC, salivary cortisol, cortisol in sweat and individuals' sweating rate (single assessment) were conducted on the experimental day and at a next-day follow-up. Results across the two studies consistently revealed that HCC were not altered by the acute interventions. Further, HCC were found to be unrelated to acute salivary cortisol reactivity, sweat cortisol levels, sweating rate or the time of examination. In line with previous data, cortisol levels in sweat were strongly related to total salivary cortisol output across the examined periods. The present results oppose recent case report data by showing that single sweat-inducing interventions do not result in acute changes in HCC. Our data also tentatively speak against the notion that cortisol in sweat may be a dominant source of HCC. Further, our findings also indicate that HCC are not subject to diurnal variation. This research provides further support for hair cortisol analysis as a marker of integrated long-term systemic cortisol secretion.

  3. Cortisol influences the antipredator behavior induced by chemical alarm cues in the Frillfin goby.

    PubMed

    Barreto, Rodrigo Egydio; Barbosa-Júnior, Augusto; Urbinati, Elisabeth Criscuolo; Hoffmann, Anette

    2014-04-01

    We evaluated the effect of increased plasma cortisol levels on fish antipredator behavior induced by conspecific chemical alarm cues. The experimental model for the study was the Frillfin goby Bathygobius soporator. We first confirmed that the alarm substance induces typical defensive antipredator responses in Frillfin gobies and described their alarm substance cells (epidermal 'club' cells). Second, we confirmed that intraperitoneal cortisol implants increase plasma cortisol levels in this species. We then demonstrated that exogenous cortisol administration and subsequent exposure to an alarm substance decreased swimming activity to a greater extent than the activity prompted by either stimulus alone. In addition, cortisol did not abolish the sheltering response to the alarm chemical cue even though it decreased activity. As predators use prey movements to guide their first contact with the prey, a factor that decreases swimming activity clearly increases the probability of survival. Consequently, this observation indicates that cortisol helps improve the antipredator response in fish.

  4. 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

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

    PubMed

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

    2015-11-18

    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.

  6. Classical analog of electromagnetically induced transparency

    NASA Astrophysics Data System (ADS)

    Garrido Alzar, C. L.; Martinez, M. A. G.; Nussenzveig, P.

    2002-01-01

    We present a classical analog of electromagnetically induced transparency (EIT). In a system of just two coupled harmonic oscillators subject to a harmonic driving force, we reproduce the phenomenology observed in EIT. We also describe a simple experiment with two linearly coupled RLC circuits which can be incorporated into an undergraduate laboratory.

  7. Physical activity moderates stressor-induced rumination on cortisol reactivity

    PubMed Central

    Puterman, Eli; O’Donovan, Aoife; Adler, Nancy E.; Tomiyama, A. Janet; Kemeny, Margaret; Wolkowitz, Owen M.; Epel, Elissa

    2011-01-01

    Objective Physically active individuals have lower rates of morbidity and mortality, and recent evidence indicates that physical activity may be particularly beneficial to those experiencing chronic stress. The tendency to ruminate increases and prolongs physiological stress responses, including hypothalamic-pituitary adrenal (HPA) axis responses as indexed by cortisol reactivity to stressful experiences. We examined the association between ruminating in response to a laboratory stressor task and HPA axis reactivity and recovery, and whether a physically active lifestyle moderates the associations between rumination and cortisol output trajectories. Methods Forty-six post-menopausal women underwent the Trier Social Stress Test while salivary cortisol was repeatedly measured. Twenty-five minutes after the end of the stressor, participants reported level of rumination in response to the stress. Results Findings indicate that physical activity moderated the initial rate (B = −.10, SE = .04, p < .05) and curvature (B = −.03, SE = .01, p = .06) of the relationship between rumination and log-transformed cortisol trajectory. Among sedentary participants, those who responded to the stressor with higher levels of rumination had a more rapid initial increase in cortisol (0.26 vs 0.21, p < .001), a later peak (56 vs. 39 minutes), and a delayed recovery (curvature −0.07 vs. −0.08, p < .001) compared to those with lower levels of rumination. In active participants, cortisol trajectories were equivalent, regardless of level of rumination. Conclusions In sum, individuals who maintain a physically active lifestyle may be protected against the effects of rumination on HPA axis reactivity to and recovery from acute stress. PMID:21873586

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

    PubMed

    Maes, M; van West, D; De Vos, N; Westenberg, H; Van Hunsel, F; Hendriks, D; Cosyns, P; Scharpé, S

    2001-01-01

    There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

  16. Mental task-induced strain and its after-effect assessed through variations in plasma cortisol levels.

    PubMed

    Wittersheim, G; Brandenberger, G; Follenius, M

    1985-09-01

    Plasma cortisol levels were measured in 20 healthy men while they carried out mental tasks in intermittent noise. Half the subjects performed a serial short-term memory task and, later on, a multiple-choice task, whereas the other half performed only the multiple-choice task. The aim of the experiment was to determine whether enhanced cortisol release, due to a centrally mediated arousal reaction, depressed the cortisol level when the subjects had to cope with a new task situation. In a previous study, such a regulatory after-effect was revealed in the midday meal-related cortisol peak, but not in a subsequent exercise-induced cortisol peak, although cortisol release in both cases could be related to metabolic changes. The results showed that the second mental task still induced a pronounced rise in cortisol levels. No changes in task performances were found. It is concluded that different regulatory mechanisms are involved in adrenocortical secretion, depending on the origin of the stimulation, and that cortisol responses are closely related to individual coping abilities and strategies.

  17. 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

  18. Stress-induced cortisol secretion impairs detection performance in x-ray baggage screening for hidden weapons by screening novices.

    PubMed

    Thomas, Livia; Schwaninger, Adrian; Heimgartner, Nadja; Hedinger, Patrik; Hofer, Franziska; Ehlert, Ulrike; Wirtz, Petra H

    2014-09-01

    Aviation security strongly depends on screeners' performance in the detection of threat objects in x-ray images of passenger bags. We examined for the first time the effects of stress and stress-induced cortisol increases on detection performance of hidden weapons in an x-ray baggage screening task. We randomly assigned 48 participants either to a stress or a nonstress group. The stress group was exposed to a standardized psychosocial stress test (TSST). Before and after stress/nonstress, participants had to detect threat objects in a computer-based object recognition test (X-ray ORT). We repeatedly measured salivary cortisol and X-ray ORT performance before and after stress/nonstress. Cortisol increases in reaction to psychosocial stress induction but not to nonstress independently impaired x-ray detection performance. Our results suggest that stress-induced cortisol increases at peak reactivity impair x-ray screening performance.

  19. Role of cortisol and superoxide dismutase in psychological stress induced anovulation.

    PubMed

    Kala, Manika; Nivsarkar, Manish

    2016-01-01

    Stress has been identified as a potential trigger for reproductive dysfunctions, but the psycho-physiological pathway behind the effect of stress on ovulation remains unexplored. The present research work highlights the plausible mechanism of psychological stress on ovulation in mice by targeting superoxide dismutase (SOD), an enzyme involved in ovulation. For this, three consecutive studies were carried out. The first study aimed to determine the effect of psychological stress induced change in cortisol level, behavioral parameters and normal estrous cyclicity. The effect on mRNA expression of SOD subtypes, follicular growth in histological sections of ovaries and the difference in oocyte quality and number, upon superovulation were assessed in the subsequent studies. The results indicate that psychological stress model causes an increase in cortisol level (p⩽0.05) with development of anhedonia, depression and anxiety. An irregular estrous cycle was observed in stressed mice with an upregulation in mRNA expression of SOD subtypes. Histological sections revealed an increase in atretic antral follicle with an impaired follicular development. Moreover, immature oocytes were obtained from superovulated stressed mice. The study concludes that psychological stress results in anovulation which may be due to increase in cortisol level and SOD activity in stressed mice.

  20. Cortisol and induced cognitive fatigue: effects on memory activation in healthy males.

    PubMed

    Klaassen, Elissa B; de Groot, Renate H M; Evers, Elisabeth A T; Nicolson, Nancy A; Veltman, Dick J; Jolles, Jelle

    2013-09-01

    We investigated the relationship between individual differences in acute fatigue and endogenous cortisol changes elicited by the sustained performance of cognitively demanding tasks (fatigue condition). Healthy males provided salivary cortisol measurements and subjective fatigue ratings, and were scanned (functional magnetic resonance imaging) during memory encoding and recognition tasks in fatigue and control conditions. A group of 15 'responders' showed significantly higher cortisol levels in the fatigue condition than 12 'non-responders'. Responders showed higher subjective fatigue and reduced encoding and recognition activation than non-responders in the fatigue condition. An interaction in activation changes in the right hippocampus during encoding reflected decreased activation in responders, but somewhat increased activation in non-responders in the fatigue compared to control condition. Moreover, decreased hippocampal activation in responders was associated with increased subjective fatigue. Findings are consistent with a central role for the hippocampus in differences between responders and non-responders and also implicate the right hippocampus in individual differences in induced cognitive fatigue effects.

  1. Stress-induced changes in mood and cortisol release predict mood effects of amphetamine

    PubMed Central

    Hamidovic, Ajna; Childs, Emma; Conrad, Megan; King, Andrea; de Wit, Harriet

    2010-01-01

    Background Stress is thought to contribute to both initiation and relapse to drug abuse. However, the mechanisms by which stress influences drug use are unclear. Interestingly, responses to acute administration of stimulant drugs resemble certain neuronal and hormonal responses to acute stress, and there is accumulating evidence that individual variation in the positive reinforcing or euphorigenic effects of a drug are related to individual differences in responsivity to acute stress. Methods In this study we evaluated relationships between physiological and subjective responses to a stressful task and to an oral dose of d-amphetamine in healthy adult volunteers (N=34). Individuals participated in four experimental sessions; two behavioral sessions involving a stressful task (i.e. public speech) or a non-stressful control task, and two drug sessions involving oral administration of d-amphetamine (20mg) or a placebo. The dependent measures included salivary cortisol, heart rate, mean arterial pressure, and subjective ratings of mood. Results As expected, both stress and d-amphetamine increased cortisol, heart rate and blood pressure. Stress increased negative mood, whereas d-amphetamine induced prototypic stimulant effects and increased ratings of drug liking. Analyses revealed that increased negative mood states after stress were correlated with positive mood after amphetamine. In addition, increased cortisol after stress was correlated with positive mood responses to amphetamine. Finally, there were modest positive correlations between cortisol and heart rate increases after stress and mean arterial pressure after amphetamine. Conclusions These results support and extend previous observations that responses to acute stress are correlated with certain subjective, hormonal and cardiovascular effects of a stimulant drug. PMID:20176450

  2. 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

  3. 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.

  4. Cortisol modification of HeLa 65 alkaline phosphatase. Decreased phosphate content of the induced enzyme.

    PubMed

    Bazzell, K L; Price, G; Tu, S; Griffin, M

    1976-01-15

    Alkaline phosphatase activity of HeLa cells is increased 5-20-fold during growth in medium with cortisol. The increase in enzyme activity is due to an enhanced catalytic efficiency rather than an increase in alkaline phosphatase protein in induced cells. In the present study the chemical composition of control and induced forms of alkaline phosphatase were investigated to determine the enzyme modification that may be responsible for the increased catalytic activity. HeLa alkaline phosphatase is a phosphoprotein and the induced form of the enzyme has approximately one-half of the phosphate residues associated with control enzyme. The decrease in phosphate residues of the enzyme apparently alters its catalytic activity. Other chemical components of purified alkaline phosphatase from control and induced cells are similar; these include sialic acid, hexosamine and sulfhydryl residues. PMID:1248469

  5. Basal or stress-induced cortisol and asthma development: the TRAILS study.

    PubMed

    Vink, Nienke M; Boezen, H Marike; Postma, Dirkje S; Rosmalen, Judith G M

    2013-04-01

    We examined the association between: 1) cortisol levels and asthma or asthma development; 2) cortisol levels upon stress and asthma. In addition, we performed a post hoc meta-analysis on results from the literature. Cortisol, cortisol upon stress, asthma (doctor diagnosis of asthma and/or symptoms and/or treatment in the past 12 months) and asthma development (asthma at a specific survey while not having asthma at the previous survey(s)) were assessed in the TRAILS study (n=2230, mean age at survey 1 11 years, survey 2 14 years and survey 3 16 years). Logistic regression models were used to study associations between: 1) cortisol (cortisol awakening response, area under the curve (AUC) with respect to the ground (AUCg) or with respect to the increase (AUCi), and evening cortisol) and asthma or asthma development; 2) cortisol upon stress (AUCg or AUCi) and asthma. The meta-analyses included nine case-control articles on basal cortisol in asthma. No significant association was found between: 1) cortisol and asthma (age 11 years) or asthma development (age 14 or 16 years); 2) cortisol upon stress and asthma (age 16 years). The meta-analysis found lower morning and evening cortisol levels in asthmatics compared to non-asthmatics; however, the summary estimates were not significant. We found no evidence supporting a role for cortisol in asthma and asthma development.

  6. 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

  7. 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

  8. Fitness and behavioral correlates of pre-stress and stress-induced plasma cortisol titers in pink salmon (Oncorhynchus gorbuscha) upon arrival at spawning grounds.

    PubMed

    Cook, K V; McConnachie, S H; Gilmour, K M; Hinch, S G; Cooke, S J

    2011-11-01

    Semelparous Pacific salmon (Onchorynchus spp.) serve as an excellent model for examining the relationships between life history, behavior and individual variation in glucocorticoid (GC) stress hormone levels because reproductive behaviors are highly variable between individuals and failure to reproduce results in zero fitness. Pink salmon (O. gorbuscha) were intercepted upon arrival at the spawning grounds across three time periods. Pre-stress and stress-induced plasma cortisol concentrations were assessed in relation to behavior, longevity and reproductive success. Results revealed differences between sexes and with arrival time. The study period marked a year of high reproductive success and only nine females (12% of sample) failed to spawn. Female pre-spawn mortalities were characterized by significantly elevated stress-induced cortisol concentrations and decreased longevity as well as pre-stress cortisol above the normal range in pink salmon from the study area. Interestingly, reproductive behaviors were only associated with pre-stress cortisol levels. For females, aggression and mate interaction time were reduced in individuals with elevated pre-stress cortisol concentrations. In males, a similar negative relationship between pre-stress cortisol concentration and mate interaction time was detected. The observed behavioral correlations are likely a factor of social status where dominant individuals, known to have higher reproductive success, are characterized by lower cortisol levels relative to subordinate conspecifics. Findings show both elevated pre-stress and stress-induced cortisol concentrations at arrival to the spawning grounds to be associated with reduced survival.

  9. 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…

  10. 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.

  11. Cortisol administration induces sex change from ovary to testis in the protogynous Wrasse, Halichoeres trimaculatus.

    PubMed

    Nozu, Ryo; Nakamura, Masaru

    2015-01-01

    Steroid hormones have been shown to play important roles in triggering sex change. However, the upstream mechanism that regulates the secretion of sex steroid hormones controlling sex change is not yet known. Cortisol, the primary glucocorticoid in teleost fish, is known to exhibit anti-stress action and is involved in many physiological functions, including regulation of steroidogenesis. Therefore, cortisol could be one of the candidate factors involved in the onset of sex change. In this study, we investigated the role of cortisol in sex change in the three-spot wrasse, Halichoeres trimaculatus, by prolonged administration of cortisol. Our results showed that gonads of all individuals treated with cortisol (1,000 µg/g diet) for 6 weeks contained spermatogenic germ cells. One of them exhibited matured testes with an ovarian cavity, indicating sex change. Additionally, the plasma estradiol-17β level in the cortisol treatment group was significantly lower than in the control group suggesting that cortisol plays a direct and/or indirect role in the regulation of estrogen production. These data imply that cortisol might be involved in the regulation of steroidogenesis by causing a decrease in the estrogen level, leading to the onset of sex change.

  12. 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 ...

  13. 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

  14. 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.

  15. The influence of aspirin on exercise-induced changes in adrenocorticotrophic hormone (ACTH), cortisol and aldosterone (ALD) concentrations.

    PubMed

    Przybyłowski, Jan; Obodyński, Kazimierz; Lewicki, Czesław; Kuźniar, Jerzy; Zaborniak, Stanisław; Drozd, Sławomir; Czarny, Wojciech; Garmulewicz, Maciej

    2003-04-01

    The influence of aspirin (ASA) on the endocrinology system and prostaglandin (PGs) synthesis is not completely clear. The aim of the study was to estimate the influence of ASA on the changes in the concentration of ACTH, cortisol and aldosterone (ALD) induced by physical exercise. This study was conducted on 19 healthy students (age 21-23 years). They were subjected to intensive physical exercise on a cycle ergometer. On the day prior to the experiment, 12 subjects took two 0.5-g doses of ASA in a wafer, and another 0.5 g 3-4 h before the test on the day of the investigation (ASA group). The remaining seven subjects (control group) received placebo. Hematocrit, lactate concentration and concentrations of ACTH, cortisol and ALD were determined before exercise, after exercise, and after 30 min of recovery, in a blood sample taken from a cubital vein. Before exercise, the degree of platelet aggregation in response to arachidonic acid was estimated, in order to confirm the correct allocation to the two groups. Aggregation should only occur in the ASA group. ASA and control groups exercised for 30.3 (3.1) min and 30.2 (1.6) min, respectively. Maximal heart rate and lactate concentration were similar in both groups, as were the basal concentrations of ACTH and cortisol; the ALD concentration seemed lower in the ASA group, but the difference was not significant (p<0.1). In both groups after exercise ACTH, cortisol and ALD concentrations were significantly increased, however when compared to the control group, the increase of ACTH in the ASA group was significantly higher, and ALD increase significantly lower. After recovery there was a significant decrease in ACTH concentration, whereas the concentrations of ALD and cortisol did not change. The concentrations of cortisol in both groups after exercise and recovery were similar. That is most likely because the ACTH concentrations in the ASA and control groups were sufficient for almost maximal cortisol secretion. It is

  16. Effects of cortisol administration on craving in heroin addicts

    PubMed Central

    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

  17. 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.

  18. Obesity and cortisol.

    PubMed

    Björntorp, P; Rosmond, R

    2000-10-01

    Cortisol in obesity is a much-studied problem. Previous information indicates that cortisol secretion is elevated but that circulatory concentrations are normal or low, suggesting that peripheral disappearance rate is elevated. These studies have usually not taken into account the difference between central and peripheral types of obesity. Recent studies using saliva cortisol have indicated that the problem is complex with both high and low secretion of cortisol, perhaps depending on the status of the function of the hypothalamic-pituitary-adrenal gland axis. A significant background factor seems to be environmental stress. The results also suggest that the pattern of cortisol secretion may be important. Other neuroendocrine pathways are also involved, including the central sympathetic nervous system, the gonadal and growth hormone axes, and the leptin system. In concert, these abnormalities seem to be responsible for the abnormal metabolism often seen in central obesity. Several associated polymorphisms of candidate genes may provide a genetic background. Cortisol conversion to inactive metabolites may be a factor increasing central signals to secretion and may add to the increased secretion of cortisol induced by centrally acting factors. Perinatal factors have been found to be involved in the pathogenesis of obesity and its complications. The mechanism involved is not known, but available information suggests that programming of the hypothalamic-pituitary-adrenal axis may be responsible.

  19. 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

  20. 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...

  1. 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

  2. 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

  3. 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 ...

  4. Decreased cortisol response to insulin induced hypoglycaemia in asthmatics treated with inhaled fluticasone propionate

    PubMed Central

    Mahachoklertwatta..., P; Sudkronrayudh, K; Direkwattanachai, C; Choubtum, L; Okascharoen, C

    2004-01-01

    Aims: To assess adrenal function in asthmatic children treated with inhaled fluticasone propionate for up to 16 weeks. Methods: Children with asthma and bronchial hyperresponsiveness to inhaled methacholine were treated with inhaled fluticasone 250–750 µg/day via Volumatic spacer. The insulin tolerance test (ITT) was performed to assess adrenal function. Results: Eighteen asthmatic patients (10 boys, 8 girls), aged 7–17 years received inhaled fluticasone therapy at a median dose of 477 µg/m2 per day for 5–16 weeks. Adrenal suppression, defined as 60 minute serum cortisol less than 500 nmol/l, was found in 9 of 18 children. Following the ITT, the median basal and 60 minute serum cortisol concentrations of the suppressed group were 135.0 and 350.0 nmol/l, respectively; the corresponding values for the unsuppressed group were 242.2 and 564.7 nmol/l. Repeat ITT in the suppressed group 2–3 months after discontinuation of fluticasone revealed that all patients had a 60 minute serum cortisol greater than 500 nmol/l. Conclusion: After therapy for asthma with inhaled fluticasone at approximately 500 µg daily for up to 16 weeks, half the children had evidence of adrenal suppression. PMID:15499064

  5. 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

  6. Increased secretion of growth hormone, prolactin, antidiuretic hormone, and cortisol induced by the stress of motion sickness.

    PubMed

    Eversmann, T; Gottsmann, M; Uhlich, E; Ulbrecht, G; von Werder, K; Scriba, P C

    1978-01-01

    The stress of motion sickness was experimentally provoked by Coriolis effect. Significant and reproducible increases from the basal serum level (delta mean +/- S.E.) of antidiuretic hormone delta - ADH: 48.2 +/- 4.6 pg/ml; p less than 0.0005), of growth hormone (delta - hGH: 10.0 +/- 1.2 ng/ml; p less than 0.0005), of prolactin (delta - hPRL: 186.5 +/- 29.9 muU/ml; p less than 0.0005), and of cortisol (delta - F; 12.3 +/- 0.9 microgram%; p less than 0.0005) were observed, whereas the luteinizing hormone levels did not change significantly. The stimulation of hormone secretion induced by different degrees of motion sickness seems to correlate with the severity of motion sickness. The secretion of antidiuretic hormones is the most sensitive indicator for the stress of motion sickness whereas growth hormone, prolactin, and cortisol responses to the stress of motion sickness are more delayed and less pronounced.

  7. The cortisol and androgen pathways cross talk in high temperature-induced masculinization: the 11β-hydroxysteroid dehydrogenase as a key enzyme.

    PubMed

    Fernandino, Juan Ignacio; Hattori, Ricardo Shohei; Kishii, Ai; Strüssmann, Carlos Augusto; Somoza, Gustavo Manuel

    2012-12-01

    In many ectotherm species the gonadal fate is modulated by temperature early in life [temperature-dependent sex determination (TSD)] but the transducer mechanism between temperature and gonadal differentiation is still elusive. We have recently shown that cortisol, the glucocorticoid stress-related hormone in vertebrates, is involved in the TSD process of pejerrey, Odontesthes bonariensis. Particularly, all larvae exposed to a male-producing temperature (MPT, 29 C) after hatching showed increased whole-body cortisol and 11-ketotestosterone (11-KT; the main bioactive androgen in fish) levels and developed as males. Moreover, cortisol administration at an intermediate, mixed sex-producing temperature (MixPT, 24 C) caused increases in 11-KT and in the frequency of males, suggesting a relation between this glucocorticoid and androgens during the masculinization process. In order to clarify the link between stress and masculinization, the expression of hydroxysteroid dehydrogenase (hsd)11b2, glucocorticoid receptors gr1 and gr2, and androgen receptors ar1 and ar2 was analyzed by quantitative real time PCR and in situ hybridization in larvae reared at MPT, MixPT, and female-producing temperature (FPT, 17 C) during the sex determination period. We also analyzed the effects of cortisol treatment in larvae reared at MixPT and in adult testicular explants incubated in vitro. MPT and cortisol treatment produced significant increases in hsd11b2 mRNA expression. Also, gonadal explants incubated in the presence of cortisol showed increases of 11-KT levels in the medium. Taken together these results suggest that cortisol promotes 11-KT production during high temperature-induced masculinization by modulation of hsd11b2 expression and thus drives the morphogenesis of the testes.

  8. Effect of Drug Alprazolam on Restrained Stress Induced Alteration of Serum Cortisol and Antioxidant Vitamins (Vitamin C and E) in Male Albino Rats

    PubMed Central

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H.; Desai, S.D.

    2016-01-01

    Introduction Stress can cause harmful effects in the body that induce a wide range of biochemical and behavioural changes. As anti-stress drugs are routinely used to combat stress hence study is needed to assess the contraindication of these drugs in the physiological systems. Aim To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. Materials and Methods Adult male albino rats (body weight 175-225g) were divided into four groups of six animals in each. Group I (control), kept undisturbed in the metabolic cage throughout the 42 days experimental period. Group II (stress) rats were kept in a wire mesh restrainer for 6 hr/day for 42 days. Group III (stress+ withdrawal) rats were stressed for 21 days and withdrawal of stress for remaining 21 days (total 42 days). Group IV (stress + alprazolam) rats were only stressed for 21 days and treated with drug alprazolam (5mg/kg body weight, intraperitoneal) in continuation with stress for remaining 21 days (total period is 42 days). At the end of 42 days all the rats were sacrificed and serum cortisol, vitamin C and E levels were estimated. Results Group II (stressed) showed a significant increase in serum cortisol level with concomitant decrease of serum vitamin C and E levels. Group III (withdrawal) and Group IV (+alprazolam) rats showed significant reduction of serum cortisol along with subsequent increase of serum vitamin C and E concentrations. Conclusion Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels. PMID:27656428

  9. 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

  10. 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

  11. 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.

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

    PubMed

    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 24h. 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

  13. Synthesis of the Rosette-Inducing Factor RIF-1 and Analogs

    PubMed Central

    2015-01-01

    Studies on the origin of animal multicellularity have increasingly focused on one of the closest living relatives of animals, the choanoflagellate Salpingoeca rosetta. Single cells of S. rosetta can develop into multicellular rosette-shaped colonies through a process of incomplete cytokinesis. Unexpectedly, the initiation of rosette development requires bacterially produced small molecules. Previously, our laboratories reported the planar structure and femtomolar rosette-inducing activity of one rosette-inducing small molecule, dubbed rosette-inducing factor 1 (RIF-1), produced by the Gram-negative Bacteroidetes bacterium Algoriphagus machipongonensis. RIF-1 belongs to the small and poorly explored class of sulfonolipids. Here, we report a modular total synthesis of RIF-1 stereoisomers and structural analogs. Rosette-induction assays using synthetic RIF-1 stereoisomers and naturally occurring analogs defined the absolute stereochemistry of RIF-1 and revealed a remarkably restrictive set of structural requirements for inducing rosette development. PMID:24983513

  14. Autocrine TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in breast cells.

    PubMed

    Yang, L; Yang, J; Venkateswarlu, S; Ko, T; Brattain, M G

    2001-09-01

    In this study, we address whether TGFbeta signaling mediates vitamin D3 analog-induced growth inhibition in nonmalignant and malignant breast cells. Normal mammary epithelial cells (184), immortalized nonmalignant mammary epithelial cells (184A1 and MCF10A), and breast cancer cells (early passage MCF7: MCF7E) were sensitive to the inhibitory effects of vitamin D3 analogs (EB1089 and MC1288) while late passage MCF7 breast cancer (MCF7L) cells were relatively resistant. A similar pattern of sensitivity to TGFbeta was observed with these cells. Thus, the sensitivity to the vitamin D3 analogs correlated with the sensitivity to TGFbeta. MCF7L TGFbetaRII-transfected cells, which have autocrine TGFbeta activity, were more sensitive to EB1089 than MCF7L cells. TGFbeta neutralizing antibody was found to block the inhibitory effects of these analogs. These results are consistent with the idea that autocrine TGFbeta signaling mediates the anti-proliferative effects of the vitamin D3 analogs in these cells. The expression of TGFbeta isoforms and/or TGFbeta receptors was induced by the analogs in the vitamin D3 and TGFbeta sensitive cells. Vitamin D3 analogs did not induce TGFbeta or TGFbeta receptor expression in the resistant MCF7L cells. Therefore, EB1089 induces autocrine TGFbeta activity through increasing expression of TGFbeta isoforms and/or TGFbeta receptors. In addition, EB1089 induced nuclear VDR protein levels in the sensitive 184A1 cells but not in the resistant MCF7L cells. 184A1 cells were more sensitive to EB1089-induced VDR-dependent transactivation than MCF7L cells as measured by a luciferase reporter construct containing the VDRE, indicating a defect of VDR signaling in MCF7L cells. Smad3, a TGFbeta signaling mediator, coactivated VDR-dependent transactivation in 184A1 cells but not in MCF7L cells. These results indicate that Smad3 coactivates VDR to further enhance TGFbeta signaling and vitamin D3 signaling in the sensitive 184A1 cells. The results also

  15. Inhibition of nicotine-induced toxicity by curcumin and curcumin analog: a comparative study.

    PubMed

    Kalpana, C; Menon, Venugopal P

    2004-01-01

    The present study was undertaken to evaluate the effects of curcumin and curcumin analog on blood oxidant-antioxidant status during nicotine-induced toxicity in male Wistar rats. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks). The enhanced circulatory lipid peroxides in nicotine-treated rats was accompanied by a significant decrease in the levels of ascorbic acid, vitamin E, reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase. There was a reduction in the levels of zinc with an elevation of copper and ferritin in nicotine-treated rats. Administration of curcumin and curcumin analog significantly lowered the lipid peroxidation and enhanced the antioxidant status with modulation in the levels of zinc, copper, and ferritin. However, the effect was more significant in curcumin analog-treated rats than in curcumin-treated rats. The results of the present study suggest that curcumin and curcumin analog exert their protective effects by modulating the extent of lipid peroxidation and enhancing the antioxidant status. PMID:15671691

  16. 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

  17. 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.

  18. IL-1beta-induced cortisol stimulates lung fluid absorption in fetal guinea pigs via SGK-mediated Nedd4-2 inhibition.

    PubMed

    Li, Tianbo; Koshy, Shyny; Folkesson, Hans G

    2009-03-01

    We tested the hypothesis that interleukin (IL)-1beta-induced cortisol synthesis stimulates distal lung fluid absorption in fetal guinea pigs via induction of serum- and glucocorticoid-regulated kinase (SGK) and inhibition of neural precursor cell expressed, developmentally downregulated protein 4-2 (Nedd4-2). IL-1beta was subcutaneously administered daily to timed-pregnant guinea pigs over 3 days. Fetuses were obtained by abdominal hysterotomy at gestation day (GD)61 and GD68 and instilled with an isosmolar 5% albumin solution into the lungs. Distal lung fluid movement was measured over 1 h from the change in distal air space protein concentration. Fetal lungs were secreting lung fluid at GD61 while absorbing lung fluid at GD68. Distal lung fluid absorption was induced at GD61 by IL-1beta but unaffected at GD68. Plasma cortisol concentrations were increased by IL-1beta at GD61 and endogenously at GD68. Distal lung fluid absorption was measured and correlated to SGK and Nedd4-2 expression and to alpha-epithelial Na channel (ENaC) expression. SGK was increased by IL-1beta and late during gestation (GD68), while Nedd4-2 was decreased by IL-1beta and late during gestation. alpha-ENaC was induced by IL-1beta at GD61 and increased late during gestation. Thus our study suggests that cortisol-stimulated fetal lung fluid absorption is mediated by increased ENaC expression and may be governed by the SGK/Nedd4-2 pathway. These observations may explain why babies delivered preterm after intrauterine inflammation have a reduced risk of developing severe respiratory distress. PMID:19136575

  19. Prostaglandin-induced radioprotection of murine intestinal crypts and villi by a PGE diene analog (SC-44932) and a PGI analog (Iloprost)

    NASA Astrophysics Data System (ADS)

    Hanson, Wayne R.; Collins, Paul W.

    The aminothiols exemplified by WR-2721 are effective radioprotectors; however, their toxicity associated with hypotension, nausea, and emesis has limited their development for applications in medicine or in hazardous radiation environments. There is a need for new radioprotectors that have fewer toxic side effects when given alone or combined with reduced amounts of thiols. A variety of prostaglandins (PGs) have been shown to be radioprotective agents and some appear to have fewer toxic side effects than the aminothiols. Iloprost, a stable PGI, analog protects the clonogenic epithelial cells of intestinal crypts but does not protect epithelial cells of the villi. In contrast, an E-series omega chain diene analog designated SC-44932 protects epithelial cells of both crypts and villi. When the two are combined, protection of the crypts is additive and the villi are protected to the same degree as when SC-44932 is given alone. Since radioprotection for some PGs has been shown to be dependent upon receptors, we suggest that the pattern of radioprotection seen with these two analogs depend on the location of the respective receptors or on the ability of differentiated villus cells to respond to PGs. By studying different analogs, we hope to identify mechanisms associated with PG-induced radioprotection and to identify the most protective PG analogs for applications of radioprotection.

  20. Cortisol blood test

    MedlinePlus

    Serum cortisol ... early in the morning. This is important, because cortisol level varies throughout the day. You may be ... drugs Estrogen Human-made (synthetic) glucocorticoids, such as hydrocortisone, prednisone and prednisolone Androgens

  1. Sleep deprivation attenuates endotoxin-induced cytokine gene expression independent of day length and circulating cortisol in male Siberian hamsters (Phodopus sungorus).

    PubMed

    Ashley, Noah T; Walton, James C; Haim, Achikam; Zhang, Ning; Prince, Laura A; Fruchey, Allison M; Lieberman, Rebecca A; Weil, Zachary M; Magalang, Ulysses J; Nelson, Randy J

    2013-07-15

    Sleep is restorative, whereas reduced sleep leads to negative health outcomes, such as increased susceptibility to disease. Sleep deprivation tends to attenuate inflammatory responses triggered by infection or exposure to endotoxin, such as bacterial lipopolysaccharide (LPS). Previous studies have demonstrated that Siberian hamsters (Phodopus sungorus), photoperiodic rodents, attenuate LPS-induced fever, sickness behavior and upstream pro-inflammatory gene expression when adapted to short day lengths. Here, we tested whether manipulation of photoperiod alters the suppressive effects of sleep deprivation upon cytokine gene expression after LPS challenge. Male Siberian hamsters were adapted to long (16 h:8 h light:dark) or short (8 h:16 h light:dark) photoperiods for >10 weeks, and were deprived of sleep for 24 h using the multiple platform method or remained in their home cage. Hamsters received an intraperitoneal injection of LPS or saline (control) 18 h after starting the protocol, and were killed 6 h later. LPS increased liver and hypothalamic interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF) gene expression compared with vehicle. Among LPS-challenged hamsters, sleep deprivation reduced IL-1 mRNA levels in liver and hypothalamus, but not TNF. IL-1 attenuation was independent of circulating baseline cortisol, which did not increase after sleep deprivation. Conversely, photoperiod altered baseline cortisol, but not pro-inflammatory gene expression in sleep-deprived hamsters. These results suggest that neither photoperiod nor glucocorticoids influence the suppressive effect of sleep deprivation upon LPS-induced inflammation.

  2. Effect of vitamin E supplementation on arsenic induced alteration in blood biochemical profile, oxidant/antioxidant status, serum cortisol level and retention of arsenic and selenium in goats.

    PubMed

    Mohanta, Ranjan Kumar; Garg, Anil Kumar; Dass, Ram Sharan

    2015-01-01

    Arsenic (As) exerts oxidative stress with depletion of body selenium in monogastric animals. But in ruminants this fact is not yet verified. Vitamin E is an effective dietary antioxidant. Thus, in this experiment, the protective effect of vitamin E against arsenic toxicity induced by sodium arsenite (60mg As/kg diet) was investigated in goat kids. For this, 21 male kids were divided into three equal groups and fed either basal diet as such (control), or supplemented with 60mg As/kg diet and 60mg As/kg diet+250IU vitamin E/kg diet for 180 days. Vitamin E supplementation alleviated the toxic effects caused by arsenic on serum alanine aminotransferase and aspartate aminotransferase and lipid peroxidation. It also prevented the depletion of reduced glutathione content and reduction in activity of catalase, superoxide dismutase and glutathione-s-transferase in erythrocytes resulted from arsenic intoxication. The elevated levels of arsenic and reduced levels of selenium in the serum and tissues in arsenic treated animals were attenuated by vitamin E supplementation, though not completely. However, serum cortisol level was not affected by arsenic. It was concluded that arsenic exerts cortisol independent stressor mechanism and supplementation of vitamin E at a level of 250IU/kg diet was partially effective in reducing tissue accumulation of arsenic in the body and protect the kids from oxidative stress induced by arsenic.

  3. 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

  4. 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

  5. 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

  6. The use of saliva cortisol, urinary cortisol, and catecholamine measurements for a noninvasive assessment of stress responses in dogs.

    PubMed

    Beerda, B; Schilder, M B; Janssen, N S; Mol, J A

    1996-09-01

    A problem in assessing animal welfare is that collecting data in itself may be stressful to the animals. Therefore, noninvasive methods for collecting data have to be devised and tested. A first step in investigating saliva cortisol, urinary cortisol, and urinary catecholamine as noninvasive indicators of canine well-being is the validation of these hormonal measures as alternatives for those in plasma. Using a model of insulin (0.2 U/kg)-induced hypoglycemia, we report on stress-induced responses in saliva cortisol, urinary cortisol, and urinary catacholamines relative to cortisol and catecholamine responses in plasma. Hypoglycemia in six dogs induced significant (P < 0.05) increases in plasma cortisol and adrenaline but not noradrenaline. Saliva cortisol responses expressed as net area under the response curve correlated significantly with plasma cortisol responses (r > 0.92). Saliva cortisol levels measured 7 to 12% of plasma cortisol concentrations. Cortisol/creatinine rations in urine were significantly higher when voided after insulin administeration, compared to when voided after saline treatment. Insulin-induced increments in cortisol/ creatinine ratios were nonsignificant when urine samples were assayed after dichloromethane extraction. Although urinary adrenaline/creatinine (A/C) ratios were significantly correlated with maximum plasma adrenaline values after insulin administration, A/C ratios did not differ significantly between insulin and saline treatment. The present experiment provides strong support for using saliva sampling and urine collection as noninvasive methods to establish stress-induced cortisol responses. For measuring acute plasma adrenaline responses, measuring A/C ratios may not be a valid alternative.

  7. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

    PubMed Central

    Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu; LaRiviere, Patrick J.; Sammani, Saad; Lussier, Yves A.; Dudek, Steven M.; Natarajan, Viswanathan; Weichselbaum, Ralph R.; Garcia, Joe G. N.

    2011-01-01

    Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1−/−) or with reduced expression of S1P receptors (S1PR1+/−, S1PR2−/−, and S1PR3−/−) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2×/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2×/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.—Mathew, B., Jacobson, J. R., Berdyshev, E., Huang, Y., Sun, X., Zhao, Y., Gerhold, L. M., Siegler, J., Evenoski, C., Wang, T., Zhou, T., Zaidi, R., Moreno-Vinasco, L., Bittman, R., Chen, C. T., LaRiviere, P. J., Sammani, S., Lussier, Y. A., Dudek, S. M., Natarajan, V., Weichselbaum, R. R., Garcia, J. G. N. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. PMID:21712494

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. Fumonisins and Alternaria alternata lycopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells.

    PubMed Central

    Wang, W; Jones, C; Ciacci-Zanella, J; Holt, T; Gilchrist, D G; Dickman, M B

    1996-01-01

    Fusarium moniliforme toxins (fumonisins) and Alternaria alternata lycopersici (AAL) toxins are members of a new class of sphinganine analog mycotoxins that occur widely in the food chain. These mycotoxins represent a serious threat to human and animal health, inducing both cell death and neoplastic events in mammals. The mechanisms by which this family of chemical congeners induce changes in cell homeostasis were investigated in African green monkey kidney cells (CV-1) by assessing the appearance of apoptosis, cell cycle regulation, and putative components of signal transduction pathways involved in apoptosis. Structurally, these mycotoxins resemble the sphingoid bases, sphingosine and sphinganine, that are reported to play critical roles in cell communication and signal transduction. The addition of fumonisin B1 or AAL toxin, TA, to CV-1 cells induced the stereotypical hallmarks of apoptosis, including the formation of DNA ladders, compaction of nuclear DNA, and the subsequent appearance of apoptotic bodies. Neither mycotoxin induced cell death, DNA ladders, or apoptotic bodies in CV-1 cells expressing simian virus 40 large T antigen (COS-7) at toxin concentrations that readily killed CV-1 cells. Fumonisin B1 induced cell cycle arrest in the G1 phase in CV-1 cells but not in COS-7 cells. AAL toxin TA did not arrest cell cycle progression in either cell line. The induction of apoptosis combined with the widespread presence of these compounds in food crops and animal feed identifies a previously unrecognized health risk to humans and livestock. These molecules also represent a new class of natural toxicants that can be used as model compounds to further characterize the molecular and biochemical pathways leading to apoptosis. Images Fig. 2 Fig. 3 Fig. 4 PMID:8622958

  19. Interplay between cell cycle and autophagy induced by boswellic acid analog

    PubMed Central

    Pathania, Anup S.; Guru, Santosh K.; Kumar, Suresh; Kumar, Ashok; Ahmad, Masroor; Bhushan, Shashi; Sharma, Parduman R.; Mahajan, Priya; Shah, Bhahwal A.; Sharma, Simmi; Nargotra, Amit; Vishwakarma, Ram; Korkaya, Hasan; Malik, Fayaz

    2016-01-01

    In this study, we investigated the role of autophagy induced by boswellic acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins. It was further observed that BA145 induced autophagy by targeting mTOR kinase (IC50 1 μM), leading to reduced expression of p-mTOR, p-p70S6K (T389), p-4EBP (T37/46) and p-S6 (S240/244). Notably, inhibition of mTOR signalling by BA145 was followed by attendant activation of AKT and its membrane translocation. Inhibition of Akt through pharmacological inhibitors or siRNAs enhanced BA145 mediated autophagy, G2/M arrest and reduced expression of G2/M regulators. Further studies revealed that BA145 arbitrated inhibition of mTOR led to the activation of Akt through IGFR/PI3k/Akt feedback loop. Intervention in IGFR/PI3k/Akt loop further depreciated Akt phosphorylation and its membrane translocation that culminates in augmented autophagy with concomitant G2/M arrest and cell death. PMID:27680387

  20. Comparative effects of curcumin and its analog on alcohol- and polyunsaturated fatty acid-induced alterations in circulatory lipid profiles.

    PubMed

    Rukkumani, Rajagopalan; Aruna, Kode; Varma, Penumathsa Suresh; Rajasekaran, Kallikat Narayanan; Menon, Venugopal P

    2005-01-01

    Excessive alcohol intake induces hyperlipidemia. Studies suggest that natural principles and their analogs are known to possess anti-hyperlipidemic properties. In the present work we tested the effect of curcumin, an active principle of turmeric (Curcuma longa), and a curcumin analog on alcohol- and thermally oxidized polyunsaturated fatty acid (deltaPUFA)- induced hyperlipidemia. Male albino Wistar rats were used for the experimental study. Anti-hyperlipidemic activity of curcumin and curcumin analog was evaluated by analyzing the levels of cholesterol, triglycerides (TGs), phospholipids (PLs), and free fatty acids (FFAs). The results showed that the levels of cholesterol, TGs, PLs, and FFAs were increased significantly in alcohol-, deltaPUFA-, and alcohol + deltaPUFA-treated groups, which were brought down significantly on treatment with either of the curcuminoids. Curcumin analog treatment was found to be more effective than curcumin treatment. From the results obtained, we conclude that both curcumin and its analog effectively protect the system against alcohol- and deltaPUFA-induced hyperlipidemia and are possible candidates for the treatment of hyperlipidemia.

  1. Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to antisocial behavior and stress-induced cortisol response. The TRAILS study.

    PubMed

    Schaefer, Johanna M; Fetissov, Serguei O; Legrand, Romain; Claeyssens, Sophie; Hoekstra, Pieter J; Verhulst, Frank C; Van Oort, Floor V A

    2013-12-01

    Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in males with conduct disorder, suggesting their involvement in the biology of antisocial behavior. We first aimed to confirm these findings in a large general population sample of adolescents. Secondly, we studied the association between ACTH IgG levels and hypothalamic-pituitary-adrenal (HPA) axis response to stress. Free and total ACTH IgG levels were measured in sera of 1230 adolescents (15-18 years). HPA axis activity was determined by measuring salivary cortisol before, during, and after a social stress test. Antisocial behavior was assessed using the Antisocial Behavior Questionnaire. ACTH peptide and IgG affinity kinetics for ACTH were assayed in a subsample of 90 adolescents selected for high or low ACTH IgG levels. In boys, higher total ACTH IgG levels were associated with higher antisocial behavior scores (β=1.05, p=0.04), especially at high levels of free ACTH IgG. In girls, antisocial behavior was associated with low free ACTH IgG levels (β=-0.20, p=0.04). Stress-induced cortisol release was associated with free ACTH IgG in boys (βareaunderthecurve=-0.67, p<0.01), and with total ACTH IgG in girls (βrecovery=0.84, p=0.05). The affinity kinetics assay showed that ACTH IgG association rates were lower in both boys and girls with high ACTH IgG levels. These data show that ACTH IgG levels are related to antisocial behavior and HPA axis response to stress in adolescents. The mechanisms behind these associations, including different ACTH binding properties of IgG in subjects with antisocial behavior, deserve further attention.

  2. 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

  3. Intracisternal TRH analog induces Fos expression in gastric myenteric neurons and glia in conscious rats.

    PubMed

    Miampamba, M; Yang, H; Sharkey, K A; Taché, Y

    2001-05-01

    Activation of gastric myenteric cells by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368, at a dose inducing near maximal vagal cholinergic stimulation of gastric functions, was investigated in conscious rats. Fos immunoreactivity was assessed in gastric longitudinal muscle-myenteric plexus whole mount preparations 90 min after intracisternal injection. Fos-immunoreactive cells were rare in controls (~1 cell/ganglion), whereas intracisternal RX-77368 (50 ng) increased the number to 24.8 +/- 1.8 and 26.8 +/- 2.2 cells/ganglion in the corpus and antrum, respectively. Hexamethonium (20 mg/kg sc) prevented Fos expression by 90%, whereas atropine (2 mg/kg sc) had no effect. The neuronal marker protein gene product 9.5 and the glial markers S-100 and glial fibrillary acidic proteins showed that RX-77368 induced Fos in both myenteric neurons and glia. Vesicular ACh transporter and calretinin were detected around the activated myenteric neurons. These results indicated that central vagal efferent stimulation by intracisternal RX-77368 activates gastric myenteric neurons as well as glial cells mainly through nicotinic ACh receptors in conscious rats.

  4. 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...

  5. Hair cortisol measurement in mitotane-treated adrenocortical cancer patients.

    PubMed

    Manenschijn, L; Quinkler, M; van Rossum, E F C

    2014-04-01

    The only approved drug for the treatment of adrenocortical cancer (ACC) is mitotane. Mitotane is adrenolytic and therefore, hydrocortisone replacement therapy is necessary. Since mitotane increases cortisol binding globulin (CBG) and induces CYP3A4 activity, high doses of hydrocortisone are thought to be required. Evaluation of hydrocortisone therapy in mitotane-treated patients has been difficult since there is no good marker to evaluate hydrocortisone therapy. Measurement of cortisol in scalp hair is a novel method that offers the opportunity to measure long-term cortisol levels. Our aim was to evaluate whether hair cortisol measurements could be useful in evaluating recent hydrocortisone treatment in mitotane-treated ACC patients. Hair cortisol levels were measured in 15 mitotane-treated ACC patients on hydrocortisone substitution and 96 healthy individuals. Cortisol levels were measured in 3 cm hair segments, corresponding to a period of 3 months. Hair cortisol levels were higher in ACC patients compared to healthy individuals (p<0.0001). Seven ACC patients (47%) had hair cortisol levels above the reference range. None of the patients had hair cortisol levels below normal. In contrast to hydrocortisone doses (β=0.03, p=0.93), hair cortisol levels were associated with BMI (β=0.53, p=0.042). There was no correlation between hair cortisol levels and hydrocortisone doses (β=0.41, p=0.13). Almost half of the ACC patients had high hair cortisol levels, suggesting long-term over-substitution of hydrocortisone in some of the patients, whereas none of the patients was under-substituted. Hair cortisol measurements might be useful in long-term monitoring hydrocortisone treatment in mitotane-treated ACC patients.

  6. Effects of basal and acute cortisol on cognitive flexibility in an emotional task switching paradigm in men.

    PubMed

    Dierolf, Angelika Margarete; Arlt, Lea Esther; Roelofs, Karin; Kölsch, Monika; Hülsemann, Mareike Johanna; Schächinger, Hartmut; Naumann, Ewald

    2016-05-01

    The stress hormone cortisol is assumed to influence cognitive functions. While cortisol-induced alterations of declarative memory in particular are well-investigated, considerably less is known about its influence on executive functions. Moreover, most research has been focused on slow effects, and rapid non-genomic effects have not been studied. The present study sought to investigate the impact of acute cortisol administration as well as basal cortisol levels on cognitive flexibility, a core executive function, within the non-genomic time frame. Thirty-eight healthy male participants were randomly assigned to intravenously receive either cortisol or a placebo before performing a task switching paradigm with happy and angry faces as stimuli. Cortisol levels were measured at six points during the experiment. Additionally, before the experiment, basal cortisol measures for the cortisol awakening response were collected on three consecutive weekdays immediately following awakening and 30, 45, and 60min after. First and foremost, results showed a pronounced impact of acute and basal cortisol on reaction time switch costs, particularly for angry faces. In the placebo group, low basal cortisol was associated with minimal switch costs, whereas high basal cortisol was related to maximal switch costs. In contrast, after cortisol injection, basal cortisol levels showed no impact. These results show that cognitive flexibility-enhancing effects of acute cortisol administration are only seen in men with high basal cortisol levels. This result supports the context dependency of cortisol administration and shows the relevance of taking basal cortisol levels into account. PMID:26944609

  7. Vitamin E analog, alpha-tocopherol ether-linked acetic acid analog, alone and in combination with celecoxib, reduces multiplicity of ultraviolet-induced skin cancers in mice.

    PubMed

    Riedel, Shelley B; Fischer, Susan M; Sanders, Bob G; Kline, Kimberly

    2008-02-01

    The goals of this study were to determine whether alpha-tocopherol ether-linked acetic acid analog (alpha-TEA), a novel vitamin E analog, and celecoxib, alone or in combination, when administered as a late intervention can reduce the ultraviolet-induced nonmelanoma skin-tumor burden of established tumors, prevent additional tumors from developing, and prevent tumor recurrence once treatments are stopped. Hairless SKH-1 female mice were ultraviolet-irradiated for 24 weeks, divided into treatment groups so that each group had approximately 5.8 tumors/mouse, and then treated with 72 mug of liposome-formulated alpha-TEA by aerosol inhalation, 500 p.p.m. celecoxib in AIN-76 A diet, or a combination of alpha-TEA and celecoxib for 4 weeks. At the end of 4 weeks of treatment, each treatment group was subdivided, with one subgroup continuing to receive treatment and with treatment being stopped in the other. Skin-tumor development was monitored visually throughout the study and by histologic evaluation at the end. After 4 weeks of treatment, all treatments showed statistically significant reductions in tumor number when compared with controls. After termination of treatment, only alpha-TEA prevented a significant increase in tumor recurrence; however, continuous combination treatment resulted in the lowest total number of tumors. In conclusion alpha-TEA is an effective late-stage chemopreventive agent for nonmelanoma skin cancer that exhibits lasting benefits.

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

    PubMed

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

    2015-09-09

    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.

  9. 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.

  10. 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

  11. A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis.

    PubMed

    Nikitopoulou, Ioanna; Kaffe, Eleanna; Sevastou, Ioanna; Sirioti, Ivi; Samiotaki, Martina; Madan, Damian; Prestwich, Glenn D; Aidinis, Vassilis

    2013-01-01

    Rheumatoid arthritis (RA) is a destructive arthropathy with systemic manifestations, characterized by chronic synovial inflammation. Under the influence of the pro-inflammatory milieu synovial fibroblasts (SFs), the main effector cells in disease pathogenesis become activated and hyperplastic while releasing a number of signals that include pro-inflammatory factors and tissue remodeling enzymes. Activated RA SFs in mouse or human arthritic joints express significant quantities of autotaxin (ATX), a lysophospholipase D responsible for the majority of lysophosphatidic acid (LPA) production in the serum and inflamed sites. Conditional genetic ablation of ATX from SFs resulted in attenuation of disease symptoms in animal models, an effect attributed to diminished LPA signaling in the synovium, shown to activate SF effector functions. Here we show that administration of 1-bromo-3(S)-hydroxy-4-(palmitoyloxy)butyl-phosphonate (BrP-LPA), a metabolically stabilized analog of LPA and a dual function inhibitor of ATX and pan-antagonist of LPA receptors, attenuates collagen induced arthritis (CIA) development, thus validating the ATX/LPA axis as a novel therapeutic target in RA.

  12. Novel 8-hydroxylquinoline analogs induce copper-dependent proteasome inhibition and cell death in human breast cancer cells.

    PubMed

    Milacic, Vesna; Jiao, Peifu; Zhang, Bin; Yan, Bing; Dou, Q Ping

    2009-12-01

    An elevated level of copper (Cu), which is necessary for the growth and metastasis of tumor cells, has been found in many types of cancer, including breast, prostate, lung and brain. Although its molecular basis is unclear, this tumor-specific Cu elevation has been proposed to be a novel target for developing selective anti-cancer therapies. We previously reported that 8-hydroxylquinoline (8-OHQ) is able to form a Cu complex that inhibits the proteasome and induces apoptosis in cultured cancer cells. Toward the goal of discovering novel 8-OHQ analogs as potential anti-copper and anti-cancer drugs, in the current study we synthesized several 8-OHQ analogs and their copper complexes and evaluated their biological activities in human breast cancer cells. We report that when substitutions are made on the hydroxyl group of 8-OHQ, their copper mixtures have profound effects on the proteasome-inhibitory and apoptosis-inducing abilities in breast cancer MDA-MB-231 cells. In addition, the proteasome-inhibitory and apoptosis-inducing activities of 8-OHQ analog-copper mixtures are determined by both the polarity and position of the substituents. Finally, a synthetic complex of 8-OHQ analog-copper was able to inhibit the proteasome activity, induce cell death and suppress the growth selectively in breast cancer MDA-MB-231 cells, but not in normal immortalized human breast MCF-10A cells. Our results support the concept that human cancer cells and tissues, which contain an elevated copper level and are highly dependent on proteasome activity for their survival, should be sensitive to treatment with anti-copper drugs such as the novel 8-OHQ analogs described here.

  13. 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).

  14. Novel acridine-based N-acyl-homoserine lactone analogs induce endoreduplication in the human oral squamous carcinoma cell line SAS.

    PubMed

    Chai, Hongbo; Hazawa, Masaharu; Hosokawa, Yoichiro; Igarashi, Jun; Suga, Hiroaki; Kashiwakura, Ikuo

    2012-01-01

    The cytotoxicity of novel acridine-based N-acyl-homoserine lactone (AHL) analogs was investigated on the human oral squamous carcinoma cell line SAS. One analog induced G2/M phase arrest at 5.3-10.6 µM and induced polyploidy at a higher dose (21.2 µM). Importantly, treatment of SAS cells with a combination of the AHL analog and the Jun N-terminal kinase (JNK) inhibitor, SP600125, prevented mitosis and induced polyploidy. The AHL analog synergized with X-irradiation to inhibit clonogenic survival of SAS cells; however, its radiosensitizing effects were relative to not X-irradiation-induced apoptosis but mitotic failure following enhanced expression of Aurora A and B. These results suggest that the active AHL analog showed growth-suppressive and radiosensitizing effects, which involve polyploidy followed by G2/M accumulation and atypical cell death in the SAS cell line.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Modulatory effects of curcumin and curcumin analog on circulatory lipid profiles during nicotine-induced toxicity in Wistar rats.

    PubMed

    Kalpana, C; Rajasekharan, K N; Menon, Venugopal P

    2005-01-01

    Nicotine, a major toxic component of cigarette smoke, plays a key role in the development of cardiovascular disease and lung cancer. In the present study, we have synthesized an analog of curcumin and biomonitored its influence over biochemical marker enzymes and lipid profiles on nicotine-induced toxicity in Wistar rats. The effects were compared with that of curcumin, a well-known antioxidant and anti-hyperlipidemic agent. Toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks), and curcumin (80 mg/kg) was given simultaneously along with nicotine by intragastric intubation for 22 weeks. Measurements of activities of the biochemical marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase and of plasma lipid profiles were used to monitor the anti-hyperlipidemic effects of curcuminoids. In nicotine-treated rats, enhanced plasma marker enzymes and lipid profiles were observed. Administration of curcumin or curcumin analog to nicotine-treated rats significantly reduced the activity of marker enzymes and plasma lipid levels. Thus, our findings suggest that curcumin and its analog exert an anti-hyperlipidemic effect against nicotine-induced lung toxicity and may be a promising agent for treatment of hyperlipidemia and atherosclerosis.

  20. Renin, cortisol, and aldosterone during transcendental meditation.

    PubMed

    Michaels, R R; Parra, J; McCann, D S; Vander, A J

    1979-02-01

    The effects of transcendental meditation (TM) on plasma renin activity (PRA) and plasma concentrations of aldosterone, cortisol, and lactate were studied by measuring these variables before, during, and after 20--30 min of meditation. Subjects, who rested quietly rather than meditating, served as controls. There were no differences in the basal values for these variables between meditators and controls, but controls, in contrast to meditators, showed a significant increase in cortisol between the first (A) and second (B) samples of the control period. PRA increased slightly (14%) but significantly (p less than 0.03) during TM, but not during quiet rest in controls. Cortisol decreased progressively (after sample B) throughout the experiment to the same degree in both groups. Aldosterone and lactate did not change. The data do not support the hypothesis that TM induces a unique state characterized by decreased sympathetic activity or release from stress, but do suggest that meditators may be less responsive to an acute stress.

  1. Cortisol and corticosterone independence in cortisol-dominant wildlife.

    PubMed

    Koren, Lee; Whiteside, Douglas; Fahlman, Sa; Ruckstuhl, Kathreen; Kutz, Susan; Checkley, Sylvia; Dumond, Mathieu; Wynne-Edwards, Katherine

    2012-05-15

    Species have traditionally been defined as cortisol-dominant or corticosterone-dominant, depending on the glucocorticoid that is reported. To assess the degree of covariance versus independence between cortisol and corticosterone, 245 serum samples belonging to 219 individuals from 18 cortisol-dominant, non-domesticated species (6 mammalian orders) were compared by mass spectrometry. In these samples, which were elevated above baseline, concentration ranges were overlapping for cortisol and corticosterone although cortisol was dominant in every sample except one of 17 bighorn sheep with a corticosterone-biased cortisol-to-corticosterone ratio of 0.17. As expected, cortisol and corticosterone were strongly associated among species (r(2)=0.8; species with high absolute cortisol tend to have high absolute corticosterone concentrations), with wide variation in the species-average cortisol-to-corticosterone ratio (range 7.5-49) and an even wider ratio range across individuals (0.2-341). However, only 9 out of 13 species with >7 individuals showed a positive association between cortisol and corticosterone among individuals, and repeated measures of the cortisol-to-corticosterone ratio within individuals were weakly associated (CV range 3-136%). We conclude that corticosterone, although at lower concentrations, has the potential to signal independently of cortisol, and should be included in integrated endocrine models of stress responses.

  2. 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.

  3. Cortisol-Induced Masculinization: Does Thermal Stress Affect Gonadal Fate in Pejerrey, a Teleost Fish with Temperature-Dependent Sex Determination?

    PubMed Central

    Hattori, Ricardo S.; Fernandino, Juan I.; Kishii, Ai; Kimura, Hiroyuki; Kinno, Tomomi; Oura, Miho; Somoza, Gustavo M.; Yokota, Masashi; Strüssmann, Carlos A.; Watanabe, Seiichi

    2009-01-01

    Background Gonadal fate in many reptiles, fish, and amphibians is modulated by the temperature experienced during a critical period early in life (temperature-dependent sex determination; TSD). Several molecular processes involved in TSD have been described but how the animals “sense” environmental temperature remains unknown. We examined whether the stress-related hormone cortisol mediates between temperature and sex differentiation of pejerrey, a gonochoristic teleost fish with marked TSD, and the possibility that it involves glucocorticoid receptor- and/or steroid biosynthesis-modulation. Methodology/Principal Findings Larvae maintained during the period of gonadal sex differentiation at a masculinizing temperature (29°C; 100% males) consistently had higher cortisol, 11-ketotestoterone (11-KT), and testosterone (T) titres than those at a feminizing temperature (17°C; 100% females). Cortisol-treated animals had elevated 11-KT and T, and showed a typical molecular signature of masculinization including amh upregulation, cyp19a1a downregulation, and higher incidence of gonadal apoptosis during sex differentiation. Administration of cortisol and a non-metabolizable glucocorticoid receptor (GR) agonist (Dexamethasone) to larvae at a “sexually neutral” temperature (24°C) caused significant increases in the proportion of males. Conclusions/Significance Our results suggest a role of cortisol in the masculinization of pejerrey and provide a possible link between stress and testicular differentiation in this gonochoristic TSD species. Cortisol role or roles during TSD of pejerrey seem(s) to involve both androgen biosynthesis- and GR-mediated processes. These findings and recent reports of cortisol effects on sex determination of sequential hermaphroditic fishes, TSD reptiles, and birds provide support to the notion that stress responses might be involved in various forms of environmental sex determination. PMID:19662094

  4. 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.

  5. Testosterone suppression of CRH-stimulated cortisol in men.

    PubMed

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

    2005-10-01

    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 10 men (ages 18-45 years) 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<0.05, 0.005, and 0.01, 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<0.1). Paradoxically, CRH-stimulated corticotropin (ACTH) was increased significantly during testosterone replacement (p<0.05). The cortisol : ACTH ratio, a measure of adrenal sensitivity, was lower during testosterone replacement (p<0.1). 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.

  6. 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

  7. 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

  8. Antitumor triptycene analogs induce a rapid collapse of mitochondrial transmembrane potential in HL-60 cells and isolated mitochondria.

    PubMed

    Wang, Yang; Perchellet, Elisabeth M; Ward, Mary M; Lou, Kaiyan; Zhao, Huiping; Battina, Srinivas K; Wiredu, Bernard; Hua, Duy H; Perchellet, Jean-Pierre H

    2006-01-01

    Since synthetic analogs of triptycene (TT code number), such as bisquinones TT2 and TT13, can trigger cytochrome c release without caspase activation and retain their ability to induce apoptosis in multidrug-resistant (MDR) tumor cells, fluorescent probes of transmembrane potential have been used to determine whether these antitumor compounds might directly target mitochondria in cell and cell-free systems to cause the collapse of mitochondrial membrane potential ( downward arrow Deltapsim) that is linked to permeability transition pore (PTP) opening. Using JC-1 dye, the abilities of various TT analogs to induce the downward arrow Deltapsim in wild-type and MDR HL-60 cells are rapid (within 5-20 min), irreversible after drug removal, concentration dependent in the 0.64-25 microM range, and generally related to their antitumor activities in vitro. The downward arrow Deltapsim caused by TT2 and TT13, which are more potent than mitoxantrone, staurosporine and the reference depolarizing agent, carbonyl cyanide m-chlorophenylhydrazone (CCCP), in HL-60 cells, are not prevented by caspase-2 or -8 inhibitors, suggesting that activation of these apical caspases upstream of mitochondria is not involved in this process. Antitumor TT analogs (0.64-25 microM) also mimic the abilities of the known depolarizing agents, CCCP, alamethicin, gramicidin A and 100 microM CaCl(2), to directly induce within 20 min the downward arrow Deltapsim in isolated mitochondria prepared from mouse liver and loaded with rhodamine 123 dye. The fact that 20 microM Ca(2+), which is insufficient to trigger depolarization on its own, is required to reveal the depolarizing effect of TT2 in isolated mitochondria suggests that antitumor TT analogs might interact with the PTP to alter its conformation and increase its Ca(2+) sensitivity. Indeed, such Ca(2+)-dependent downward arrowDeltapsim of isolated mitochondria treated with 25 microM TT2 or 100 microM Ca(2+) are blocked by ruthenium red. Daunorubicin

  9. 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.

  10. Critical difference applied to exercise-induced salivary testosterone and cortisol using enzyme-linked immunosorbent assay (ELISA): distinguishing biological from statistical change.

    PubMed

    Hayes, Lawrence D; Sculthorpe, Nicholas; Young, John D; Baker, Julien S; Grace, Fergal M

    2014-12-01

    Due to its noninvasive, convenient, and practical nature, salivary testosterone (sal-T) and cortisol (sal-C) are frequently used in a clinical and applied setting. However, few studies report biological and analytical error and even fewer report the 'critical difference' which is the change required before a true biological difference can be claimed. It was hypothesized that (a) exercise would result in a statistically significant change in sal-C and sal-T and (b) the exercise-induced change would be within the critical difference for both salivary hormones. In study 1, we calculated the critical difference of sal-T and sal-C of 18 healthy adult males aged 23.2 ± 3.0 years every 60 min in a seated position over a 12-h period (08:00-20:00 hours [study 1]). As proof-of-concept, sal-C and sal-T was also obtained pre and at 5 and 60 min post a maximal exercise protocols in a separate group of 17 healthy males (aged 20.1 ± 2.8 years [study 2]). The critical difference of sal-T calculated as 90 %. For sal-C, the critical difference was 148 % (study 1). Maximal exercise was associated with a statistically significant (p < 0.05) changes in sal-T and sal-C. However, these changes were all within the critical difference range. Results from this investigation indicate that a large magnitude of change for sal-C and sal-T is required before a biologically significant mean change can be claimed. Studies utilizing sal-T and sal-C should appreciate the critical difference of these measures and assess the biological significance of any statistical changes.

  11. 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.

  12. Examining the relationships between egg cortisol and oxidative stress in developing wild sockeye salmon (Oncorhynchus nerka).

    PubMed

    Taylor, Jessica J; Sopinka, Natalie M; Wilson, Samantha M; Hinch, Scott G; Patterson, David A; Cooke, Steven J; Willmore, William G

    2016-10-01

    Maternally-derived hormones in oocytes, such as glucocorticoids (GCs), play a crucial role in embryo development in oviparous taxa. In fishes, maternal stressor exposure increases circulating and egg cortisol levels, the primary GC in fishes, as well as induces oxidative stress. Elevated egg cortisol levels modify offspring traits but whether maternal oxidative stress correlates with circulating and egg cortisol levels, and whether maternal/egg cortisol levels correlate with offspring oxidative stress have yet to be determined. The objective of this study was to examine the relationships among maternal and egg cortisol, and maternal and offspring oxidative stress to provide insight into the potential intergenerational effects of stressor exposure in sockeye salmon (Oncorhynchus nerka). Antioxidant concentration and oxidative stress were measured in maternal tissues (plasma, brain, heart and liver) as well as offspring developmental stages (pre-fertilization, 24h post-fertilization, eyed, and hatch), and were compared to both naturally-occurring and experimentally-elevated (via cortisol egg bath) levels of cortisol in eggs. Oxygen radical absorptive capacity of tissues from maternal sockeye salmon was measured spectrophotometrically and was not correlated with maternal or egg cortisol concentrations. Also, naturally-occurring and experimentally-elevated cortisol levels in eggs (to mimic maternal stress) did not affect oxidative stress or antioxidant capacity of the offspring. We conclude that the metrics of maternal stress examined in sockeye salmon (i.e., maternal/egg cortisol, maternal oxidative stress) are independent of each other, and that egg cortisol content does not influence offspring oxidative stress.

  13. 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.

  14. 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

  15. 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

    Advanced composite aircraft designs include fault-tolerant computer-based digital control systems with thigh reliability requirements for adverse as well as optimum operating environments. Since aircraft penetrate intense electromagnetic fields during thunderstorms, onboard computer systems maya be subjected to field-induced transient voltages and currents resulting in functional error modes which are collectively referred to as digital system upset. A methodology was developed for assessing the upset susceptibility of a computer system onboard an aircraft flying through a lightning environment. Upset error modes in a general-purpose microprocessor were studied via tests which 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 were recorded. The application of Markov modeling to upset susceptibility estimation is discussed and a stochastic model development.

  16. Interactions between spontaneous and provoked cortisol secretory episodes in man.

    PubMed

    Brandenberger, G; Follénius, M; Muzet, A

    1984-09-01

    This study describes the interactions between cortisol peaks due to spontaneous episodic release and peaks provoked by external stimuli. Successive and equidistant transitory rises of similar amplitude and duration were produced either by muscular exercise (30 min, 75% VO2max) or by injecting ACTH1-24 (Synacthen: 250 ng) before and after the midday meal-related peak. ACTH1-24 was also injected during sleep before the nocturnal sequence of the major secretory episodes. In all instances, cortisol levels had reverted to basal levels when the second stimulus was applied. ACTH-induced cortisol peaks depressed the subsequent meal-related peaks, the exercise-induced peaks, and the spontaneous secretory episodes at the end of the night, and thus had a strong depressor capacity. When exercise was the prior stimulus, the subsequent meal-related peaks were depressed, but the response to later exercise was not affected. Meal-related peaks and the spontaneous diurnal or nocturnal peaks did not depress the subsequent secretory episodes. These quantitatively comparable cortisol episodes were preceded by ACTH rises whose amplitude and duration were not identical: spontaneous and meal-related ACTH peaks were smaller than the provoked one; exercise-induced ACTH peaks were of longer duration than those after ACTH1-24 injection. The different depressor capacities of similar sized cortisol episodes and the lack of proportionality between spontaneous and provoked ACTH and cortisol peaks suggest that there are separate adrenocortical activation channels, which depend on the origin of the stimulation.

  17. 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

  18. LPS-induced c-Fos activation in NTS neurons and plasmatic cortisol increases in septic rats are suppressed by bilateral carotid chemodenervation.

    PubMed

    Reyes, Edison-Pablo; Abarzúa, Sebastián; Martin, Aldo; Rodríguez, Jorge; Cortés, Paula P; Fernández, Ricardo

    2012-01-01

    Lipopolysaccharide (LPS) administered I.P. increases significantly the activation of c-Fos in neurons of the nucleus of the solitary tract (NTS), which in turn activates hypothalamus-pituitary-adrenal axis. The vagus nerve appears to play a role in conveying cytokines signals to the central nervous system (CNS), since -in rodent models of sepsis- bilateral vagotomy abolishes increases in plasmatic glucocorticoid levels, but does not suppress c-Fos NTS activation. Considering that NTS also receives sensory inputs from carotid body chemoreceptors, we evaluated c-Fos activation and plasmatic cortisol levels 90 min after I.P. administration of 15 mg/kg LPS. Experiments were performed in male Sprague-Dawley rats, in control conditions and after bilateral carotid neurotomy (BCN). LPS administration significantly increases the number of c-Fos positive NTS neurons and plasmatic cortisol levels in animals with intact carotid/sinus nerves. When LPS was injected after BCN, the number of c-Fos positive NTS neurons, and plasmatic cortisol levels were not significantly modified. Our data suggest that carotid body chemoreceptors might mediate CNS activation during sepsis.

  19. 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.

  20. Depressive rumination alters cortisol decline in Major Depressive Disorder.

    PubMed

    LeMoult, Joelle; Joormann, Jutta

    2014-07-01

    Depressive rumination - a central characteristic of Major Depressive Disorder (MDD) - is a maladaptive emotion regulation strategy that prolongs sad mood and depressive episodes. Considerable research demonstrates the emotional and behavioral consequences of depressive rumination, yet few studies investigate its effect on neuroendocrine functioning. The current study examined the effect of an emotion regulation manipulation on the trajectory of cortisol concentrations among individuals with MDD and healthy controls (CTL). Sadness was induced via forced failure. Participants then were randomly assigned to a depressive rumination or distraction emotion regulation induction. MDDs in the rumination condition exhibited less cortisol decline compared to MDDs in the distraction condition and compared to CTLs in either condition. Findings suggest that depressive rumination alters the trajectory of cortisol secretion in MDD and may prolong cortisol production. Results thereby provide important insights into the interaction of biological and psychological factors through which distress contributes to MDD.

  1. The effect of octreotide, an analog of somatostatin, on bleomycin-induced interstitial pulmonary fibrosis in rats.

    PubMed

    Tug, Tuncer; Kara, Haki; Karaoglu, Aziz; Karatas, Fikret; Turgut, Nergiz Hacer; Ayan, Erhan; Boran, Cetin; Tug, Esra

    2013-04-01

    In this study, octreotide (OCT), a synthetic somatostatin analog, was tested for its beneficial effects in the prevention of interstitial pulmonary fibrosis (IPF) induced by bleomycin (BLM) in rats by histological examination and by evaluating tissue OH-proline levels. Thirty male Wistar rats were divided randomly into three groups: group I: intratracheal (i.t.) BLM (7.5 mg/kg, single dose) + saline solution [0.9% NaCl, subcutaneously (s.c.), once-daily for 7 days]; group II: i.t. BLM (7.5 mg/kg, single dose) + OCT acetate (82.5 µg/kg, s.c., once-daily for 7 days); and the control group. At the end of the 7 days, lung tissues were excised and examined by histopathological methods. Levels of tissue hydroxyproline (OH-proline) were determined. BLM administration resulted in prominent histopathologic findings, such as diffuse alveolar damage and interstitial pulmonary fibrosis, as well as a significant increase in OH-proline level, as compared to controls. OCT application explicitly attenuated the histopathologic changes to a significant extent. OCT decreased paranchymal fibrosis and structural deformities in BLM-induced lung fibrosis. These results suggest that OCT administration to rats with BLM-induced IPF has a protective effect. Further studies are necessary to reveal the molecular mechanism(s) of OCT-induced protective effect.

  2. 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

  3. Time-related effects of gonadotropin-releasing hormone analog treatment in experimentally induced endometriosis in the rat.

    PubMed

    Zanagnolo, V L; Beck, R; Schlaff, W D; Damewood, M D; Bobbie, D; Rock, J A

    1991-02-01

    The purpose of our study was to characterize the time-dependent effect of gonadotropin-releasing hormone analog (GnRH-a) therapy on endometriosis explant using the rat model. Endometriosis was induced in 60 mature female rats. One group of treated animals as well as controls were killed at 2, 4, 6 and 8 weeks of treatment at which time the explant was evaluated. Explant volume was significantly reduced in all treatment groups, an effect that was more significant in animals treated for greater than or equal to 4 weeks compared with those treated for only 2 weeks. We conclude that GnRH-a treatment caused gradual regression of endometrial explant that was effectively complete by 4 weeks of treatment. We further conclude that this experimental model may be useful in the evaluation of other modes of endometriosis therapy.

  4. Analog of the electromagnetically-induced-transparency effect for two nanomechanical or micromechanical resonators coupled to a spin ensemble

    SciTech Connect

    Chang Yue; Sun, C. P.

    2011-05-15

    We study a hybrid nanomechanical system coupled to a spin ensemble as a quantum simulator to favor a quantum interference effect, electromagnetically induced transparency (EIT). This system consists of two nanomechanical resonators (NAMRs), each of which is coupled to a nuclear spin ensemble, and can be regarded as a crucial element in the quantum network of NAMR arrays coupled to spin ensembles. Here, the nuclear spin ensembles behave as a long-lived transducer to store and transfer the NAMRs' quantum information. This system shows the analog of the EIT effect under the driving of a probe microwave field. The double EIT phenomenon emerges in the large-N (the number of nuclei) limit within the low excitation approximation, because the interactions between the spin ensemble and the two NAMRs are reduced to the coupling of three harmonic oscillators. Furthermore, the group velocity is reduced in the two absorption windows.

  5. Effect of somatostatin analog on high-fat diet-induced metabolic syndrome: involvement of reactive oxygen species.

    PubMed

    Li, Wu; Shi, Yong-hui; Yang, Rui-li; Cui, Jue; Xiao, Ying; Wang, Bin; Le, Guo-wei

    2010-04-01

    Oxidative stress plays an important role in overnutrition-induced metabolic syndrome. Somatostatin (SST) inhibits a wide variety of physiologic functions in the gastrointestinal tract, which may in turn control the levels of reactive oxygen species (ROS) derived from ingestion of macronutrients. In this study, the involvement of SST in the progression of metabolic syndrome in response to a high-fat diet (HFD) was investigated. Male C57BL/6 mice were fed either a normal diet (4.89% fat) or a high-fat diet (21.45% fat) for 4 weeks. The SST analog octreotide (20 microg/kg/day) was then administered intraperitoneally to half of the HFD mice throughout the 10-day experimental period. Body weight, adipose tissue weight, gastric acidity, total bile acid, and lipase activity were measured. Plasma lipid, glucose, insulin, SST, the levels of ROS and GSH/GSSG, and lipid peroxidation in the stomach, small intestine, pancreas, and liver were also evaluated. Following HFD intake for 38 days, a decrease in the plasma levels of SST and GSH/GSSG ratio was observed, while there was an increase in body weight, adipose tissue weight, plasma glucose, triglyceride, and levels of ROS and lipid peroxidation of the stomach, small intestine, pancreas, and liver. However, simultaneous administration of SST analog octreotide to HFD-fed mice significantly reduced ROS production of the digestive system and resulted in the improvement of all the aforesaid adverse changes, suggesting the involvement of SST in the progression of HFD-induced metabolic syndrome.

  6. Plasmonic analog of electromagnetically-induced transparency of asymmetrical slots waveguide

    NASA Astrophysics Data System (ADS)

    Sun, Lin; Wang, Jicheng; Hu, Zheng-Da; Wang, Xiaosai; Chen, Jing

    2016-02-01

    In this paper, electromagnetically-induced transparency (EIT) phenomena have been investigated numerically in the plasmonic waveguides composed of unsymmetrical slot shaped metal-insulator-metal (MIM) structures. By the transmission line theory and Fabry-Perot model, the formation and evolution mechanisms of plasmon-induced transparency were exactly analyzed. The analysis showed that the peak of EIT-like transmission could be changed easily according to certain rules by adjusting the geometrical parameters of the slot structures, including the coupling distances and slot depths. We can find a new method to design nanoscale optical switch, devices in optical storage and optical computing.

  7. 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

  8. 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.

  9. Interferon gamma induced by resveratrol analog, HS-1793, reverses the properties of tumor associated macrophages.

    PubMed

    Jeong, Soo Kyung; Yang, Kwangmo; Park, You Soo; Choi, You Jin; Oh, Su Jung; Lee, Chan Woo; Lee, Kyu Yeol; Jeong, Min Ho; Jo, Wol Soon

    2014-10-01

    Macrophages are capable of both inhibiting and promoting the growth and spread of cancers, depending on their activation state. Tumor-associated macrophages (TAM) are a kind of alternatively activated M2 macrophage, which may contribute to tumor progression. Following our previous study to evaluate the anti-tumor effect of a synthetic resveratrol analog HS-1793, the current study demonstrated that HS-1793 treatment significantly increased IFN-γ secreting cells in splenocytes and decreased CD206+ macrophage infiltration compared to CD68+ cells in the tumor site with a higher expression of IFN-γ. As these results suggested that IFN-γ increased locally at the tumor sites could modulate the status of TAM, we designed an in vitro model to study macrophage morphology and functions in relation to the tumor microenvironment. Human monocytic cell line THP-1 cells stimulated with phorbol-12-myristate-13-acetate (PMA) differentiated to macrophages with M2-like phenotypes. TAM-like properties of CD206(high), CD204(high), IL-10(high), TGF-β(high), IL-6(low), IL-12(low), VEGF(high), and MMP-9(high) and promotion of tumor cell invasion were more pronounced in M-2-polarized THP-1 macrophages generated by differentiating THP-1 cells with PMA and subsequently polarizing them with Th2 cytokines (IL-4/IL-13). Upon IFN-γ exposure, THP-1-derived TAM changed their phenotypes to the M-1-like morphology and intracellular granular pattern with an expression of an increased level of proinflammatory and immunostimulatory cytokines and a reduced level of immunosuppressive and tumor progressive mediators. These results explain the underlying mechanism of the anti-tumor activity of HS-1793. The elevated level of IFN-γ production after HS-1793 treatment evoked reprogramming of M-2 phenotype TAM, which efficiently countered the immunosuppressive and tumor progressive influences of TAM.

  10. Optical Analog to Electromagnetically Induced Transparency in Cascaded Ring-Resonator Systems

    PubMed Central

    Wang, Yonghua; Zheng, Hua; Xue, Chenyang; Zhang, Wendong

    2016-01-01

    The analogue of electromagnetically induced transparency in optical methods has shown great potential in slow light and sensing applications. Here, we experimentally demonstrated a coupled resonator induced transparency system with three cascaded ring coupled resonators in a silicon chip. The structure was modeled by using the transfer matrix method. Influences of various parameters including coupling ratio of couplers, waveguide loss and additional loss of couplers on transmission characteristic and group index have been investigated theoretically and numerically in detail. The transmission character of the system was measured by the vertical grating coupling method. The enhanced quality factor reached 1.22 × 105. In addition, we further test the temperature performance of the device. The results provide a new method for the manipulation of light in highly integrated optical circuits and sensing applications. PMID:27463720

  11. Plasmonic analog of electromagnetic-induced transparency of asymmetrical slots waveguide

    NASA Astrophysics Data System (ADS)

    Sun, Lin; Wang, Jicheng; Tang, Baojie; Wang, Xiaosai

    2015-08-01

    Electromagnetically induced transparency (EIT) has been proposed numerically in the plasmonic waveguides composed of unsymmetrical slots shaped metal-insulator-metal (MIM) structures. By the transmission line theory and Fabry-Perot model, the formation and evolution mechanisms of Plasmon induced transparency are exactly analyzed. The analysis shows that the peak of EIT-like transmission can be changed easily according to certain rules by adjusting the geometrical parameters of the slot structures, including the coupling distances and slot depths. We can find a new method to design nanoscale optical switch, devices in optical storage and optical computing. It is found that the slow light effects are emerged in the unsymmetrical slot structures. A small group velocity(c/80) can be achieved.

  12. 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.

  13. Corticotropin-releasing hormone directly stimulates cortisol and the cortisol biosynthetic pathway in human fetal adrenal cells.

    PubMed

    Sirianni, Rosa; Rehman, Khurram S; Carr, Bruce R; Parker, C Richard; Rainey, William E

    2005-01-01

    Near term the human fetal adrenals (HFAs) initiate production of cortisol, which promotes organ maturation and acts to increase placental CRH biosynthesis. The objective of the present study was to determine whether CRH directly stimulates both cortisol production and expression of the steroidogenic enzymes in HFA-definitive zone cells. CRH stimulated the production of cortisol in a time- and dose-dependent manner, with an effective concentration of as low as 0.01 nm. In real-time RT-PCR experiments, CRH treatment increased the mRNA levels of steroidogenic acute regulatory protein and each of the enzymes needed to produce cortisol. CRH induced 3beta-hydroxysteroid dehydrogenase type II (HSD3B2) by 34-fold, 21-hydroxylase (CYP21) by 55-fold, and 11beta-hydroxylase by 41-fold. Induction of steroidogenic acute regulatory protein, cholesterol side chain cleavage (CYP11A), and 17alpha-hydroxylase (CYP17) mRNA by CRH was 6-, 4-, and 6-fold, respectively. We also demonstrated that submaximal concentrations of CRH (30 pm) and ACTH (30 pm) that are seen in fetal circulation were additive on cortisol biosynthesis and 3beta-hydroxysteroid dehydrogenase type II mRNA induction. We suggest that CRH may play an important role in the late gestational rise in cortisol secretion from the HFAs, which may serve to augment placental CRH production and therefore participate in the endocrine cascade that is involved in fetal organ maturation and potentially in the timing of human parturition.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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…

  20. 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

  1. 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

  2. Cortisol release in response to UVB exposure in Xiphophorus fish.

    PubMed

    Contreras, Adam J; Boswell, Mikki; Downs, Kevin P; Pasquali, Amanda; Walter, Ronald B

    2014-06-01

    Xiphophorus fishes are comprised of 26 known species. Interspecies hybridization between select species has been utilized to produce experimental models to study melanoma development. Xiphophorus melanoma induction protocols utilize ultraviolet light (UVB) to induce DNA damage and associated downstream tumorigenesis. However, the impact of induced stress caused by the UVB treatment of the experimental animals undergoing tumor induction protocols has not been assessed. Stress is an adaptive physiological response to excessive or unpredictable environmental stimuli. The stress response in fishes may be measured by an assay of cortisol released into the water. Here, we present results from investigations of stress response during an experimental treatment and UVB exposure in Xiphophorus maculatus Jp 163 B, Xiphophorus couchianus, and F1 interspecies hybrids produced from the mating X. maculatus Jp 163 B×X. couchianus. Overall, cortisol release rates for males and females after UVB exposure showed no statistical differences. At lower UVB doses (8 and 16kJ/m(2)), X. couchianus exhibited 2 fold higher levels of DNA damage then either X. maculatus or the F1 hybrid. However, based on the cortisol release rates, none of the fish types tested induced a primary stress response at the UVB lower doses (8 and 16kJ/m(2)). In contrast, at a very high UVB dose (32kJ/m(2)) both X. maculatus and the F1 hybrid showed a 5 fold increase in the cortisol release rate. To determine the effect of pigmentation on UVB induced stress, wild type and albino Xiphophorus hellerii were exposed to UVB (32kJ/m(2)). Albino X. hellerii exhibited 3.7 fold increase in the cortisol release while wild type X. hellerii did not exhibit a significant cortisol response to UVB. Overall, the data suggest the rather low UVB doses often employed in tumor induction protocols do not induce a primary stress response in Xiphophorus fishes.

  3. 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.

  4. Genome-wide mutation avalanches induced in diploid yeast cells by a base analog or an APOBEC deaminase.

    PubMed

    Lada, Artem G; Stepchenkova, Elena I; Waisertreiger, Irina S R; Noskov, Vladimir N; Dhar, Alok; Eudy, James D; Boissy, Robert J; Hirano, Masayuki; Rogozin, Igor B; Pavlov, Youri I

    2013-01-01

    Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis.

  5. Irradiation-induced Ag nanocluster nucleation in silicate glasses: Analogy with photography

    SciTech Connect

    Espiau de Lamaestre, R.; Bea, H.; Bernas, H.; Belloni, J.; Marignier, J. L.

    2007-11-15

    The synthesis of Ag nanoclusters in soda lime silicate glasses and silica was studied by optical absorption and electron spin resonance experiments under both low (gamma ray) and high (MeV ion) deposited energy density irradiation conditions. Both types of irradiation create electrons and holes whose density and thermal evolution--notably via their interaction with defects--are shown to determine the clustering and growth rates of Ag nanocrystals. We thus establish the influence of redox interactions of defects and silver (poly)ions. The mechanisms are similar to the latent image formation in photography: Irradiation-induced photoelectrons are trapped within the glass matrix, notably on dissolved noble metal ions and defects, which are thus neutralized (reverse oxidation reactions are also shown to exist). Annealing promotes metal atom diffusion, which, in turn, leads to cluster nuclei formation. The cluster density depends not only on the irradiation fluence but also--and primarily--on the density of deposited energy and the redox properties of the glass. Ion irradiation (i.e., large deposited energy density) is far more effective in cluster formation, despite its lower neutralization efficiency (from Ag{sup +} to Ag{sup 0}) as compared to gamma photon irradiation.

  6. 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

  7. 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.

  8. Paradoxical diurnal cortisol changes in neonates suggesting preservation of foetal adrenal rhythms

    PubMed Central

    Kinoshita, Masahiro; Iwata, Sachiko; Okamura, Hisayoshi; Saikusa, Mamoru; Hara, Naoko; Urata, Chihoko; Araki, Yuko; Iwata, Osuke

    2016-01-01

    Studies suggested the presence of foetal adrenal rhythms of cortisol, which are entrained in antiphase to maternal rhythms. In contrast, neonates are thought to have no adrenal rhythm until 2–3 months after birth. To test the hypothesis that a foetal-type adrenal rhythm is preserved after birth, saliva samples were collected from 65 preterm/term infants during hospital stay (30–40 weeks corrected age) at 10:00 and 19:00 h. Cortisol levels were assessed for their diurnal difference and dependence on antenatal/postnatal clinical variables. Cortisol levels were lower during periods 15–28 days and >28 days than ≤5 days of life. Lower cortisol was associated with pregnancy-induced hypertension (PIH), gestational age <28 weeks, and mechanical ventilation after birth. Higher cortisol was associated with vaginal delivery and non-invasive ventilation support at saliva collection. PIH and non-invasive mechanical ventilation at saliva collection were associated with cortisol levels even after adjustment for postnatal age. Cortisol levels were higher in the evening than in the morning, which was unassociated with gestational and postnatal age. Higher cortisol levels in the evening suggest the preservation of a foetal-type diurnal rhythm. Cortisol levels are associated with intrinsic and extrinsic variables, such as PIH, delivery mode, gestational age, and respiratory conditions. PMID:27752095

  9. Fragmentation energetics for angiotensin II and its analogs from time- and energy-resolved surface-induced dissociation studies

    NASA Astrophysics Data System (ADS)

    Laskin, Julia; Bailey, Thomas H.; Futrell, Jean H.

    2004-05-01

    Surface-induced dissociation (SID) of four model peptides: DRVYIHPF, RVYIHPF, RVYIHAF, and RVYIHDF was studied using a novel Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for SID experiments. The energetics and dynamics of peptide fragmentation were deduced by modeling the time- and energy-resolved survival curves for each precursor ion using an RRKM based approach developed in our laboratory. Accurate dissociation parameters can be obtained from these experiments because collision-energy-resolved SID data are very sensitive to both the energetics and dynamics of dissociation. We found that transition from selective to non-selective fragmentation as ion kinetic energy is increased is associated with a substantial (ca. 0.5 eV) increase in the dissociation energy and a 3-4 orders of magnitude increase in the pre-exponential factor. Dissociation thresholds for angiotensin analogs derived from the experimental data are as follows: 1.62 eV for RVYIHAF and RVYIHPF, 1.14 eV for RVYIHDF and 1.13 eV for DRVYIHPF. Pre-exponential factors of 8.2×1011, 7.2×1012, 3.1×108, and 5.0×107 s-1 were obtained for RVYIHPF, RVYIHAF, RVYIHDF, and DRVYIHPF, respectively. Contribution from shattering to the total decomposition of the precursor ion increases for kinetically hindered fragmentation. The largest contribution is observed for a peptide ion that has the largest negative reaction entropy--DRVYIHPF.

  10. Mechanisms of peptide fragmentation from time- and energy-resolved surface-induced dissociation studies: Dissociation of angiotensin analogs

    NASA Astrophysics Data System (ADS)

    Laskin, Julia; Bailey, Thomas H.; Futrell, Jean H.

    2006-03-01

    Energetics and mechanism of dissociation of singly protonated angiotensin III (RVYIHPF) and its analogs RVYIFPF, RVYIYPF, RVYIHAF and RVYIHDF was studied using surface-induced dissociation (SID) in a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) specially configured for studying ion activation by collisions with surfaces. The energetics and dynamics of peptide fragmentation were deduced by modeling the time- and energy-resolved survival curves for each precursor ion using an RRKM-based approach developed in our laboratory. Fragmentation mechanisms were inferred from comparison of time- and energy-resolved fragmentation efficiency curves (TFECs) of different fragment ions followed by RRKM modeling of dissociation of angiotensin III into six major families of fragment ions. Detailed modeling demonstrated that dissociation of these peptides is dominated by loss of ammonia from the precursor ion and characterized by a high-energy barrier of 1.6 eV. Loss of NH3 and subsequent rearrangement of the MH+-NH3 ion results in proton mobilization and release of ca. 30 kcal/mol into internal excitation of the MH+-NH3 ion. The resulting highly excited ion accesses a variety of non-specific dissociation pathways with very high rate constants. Fast fragmentation of excited MH+-NH3 ion forms a variety of abundant bn-NH3 and an-NH3 fragment ions. Abundant XH and HX internal fragments are also formed, reflecting the stability of histidine-containing diketopiperazine structures.

  11. Is gill cortisol concentration a good acute stress indicator in fish? A study in rainbow trout and zebrafish.

    PubMed

    Gesto, Manuel; Hernández, Juan; López-Patiño, Marcos A; Soengas, José L; Míguez, Jesús M

    2015-10-01

    Cortisol is the main biomarker of physiological stress in fish. It is usually measured in plasma, which requires blood collection. Though cortisol is produced in the anterior kidney, it can diffuse easily through cell membranes due to its lipophilic nature. Taking advantage of that, some non-invasive techniques have been developed to measure cortisol directly in the water from fish-holding tanks, in skin mucus or in scales. In this study, we explored the possibility to analyze fish cortisol from gill filaments as a reliable acute stress marker. Our results show that gill cortisol levels correlate well with plasma cortisol levels in both rainbow trout and zebrafish exposed or not to an acute stress protocol. Measuring cortisol in gill filaments increases the available possibilities for stress assessment in fish. Although this approach should yet be tested for its use with other stressors, it has several advantages: In relatively large fish (i.e. above 30 g) gill cortisol levels could be measured in vivo. Sampling of gill biopsies is very fast and easy, and the procedure does not induce stress if properly performed, making it an ideal option for in vivo stress assessment. In small fish, the use of gill tissue to measure cortisol has important technical advantages with respect to the current methods using whole-body homogenates. Gill homogenates could be used directly for ELISA cortisol analysis, avoiding the need of tedious and expensive cortisol extraction protocols, and, since no organic solvent is required, contributing for a more environmentally friendly analysis.

  12. 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.

  13. 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

  14. Gender Specific Effect of Psychological Stress and Cortisol Reactivity on Adolescent Risk Taking

    PubMed Central

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

    2013-01-01

    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 minutes 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

  15. Induction of ambicoloration by exogenous cortisol during metamorphosis of spotted halibut Verasper variegatus.

    PubMed

    Yamada, Toshiyuki; Donai, Hayato; Okauchi, Masanori; Tagawa, Masatomo; Araki, Kazuo

    2011-12-01

    Cortisol, the main glucocorticoid in fish, increases during flatfish metamorphosis and peaks before the surge of thyroxine. A large body of evidence indicates the essential role of thyroxine in flatfish metamorphosis, whereas information on cortisol is limited. We administered cortisol to spotted halibut Verasper variegatus larvae in order to examine the effect on pigmentation during metamorphosis. Administration of 10 μg cortisol per mL of water from before the onset of metamorphosis (stage E) to metamorphic climax (stage G) induced the development of adult type pigment cells on the blind side of the metamorphosed juveniles and increased the occurrence of ambicolored juveniles. When 10 μg/mL cortisol was administered during stage D, stages E-F, stage G or stage H, only the administration during stages E-F induced the development of adult type pigment cells on the blind side. In addition, the expression of the gene dopachrome tautomerase (dct), a marker of melanoblasts, was enhanced at Stage E by cortisol administration. These results clearly indicated, for the first time, the enhancement of pigmentation by exogenous high-dose cortisol. Since endogenous cortisol is secreted in response to various kinds of stress in rearing conditions, these results indicate a possible influence of stress conditions in the occurrence of ambicoloration in flatfish.

  16. 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

  17. Examining the relationships between egg cortisol and oxidative stress in developing wild sockeye salmon (Oncorhynchus nerka).

    PubMed

    Taylor, Jessica J; Sopinka, Natalie M; Wilson, Samantha M; Hinch, Scott G; Patterson, David A; Cooke, Steven J; Willmore, William G

    2016-10-01

    Maternally-derived hormones in oocytes, such as glucocorticoids (GCs), play a crucial role in embryo development in oviparous taxa. In fishes, maternal stressor exposure increases circulating and egg cortisol levels, the primary GC in fishes, as well as induces oxidative stress. Elevated egg cortisol levels modify offspring traits but whether maternal oxidative stress correlates with circulating and egg cortisol levels, and whether maternal/egg cortisol levels correlate with offspring oxidative stress have yet to be determined. The objective of this study was to examine the relationships among maternal and egg cortisol, and maternal and offspring oxidative stress to provide insight into the potential intergenerational effects of stressor exposure in sockeye salmon (Oncorhynchus nerka). Antioxidant concentration and oxidative stress were measured in maternal tissues (plasma, brain, heart and liver) as well as offspring developmental stages (pre-fertilization, 24h post-fertilization, eyed, and hatch), and were compared to both naturally-occurring and experimentally-elevated (via cortisol egg bath) levels of cortisol in eggs. Oxygen radical absorptive capacity of tissues from maternal sockeye salmon was measured spectrophotometrically and was not correlated with maternal or egg cortisol concentrations. Also, naturally-occurring and experimentally-elevated cortisol levels in eggs (to mimic maternal stress) did not affect oxidative stress or antioxidant capacity of the offspring. We conclude that the metrics of maternal stress examined in sockeye salmon (i.e., maternal/egg cortisol, maternal oxidative stress) are independent of each other, and that egg cortisol content does not influence offspring oxidative stress. PMID:27316822

  18. Cortisol Levels and Longitudinal Cortisol Change as Predictors of Anxiety in Adolescents

    ERIC Educational Resources Information Center

    Schiefelbein, Virginia L.; Susman, Elizabeth J.

    2006-01-01

    Although previous research has suggested cortisol-emotion relationships, little is known regarding the effect of anxiety type on cortisol levels or relationships between anxiety and longitudinal cortisol change in adolescents. The authors examine the differential relationship of cortisol levels with generalized and social anxiety and relationships…

  19. The Stereotypy-Inducing Effects of N-Substituted Benztropine Analogs Alone and in Combination with Cocaine Do Not Account for Their Blockade of Cocaine Self-Administration

    PubMed Central

    Li, Libin; Hiranita, Takato; Hayashi, Shuichiro; Newman, Amy H.; Katz, Jonathan L.

    2015-01-01

    Rationale Previous studies have demonstrated that several N-substituted 4′,4″-diF-benztropine (BZT) analogs with high dopamine transporter affinity selectively decreased cocaine self-administration without affecting food-maintained behavior in rats. Objectives The present study examined if the decreases in cocaine self-administration are due to competition from excess behavioral activity (hyperlocomotion or stereotypy) induced by the BZT analogs alone or in combination with cocaine. Results Pretreatments with the typical dopamine uptake inhibitor methylphenidate (1.0, 3.2 and 10 mg/kg, i.p.) dose-dependently shifted the cocaine self-administration dose-effect curve (0, 0.032, 0.1, 0.32 1.0 mg/kg/injection) leftward. The shift in the dose-effect curve was obtained at doses of methylphenidate that, when administered alone, also decreased food-maintained behavior and increased locomotor activity and stereotypy. In contrast, the N-substituted BZT analogs, JHW 007 (1.0, 3.2 and 10 mg/kg, i.p.), AHN 1-055 (10 mg/kg), and, AHN 2-005 (10 mg/kg), as previously reported, decreased the maximum for the cocaine self-administration dose-effect curve, and did so at doses that were virtually without effects on food-maintained behavior. Further, the BZT analogs alone had minimal effects on locomotor activity and stereotypies and did not appreciably change the effects of cocaine on these measures when administered in combination with cocaine. Conclusions The present results suggest that the decrease in cocaine self-administration produced by the N-substituted BZT analogs is due to an antagonism of the reinforcing effects of cocaine rather than due to interference from competing behavioral overstimulation, and further supports the development of N-substituted BZT analogs as medications to treat cocaine abuse. PMID:22975727

  20. [Night workers and plasmatic cortisol].

    PubMed

    Palermo, P; Rosati, M V; Ciarrocca, M; Nicassio, P; Piccoli, F; Cerratti, D; Anzani, M F; Tomei, G; Perugi, F; Monti, C; Palitti, T; Tomao, E; Caciari, T; Tomei, F

    2007-01-01

    The aim of the study is to evaluate whether occupational exposure to night work could cause alterations in the levels of plasmatic cortisol. The interest toward this argument arises form several studies in scientific literature referring the presence of an alteration in the synthesis and release of cortisol in workers exposed to night work. We studied a population of workers employed in night security service and monitoring service of alarm systems in different museums compared to a control group not performing shift-work and/or night work. The exposed and control subjects were compared by age, length of service, smoking habit (n. cigarettes per day), habitual consumption of alcoholic drinks (n. glass of wine/beer per day). We evaluated the levels of plasmatic cortisol on 50 workers exposed to night work, all males of whom 30 smokers and 20 non-smokers and on 50 controls of whom 30 smokers and 20 non-smokers.

  1. Octapeptide somatostatin analog SMS 201-995 induces translocation of intracellular PTP1C to membranes in MCF-7 human breast adenocarcinoma cells.

    PubMed

    Srikant, C B; Shen, S H

    1996-08-01

    Somatostatin (SST) analogs exert direct antiproliferative actions in pancreatic, pituitary, and mammary tumor cells in vitro. SST receptor (SSTR)-mediated induction of membrane-associated protein tyrosine phosphatase (PTP) activity has been implicated in its anti-proliferative signaling by virtue of its ability to dephosphorylate and inactivate growth factor receptor kinases. Recently, a PTP-containing Src homology 2 domain, identified as PTP1C/SHPTP1/SHP/HCP, was found to be associated with SSTR in rat pancreatic acinar cell membranes. In the present study we investigated the antiproliferative action of the octapeptide SST analog SMS 201-995 (OCT) and its effect on PTP activity in MCF-7 human breast adenocarcinoma cells. We report here that OCT does not directly stimulate membrane-associated PTP activity, but induces translocation of intracellular PTP to the membrane in MCF-7 cells preincubated with the peptide in a time- and concentration-dependent manner. We demonstrate that this is due at least in part to OCT-induced recruitment of cytosolic PTP1C. OCT-induced recruitment of PTP1C to the cell surface as well as its ability to inhibit the growth of MCF-7 cells was G protein dependent and inhibited by orthovanadate. These findings suggest that translocation of cytosolic PTP1C by SST analogs to the cell surface is an early event in its antiproliferative signaling in tumor cells.

  2. 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

  3. 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

    2015-07-02

    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.

  4. 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

  5. Spot determinations of urinary cortisol for the screening of Cushing's syndrome.

    PubMed

    Fujita, H; Hata, K; Ogata, E; Kojima, I

    1991-08-01

    The usefulness of spot determination of urinary cortisol in the screening of Cushing's syndrome was evaluated by measuring the cortisol concentration in randomly sampled urine in 68 normal subjects and in 9 patients with Cushing's syndrome. The urinary cortisol concentration in the morning was significantly higher in patients with Cushing's syndrome but some overlap existed between normal subjects and patients with Cushing's syndrome. In contrast, there was a clear discrimination between two groups when urinary cortisol was measured in the late evening: urinary cortisol was lower than 75 micrograms per gram creatinine (microgram/gCr) in normal subjects but higher than 150 micrograms/gCr in patients with Cushing's syndrome. When 1 mg dexamethasone was administered at 2300 h in the evening, spot urinary cortisol the next morning was less than 80 micrograms/gCr in normal subjects while it was above 100 micrograms/gCr in patients with Cushing's syndrome. Dexamethasone-induced suppression of urinary cortisol in normal subjects lasted until late in the afternoon, which allows sampling of urine at any time in the morning and possibly in the afternoon. These results suggest the usefulness of spot determination of urinary cortisol in the screening of Cushings' syndrome.

  6. 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.

  7. Stress and decision-making in humans: performance is related to cortisol reactivity, albeit differently in men and women.

    PubMed

    van den Bos, Ruud; Harteveld, Marlies; Stoop, Hein

    2009-11-01

    Acutely elevated levels of cortisol are associated with euphoria and reward-like properties related to sensation-seeking behaviour. Thus, acute stress and elevated levels of cortisol may promote risk-taking behaviour. High cortisol responders are more sensitive to immediate rewards than low cortisol responders. In this study we therefore tested whether acute stress in male and female subjects, induced by the Trier Social Stress Test (TSST), affects decision-making as measured by the Iowa Gambling Task (IGT) and to what extent this is related to cortisol reactivity. Control subjects did not receive the stress manipulation. We specifically predict that high responders show risk-taking behaviour in the IGT compared to low responders and controls. The data show that the more (salivary) cortisol levels are elevated after the TSST the poorer the subsequent performance in the IGT in male subjects. In female subjects an inverse relationship between cortisol levels and IGT performance is observed: slightly elevated levels of cortisol after the TSST improve IGT performance, while highly elevated levels decrease IGT performance. Thus, acute stress as induced by the TSST affects decision-making behaviour of men and women differently and cortisol reactivity is associated with decision-making performance. PMID:19497677

  8. Salivary cortisol and testosterone responses to high-intensity cycling before and after an 11-day intensified training period.

    PubMed

    Hough, John; Corney, Robert; Kouris, Antonios; Gleeson, Michael

    2013-01-01

    This study examined salivary cortisol and testosterone responses to two, different high-intensity, ∼30-min cycles separated by 2 h rest before and after an 11-day intensified training period. Twelve recreationally active, healthy males completed the study. Saliva samples were collected before, immediately after and 30 min after both bouts with salivary cortisol and testosterone concentrations assessed. Compared with pre-training blunted exercise-induced salivary cortisol, testosterone and cortisol/testosterone responses to both bouts post-training were observed (P < 0.05 for all). Comparing pre- with post-training the absolute exercise-induced salivary cortisol, testosterone and cortisol/testosterone decreased from 11.1 to 3.1 and 7.0 to 4.4 nmol · L⁻¹ (cortisol), from 407 to 258 and from 473 to 274 pmol · L⁻¹ (testosterone) and from 12 to 4 and 7 to 5 (cortisol/testosterone) for the first and second bouts, respectively (P < 0.05). No differences in the pre- and post-training rating of perceived exertion (RPE) and heart rate (HR) responses during the cycles or times to fatigue were found (P > 0.05). Fatigue and Burnout scores were higher post- compared with pre-training (P < 0.05). These high-intensity exercise bouts can detect altered hormonal responses following intensified training. This test could assess an athlete's current hormonal status, reductions in salivary cortisol and testosterone responses suggestive of increased fatigue.

  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.

  10. 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...

  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. Romidepsin (FK228) and its analogs directly inhibit phosphatidylinositol 3-kinase activity and potently induce apoptosis as histone deacetylase/phosphatidylinositol 3-kinase dual inhibitors.

    PubMed

    Saijo, Ken; Katoh, Tadashi; Shimodaira, Hideki; Oda, Akifumi; Takahashi, Ohgi; Ishioka, Chikashi

    2012-11-01

    Activation of phosphatidylinositol 3-kinase (PI3K) signaling is involved in carcinogenesis and cancer progression. The PI3K inhibitors are considered candidate drugs for cancer treatment. Here, we describe a drug screening system for novel PI3K inhibitors using Saccharomyces cerevisiae strains with deleterious mutations in the ATP-binding cassette transporter genes, because wild-type S. cerevisiae uses drug efflux pumps for reducing intracellular drug concentrations. By screening the chemical library of the Screening Committee of Anticancer Drugs, we identified the histone deacetylase (HDAC) inhibitor romidepsin (FK228) and its novel analogs. In vitro PI3K activity assays confirmed that these compounds directly inhibit PI3K activity at μM-range concentrations. FK-A5 analog was the most potent inhibitor. Western blotting revealed that these compounds inhibit phosphorylation of protein kinase B and downstream signaling components. Molecular modeling of the PI3K-FK228 complex indicated that FK228 binds to the ATP-binding pocket of PI3K. At μM-range concentrations, FK228 and FK-A5 show potent cytotoxicity, inducing apoptosis even in HDAC inhibitor-resistant cells. Furthermore, HDAC/PI3K dual inhibition by FK228 and FK-A5 at μM-range concentrations potentiates the apoptosis induction, mimicking the effect of combining specific HDAC and PI3K inhibitors. In this study, we showed that FK228 and its analogs directly inhibit PI3K activity and induce apoptosis at μM-range concentrations, similar to HDAC/PI3K dual inhibition. In future, optimizing the potency of FK228 and its analogs against PI3K may contribute to the development of novel HDAC/PI3K dual inhibitors for cancer treatment.

  13. Consequences of acute stress and cortisol manipulation on the physiology, behavior, and reproductive outcome of female Pacific salmon on spawning grounds.

    PubMed

    McConnachie, Sarah H; Cook, Katrina V; Patterson, David A; Gilmour, Kathleen M; Hinch, Scott G; Farrell, Anthony P; Cooke, Steven J

    2012-06-01

    Life-history theory predicts that stress responses should be muted to maximize reproductive fitness. Yet, the relationship between stress and reproduction for semelparous salmon is unusual because successfully spawning individuals have elevated plasma cortisol levels. To tease apart the effects of high baseline cortisol levels and stress-induced elevation of cortisol titers, we determined how varying degrees of cortisol elevation (i.e., acute and chronic) affected behavior, reproductive physiology, and reproductive success of adult female pink salmon (Oncorhynchus gorbuscha) relative to different states of ovulation (i.e., ripe and unripe). Exhaustive exercise and air exposure were applied as acute stressors to manipulate plasma cortisol in salmon either confined to a behavioral arena or free-swimming in a spawning channel. Cortisol (eliciting a cortisol elevation to levels similar to those in post-spawn female salmon) and metyrapone (a corticosteroid synthesis inhibitor) implants were also used to chemically manipulate plasma cortisol. Cortisol implants elevated plasma cortisol, and impaired reproductive success; cortisol-treated fish released fewer eggs and died sooner than fish in other treatment groups. In contrast, acute stressors elevated plasma cortisol and the metyrapone implant suppressed plasma cortisol, but neither treatment significantly altered reproductive success, behavior, or physiology. Our results suggest that acute stressors do not influence behavior or reproductive outcome when experienced upon arrival at spawning grounds. Thus, certain critical aspects of salmonid reproduction can become refractory to various stressful conditions on spawning grounds. However, there is a limit to the ability of these fish to tolerate elevated cortisol levels as revealed by experimental elevation of cortisol.

  14. 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

  15. 2-Substituted 3β-Aryltropane Cocaine Analogs Produce Atypical Effects without Inducing Inward-Facing Dopamine Transporter Conformations.

    PubMed

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

    2016-03-01

    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

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

    PubMed

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

    2016-03-01

    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.

  17. 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

  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.

  19. 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

  20. 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.

  1. Menstrual cycle effects on cortisol responsivity and emotional retrieval following a psychosocial stressor

    PubMed Central

    Maki, Pauline M.; Mordecai, Kristen L.; Rubin, Leah H.; Sundermann, Erin; Savarese, Antonia; Eatough, Erin; Drogos, Lauren

    2016-01-01

    Laboratory-induced stress produces elevations in cortisol and deficits in memory, especially when stress is induced immediately before retrieval of emotionally valent stimuli. Sex and sex steroids appear to influence these stress-induced outcomes, though no study has directly compared the effects of laboratory-induced stress on cortisol and emotional retrieval across the menstrual cycle. We examined the effect of psychosocial stress on cortisol responsivity and emotional retrieval in women tested during either the follicular phase (low estradiol and progesterone) or the luteal phase (higher estradiol and progesterone). Forty women (50%White; age 18–40 years) participated in the study; 20 completed the task during the luteal phase and 20 during the follicular phase. Psychosocial stress was induced with the Trier Social Stress Test (TSST). On the day before the TSST, participants learned two lists of word pairs to 100% criterion. The next day, participants recalled one list after the control condition and the other after the TSST. Women in the follicular phase, but not the luteal phase, demonstrated a significant cortisol response to the TSST. There was a stress-induced decrease in emotional retrieval following the TSST, but this effect was not modified by menstrual phase. However, regression and correlational analyses showed that individual differences in stress-induced cortisol levels were associated with impaired emotional retrieval in the follicular phase only. The present findings indicate that cortisol responsivity and the impairing effects of cortisol on emotional memory are lower when levels of estradiol and progesterone are high compared to when levels are low. PMID:26187711

  2. Menstrual cycle effects on cortisol responsivity and emotional retrieval following a psychosocial stressor.

    PubMed

    Maki, Pauline M; Mordecai, Kristen L; Rubin, Leah H; Sundermann, Erin; Savarese, Antonia; Eatough, Erin; Drogos, Lauren

    2015-08-01

    This article is part of a Special Issue "Estradiol and cognition". Laboratory-induced stress produces elevations in cortisol and deficits in memory, especially when stress is induced immediately before retrieval of emotionally valent stimuli. Sex and sex steroids appear to influence these stress-induced outcomes, though no study has directly compared the effects of laboratory-induced stress on cortisol and emotional retrieval across the menstrual cycle. We examined the effect of psychosocial stress on cortisol responsivity and emotional retrieval in women tested during either the follicular phase (low estradiol and progesterone) or the luteal phase (higher estradiol and progesterone). Forty women (50% White; age 18-40 years) participated in the study; 20 completed the task during the luteal phase and 20 during the follicular phase. Psychosocial stress was induced with the Trier Social Stress Test (TSST). On the day before the TSST, participants learned two lists of word pairs to 100% criterion. The next day, participants recalled one list after the control condition and the other after the TSST. Women in the follicular phase, but not the luteal phase, demonstrated a significant cortisol response to the TSST. There was a stress-induced decrease in emotional retrieval following the TSST, but this effect was not modified by menstrual phase. However, regression and correlational analyses showed that individual differences in stress-induced cortisol levels were associated with impaired emotional retrieval in the follicular phase only. The present findings indicate that cortisol responsivity and the impairing effects of cortisol on emotional memory are lower when levels of estradiol and progesterone are high compared to when levels are low.

  3. 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...

  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. 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.

  6. Clinical applications of cortisol measurements in hair.

    PubMed

    Wester, Vincent L; van Rossum, Elisabeth F C

    2015-10-01

    Cortisol measurements in blood, saliva and urine are frequently used to examine the hypothalamus-pituitary-adrenal (HPA) axis in clinical practice and in research. However, cortisol levels are subject to variations due to acute stress, the diurnal rhythm and pulsatile secretion. Cortisol measurements in body fluids are not always a reflection of long-term cortisol exposure. The analysis of cortisol in scalp hair is a relatively novel method to measure cumulative cortisol exposure over months up to years. Over the past years, hair cortisol concentrations (HCC) have been examined in association with a large number of somatic and mental health conditions. HCC can be used to evaluate disturbances of the HPA axis, including Cushing's syndrome, and to evaluate hydrocortisone treatment. Using HCC, retrospective timelines of cortisol exposure can be created which can be of value in diagnosing cyclic hypercortisolism. HCC have also been shown to increase with psychological stressors, including major life events, as well as physical stressors, such as endurance exercise and shift work. Initial studies show that HCC may be increased in depression, but decreased in general anxiety disorder. In posttraumatic stress disorder, changes in HCC seem to be dependent on the type of traumatic experience and the time since traumatization. Increased hair cortisol is consistently linked to obesity, metabolic syndrome and cardiovascular disease. Potentially, HCC could form a future marker for cardiovascular risk stratification, as well as serve as a treatment target.

  7. Spatially uniform microflows induced by thermoviscous expansion along a traveling temperature wave: Analogies with electro-osmotic transport

    NASA Astrophysics Data System (ADS)

    Pal, Debashis; Chakraborty, Suman

    2012-07-01

    We discover that thermoviscous expansion along a traveling wave in a microfluidic channel may be capable of generating a spatially uniform flow profile in a time-averaged sense. We further delineate that the resultant complex flow characteristics, realized by virtue of an intricate interplay between thermal compression-expansion waves and temperature-dependent viscosity variations and controlled by an external heating, may be remarkably characterized by a unique thermal penetration depth scale (analogous to Debye length in electro-osmosis) and a velocity scale (analogous to the Helmholtz Smulochowski velocity in electro-osmosis) that in turn depends on the considerations of “thin” and “thick” microchannel limits, as dictated by the thermal penetration depth as compared to the lateral extent of the microfluidic channel. We show that, when the thermal penetration depth is small as compared to the channel height, a uniform velocity profile is generated in the channel in a time-averaged sense. The velocity scale characterizing this uniform flow may be represented by a function of the thermal diffusivity, volumetric expansion coefficient and thermal viscosity coefficient of the fluid, characteristic amplitude and speed of the thermal wave, as well as the channel height. Results from the present study are expected to provide valuable insights towards arresting hydrodynamic dispersion in microchannels by nonelectrochemical means, following a pH-independent route.

  8. 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

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

    PubMed

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

    2015-04-01

    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.

  10. Chemical communication of predation risk in zebrafish does not depend on cortisol increase

    PubMed Central

    Barcellos, Leonardo J. G.; Koakoski, Gessi; da Rosa, João G. S.; Ferreira, Daiane; Barreto, Rodrigo E.; Giaquinto, Percília C.; Volpato, Gilson L.

    2014-01-01

    We investigated chemical cues among groups of zebrafish (Danio rerio) when communicating information about the risk of predation. We found that visual cues of the predator (tiger Oscar, Astronotus ocellatus) did not increase whole-body cortisol levels in groups of zebrafish but that water conditioned by these (donor) zebrafish stressed (target) conspecifics, thereby increasing whole-body cortisol. This finding was confirmed when these zebrafish groups were in different aquaria and communicated exclusively via water transfer. This result indicates that the stress induced in the target zebrafish does not depend on an increase in whole-body cortisol levels in the donor zebrafish. Because cortisol participation is rejected in this predation-risk communication, other chemicals from the stress systems should be investigated. PMID:24861706

  11. Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland

    PubMed Central

    Torres-Farfan, Claudia; Richter, Hans G; Germain, Alfredo M; Valenzuela, Guillermo J; Campino, Carmen; Rojas-García, Pedro; Forcelledo, María Luisa; Torrealba, Fernando; Serón-Ferré, María

    2004-01-01

    We tested the hypothesis that in primates, maternal melatonin restrains fetal and newborn adrenal cortisol production. A functional G-protein-coupled MT1 membrane-bound melatonin receptor was detected in 90% gestation capuchin monkey fetal adrenals by (a) 2-[125I] iodomelatonin binding (Kd, 75.7 ± 6.9 pm; Bmax, 2.6 ± 0.4 fmol (mg protein)−1), (b) cDNA identification, and (c) melatonin inhibition of adrenocorticotrophic hormone (ACTH)- and corticotrophin-releasing hormone (CRH)-stimulated cortisol but not of dehydroepiandrosterone sulphate (DHAS) production in vitro. Melatonin also inhibited ACTH-induced 3β-hydroxysteroid dehydrogenase mRNA expression. To assess the physiological relevance of these findings, we next studied the effect of chronic maternal melatonin suppression (induced by exposure to constant light during the last third of gestation) on maternal plasma oestradiol during gestation and on plasma cortisol concentration in the 4- to 6-day-old newborn. Constant light suppressed maternal melatonin without affecting maternal plasma oestradiol concentration, consistent with no effect on fetal DHAS, the precursor of maternal oestradiol. However, newborns from mothers under constant light condition had twice as much plasma cortisol as newborns from mothers maintained under a normal light–dark schedule. Newborns from mothers exposed to chronic constant light and daily melatonin replacement had normal plasma cortisol concentration. Our results support a role of maternal melatonin in fetal and neonatal primate cortisol regulation. PMID:14673186

  12. Cortisol regulates sodium homeostasis by stimulating the transcription of sodium-chloride transporter (NCC) in zebrafish (Danio rerio).

    PubMed

    Lin, Chia-Hao; Hu, Huei-Jyun; Hwang, Pung-Pung

    2016-02-15

    In mammals, sodium/hydrogen exchanger (NHE) and sodium-chloride cotransporter (NCC) are expressed in renal tubules, and exhibit functional redundancy and mutual compensation in Na(+) uptake. In teleosts, the gills of the adult and skin of the embryonic stage function as external kidneys, and ionocytes are responsible for ionoregulation in these tissues. NHE- and NCC-expressing ionocytes mutually cooperate to adjust Na(+) uptake, which is analogous to the activity of the mammalian kidney. Cortisol is a hormone that controls Na(+) uptake through regulating NCC expression and activity in mammals; however, cortisol-mediated control of NCC expression is little understood in non-mammalian vertebrates, such as teleosts. It is essential for our understanding of the evolution of such regulation to determine whether cortisol has a conserved effect on NCC in vertebrates. In the present study, we treated zebrafish embryos with low Na(+) medium (LNa, 0.04 mM Na(+)) for 3 d to stimulate the mRNA expression of nhe3b, ncc, and cyp11b1 (a cortisol-synthesis enzyme) and whole body cortisol level. Exogenous cortisol treatment (20 mg/l, 3 d) resulted in an elevation of whole-body Na(+) content, ncc expression, and the density of ncc-expressing cells in zebrafish larvae. In loss-of-function experiments, microinjection of glucocorticoid receptor (gr) morpholino (MO) suppressed sodium content, ncc expression, and the density of ncc-expressing cells, but injection of mr MO had no such effects. In addition, exogenous cortisol treatment and gr MO injection also altered ncc expression and the density of ncc-expressing cells in gcm2 morphant larvae. Taken together, cortisol and GR appear to regulate Na(+) absorption through stimulating ncc expression and the differentiation of ncc-expressing ionocytes, providing new insights into the actions of cortisol on Na(+) uptake.

  13. 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

  14. 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.

  15. Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: Comparison to salivary cortisol

    PubMed Central

    D’Anna-Hernandez, Kimberly L.; Ross, Randal G.; Natvig, Crystal L.; Laudenslager, Mark L.

    2011-01-01

    Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair cortisol provides a simple way to monitor total cortisol release over an extended period of time. Hair cortisol levels were determined from each trimester (15, 26 and 36 wks gestation) and 3 months postpartum. Hair cortisol levels were compared to diurnal salivary cortisol collected over 3 days (3 times/day) at 14, 18, 23, 29, and 34 wks gestational age and 6 wks postpartum from 21 pregnant women. Both salivary and hair cortisol levels rose during pregnancy as expected. Hair cortisol and diurnal salivary cortisol area under the curve with respect to ground (AUCg) were also correlated throughout pregnancy. Levels of cortisol in hair are a valid and useful tool to measure long-term cortisol activity. Hair cortisol avoids methodological problems associated with collection other cortisol measures such as plasma, urine, or saliva and is a reliable metric of HPA activity throughout pregnancy reflecting total cortisol release over an extended period. PMID:21397617

  16. Salivary Cortisol Lower in Posttraumatic Stress Disorder

    PubMed Central

    Wahbeh, Helané; Oken, Barry S.

    2013-01-01

    Altered cortisol has been demonstrated to be lower in posttraumatic stress disorder (PTSD) in most studies. This cross-sectional study evaluated salivary cortisol at waking, 30 minutes after, and bedtime in 51 combat veterans with PTSD compared to 20 veterans without PTSD. It also examined the relationship of cortisol to PTSD symptoms using two classifications: DSM-IV and the more recent four-factor classification proposed for DSM-V. The PTSD group had lower cortisol values than the control group (F(6, 69) = 3.35, p = .006). This significance did not change when adding age, body mass index, smoking, medications affecting cortisol, awakening time, sleep duration, season, depression, perceived stress, service era, combat exposure, and lifetime trauma as covariates. Post-hoc analyses revealed that the PTSD group had lower area under the curve ground and waking, 30min, and bedtime values while the cortisol awakening response and area under the curve increase were not different between groups. The four-factor avoidance PTSD symptom cluster was associated with cortisol but not the other symptom clusters. This study supports the finding that cortisol is lower in people with PTSD. PMID:23529862

  17. Cortisol levels in human follicular fluid.

    PubMed

    Fateh, M; Ben-Rafael, Z; Benadiva, C A; Mastroianni, L; Flickinger, G L

    1989-03-01

    This study shows that cortisol levels in follicular fluids in stimulated cycles were correlated with oocyte maturity and in vitro fertilizability. The levels were significantly higher than the concentrations found in spontaneous cycles. Our findings suggest that the presence of cortisol in follicular fluid may play a role in follicular development and oocyte maturation.

  18. Electrochemical Sensing of Cortisol: A Recent Update

    PubMed Central

    Singh, Aparajita; Kaushik, Ajeet; Kumar, Rajesh; Nair, Madhavan; Bhansali, Shekhar

    2014-01-01

    Psychological stress caused by everyday life style contributes to health disparities experience by individuals. It affects many biomarkers, but cortisol “a steroid hormone” is known as a potential biomarker for psychological stress detection. Abnormal levels of cortisol, is indicative of conditions such as Cushing’s syndrome Addison’s disease, adrenal insufficiencies and more recently post-traumatic stress disorder (PTSD). Chromatographic techniques, which are traditionally used to detect cortisol, are a complex system requiring multistep extraction/purification. This limits its application for point-of-care (POC) detection of cortisol. However, electrochemical immunosensing of cortisol is a recent advancement towards POC application. This review highlights simple, low-cost, and label-free electrochemical immunosensing platforms which have been developed recently for sensitive and selective detection of cortisol in biofluids. Electrochemical detection is utilized for the detection of cortisol using Anti-Cortisol antibodies (Anti-Cab) covalently immobilized on nanostructures such as self-assembled monolayer (SAM), polymer composite, etc. for POC integration of sensors. The observed information can be used as prototype to understand behavioral changes in humans in case to case such as farmers, fire fighters, etc. Keeping the future directions and challenges in mind the focus of the BioMEMS and Microsystems Research Group at Florida International University is on development of POC devices for immunosensing, integration of these devices with microfluidics, cross validation with existing technologies, and analysis of real sample. PMID:24723204

  19. 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

  20. 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

  1. 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

  2. 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

  3. Myeloid differentiation and retinoblastoma phosphorylation changes in HL-60 cells induced by retinoic acid receptor- and retinoid X receptor-selective retinoic acid analogs.

    PubMed

    Brooks, S C; Kazmer, S; Levin, A A; Yen, A

    1996-01-01

    The ability of subtypes of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) singly and in combination to elicit myeloid differentiation, G1/0-specific growth arrest, and retinoblastoma (RB) tumor suppressor protein dephosphorylation was determined in the human myeloblastic leukemia cell line HL-60 using subtype-selective retinoic acid (RA) analogs. RA analogs that selectively bind only to RARs (Am580 and/or TTNPB) or to RXRs (Ro 25-6603, SR11237, and/or SR11234) did not elicit the above-mentioned three cellular responses. In contrast, simultaneous treatment with both an RAR-selective ligand (Am580 or TTNPB) and an RXR-selective ligand (Ro 25-6603, SR11237, or SR11234) induced all three cellular processes. An RAR alpha-selective ligand used with an RXR-selective ligand generated the same responses as did all-trans RA or 9-cis RA, which affect both families of receptors, suggesting an important role for RAR alpha among RAR subtypes in eliciting cellular response. Consistent with this finding, the RAR alpha antagonist, Ro 41-5253, reduced the level of the cellular responses elicited by treatment with an RAR alpha-selective ligand plus RXR-selective ligand. The coupling of the shift of RB to its hypophosphorylated form with G1/0 arrest and differentiation in response to ligands is consistent with a possible role of RB as a downstream target or effector of RAR alpha and RXR in combination.

  4. Expensive Egos: Narcissistic Males Have Higher Cortisol

    PubMed Central

    Reinhard, David A.; Konrath, Sara H.; Lopez, William D.; Cameron, Heather G.

    2012-01-01

    Background Narcissism is characterized by grandiosity, low empathy, and entitlement. There has been limited research regarding the hormonal correlates of narcissism, despite the potential health implications. This study examined the role of participant narcissism and sex on basal cortisol concentrations in an undergraduate population. Methods and Findings Participants were 106 undergraduate students (79 females, 27 males, mean age 20.1 years) from one Midwestern and one Southwestern American university. Narcissism was assessed using the Narcissistic Personality Inventory, and basal cortisol concentrations were collected from saliva samples in a laboratory setting. Regression analyses examined the effect of narcissism and sex on cortisol (log). There were no sex differences in basal cortisol, F(1,97) = .20, p = .65, and narcissism scores, F(1,97) = .00, p = .99. Stepwise linear regression models of sex and narcissism and their interaction predicting cortisol concentrations showed no main effects when including covariates, but a significant interaction, β = .27, p = .04. Narcissism was not related to cortisol in females, but significantly predicted cortisol in males. Examining the effect of unhealthy versus healthy narcissism on cortisol found that unhealthy narcissism was marginally related to cortisol in females, β = .27, p = .06, but significantly predicted higher basal cortisol in males, β = .72, p = .01, even when controlling for potential confounds. No relationship was found between sex, narcissism, or their interaction on self-reported stress. Conclusions Our findings suggest that the HPA axis is chronically activated in males with unhealthy narcissism. This constant activation of the HPA axis may have important health implications. PMID:22292062

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Effects of binary mixtures of inducers (toluene analogs) and of metals on bioluminescence induction of a recombinant bioreporter strain.

    PubMed

    Kong, In Chul

    2014-10-13

    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.

  10. 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

  11. Prenatal Cocaine Exposure Alters Cortisol Stress Reactivity in 11 Year Old Children

    PubMed Central

    Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Lin, Richard; Das, Abhik; Higgins, Rosemary

    2011-01-01

    Objective Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school aged children. Study design Subjects included 743 11 year old children (n=320 cocaine exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse and quality of the home. Results With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Cocaine exposed children exposed to domestic violence showed the strongest effects. Conclusion The combination of prenatal cocaine exposure and an adverse postnatal environment could down regulate the hypothalamic-pituitary-adrenal axis (HPA) resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease. PMID:20400094

  12. 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.

  13. 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.

  14. The onset of cortisol synthesis and the stress response is independent of changes in CYP11B or CYP21 mRNA levels in larval red drum (Sciaenops ocellatus).

    PubMed

    Applebaum, Scott L; Wilson, C Alexander; Holt, G Joan; Nunez, B Scott

    2010-01-15

    Although cortisol plays an important role in teleost development, the onset of cortisol production and the cortisol stress response in teleosts remain poorly understood. Here we have reported basal cortisol levels and the development of the cortisol stress response in larval red drum (Sciaenops ocellatus). We isolated partial nucleic acid sequences encoding two key corticosteroidogenic enzymes, CYP11B and CYP21 and assessed ontogenetic patterns of their mRNA levels relative to basal and stress-induced cortisol production. Basal cortisol was first detected 3 days post-hatch (DPH) and reached a maximum at 9 DPH. Cortisol did not increase in response to an acute stressor prior to 6 DPH. From 6 DPH forward, stress caused significant increases in larval cortisol content. Stress-induced cortisol levels in 6-9 DPH larvae were highest 1h post-stress. In larvae 11 DPH and older, the highest cortisol measurements occurred 0.5h post-stress. Elevated cortisol was still evident after 3h in 6 DPH larvae. From 11 DPH onward, basal cortisol levels were reestablished in larvae by 1h post-stress. CYP11B and CYP21 transcripts were detected in red drum 12h prior to hatching and in all post-hatch larvae examined. Changes in CYP11B and CYP21 mRNA levels did not occur in association with the ontogenetic appearance of cortisol, or the onset of the stress response. As larvae developed, the dynamics of the cortisol stress response matured from a low magnitude, slow recovery response, to a response similar to that observed in juvenile and adult fish. PMID:19595692

  15. 3' -> 5' Exonucleases of DNA Polymerases ε and δ Correct Base Analog Induced DNA Replication Errors on opposite DNA Strands in Saccharomyces Cerevisiae

    PubMed Central

    Shcherbakova, P. V.; Pavlov, Y. I.

    1996-01-01

    The base analog 6-N-hydroxylaminopurine (HAP) induces bidirectional GC -> AT and AT -> GC transitions that are enhanced in DNA polymerase ε and δ 3' -> 5' exonuclease-deficient yeast mutants, pol2-4 and pol3-01, respectively. We have constructed a set of isogenic strains to determine whether the DNA polymerases δ and ε contribute equally to proofreading of replication errors provoked by HAP during leading and lagging strand DNA synthesis. Site-specific GC -> AT and AT -> GC transitions in a Pol(+), pol2-4 or pol3-01 genetic background were scored as reversions of ura3 missense alleles. At each site, reversion was increased in only one proofreading-deficient mutant, either pol2-4 or pol3-01, depending on the DNA strand in which HAP incorporation presumably occurred. Measurement of the HAP-induced reversion frequency of the ura3 alleles placed into chromosome III near to the defined active replication origin ARS306 in two orientations indicated that DNA polymerases ε and δ correct HAP-induced DNA replication errors on opposite DNA strands. PMID:8849882

  16. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis.

    PubMed

    Li, Mei; Hener, Pierre; Zhang, Zhikun; Kato, Shigeaki; Metzger, Daniel; Chambon, Pierre

    2006-08-01

    We have demonstrated that cytokine thymic stromal lymphopoietin (TSLP), whose expression is rapidly induced upon keratinocyte-selective ablation of retinoid X receptors (RXRs) -alpha and -beta in the mouse (RXRalphabeta(ep-/-) mice), plays a key role in initiating a skin and systemic atopic dermatitis-like phenotype. We show here that topical application of the physiologically active ligand [1alpha,25-(OH)(2)D(3); calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome mimicking that seen in RXRalphabeta(ep-/-) mutants and transgenic mice overexpressing TSLP in keratinocytes. Furthermore, topical application of retinoic acid receptor RARgamma-selective agonist BMS961 also induces TSLP expression either on its own or synergistically with 1alpha,25-(OH)(2)D(3). Our data demonstrate that RXR/vitamin D receptor and RXR/retinoic acid receptor-gamma heterodimers and their ligands cell-autonomously control the expression of TSLP in epidermal keratinocytes of the mouse. We propose molecular mechanisms through which vitamin D3 and retinoic acid signalings could be involved in the pathogenesis of atopic diseases.

  17. Heart rate and salivary cortisol concentrations in foals at birth.

    PubMed

    Nagel, C; Erber, R; Ille, N; Wulf, M; Aurich, J; Möstl, E; Aurich, C

    2015-02-01

    Heart rate (HR), HR variability (HRV) and salivary cortisol concentrations were determined in foals (n = 13) during the perinatal phase and until 5 months of age. In the fetus, HR decreased from 77 ± 3 beats/min at 120 min before birth to 60 ± 1 beats/min at 5 min before birth (P <0.01). Within 30 min of birth, HR increased to 160 ± 9 beats/min (P <0.01). Salivary cortisol concentrations immediately after birth were 11.9 ± 3.6 ng/mL and within 2 h increased to a maximum of 52.5 ± 12.3 ng/mL (P <0.01). In conclusion, increases in HR and salivary cortisol concentrations in foals are not induced during parturition, but occur immediately after birth.

  18. Acute lymphopenia, stress, and plasma cortisol.

    PubMed Central

    Ramaekers, L H; Theunissen, P M; Went, K

    1975-01-01

    Plasma cortisol levels were determined in 51 children on admission to hospital for a variety of acute illnesses which were associated with a lymphopenia, and again when the lymphocyte count had returned to normal. The ratio cortisol level/lymphocyte count was much higher in the acute phase of the illness than later when the lymphocyte count had returned to normal. It is concluded that the lymphocyte count is a useful means of detecting an acute stress condition, and the time of return of normal plasma cortisol levels. PMID:1167069

  19. 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

  20. The novel carboxamide analog ITR-284 induces caspase-dependent apoptotic cell death in human hepatocellular and colorectal cancer cells.

    PubMed

    Liao, Yu-Ren; Lu, Chi-Cheng; Lai, Kuang-Chi; Yang, Jai-Sing; Kuo, Sheng-Chu; Wen, Yen-Fang; Fushiya, Shinji; Wu, Tian-Shung

    2013-05-01

    We have previously reported that ITR-284, a potent carboxamide-derived anticancer agent, induced apoptosis in leukemia cells. However, there are no reports showing that ITR-284 inhibits human hepatocellular and colorectal cancer cells. In this study, we investigated the antiproliferative effects and apoptotic induction of ITR-284 on various types of human hepatocellular and colorectal cancer cells in vitro. The growth inhibition effect of ITR-284 on cancer cells was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay. Cell morphology was examined under a phase-contrast microscope. The activities of caspase-3, -8 and -9 were determined by caspase colorimetric assay. ITR-284 reduced the cell viability in human hepatocellular cancer cells (Hep G2, Hep 3B, SK-HEP-1 and J5) and colorectal cancer cells (HT 29, COLO 205, HCT 116 and SW 620). ITR-284 had highly selective effects on Hep 3B and COLO 205 cells. ITR-284 stimulated morphological changes of Hep 3B and COLO 205 cells. The activation of caspase-3, -8 and -9 contributed to ITR-284-induced apoptosis. ITR-284-triggered growth inhibition was significantly attenuated by the inhibitors of caspase-3, -8 and -9 in Hep 3B and COLO 205 cells. ITR-284 induced apoptosis in Hep 3B and COLO 205 cells through the caspase cascade-dependent signaling pathway.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. IN-SITU PROBING OF RADIATION-INDUCED PROCESSING OF ORGANICS IN ASTROPHYSICAL ICE ANALOGS-NOVEL LASER DESORPTION LASER IONIZATION TIME-OF-FLIGHT MASS SPECTROSCOPIC STUDIES

    SciTech Connect

    Gudipati, Murthy S.; Yang Rui E-mail: ryang73@ustc.edu

    2012-09-01

    Understanding the evolution of organic molecules in ice grains in the interstellar medium (ISM) under cosmic rays, stellar radiation, and local electrons and ions is critical to our understanding of the connection between ISM and solar systems. Our study is aimed at reaching this goal of looking directly into radiation-induced processing in these ice grains. We developed a two-color laser-desorption laser-ionization time-of-flight mass spectroscopic method (2C-MALDI-TOF), similar to matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectroscopy. Results presented here with polycyclic aromatic hydrocarbon (PAH) probe molecules embedded in water-ice at 5 K show for the first time that hydrogenation and oxygenation are the primary chemical reactions that occur in astrophysical ice analogs when subjected to Ly{alpha} radiation. We found that hydrogenation can occur over several unsaturated bonds and the product distribution corresponds to their stabilities. Multiple hydrogenation efficiency is found to be higher at higher temperatures (100 K) compared to 5 K-close to the interstellar ice temperatures. Hydroxylation is shown to have similar efficiencies at 5 K or 100 K, indicating that addition of O atoms or OH radicals to pre-ionized PAHs is a barrierless process. These studies-the first glimpses into interstellar ice chemistry through analog studies-show that once accreted onto ice grains PAHs lose their PAH spectroscopic signatures through radiation chemistry, which could be one of the reason for the lack of PAH detection in interstellar ice grains, particularly the outer regions of cold, dense clouds or the upper molecular layers of protoplanetary disks.

  6. Post-marathon wearing of Masai Barefoot Technology shoes facilitates recovery from race-induced fatigue: an evaluation utilizing a visual analog scale

    PubMed Central

    Nakagawa, Kento; Obu, Takashi; Kanosue, Kazuyuki

    2014-01-01

    Purpose To investigate the potential benefit of post-race wearing of unstable shoes (Masai Barefoot Technology [MBT]) on recovery from marathon race–induced fatigue. Patients and methods Forty-five runners who participated in a full marathon race were divided into three groups: 1) MBT shoes, 2) trail running shoes, and 3) control (CON). Participants ran a full marathon with their own running shoes, and then put on the assigned shoes immediately after the race. They continued to wear the assigned shoes for the ensuing 3 days. The CON group wore their usual shoes. Estimates of post-race fatigue were made by the participants on questionnaires that utilized a visual analog scale. Estimates were made just after the race, as well as for the next 3 days. Results The subjective fatigue of the MBT group was lower than that of the CON (P<0.05) or trail running shoe groups (P<0.05) on day 3. Conclusion MBT shoe intervention can promote recovery from the fatigue induced by running a full marathon. PMID:25525398

  7. 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

  8. 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

  9. Effects of pre-learning stress on memory for neutral, positive and negative words: Different roles of cortisol and autonomic arousal.

    PubMed

    Schwabe, Lars; Bohringer, Andreas; Chatterjee, Monischa; Schachinger, Hartmut

    2008-07-01

    Stress can have enhancing or impairing effects on memory. Here, we addressed the effect of pre-learning stress on subsequent memory and asked whether neutral and emotionally valent information are differentially affected by specific stress components, autonomic arousal and stress-induced cortisol. Ninety-six healthy men and women underwent either a stressor (modified cold pressor test) or a control warm water exposure. During stress, participants showed comparable autonomic arousal (heart rate, blood pressure), while 60 percent showed an increase of cortisol (responders vs. 40 percent non-responders). Ten minutes after the cold pressor test neutral, positive and negative words were presented. Free recall was tested 1 and 24h later. Overall, positive and negative words were better recalled than neutral words. Stress enhanced the recall of neutral words independently of cortisol response. In contrast, the free recall of negative words was enhanced in cortisol responders in the 1-h but not 24-h test which might suggest different effects of cortisol on consolidation and reconsolidation processes. Recall for positive words was unaffected by stress-induced cortisol. To summarize, (i) pre-learning stress can enhance memory for neutral words independently of cortisol and (ii) stress effects on memory for negative words appear to rely on stress-induced cortisol elevations, the absence of this effect for positive words might be at least partly due to differences in arousal evoked by positive vs. negative words.

  10. 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

  11. 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

  12. Zinc oxide nanostructures for electrochemical cortisol biosensing

    NASA Astrophysics Data System (ADS)

    Vabbina, Phani Kiran; Kaushik, Ajeet; Tracy, Kathryn; Bhansali, Shekhar; Pala, Nezih

    2014-05-01

    In this paper, we report on fabrication of a label free, highly sensitive and selective electrochemical cortisol immunosensors using one dimensional (1D) ZnO nanorods (ZnO-NRs) and two dimensional nanoflakes (ZnO-NFs) as immobilizing matrix. The synthesized ZnO nanostructures (NSs) were characterized using scanning electron microscopy (SEM), selective area diffraction (SAED) and photoluminescence spectra (PL) which showed that both ZnO-NRs and ZnO-NFs are single crystalline and oriented in [0001] direction. Anti-cortisol antibody (Anti-Cab) are used as primary capture antibodies to detect cortisol using electrochemical impedance spectroscopy (EIS). The charge transfer resistance increases linearly with increase in cortisol concentration and exhibits a sensitivity of 3.078 KΩ. M-1 for ZnO-NRs and 540 Ω. M -1 for ZnO-NFs. The developed ZnO-NSs based immunosensor is capable of detecting cortisol at 1 pM. The observed sensing parameters are in physiological range. The developed sensors can be integrated with microfluidic system and miniaturized potentiostat to detect cortisol at point-of-care.

  13. 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

  14. Elevated content of cortisol in hair of patients with severe chronic pain: a novel biomarker for stress.

    PubMed

    Van Uum, S H M; Sauvé, B; Fraser, L A; Morley-Forster, P; Paul, T L; Koren, G

    2008-11-01

    Hair analysis has been used to reflect long-term systemic exposure to exogenous drugs and toxins. Several studies have demonstrated the feasibility of measuring endogenous steroid hormones, e.g. cortisol, in hair. Recently, a study in macaques showed a significant increase in hair cortisol levels induced by stress. We explored whether hair cortisol levels may be used as a biomarker for long-term stress in humans. Patients with severe chronic pain, aged 18 years or older, receiving opioid treatment for at least one year were recruited. Controls were non-obese (body mass index, BMI < 30 mg/kg(2)) adults. The Perceived Stress Scale (PSS) questionnaire was used to assess perceived stress over the last 4 weeks. A hair sample was obtained from the vertex posterior. Cortisol was measured using an enzyme-linked immunosorbent assay. We included fifteen patients (nine females and six males) and 39 non-obese control subjects (20 females, 19 males). PSS scores (median and range) were significantly higher in chronic pain patients (24: 12-28) than in controls (12: 3-31)(P < 0.001). Hair cortisol contents (median and range) were significantly greater in chronic pain patients (83.1: 33.0-205 g/mg) than in controls (46.1: 27.2-200 pg/mg) (P < 0.01). We conclude that hair cortisol contents are increased in patients with major chronic stress. Measurement of cortisol levels in hair constitutes a novel biomarker of prolonged stress. PMID:18609301

  15. Does season alter responsiveness of the reproductive neuroendocrine axis to the suppressive actions of cortisol in ovariectomized ewes?

    PubMed

    Breen, Kellie M; Karsch, Fred J

    2006-01-01

    Season can profoundly influence activity of the hypothalamic-pituitary-adrenal axis and alter reproductive neuroendocrine responsiveness to stress and gonadal steroids. Here we tested the hypothesis that the inhibitory effect of a stress-like increment in plasma concentration of the adrenal steroid cortisol on pulsatile LH secretion varies with season. LH pulse patterns were monitored prior to and during the administration of cortisol in the same seven ovariectomized ewes during three stages of the yearly breeding cycle: breeding season, transition to anestrus, and midanestrus. The elevation in cortisol mimicked the rise in plasma level of cortisol in response to an immune/inflammatory stress. During all three seasons, cortisol acutely suppressed the pulsatile release of LH. This inhibition reflected a marked reduction of LH pulse amplitude and a minimal suppression of LH pulse frequency. Of interest, the suppressive effect of this physiologic increment in cortisol did not vary across seasons. This provides initial evidence that, in ovariectomized ewes, cortisol-induced suppression of pulsatile LH secretion differs from that of gonadal steroids in that it is not profoundly influenced by season.

  16. 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

  17. Treatment-related alteration of cortisol predicts change in neuropsychological function during acute treatment of late-life anxiety disorder

    PubMed Central

    Lenze, Eric J.; Dixon, David; Mantella, Rose C.; Dore, Peter M.; Andreescu, Carmen; Reynolds, Charles F.; Newcomer, John W.; Butters, Meryl A.

    2012-01-01

    Objective Older adults with anxiety disorders are burdened by impairment in neurocognition, which may be mediated by elevated circulating cortisol levels. In a randomized controlled trial of acute serotonin-reuptake inhibitor treatment for late-life anxiety disorder, we examined whether change in salivary cortisol concentrations during treatment predicted improvements in measures of memory and executive function. Methods We examined 60 adults aged 60 and older, who took part in a 12-week trial of escitalopram vs. placebo for Generalized Anxiety Disorder. All subjects had pre- and post-treatment assessments that included monitoring of peak and total daily cortisol and a comprehensive neuropsychological evaluation. Results Salivary cortisol changes during treatment showed significant associations with changes in immediate and delayed memory, but no association with executive tasks (measures of working memory and set-shifting). Analyses suggested that a decrease in cortisol due to serotonin-reuptake inhibitor treatment was responsible for the memory changes: memory improvement was seen with cortisol reduction among patients receiving escitalopram, but not among patients receiving placebo. Conclusion Serotonin-reuptake inhibitor-induced alteration in circulating cortisol during treatment of Generalized Anxiety Disorder predicted changes in immediate and delayed memory. This finding suggests a novel treatment strategy in late-life anxiety disorders: targeting HPA axis dysfunction to improve memory. PMID:21681817

  18. 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.

  19. Analog current mode analog/digital converter

    NASA Technical Reports Server (NTRS)

    Hadidi, Khayrollah (Inventor)

    1996-01-01

    An improved subranging or comparator circuit is provided for an analog-to-digital converter. As a subranging circuit, the circuit produces a residual signal representing the difference between an analog input signal and an analog of a digital representation. This is achieved by subdividing the digital representation into two or more parts and subtracting from the analog input signal analogs of each of the individual digital portions. In another aspect of the present invention, the subranging circuit comprises two sets of differential input pairs in which the transconductance of one differential input pair is scaled relative to the transconductance of the other differential input pair. As a consequence, the same resistor string may be used for two different digital-to-analog converters of the subranging circuit.

  20. Rearrangements Leading to Fragmentations of Hydrocinnamate and Analogous Nitrogen-Containing Anions Upon Collision-Induced Dissociation

    NASA Astrophysics Data System (ADS)

    Gillis, Elizabeth A. L.; Grossert, J. Stuart; White, Robert L.

    2014-03-01

    Tandem mass spectrometry (MS/MS) confirmed decarboxylation as the major collision-induced dissociation (CID) pathway of deprotonated hydrocinnamic acid (C6H5CH2CH2CO2H), N-phenylglycine (C6H5NHCH2CO2H) and 3-pyridin-2-ylpropanoic acid (C5H4NCH2CH2CO2H). The structure and stability of isomeric precursor and product anions were examined using density functional theory and ab initio methods. Geometry optimizations and frequency calculations were performed using the B3LYP/6-31++G(2d,p) level of theory and basis set with additional single point energies calculated at the MP2/6-311++G(2d,p) level. The formation of a delocalized product anion by carboxyl group-mediated migration of a benzylic proton to the ortho position of the ring and subsequent Cα-CO2 - bond cleavage was energetically more favorable than direct decarboxylation and rearrangements of anions within ion-neutral complexes with carbon dioxide. The energy barrier for rearrangement of the delocalized product anion to the more stable benzylic anion was lowest in the fragmentation pathway of 3-pyridin-2-ylpropanoate. More energetically demanding fragmentation processes were indicated by the formation of other product anions at higher collision energy. Computations supported the feasibility of the formation of hydroxycarbonyl, styrene, and phenide ions from the benzylic anion of hydrocinnamate and the corresponding product anions from the nitrogen-containing analogues. The loss of dihydrogen from decarboxylated 3-pyridin-2-ylpropanoate was characterized computationally as hydride abstraction of an aryl proton. Overall, the results highlight the importance of exploring rearrangements in the fragmentation pathways of ions formed by electrospray ionization (ESI).

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. A model of the radiation-induced bystander effect based on an analogy with ferromagnets. Application to modelling tissue response in a uniform field

    NASA Astrophysics Data System (ADS)

    Vassiliev, O. N.

    2014-12-01

    We propose a model of the radiation-induced bystander effect based on an analogy with magnetic systems. The main benefit of this approach is that it allowed us to apply powerful methods of statistical mechanics. The model exploits the similarity between how spin-spin interactions result in correlations of spin states in ferromagnets, and how signalling from a damaged cell reduces chances of survival of neighbour cells, resulting in correlated cell states. At the root of the model is a classical Hamiltonian, similar to that of an Ising ferromagnet with long-range interactions. The formalism is developed in the framework of the Mean Field Theory. It is applied to modelling tissue response in a uniform radiation field. In this case the results are remarkably simple and at the same time nontrivial. They include cell survival curves, expressions for the tumour control probability and effects of fractionation. The model extends beyond of what is normally considered as bystander effects. It offers an insight into low-dose hypersensitivity and into mechanisms behind threshold doses for deterministic effects.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. 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

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

    PubMed

    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.

  16. The influence of perceived control and locus of control on the cortisol and subjective responses to stress.

    PubMed

    Bollini, Annie M; Walker, Elaine F; Hamann, Stephan; Kestler, Lisa

    2004-11-01

    Stress has been implicated in the etiology of numerous mental and physical illnesses. Thus, it is important to identify factors that buffer individuals against stress. The purpose of this study was to examine the influence of perceived control (PC) on the biological and subjective stress responses, and to investigate the potential moderating effect of locus of control (LOC) on this relationship. Stress was induced with a noise-cognitive paradigm, and PC was manipulated by offering the option of manual control over noise intensity. Saliva cortisol and subjective stress were measured. There was no main effect of control on cortisol. However, LOC moderated the relation between control and cortisol; participants with more internal LOC, who also perceived themselves to have control over the stressor, showed a reduced cortisol response in the PC condition. The results are discussed in light of their implications for elucidating the determinants of the effects of perceived control on stress.

  17. Cortisol response and desire to binge following psychological stress: comparison between obese subjects with and without binge eating disorder.

    PubMed

    Rosenberg, Noa; Bloch, Miki; Ben Avi, Irit; Rouach, Vanessa; Schreiber, Shaul; Stern, Naftali; Greenman, Yona

    2013-07-30

    While stress and negative affect are known to precede "emotional eating", this relationship is not fully understood. The objective of this study was to explore the relationship between induced psychological stress, hypothalamic-pituitary-adrenal (HPA) axis activity, and eating behavior in binge eating disorder (BED). The Trier Social Stress Test (TSST) was applied in obese participants with (n=8) and without BED (n=8), and normal weight controls (n=8). Psychological characteristics, eating-related symptoms, and cortisol secretion were assessed. Baseline stress, anxiety and cortisol measures were similar in all groups. At baseline desire to binge was significantly higher among the BED group. While the TSST induced an increase in cortisol levels, a blunted cortisol response was observed in the BED group. In the BED group, a positive correlation was found between cortisol (area under the curve) levels during the TSST and the change in VAS scores for desire to binge. Post-TSST desire to binge and sweet craving were significantly higher in the BED group and correlated positively with stress, anxiety, and cortisol response in the BED group only. These results suggest chronic down-regulation of the HPA axis in participants with BED, and a relationship between psychological stress, the acute activation of the HPA axis, and food craving.

  18. Acute stress, memory, attention and cortisol.

    PubMed

    Vedhara, K; Hyde, J; Gilchrist, I D; Tytherleigh, M; Plummer, S

    2000-08-01

    An investigation was conducted to explore the relationship between acute changes in cortisol and memory and attention in the context of an acute naturalistic stressor, namely, examination stress. Sixty students (36 male, 24 female) participated in an assessment of self-reported levels of stress, salivary cortisol, short term memory, selective and divided attention and auditory verbal working memory. Assessments were conducted during a non-exam and exam period. The results revealed that the exam period was associated with an increase in perceived levels of stress, but also a significant reduction in levels of salivary cortisol, compared with the non-exam period. This reduction in cortisol was associated with enhanced short-term memory (as measured by the total number of words recalled in a free recall task), impaired attention and an impairment in the primacy effect (a hippocampal-specific index of short term memory), but no significant effects on auditory verbal working memory. It was concluded that the results support the view that cortisol can modulate cognitive processes and that the effects of corticosteroids on cognitive function are selective.

  19. 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.

  20. 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).

  1. Circulating cortisol levels after exogenous cortisol administration are higher in women using hormonal contraceptives: data from two preliminary studies.

    PubMed

    Gaffey, Allison E; Wirth, Michelle M; Hoks, Roxanne M; Jahn, Allison L; Abercrombie, Heather C

    2014-07-01

    Exogenous cortisol administration has been used to test the influence of glucocorticoids on a variety of outcomes, including memory and affect. Careful control of factors known to influence cortisol and other endogenous hormone levels is central to the success of this research. While the use of hormonal birth control (HBC) is known to exert many physiological effects, including decreasing the salivary cortisol response to stress, it is unknown how HBC influences circulating cortisol levels after exogenous cortisol administration. To determine those effects, we examined the role of HBC on participants' cortisol levels after receiving synthetic cortisol (hydrocortisone) in two separate studies. In Study 1, 24 healthy women taking HBC and 26 healthy men were administered a 0.1 mg/kg body weight intravenous dose of hydrocortisone, and plasma cortisol levels were measured over 3 h. In Study 2, 61 participants (34 women; 16 were on HBC) received a 15 mg hydrocortisone pill, and salivary cortisol levels were measured over 6 h. Taken together, results from these studies suggest that HBC use is associated with a greater cortisol increase following cortisol administration. These data have important methodological implications: (1) when given a controlled dose of hydrocortisone, cortisol levels may increase more dramatically in women taking HBC versus women not on HBC or men; and (2) in studies manipulating cortisol levels, women on hormonal contraceptives should be investigated as a separate group.

  2. The associations between adolescent sleep, diurnal cortisol patterns and cortisol reactivity to dexamethasone suppression test.

    PubMed

    Pesonen, Anu-Katriina; Martikainen, Silja; Kajantie, Eero; Heinonen, Kati; Wehkalampi, Karoliina; Lahti, Jari; Strandberg, Timo; Räikkönen, Katri

    2014-11-01

    Information on the associations between objectively measured sleep and hypothalamic-pituitary-adrenal axis function in early adolescence is scarce. We examined associations between average sleep duration and quality (sleep efficiency and wake after sleep onset) over 8 days with actigraphs and (1) diurnal cortisol patterns and (2) cortisol reactivity to a low-dose (3 μg/kg) overnight dexamethasone suppression test (DST) in a birth cohort born in 1998 (N=265 participants, mean age 12.3 years, SD=0.5). We also explored (3) if sleep duration and quality were affected the nights after the DST exposure. Cortisol was measured during 2 days, and participants were exposed to dexamethasone in the evening of first day. In boys, short sleep duration was associated with higher cortisol upon awakening and lower cortisol awakening response (CAR; P<0.05 and P<0.01). Long sleep duration in boys associated with higher CAR (P<0.02). Lower sleep quality in boys associated with lower CAR, but fell slightly short of significance (P<0.06). In girls, no significant associations were detected. Sleep quantity and quality were not associated with responses to the DST. There were no effects of DST on sleep (P>0.15 in between-subject analyses). The average sleep patterns showed associations with diurnal cortisol patterns during early adolescence, but only in boys. Sleep was not associated with cortisol reactivity to DST and the exogenous corticosteroid exposure did not affect sleep significantly.

  3. Children's Context Inappropriate Anger and Salivary Cortisol

    PubMed Central

    Locke, Robin L.; Davidson, Richard J.; Kalin, Ned H.; Goldsmith, H. Hill

    2009-01-01

    Some children show emotion that is not consistent with normative appraisal of the context and can therefore be defined as context inappropriate (CI). The authors used individual growth curve modeling and hierarchical multiple regression analyses to examine whether CI anger predicts differences in hypothalamic-pituitary-adrenal axis activity, as manifest in salivary cortisol measures. About 23% of the 360 children (ages 6–10 years, primarily 7–8) showed at least 1 expression of CI anger in situations designed to elicit positive affect. Expression of anger across 2 positive assessments was less common (around 4%). CI anger predicted the hypothesized lower levels of cortisol beyond that attributed to context appropriate anger. Boys' CI anger predicted lower morning cortisol and flatter slopes. Results suggest that this novel approach to studying children's emotion across varying contexts can provide insight into affective style. PMID:19702392

  4. Social regulation of cortisol receptor gene expression

    PubMed Central

    Korzan, Wayne J.; Grone, Brian P.; Fernald, Russell D.

    2014-01-01

    In many social species, individuals influence the reproductive capacity of conspecifics. In a well-studied African cichlid fish species, Astatotilapia burtoni, males are either dominant (D) and reproductively competent or non-dominant (ND) and reproductively suppressed as evidenced by reduced gonadotropin releasing hormone (GnRH1) release, regressed gonads, lower levels of androgens and elevated levels of cortisol. Here, we asked whether androgen and cortisol levels might regulate this reproductive suppression. Astatotilapia burtoni has four glucocorticoid receptors (GR1a, GR1b, GR2 and MR), encoded by three genes, and two androgen receptors (ARα and ARβ), encoded by two genes. We previously showed that ARα and ARβ are expressed in GnRH1 neurons in the preoptic area (POA), which regulates reproduction, and that the mRNA levels of these receptors are regulated by social status. Here, we show that GR1, GR2 and MR mRNAs are also expressed in GnRH1 neurons in the POA, revealing potential mechanisms for both androgens and cortisol to influence reproductive capacity. We measured AR, MR and GR mRNA expression levels in a microdissected region of the POA containing GnRH1 neurons, comparing D and ND males. Using quantitative PCR (qPCR), we found D males had higher mRNA levels of ARα, MR, total GR1a and GR2 in the POA compared with ND males. In contrast, ND males had significantly higher levels of GR1b mRNA, a receptor subtype with a reduced transcriptional response to cortisol. Through this novel regulation of receptor type, neurons in the POA of an ND male will be less affected by the higher levels of cortisol typical of low status, suggesting GR receptor type change as a potential adaptive mechanism to mediate high cortisol levels during social suppression. PMID:25013108

  5. Methylprednisolone pharmacokinetics, cortisol response, and adverse effects in black and white renal transplant recipients.

    PubMed

    Tornatore, K M; Biocevich, D M; Reed, K; Tousley, K; Singh, J P; Venuto, R C

    1995-03-15

    It is generally assumed that chronic glucocorticoid therapy is similar pharmacologically when administered to either black or white renal transplant recipients, resulting in adrenal suppression, low circulating plasma cortisol concentrations, and a similar degree of drug exposure and toxicity. To examine this theory and to investigate the relationship of glucocorticoid metabolism to steroid-induced adverse effects among specific ethnic groups of renal transplant recipients, 9 black and 9 white male patients chronically receiving methylprednisolone were enrolled. All patients had stable renal function and were matched for age, weight, and time since transplant. Standard pharmacokinetic parameters for methylprednisolone were determined and cortisol responses were characterized by total cortisol area under the concentration curve (AUC), return cortisol AUC, and cortisol suppression half-life. All patients received their daily oral dose of methylprednisolone (mean daily dose = 11 mg for blacks and 11 mg for whites) as an intravenous infusion with serial plasma samples obtained over 24 h. The patients were assessed for the presence of specific cushingoid manifestations (buffalo hump, moon facies) and steroid-associated diabetes. Methylprednisolone and cortisol were analyzed via HPLC. In the black patients, the mean clearance of methylprednisolone (206 +/- 70 ml/hr/kg) was significantly slower with a smaller volume of distribution (0.95 +/- 0.32 L/kg) when compared with the white group (327 +/- 129 ml/hr/kg, P = 0.03; volume of distribution = 1.33 +/- 0.27 L/kg, P = 0.015). Despite chronic methylprednisolone therapy, a definite 24-hr cortisol response pattern was noted in 15 of the 18 patients with a mean total cortisol AUC of 732 +/- 443 ng.hr/ml in blacks and 539 +/- 361 ng.hr/ml in whites (P = 0.17, black vs. white). The mean cortisol suppression half-life was 4.31 +/- 1.54 hr in black recipients and 4.11 +/- 1.49 hr in whites (P = 0.48). The mean return cortisol AUC

  6. 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)

  7. Inhibition of epidermal growth factor-induced mitogenesis by amiloride and an analog: evidence against a requirement for Na+/H+ exchange.

    PubMed Central

    Besterman, J M; Tyrey, S J; Cragoe, E J; Cuatrecasas, P

    1984-01-01

    We have tested the hypothesis that the rapid stimulation of Na+/H+ exchange by epidermal growth factor (EGF) is a requirement for induction of mitogenesis. BALB/c 3T3 cells exposed for 4 hr at 37 degrees C to both EGF at 1 ng/ml and either 0.2-1 mM amiloride (an inhibitor of Na+/H+ exchange) or 10 microM MK-685 (an amiloride analog and more potent inhibitor of Na+/H+ exchange) incorporated no less [methyl-3H]thymidine during a 1-hr pulse 20 hr later than did cells exposed for 4 hr to EGF alone. Control experiments utilizing low external pH (to dissociate EGF from its receptor) and anti-EGF antibodies indicated that the failure of amiloride to inhibit mitogenesis when copresent with EGF during the first 4 hr was not due to incomplete removal of EGF and complete removal of amiloride at t4. Cells incubated with 200 microM amiloride for 24 hr showed nearly complete inhibition of stimulation by EGF. In comparison, cells incubated with 10 microM MK-685 for 24 hr showed only a slight inhibition of stimulation by EGF. Incubations with amiloride or MK-685 for shorter periods of time indicated that only amiloride inhibited mitogenesis and that this inhibition happened between 4 (t4) and 10(t10) hr after EGF addition, during which time increases in RNA and protein synthesis (required for mitogenesis) occurred. Amiloride inhibited both RNA and protein syntheses in intact cells during this prereplicative period, while MK-685 was without effect. We conclude that (i) inhibition of EGF-induced mitogenesis by amiloride is due not to inhibition of EGF-stimulated Na+/H+ exchange but rather to inhibition of necessary events occurring during the hours immediately prior to the onset of DNA synthesis, these events probably being RNA and protein synthesis and (ii) in cell culture medium buffered with CO2/HCO3-, complete inhibition of EGF-stimulated Na+/H+ exchange does not inhibit EGF-induced mitogenesis and, thus, stimulation of Na+/H+ exchange is not necessary for induction of

  8. Milk-based phospholipids increase morning cortisol availability and improve memory in chronically stressed men.

    PubMed

    Schubert, Melanie; Contreras, Carina; Franz, Nadin; Hellhammer, Juliane

    2011-06-01

    Phospholipids (PLs) have been shown to dampen the activity and reactivity of the hypothalamic-pituitary-adrenal axis (HPAA). To further investigate stress protective effects of PL, 75 chronically stressed men aged 30 to 51 years were enrolled in a randomized and placebo-controlled trial. The subjects received a bovine milk drink with either 0.5% PL, 1% PL, or a placebo for 42 days to test the hypothesis that supplementation with specific phospholipids would normalize the cortisol response of the HPAA. For determining HPAA activity, the cortisol awakening response was studied before and after treatment. In addition, participants were exposed to an acute stressor, the Trier Social Stress Test, to assess treatment effects on stress reactivity and stress-related memory impairment. After receiving PL-enriched milk, both PL groups showed a delayed decline from peak levels in morning salivary cortisol, suggesting a prolonged availability of free cortisol. Treatment with 0.5% PL additionally resulted in a stronger increase of cortisol after awakening, whereas no such differences could be observed in the 1% PL group and the placebo group, respectively. The acute stress response did not significantly differ among placebo and PL groups. An exploratory data analysis further revealed that elderly participants receiving the higher PL dosage had a significant better memory performance after the Trier Social Stress Test as compared with elderly participants from the placebo and low-PL dosage group; no such difference was observed at baseline. Our results suggest that PL may increase the availability of cortisol in chronically stressed men and may attenuate stress-induced memory impairments. Results of the present study are discussed within the context of previous research and current state of knowledge.

  9. Higher Crash and Near-Crash Rates in Teenaged Drivers With Lower Cortisol Response

    PubMed Central

    Ouimet, Marie Claude; Brown, Thomas G.; Guo, Feng; Klauer, Sheila G.; Simons-Morton, Bruce G.; Fang, Youjia; Lee, Suzanne E.; Gianoulakis, Christina; Dingus, Thomas A.

    2014-01-01

    IMPORTANCE Road traffic crashes are one of the leading causes of injury and death among teenagers worldwide. Better understanding of the individual pathways to driving risk may lead to better-targeted intervention in this vulnerable group. OBJECTIVE To examine the relationship between cortisol, a neurobiological marker of stress regulation linked to risky behavior, and driving risk. DESIGN, SETTING, AND PARTICIPANTS The Naturalistic Teenage Driving Study was designed to continuously monitor the driving behavior of teenagers by instrumenting vehicles with kinematic sensors, cameras, and a global positioning system. During 2006–2008, a community sample of 42 newly licensed 16-year-old volunteer participants in the United States was recruited and driving behavior monitored. It was hypothesized in teenagers that higher cortisol response to stress is associated with (1) lower crash and near-crash (CNC) rates during their first 18 months of licensure and (2) faster reduction in CNC rates over time. MAIN OUTCOMES AND MEASURES Participants’ cortisol response during a stress-inducing task was assessed at baseline, followed by measurement of their involvement in CNCs and driving exposure during their first 18 months of licensure. Mixed-effect Poisson longitudinal regression models were used to examine the association between baseline cortisol response and CNC rates during the follow-up period. RESULTS Participants with a higher baseline cortisol response had lower CNC rates during the follow-up period (exponential of the regression coefficient, 0.93; 95%CI, 0.88–0.98) and faster decrease in CNC rates over time (exponential of the regression coefficient, 0.98; 95%, CI, 0.96–0.99). CONCLUSIONS AND RELEVANCE Cortisol is a neurobiological marker associated with teenaged-driving risk. As in other problem-behavior fields, identification of an objective marker of teenaged-driving risk promises the development of more personalized intervention approaches. PMID:24710522

  10. 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

  11. Phosphorylation of STAT3 mediates the induction of cyclooxygenase-2 by cortisol in the human amnion at parturition.

    PubMed

    Wang, Wangsheng; Guo, Chunming; Zhu, Ping; Lu, Jiangwen; Li, Wenjiao; Liu, Chao; Xie, Huiliang; Myatt, Leslie; Chen, Zi-Jiang; Sun, Kang

    2015-10-27

    The induction of cyclooxygenase-2 (COX-2) and subsequent production of prostaglandin E2 (PGE2) by cortisol in the amnion contrast with the effect of cortisol on most other tissues, but this proinflammatory effect of cortisol may be a key event in human parturition (labor). We evaluated the underlying mechanism activated by cortisol in primary human amnion fibroblasts. Exposure of the amnion fibroblasts to cortisol led to the activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, which induced the phosphorylation of the kinase SRC and STAT3 (signal transducer and activator of transcription 3). STAT3 interacted with the glucocorticoid receptor (GR) and the transcription factor CREB-1 (cAMP response element-binding protein 1) at the promoter of the gene encoding COX-2, which promoted the production of the secreted prostaglandin PGE2. PGE2 activates the prostaglandin receptors EP2 and EP4, which stimulate cAMP-PKA signaling. Thus, cortisol reinforced the activation of cAMP-PKA signaling through an SRC-STAT3-COX-2-PGE2-mediated feedback loop. Inhibiting STAT3, SRC, or the cAMP-PKA pathway attenuated the cortisol-stimulated induction of COX-2 and PGE2 production in amnion fibroblasts. In human amnion tissue, the amount of phosphorylated STAT3 correlated positively with that of cortisol, COX-2, and PGE2, and all were more abundant in tissue obtained after active labor than in tissue obtained from cesarean surgeries in the absence of labor. These results indicated that the coordinated recruitment of STAT3, CREB-1, and GR to the promoter of the gene encoding COX-2 contributes to the feed-forward induction of COX-2 activity and prostaglandin synthesis in the amnion during parturition.

  12. 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

  13. 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.

  14. 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

  15. Nocturnal cortisol release in relation to sleep structure.

    PubMed

    Follenius, M; Brandenberger, G; Bandesapt, J J; Libert, J P; Ehrhart, J

    1992-02-01

    The relationship between the temporal organization of cortisol secretion and sleep structure is controversial. To determine whether the cortisol profile is modified by 4 hours of sleep deprivation, which shifts slow-wave sleep (SWS) episodes, 12 normal men were studied during a reference night, a sleep deprivation night and a recovery night. Plasma cortisol was measured in 10-minute blood samples. Analysis of the nocturnal cortisol profiles and the concomitant patterns of sleep stage distribution indicates that the cortisol profile is not influenced by sleep deprivation. Neither the starting time of the cortisol increase nor the mean number and amplitude of pulses was significantly different between the three nights. SWS episodes were significantly associated with declining plasma cortisol levels (p less than 0.01). This was especially revealed after sleep deprivation, as SWS episodes were particularly present during the second half of the night, a period of enhanced cortisol secretion. In 73% of cases, rapid eye movement sleep phases started when cortisol was reflecting diminished adrenocortical activity. Cortisol increases were not concomitant with a specific sleep stage but generally accompanied prolonged waking periods. These findings tend to imply that cortisol-releasing mechanisms may be involved in the regulation of sleep.

  16. Analog, still without fear

    NASA Astrophysics Data System (ADS)

    Delagrange, A. D.

    1984-09-01

    This report is an update of one issued in 1977 which predicted that the predicted death of analog circuitry (also called linear) would not occur; in fact, the patient appeared remarkably healthy. The report proved correct. We have the same situation again today: the same predictions and counter-prediction. Each year brings significant advances in the field of analog integrated circuitry. Many of the traditional arguments against analog circuitry are no longer valid. This report attempts to summarize what is available now, and what can (and cannot) be done with analog integrated circuits. It defines analog and makes some comparisons with digital. The most common types of analog integrated circuits are then listed and discussed. Lastly, some design and trouble-shooting hints are given, and the state-of-the-art is discussed.

  17. 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.

  18. 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

  19. Stronger pharmacological cortisol suppression and anticipatory cortisol stress response in transient global amnesia.

    PubMed

    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

  20. Stronger pharmacological cortisol suppression and anticipatory cortisol stress response in transient global amnesia.

    PubMed

    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.

  1. 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 ...

  2. Epizootic cutaneous papillomatosis, cortisol and male ornamentation during and after breeding in the roach Rutilus rutilus.

    PubMed

    Vainikka, Anssi; Kortet, Raine; Taskinen, Jouni

    2004-09-01

    The prevalence of epidermal papillomatosis in roach is known to peak during the spawning period and to be higher in males than in females. The high occurrence of papillomatosis in polluted waters suggests that stress may contribute to the outbreak of the disease. However, little is known about breeding-induced stress in fish and its relationship with diseases. In this study, plasma cortisol concentration, hematocrit and the relative size of the spleen were determined in healthy and diseased male and female roach Rutilus rutilus during and shortly after spawning in a wild population. In addition, the sexual ornamentation (breeding tubercles on the lateral sides and on the frontal) of male roach during spawning was examined. Plasma cortisol concentration was higher during than after the spawning period, and higher in males than in females during spawning, indicating a spawning-induced stress and higher spawning stress among males. There was no correlation between cortisol concentration and the intensity of papillomatosis (number of scales under papilloma tumors) among the diseased fish. However, the significant interaction sex x disease status revealed by ANCOVA suggested that diseased males could be more prone to increased cortisol levels than diseased females or healthy males. Hematocrit values (ratio of the volume of red blood cells to total volume of blood) but not condition factor were lowered in papilloma-diseased fish after spawning. The relative size of the spleen was greater in males than in females. The number of frontal breeding tubercles correlated negatively with the intensity of papillomatosis. Experimental studies are needed to investigate the association of papillomatosis with stress and cortisol. PMID:15521317

  3. Depressive symptoms and diurnal salivary cortisol patterns among female caregivers of stroke survivors.

    PubMed

    Saban, Karen L; Mathews, Herbert L; Bryant, Fred B; O'Brien, Timothy E; Janusek, Linda Witek

    2012-10-01

    Informal caregivers of stroke survivors experience elevated chronic stress and are at risk of developing depressive symptoms. The cumulative effects of chronic stress can increase allostatic load and dysregulate biological processes, thus increasing risk of stress-related disease. Stress-induced alterations in the pattern of cortisol secretion vary with respect to stressor onset, intensity, and chronicity. Little is known about the psychoendocrine response to stress in female caregivers of stroke survivors. The purpose of this study was to examine perceived stress, caregiver burden, and the association between caregiver depressive symptoms and diurnal cortisol in 45 females caring for a significant other who experienced a stroke within the past year. Women completed the Center for Epidemiologic Studies Depression Scale (CES-D) and collected saliva for cortisol upon awakening, 30 min postawakening, noon, and bedtime for 2 consecutive days. Results revealed that women had high levels of perceived stress and caregiver burden. In women with CES-D scores ≥ 16, salivary cortisol levels were significantly lower across the day relative to women with CES-D scores < 16. This difference persisted after adjusting for age, number of caregiving hours per week, perceived social support, and quality of sleep. Younger age was associated with more depressive symptoms as well as lower levels of cortisol at awakening and 30 min postawakening. Results demonstrate that the burden of caregiving increases risk of depressive symptoms and hypocortisolism across the day. Hypocortisolism may contribute to increased risk of depressive symptoms as a result of the loss of glucocorticoid attenuation of stress-induced inflammation.

  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. 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

  6. Salivary cortisol response to stress in young children with atopic dermatitis.

    PubMed

    Kojima, Reiji; Matsuda, Akio; Nomura, Ichiro; Matsubara, Osamu; Nonoyama, Shigeaki; Ohya, Yukihiro; Saito, Hirohisa; Matsumoto, Kenji

    2013-01-01

    Poor responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis under stress may be one explanation for stress-induced exacerbation of atopic dermatitis (AD) symptoms. In previous studies, children and adults with AD showed attenuated salivary cortisol responses to psychosocial stress, suggesting hyporesponsiveness of the HPA axis, but few studies have been conducted in young children, who are vulnerable to systemic side effects of topical corticosteroid (TCS) therapy. We evaluated whether salivary cortisol responses to the stress of venipuncture in young children with AD were related to the severity of AD or performance of TCS therapy. We studied 38 young children with AD (median age 16.5 mos, range 3-66 mos) being treated at our outpatient unit. Patients were divided into three groups according to the scoring of atopic dermatitis index: mild (n = 12), moderate (n = 14), and severe (n = 12). To evaluate the responsiveness of the HPA axis to stress, salivary cortisol was determined before and after venipuncture. Salivary cortisol responsiveness to stress correlated negatively with severity of AD (p = 0.048) but not with previous use of TCS (p = 0.43) in young children with AD. Our findings suggest that the disease activity of AD, rather than TCS use, is responsible for HPA axis dysfunction in children with AD.

  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. Changes in endocrine and neurochemical profiles in neonatal pigs prenatally exposed to increased maternal cortisol.

    PubMed

    Kanitz, Ellen; Otten, Winfried; Tuchscherer, Margret

    2006-10-01

    Early life environmental factors are able to influence prenatal development and may cause structural and functional effects on hypothalamic-pituitary-adrenal (HPA) axis and neurotransmitter systems in the offspring. These effects seem to be species specific and may depend on the period of gestation when the factors are effective. Elevated maternal cortisol levels are assumed to play a crucial role as a programming factor during prenatal development. Thus, the present study was performed in order to examine the effects of increased maternal cortisol levels during mid- and late gestation on central and peripheral alterations of the HPA axis and brain neurotransmitter profiles in piglets. Endogenous cortisol release was induced by i.m. administration of ACTH to sows every second day either during mid- (day 49 until 75) or late gestation (day 85 until 107). Controls received injections of saline. ACTH treatment of sows during mid- and late gestation had no effects on the gestation length, the number of total born and the frequency of stillborn piglets. However, ACTH treatment during late gestation caused an increase of birth weight (P < 0.04) and affected the organ:body weight ratios (brain and adrenal) in the offspring. There was an impact of increased maternal cortisol on the HPA axis and on central neurotransmitter systems in the offspring. ACTH treatment during mid gestation caused a significant decrease of plasma corticosteroid-binding globulin (CBG; P < 0.03) and an increase of the noradrenergic activity in the locus coeruleus (LC) region (P < 0.02). Elevated maternal cortisol during late gestation also produced a significant decrease of plasma CBG (P < 0.05), but significantly increased the plasma noradrenaline (NA) concentration (P < 0.02) and decreased the serotonergic activity in the LC at both postnatal day 1 (P < 0.016) and day 28 (P < 0.003). Furthermore, there were sex-specific effects of ACTH treatment on plasma CBG, NA and brain monoamine turnover, with

  9. Cortisol and Treatment Effect in Children with Disruptive Behavior Disorders: A Preliminary Study.

    ERIC Educational Resources Information Center

    van de Wiel, Nicolle M.H.; van Goozen, Stephanie H.M.; Matthys, Walter; Snoek, Heddeke; van Engeland, Herman

    2004-01-01

    Objective: Basal cortisol and cortisol stress responsivity are valuable biological characteristics of children with disruptive behavior disorder (DBD). In this study, the predictive value of cortisol to outcome of intervention was investigated. Method: Basal cortisol levels and cortisol levels under stress were studied in 22 children with DBD…

  10. 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.

  11. 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…

  12. 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

  13. 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…

  14. Interacting influence of potassium and polychlorinated biphenyl on cortisol and aldosterone biosynthesis

    SciTech Connect

    Li, L.-A. . E-mail: lihann@nhri.org.tw; Lin, Tsu-Chun Emma

    2007-05-01

    Giving human adrenocortical H295R cells 14 mM KCl for 24 h significantly induced not only aldosterone biosynthesis but also cortisol biosynthesis. Pre-treating the cells with polychlorinated biphenyl 126 (PCB126) further increased potassium-induced aldosterone and cortisol productions in a dose-dependent manner, but all examined concentrations of PCB126 had little effect on the yields of precursor steroids progesterone and 17-OH-progesterone. Subsequent examinations revealed that CYP11B1 and CYP11B2 genes, responsible for the respective final steps of the cortisol and aldosterone biosynthetic pathways, exhibited increased responsiveness to PCB126 under high potassium. While 10{sup -5} M PCB126 was needed to induce a significant increase in the basal mRNA abundance of either gene, PCB126 could enhance potassium-induced mRNA expression of CYP11B1 at 10{sup -7} M and CYP11B2 at 10{sup -9} M. Actually, potassium and PCB126 synergistically upregulated mRNA expression of both genes. Potassium raised the transcriptional rates of CYP11B1 and CYP11B2 probably through a conserved Ad5 cis-element, whereas PCB126 appeared to regulate these two genes at the post-transcriptional level. Positive potassium-PCB126 synergism was also detected in CYP11B2 enzyme activity estimated by aldosterone/progesterone ratio. In contrast, potassium and PCB126 increased CYP11B1 enzyme activity or cortisol/17-OH-progesterone ratio additively. Moreover, potassium improved the time effect of PCB126 on gene expression and enzyme activity of CYP11B2, but not the PCB126 time response of CYP11B1. These data demonstrated that potassium differentially enhanced the potency of PCB126 to induce CYP11B1- and CYP11B2-mediated steroidogenesis.

  15. 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

  16. Sex steroid modulation of cortisol secretion in sheep.

    PubMed

    van Lier, E; Carriquiry, M; Meikle, A

    2014-06-01

    RNA than the ones without steroid replacement. Gonadectomised rams with TC also had greater AR mRNA, ERS1 mRNA and MC2R mRNA expression than ewes treated with EB. The relative amount of STAR transcript was not different among the different groups. The results confirm sex differences in ACTH-induced cortisol secretion in sheep, as well as in the expression of the receptor proteins for both 17β-oestradiol and testosterone in the sheep adrenal gland. However, the underlying mechanisms for sex steroid modulation remain unresolved.

  17. Cortisol levels in fetal scalp, maternal, and umbilical cord plasma.

    PubMed

    Sybulski, S; Goldsmith, W J; Maughan, G B

    1975-09-01

    The purpose of this study was to investigate cortisol levels in the fetal circulation prior to delivery. Fetal scalp plasma cortisol levels during labor were significantly lower than those in maternal peripheral plasma but significantly higher than those in cord plasma at delivery. Cortisol levels in fetal scalp plasma did not correlate significantly with those in either maternal or cord plasma. The greater cortisol concentrations in fetal scalp plasma relative to those in cord plasma could have been transient increases caused by fetal adrenal response to the stress of the scalp sampling procedure. There was a significant correlation between cortisol levels in maternal and cord plasma, which may mean that a considerable part of the cortisol in the fetal circulation at delivery is of maternal origin.

  18. Dissociated neural effects of cortisol depending on threat escapability.

    PubMed

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

    2015-11-01

    Evolution has provided us with a highly flexible neuroendocrine threat system which, depending on threat imminence, switches between active escape and passive freezing. Cortisol, the "stress-hormone", is thought to play an important role in both fear behaviors, but the exact mechanisms are not understood. Using pharmacological functional magnetic resonance imaging we investigated how cortisol modulates the brain's fear systems when humans are under virtual-predator attack. We show dissociated neural effects of cortisol depending on whether escape from threat is possible. During inescapable threat cortisol reduces fear-related midbrain activity, whereas in anticipation of active escape cortisol boosts activity in the frontal salience network (insula and anterior cingulate cortex), which is involved in autonomic control, visceral perception and motivated action. Our findings suggest that cortisol adjusts the human neural threat system from passive fear to active escape, which illuminates the hormone's crucial role in the adaptive flexibility of fear behaviors.

  19. Neonatal Pain-Related Stress and NFKBIA Genotype Are Associated with Altered Cortisol Levels in Preterm Boys at School Age

    PubMed Central

    Grunau, Ruth E.; Cepeda, Ivan L.; Chau, Cecil M. Y.; Brummelte, Susanne; Weinberg, Joanne; Lavoie, Pascal M.; Ladd, Mihoko; Hirschfeld, Aaron F.; Russell, Evan; Koren, Gideon; Van Uum, Stan; Brant, Rollin; Turvey, Stuart E.

    2013-01-01

    Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. Adrenal enlargement and failure of suppression of circulating cortisol by dexamethasone in patients with malignancy.

    PubMed

    Jenkins, P J; Sohaib, S A; Trainer, P J; Lister, T A; Besser, G M; Reznek, R

    1999-08-01

    The aim of this study was to further elucidate the activity of the hypothalamo-pituitary-adrenal (HPA) axis in patients with malignancy and to correlate this with the size of the adrenal glands. Fourteen patients with a variety of malignancies were studied prior to receiving cytotoxic chemotherapy. During routine staging computerized tomographic (CT) scans, the size of the body, medial and lateral limbs of the adrenal glands were measured and compared with those of a normal group of patients studied previously. Measurements of 09:00 h serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were made before and after the administration of dexamethasone (0.5 mg 6-hourly for 48 h) in addition to the peak cortisol response to i.v corticotropin releasing hormone (CRH). Overall, patients with malignancy had significantly larger adrenal glands than patients without malignancy; those with non-haematological malignancies had larger glands than patients with haematological malignancies. Following dexamethasone to suppress circulating cortisol levels, nine patients (64%) demonstrated abnormal resistance with cortisol levels > 50 nmol l(-1): mean value 294 nmol l(-1) (range 67-1147). Those patients who failed to suppress after dexamethasone had significantly larger adrenal glands than those that did suppress and tended to have non-haematological malignancies. ACTH levels were undetectable or low in three patients in whom it was measured and who did not suppress with dexamethasone. Following CRH, the cortisol levels were highest (823 and 853 nmol l(-1)) in two of these patients. Malignancy is associated with diffuse enlargement of the adrenal glands and resistance to dexamethasone-induced suppression of the HPA axis, which is not due to ectopic ACTH secretion. This disturbance of the normal control of the HPA axis is unexplained and its functional significance remains uncertain.

  11. Induction of human UDP-glucuronosyltransferase 1A1 by cortisol-GR.

    PubMed

    Usui, Toru; Kuno, Takuya; Mizutani, Takaharu

    2006-06-01

    During the course of the study of UGT1A1 induction by bilirubin, we could not detect the induction of the reporter gene (-3174/+14) of human UGT1A1 in HepG2 by bilirubin (Mol. Biol. Rep. 31: 151-158 (2004)). In this report, we show the finding of the induction of the reporter gene of UGT1A1 by cortisol at 1 microM, a major natural cortico-steroid, with human glucocorticoid receptor (GR). RU486 of a typical GR antagonist at 10 microM inhibited the induction by cortisol from 5.9- to 1.8-fold. This result indicates that the induction by cortisol-GR is dependence on ligand-binding. This induction is caused by the UGT reporter gene itself, from the results of noinduction with control vector pGL2 (equal to pGV-C) in the presence of cortisol-GR. We confirmed that the induction of the reporter gene by cortisol is dependent on the position of proximal element (-97/-53) of UGT1A1. From this result, we concluded that the increase of corticosteroid in neonates must induce the elevation of UGT1A1 after birth and prevent jaundice. With the study of induction by corisol, we studied the influence of co-expression of PXR (pregnenolone xenobiotic receptor) with the UGT1A1 reporter gene and we could not find the induction of UGT1A1 expression in the presence of dexamethasone, rifampicin, or pregnenolone 16alpha-carbonitrile of the PXR ligands. These results suggest that the induction of UGT1A1 expression by GR is not mediated by PXR, unlike the induction of CYP3A4 through PXR. PMID:16817017

  12. 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

  13. 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.

  14. Challenges in Using Analogies

    NASA Astrophysics Data System (ADS)

    Lin, Shih-Yin; Singh, Chandralekha

    2011-11-01

    Learning physics requires understanding the applicability of fundamental principles in a variety of contexts that share deep features.1-7 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 physics principle is involved but that is more difficult to handle. Here, we examine introductory physics students' ability to use analogies in solving problems involving Newton's second law. Students enrolled in an algebra-based introductory physics course were given a solved problem involving tension in a rope and were then asked to solve another problem for which the physics is very similar but involved a frictional force. They were asked to point out the similarities between the two problems and then use the analogy to solve the friction problem.

  15. 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.

  16. 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.

  17. Gravito-electromagnetic analogies

    NASA Astrophysics Data System (ADS)

    Costa, L. Filipe O.; Natário, José

    2014-10-01

    We reexamine and further develop different gravito-electromagnetic (GEM) analogies found in the literature, and clarify the connection between them. Special emphasis is placed in two exact physical analogies: the analogy based on inertial fields from the so-called "1+3 formalism", and the analogy based on tidal tensors. Both are reformulated, extended and generalized. We write in both formalisms the Maxwell and the full exact Einstein field equations with sources, plus the algebraic Bianchi identities, which are cast as the source-free equations for the gravitational field. New results within each approach are unveiled. The well known analogy between linearized gravity and electromagnetism in Lorentz frames is obtained as a limiting case of the exact ones. The formal analogies between the Maxwell and Weyl tensors are also discussed, and, together with insight from the other approaches, used to physically interpret gravitational radiation. The precise conditions under which a similarity between gravity and electromagnetism occurs are discussed, and we conclude by summarizing the main outcome of each approach.

  18. Cortisol is involved in temperature-dependent sex determination in the Japanese flounder.

    PubMed

    Yamaguchi, Toshiya; Yoshinaga, Norifumi; Yazawa, Takashi; Gen, Koichiro; Kitano, Takeshi

    2010-08-01

    In vertebrates, sex is normally determined by genotype. However, in poikilothermal vertebrates, including reptiles, amphibians, and fishes, sex determination is greatly influenced by environmental factors, such as temperature. Little is known about the molecular mechanisms underlying environmental sex determination in these species. The Japanese flounder (Paralichthys olivaceus) is a teleost fish with an XX/XY sex determination system. However, XX flounder can be induced to develop into predominantly either phenotypic females or males, by rearing at 18 or 27 C, respectively, during the sex differentiation period. Therefore, the flounder provides an excellent model to study the molecular mechanisms underlying temperature-dependent sex determination. We previously showed that an aromatase inhibitor, an antiestrogen, and 27 C treatments cause masculinization of XX flounder, as well as suppression of mRNA expression of ovary-type aromatase (cyp19a1), a steroidogenic enzyme responsible for the conversion of androgens to estrogens in the gonads. Furthermore, estrogen administration completely inhibits masculinization by these treatments, suggesting suppression of cyp19a1 mRNA expression, and the resultant estrogen biosynthesis may trigger masculinization of the XX flounder induced by high water temperature. Here, we demonstrated that cortisol causes female-to-male sex reversal by directly suppressing cyp19a1 mRNA expression via interference with cAMP-mediated activation and that metyrapone (an inhibitor of cortisol synthesis) inhibits 27 C-induced masculinization of XX flounder. Moreover, cortisol concentrations in 27 C-reared juveniles were significantly higher than in 18 C-reared fishes during sexual differentiation. These results strongly suggest that masculinization by high water temperature is ascribable to elevation of cortisol concentration during gonadal sex differentiation in the flounder.

  19. Stress inhibition of melatonin synthesis in the pineal organ of rainbow trout (Oncorhynchus mykiss) is mediated by cortisol.

    PubMed

    López-Patiño, Marcos A; Gesto, Manuel; Conde-Sieira, Marta; Soengas, José L; Míguez, Jesús M

    2014-04-15

    Cortisol has been suggested to mediate the effect of stress on pineal melatonin synthesis in fish. Therefore, we aimed to determine how pineal melatonin synthesis is affected by exposing rainbow trout to different stressors, such as hypoxia, chasing and high stocking density. In addition, to test the hypothesis that cortisol is a mediator of such stress-induced effects, a set of animals were intraperitoneally implanted with coconut oil alone or containing cortisol (50 mg kg(-1) body mass) and sampled 5 or 48 h post-injection at midday and midnight. The specificity of such effect was also assessed in cultured pineal organs exposed to cortisol alone or with the general glucocorticoid receptor antagonist, mifepristone (RU486). Stress (in particular chasing and high stocking density) affected the patterns of plasma and pineal organ melatonin content during both day and night, with the greatest reduction occurring at night. The decrease in nocturnal melatonin levels in the pineal organ of stressed fish was accompanied by increased serotonin content and decreased AANAT2 enzymatic activity and mRNA abundance. Similar effects on pineal melatonin synthesis to those elicited by stress were observed in trout implanted with cortisol for either 5 or 48 h. These data indicate that stress negatively influences the synthesis of melatonin in the pineal organ, thus attenuating the day-night variations of circulating melatonin. The effect might be mediated by increased cortisol, which binds to trout pineal organ-specific glucocorticoid receptors to modulate melatonin rhythms. Our results in cultured pineal organs support this. Considering the role of melatonin in the synchronization of daily and annual rhythms, the results suggest that stress-induced alterations in melatonin synthesis could affect the availability of fish to integrate rhythmic environmental information.

  20. 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)

  1. 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

  2. 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.

  3. Serum cortisol concentrations in horses with colic.

    PubMed

    Mair, T S; Sherlock, C E; Boden, L A

    2014-09-01

    Few studies have evaluated cortisol concentrations in horses with colic. In humans with septic shock, high cortisol levels are associated with an increased risk of death. The objectives of this study were to compare the serum total cortisol concentrations (STCCs) in horses with colic to those without colic, and to assess whether the STCC relates to the pathological nature or outcome of the disease. STCCs were determined at presentation in horses with colic and in systemically healthy 'control' horses. Horses with colic were grouped based on clinical and clinico-pathological parameters at admission, treatment, lesion type and location, and outcome. Univariable and multivariable logistic regression were performed using two different outcome measures: (a) whether the horse had colic or not (yes vs. no), and (b) horse STCC (≥200 nmol/L vs. <200 nmol/L). Horses were more likely to have colic if they presented with high STCCs (≥200 nmol/L compared with <200 nmol/L). Horses with colic and with STCCs ≥200nmol/L were more likely to have moderate or severe colic signs (compared with mild colic) and heart rates >45 beats per min (compared with ≤45 beats per min). It was concluded that colic in horses is associated with elevated STCCs, and increased STCC in horses with colic appears to relate to the severity of the disease. STCCs may provide additional decision-making and prognostic information in horses with colic but further studies are required to avoid misinterpretations associated with the wide variation in STCCs.

  4. 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

  5. Cortisol emphasizes the metabolic strategies employed by common carp, Cyprinus carpio at different feeding and swimming regimes.

    PubMed

    Liew, Hon Jung; Chiarella, Daniela; Pelle, Antonella; Faggio, Caterina; Blust, Ronny; De Boeck, Gudrun

    2013-11-01

    The objective of this study was to investigate the interaction between feeding, exercise and cortisol on metabolic strategies of common carp over a 168h post-implant period. Feeding provided readily available energy and clearly increased muscle and liver protein and glycogen stores. Swimming, feeding and cortisol all induced aerobic metabolism by increasing oxygen consumption, and stimulated protein metabolism as demonstrated by the increased ammonia and urea excretion and ammonia quotient. Hypercortisol stimulated ammonia self-detoxifying mechanisms by enhancing ammonia and urea excretion, especially during severe exercise. At high swimming level, higher branchial clearance rates in cortisol treated fish succeeded in eliminating the elevation of endogenous ammonia, resulting in reduced plasma Tamm levels compared to control and sham implanted fish. Carp easily induced anaerobic metabolism, both during routine and active swimming, with elevated lactate levels as a consequence. Both feeding and cortisol treatment increased this dependence on anaerobic metabolism. Hypercortisol induced both glycogenesis and gluconeogenesis resulting in hyperglycemia and muscle and liver glycogen deposition, most likely as a protective mechanism for prolonged stress situations and primarily fuelled by protein mobilization.

  6. 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…

  7. Assessing Salivary Cortisol in Studies of Child Development.

    ERIC Educational Resources Information Center

    Schwartz, Eve B.; Granger, Douglas A.; Susman, Elizabeth J.; Gunnar, Megan R.; Laird, Brandi

    1998-01-01

    Evaluated the susceptibility of radioimmunoassays (RIA) for saliva cortisol to interference effects caused by oral stimulants (drink mix crystals) used to facilitate saliva collection in studies with children. Found that oral stimulants artificially inflated estimated cortisol concentrations, with the magnitude of the interference-effect…

  8. Reduction of Cortisol Levels and Participants' Responses Following Art Making

    ERIC Educational Resources Information Center

    Kaimal, Girija; Ray, Kendra; Muniz, Juan

    2016-01-01

    This quasi-experimental study investigated the impact of visual art making on the cortisol levels of 39 healthy adults. Participants provided saliva samples to assess cortisol levels before and after 45 minutes of art making. Participants also provided written responses about the experience at the end of the session. Results indicate that art…

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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…

  14. [Bulimia, bulimia-anorexia and nocturnal secretion of melatonin and cortisol].

    PubMed

    Parienti, V; Kennedy, S H; Brown, G M; Costa, D

    1988-01-01

    The authors compared nocturnal variations of melatonin (MT) and cortisol levels in subjects with bulimia (n = 12), 6 with a normal body weight and 6 with anorexia nervosa, as well as 6 control subjects. The hypothesis, formulated for anorexia nervosa, that a decrease of noradrenergic activity induces a decrease of pineal activity, therefore a decrease of melatonin secretion, was not confirmed by our study. Moreover, in subjects with bulimia in the absence of anorexia nervosa, no significant decrease of nocturnal melatonin secretion was reported. Significant differences were due to cortisol variations when comparing MTmax/Cmin ratios. Melatonin did not add any complementary biological cue for diagnostic assessment for subjects with eating disorder and depression. The results of this study suggest that melatonin does not appear to be a useful biological marker in bulimia.

  15. 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.

  16. 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.

  17. Husbandry of zebrafish, Danio rerio, and the cortisol stress response.

    PubMed

    Pavlidis, Michail; Digka, Nikoletta; Theodoridi, Antonia; Campo, Aurora; Barsakis, Konstantinos; Skouradakis, Gregoris; Samaras, Athanasios; Tsalafouta, Alexandra

    2013-12-01

    The effect of common husbandry conditions (crowding, social environment, water quality, handling, and background color) on the cortisol stress response in adult zebrafish, Danio rerio, was investigated to check the usefulness of zebrafish as a model organism in aquaculture research. In addition, a noninvasive methodology for assessing stress was evaluated. Zebrafish showed a fast cortisol response with high values at 30 min that returned to basal levels within 2 h of poststress. There was a significant positive correlation between trunk cortisol concentrations and the free water cortisol rate (r(2)=0.829-0.850, p<0.001), indicating that measurement of the water-borne cortisol release rate may serve as a noninvasive and reliable stress indicator at the population level. Crowding resulted in 13- to 21-fold greater mean trunk cortisol concentrations compared with controls. However, even at low stocking density (2-5 fish/L), the maintenance cost was higher than the one at higher densities (10 fish/L) due to the formation of dominance hierarchies. The background color affected trunk cortisol concentrations, with fish exposed to brighter backgrounds (green and white) showing 3- to 8-fold greater mean trunk cortisol concentrations than fish exposed to a black background or transparent aquaria. Fish exposed to high stocking densities for 2 h or 5 days had similar high mean trunk cortisol levels, indicating that exposure of fish for the period of 2 h to a specific stressor may represent a chronic situation in zebrafish. It is concluded that adult laboratory zebrafish had a preference for a transparent or black background aquarium, at a number of 10 individuals per 2 L of available water volume, to express their normal behavior and avoid increased cortisol stress reaction.

  18. 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

  19. An integrative model linking traumatization, cortisol dysregulation and posttraumatic stress disorder: Insight from recent hair cortisol findings.

    PubMed

    Steudte-Schmiedgen, Susann; Kirschbaum, Clemens; Alexander, Nina; Stalder, Tobias

    2016-10-01

    Abundant evidence suggests links between trauma exposure, altered secretion of the glucocorticoid cortisol and the development/maintenance of posttraumatic stress disorder (PTSD), albeit with some inconsistency in findings. Further insight into the complex relations underlying this process may be derived from an increasing number of studies using hair cortisol analysis, a novel assessment strategy assumed to retrospectively capture long-term integrated cortisol secretion. Here, we evaluate the utility of hair cortisol analysis as a method in trauma/PTSD research and review current findings in this context. We compare hair cortisol data on the complex links between trauma, cortisol dysregulation and PTSD against the main findings obtained using traditional cortisol assessment methods. Finally, we integrate these data into a model which proposes that traumatization leads to dose and time-dependent changes in long-term cortisol output (initial post-traumatic increase, subsequent chronic attenuation) and that such dysregulation may partly mediate the link between traumatic load and the risk of PTSD development upon additional trauma exposure ("building block effect"). PMID:27443960

  20. Hair cortisol detection in dairy cattle by using EIA: protocol validation and correlation with faecal cortisol metabolites.

    PubMed

    Tallo-Parra, O; Manteca, X; Sabes-Alsina, M; Carbajal, A; Lopez-Bejar, M

    2015-06-01

    Hair may be a useful matrix to detect cumulative cortisol concentrations in studies of animal welfare and chronic stress. The aim of this study was to validate a protocol for cortisol detection in hair from dairy cattle by enzyme immunoassay (EIA). Seventeen adult Holstein-Friesian dairy cows were used during the milking period. Hair cortisol concentration was assessed in 25-day-old hair samples taken from the frontal region of the head, analysing black and white coloured hair separately. Concentrations of cortisol metabolites were determined in faeces collected twice a week during the same period of time. There was a high correlation between cortisol values in faeces and cortisol in white colour hair samples but such correlation was not significant with the black colour hair samples. The intra- and inter-assay coefficients of variation were 4.9% and 10.6%, respectively. The linearity showed R 2=0.98 and mean percentage error of -10.8 ± 1.55%. The extraction efficiency was 89.0 ± 23.52% and the parallelism test showed similar slopes. Cortisol detection in hair by using EIA seems to be a valid method to represent long-term circulating cortisol levels in dairy cattle.

  1. 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

  2. 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

  3. 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.

  4. 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…

  5. 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.

  6. Serum sex hormone-binding globulin and cortisol concentrations are associated with overreaching during strenuous military training.

    PubMed

    Tanskanen, Minna M; Kyröläinen, Heikki; Uusitalo, Arja L; Huovinen, Jukka; Nissilä, Juuso; Kinnunen, Hannu; Atalay, Mustafa; Häkkinen, Keijo

    2011-03-01

    The purpose was (a) to study the effect of an 8-week Finnish military basic training period (BT) on physical fitness, body composition, mood state, and serum biochemical parameters among new conscripts; (b) to determine the incidence of overreaching (OR); and (c) to evaluate whether initial levels or training responses differ between OR and noOR subjects. Fifty-seven males (19.7 ± 0.3 years) were evaluated before and during BT. Overreaching subjects had to fulfill 3 of 5 criteria: decreased aerobic physical fitness (VO2max), increased rating of perceived exertion (RPE) in 45-minute submaximal test at 70% of VO2max or sick absence from these tests, increased somatic or emotional symptoms of OR, and high incidence of sick absence from daily service. VO2max improved during the first 4 weeks of BT. During the second half of BT, a stagnation of increase in VO2max was observed, basal serum sex hormone-binding globulin (SHBG) increased, and insulin-like growth factor-1 and cortisol decreased. Furthermore, submaximal exercise-induced increases in cortisol, maximum heart rate, and postexercise increase in blood lactate were blunted. Of 57 subjects, 33% were classified as OR. They had higher basal SHBG before and after 4 and 7 weeks of training and higher basal serum cortisol at the end of BT than noOR subjects. In addition, in contrast to noOR, OR subjects exhibited no increase in basal testosterone/cortisol ratio but a decrease in maximal La/RPE ratio during BT. As one-third of the conscripts were overreached, training after BT should involve recovery training to prevent overtraining syndrome from developing. The results confirm that serum SHBG, cortisol, and testosterone/cortisol and maximal La/RPE ratios could be useful tools to indicate whether training is too strenuous.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache.

    PubMed

    Leistad, Rune Bang; Stovner, Lars Jacob; White, Linda R; Nilsen, Kristian B; Westgaard, Rolf H; Sand, Trond

    2007-06-01

    The goal of this study was to explore the relationship between indicators of sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) activity and stress-induced head and shoulder-neck pain in patients with migraine or tension-type headache (TTH). We measured noradrenaline, adrenaline and cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16 TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 30 min of relaxation. Migraine patients had lower noradrenaline levels in blood platelets compared to controls. Pain responses correlated negatively with noradrenaline levels, and pain recovery correlated negatively with the cortisol change in migraineurs. TTH patients maintained cortisol secretion during the cognitive stress as opposed to the normal circadian decrease seen in controls and migraineurs. There may therefore be abnormal activation of the HPA axis in patients with TTH when coping with mental stress, but no association was found between pain and cortisol. A relationship between HPA activity and stress in TTH patients has to our knowledge not been reported before. In migraine, on the other hand, both sympathoneural activation and HPA activation seem to be linked to stress-induced muscle pain and recovery from pain respectively. The present study suggests that migraineurs and TTH patients cope differently with low-grade cognitive stress.

  12. BJ-1108, a 6-Amino-2,4,5-Trimethylpyridin-3-ol Analog, Inhibits Serotonin-Induced Angiogenesis and Tumor Growth through PI3K/NOX Pathway.

    PubMed

    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.

  13. 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

  14. 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

  15. 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…

  16. 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.

  17. 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…

  18. 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.

  19. Analog signal isolation techniques

    SciTech Connect

    Beadle, E.R.

    1992-12-31

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  20. Analog signal isolation techniques

    SciTech Connect

    Beadle, E.R.

    1992-01-01

    This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

  1. 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

  2. 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

  3. 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

  4. Sources of sampling variation in saliva cortisol in dogs.

    PubMed

    Kobelt, A J; Hemsworth, P H; Barnett, J L; Butler, K L

    2003-10-01

    The main advantage of collecting saliva cortisol as opposed to plasma cortisol is that it is non-invasive and therefore it is now widely used in stress measurement studies on farm animals and dogs. Although a plasma cortisol response to handling associated with blood collection generally occurs at 3 min from the commencement of handling, there is no information in the literature on the time course of the response of salivary cortisol concentration to handling. The aims of these experiments were to (1). determine if there is a response to up to 4 min handling that affects cortisol concentration in saliva and (2). determine the main causes of variation in saliva cortisol in dogs over time. In experiment 1, saliva was collected from six Kelpies at 0 min then 2, 3 or 4 min after the commencement of restraint. There was no handling effect found in up to 4 min sampling time. In experiment 2, saliva was collected from six Labrador Retrievers five times in 2 h (14:00-16:00), three days a week for four weeks. Some of the sources of variation in saliva cortisol over time included between dog variation that varied over a period of days and variation between occasions that affected the group of dogs as a whole.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

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

    PubMed Central

    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 between these factors is still unclear. This study aims 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 = 1.36; 125 maltreated children and 111 nonmaltreated children, 128 boys and 108 girls) who attended a week-long summer camp for two consecutive years. Saliva was collected during five days at 9:00 a.m. and 4:00 p.m.. Means of morning and afternoon cortisol, and cortisol change (difference between morning and afternoon levels, controlled for morning levels) were grouped into low, medium, and high cortisol groups. Prosocial, disruptive/aggressive, and withdrawn behaviors were assessed using information from peers and counselors. Maltreated children showed less prosocial, and more disruptive/aggressive and withdrawn behavior. Results of Structural Equation Modeling analyses indicated that there were indirect effects of maltreatment on year 2 morning cortisol via prosocial disruptive/aggressive behavior: Lower levels of prosocial behavior and higher levels of disruptive/aggressive behavior were related to lower morning cortisol levels one year later. Withdrawn behavior was related to higher afternoon cortisol values one year later. Results of this study suggest that maltreated children are more likely to experience difficulties in social functioning, which in turn is related to cortisol regulation one year later. This altered HPA-axis functioning may put children at risk for later psychopathology. PMID:21823793

  11. 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

  12. Prolonged Cortisol Reactivity to Stress and White Matter in Schizophrenia

    PubMed Central

    Nugent, Katie L.; Chiappelli, Joshua; Sampath, Hemalatha; Rowland, Laura M.; Thangavelu, Kavita; Davis, Beshaun; Du, Xiaoming; Muellerklein, Florian; Daughters, Stacey; Kochunov, Peter; Hong, L. Elliot

    2015-01-01

    Objective While acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for which cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Methods Acute and prolonged salivary cortisol response was measured outside the scanner at pre-test and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n=45) and controls (n=53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n=30) and controls (n=33). Results Patients who did not tolerate and quit the psychological stress task had greater acute (t=2.52, p=0.016; t=3.51, p=0.001 at zero and 20 minutes) and prolonged (t=3.62, p=0.001 at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r=−0.468, p=0.009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. Conclusions This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages. PMID:26186431

  13. 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.

  14. The synthetic ajoene analog SPA3015 induces apoptotic cell death through crosstalk between NF-κB and PPARγ in multidrug-resistant cancer cells.

    PubMed

    Hwang, Jee Won; Cho, Hyewon; Lee, Jae Yeon; Jeon, Youngsic; Kim, Su-Nam; Lee, Sang Jin; Bae, Gyu-Un; Yoon, Sungpil; Jeon, Raok; Kim, Yong Kee

    2016-10-01

    Multidrug resistance (MDR) caused by P-glycoprotein (P-gp) overexpression impedes successful cancer chemotherapy. In this study, we investigated the anticancer effects of SPA3015, a synthetic ajoene analog, in P-gp-overexpressing MDR cancer cells (KBV20C and MES-SA/DX5). Treatment with SPA3015 caused a dramatic decrease in the cell viabilities of both KBV20C and MES-SA/DX5 cells. This decrease was accompanied by apoptotic cell death without affecting the expression level or drug efflux function of P-gp. SPA3015 selectively suppressed NF-κB reporter gene activity, which led to decreased expression of NF-κB target genes such as CIAP1, CIAP2, XIAP, and Bcl-XL. Surprisingly, nuclear localization and DNA binding affinity of the p65 subunit were not affected by SPA3015, suggesting that SPA3015 inhibits the transcriptional activity of NF-κB at the nucleus. Indeed, SPA3015 treatment led to an increase in the physical interaction of p65 with PPARγ, which resulted in the inhibition of NF-κB activity. Our findings support the hypothesis that SPA3015 inhibits NF-κB transcriptional activity by facilitating the physical interaction of the p65 subunit and PPARγ, which leads to apoptotic cell death in MDR cancer cells.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. Hormonal modulation of the heat shock response: insights from fish with divergent cortisol stress responses.

    PubMed

    LeBlanc, Sacha; Höglund, Erik; Gilmour, Kathleen M; Currie, Suzanne

    2012-01-01

    Acute temperature stress in animals results in increases in heat shock proteins (HSPs) and stress hormones. There is evidence that stress hormones influence the magnitude of the heat shock response; however, their role is equivocal. To determine whether and how stress hormones may affect the heat shock response, we capitalized on two lines of rainbow trout specifically bred for their high (HR) and low (LR) cortisol response to stress. We predicted that LR fish, with a low cortisol but high catecholamine response to stress, would induce higher levels of HSPs after acute heat stress than HR trout. We found that HR fish have significantly higher increases in both catecholamines and cortisol compared with LR fish, and LR fish had no appreciable stress hormone response to heat shock. This unexpected finding prevented further interpretation of the hormonal modulation of the heat shock response but provided insight into stress-coping styles and environmental stress. HR fish also had a significantly greater and faster heat shock response and less oxidative protein damage than LR fish. Despite these clear differences in the physiological and cellular responses to heat shock, there were no differences in the thermal tolerance of HR and LR fish. Our results support the hypothesis that responsiveness to environmental change underpins the physiological differences in stress-coping styles. Here, we demonstrate that the heat shock response is a distinguishing feature of the HR and LR lines and suggest that it may have been coselected with the hormonal responses to stress.

  5. Development of a formula for estimating plasma free cortisol concentration from a measured total cortisol concentration when elastase-cleaved and intact corticosteroid binding globulin coexist.

    PubMed

    Nguyen, Phuong T T; Lewis, John G; Sneyd, James; Lee, Rita S F; Torpy, David J; Shorten, Paul R

    2014-05-01

    Cortisol bound to corticosteroid binding globulin (CBG) contributes up to 90% of the total cortisol concentration in circulation. Therefore, changes in the binding kinetics of cortisol to CBG can potentially impact on the concentration of free cortisol, the only form that is responsible for the physiological function of the hormone. When CBG is cleaved into elastase-cleaved CBG (eCBG) by the activity of neutrophil elastase, its affinity for cortisol is reduced. Therefore, when eCBG coexists with intact CBG (iCBG) in plasma, the calculation of free cortisol concentration based on the formulae that considers only one CBG pool with the same affinity for cortisol may be inappropriate. In this study, we developed in vivo and in vitro models of cortisol partitioning which considers two CBG pools, iCBG and eCBG, with different affinities for cortisol, and deduce a new formula for calculating plasma free cortisol concentration. The formula provides better estimates of free cortisol concentration than previously used formulae when measurements of the concentrations of the two CBG forms are available. The model can also be used to estimate the affinity of CBG and albumin for cortisol in different clinical groups. We found no significant difference in the estimated affinity of CBG and albumin for cortisol in normal, sepsis and septic shock groups, although free cortisol was higher in sepsis and septic shock groups. The in vivo model also demonstrated that the concentration of interstitial free cortisol is increased locally at a site of inflammation where iCBG is cleaved to form eCBG by the activity of elastase released by neutrophils. This supports the argument that the cleavage of iCBG at sites of inflammation leads to more lower-affinity eCBG and may be a mechanism that permits the local concentration of free cortisol to increase at these sites, while allowing basal free cortisol concentrations at other sites to remain unaffected.

  6. Prenatal Cocaine Exposure and Infant Cortisol Reactivity

    PubMed Central

    Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.

    2009-01-01

    This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed, and children's saliva was sampled before, during, and after standardized procedures designed to elicit emotional arousal. Results revealed cocaine-exposed infants had a high amplitude trajectory of cortisol reactivity compared to non-cocaine-exposed infants. Infant gender and caregiving instability moderated this association. The findings support a dual hazard vulnerability model and have implications for evolutionary-developmental theories of individual differences in biological sensitivity to context. PMID:19467009

  7. Hormones in the seminal plasma. Cortisol.

    PubMed

    Abbaticchio, G; Giorgino, R; Urago, M; Gattuccio, F; Orlando, G; Jannì, A

    1981-09-01

    The data from previous studies on the seminal concentrations of proteic hormones result in the hypothesis that there exists a selective filter for these hormones, which is between the systemic circulation and the male genital canal. Previous data regarding sexual steroids are insufficient to verify if such a filter system also operates in the case of hormones of minor molecular weight. It would appear that the study of cortisol, a non-sexual steroid, will be more useful. The concentrations of this hormone in the peripheric blood (176 +/- 59, mean +/- ds, ng/ml) prove to be much greater than in the seminal plasma (20 +/- 9.6). No significant differences are found between normozoospermic and oligo-azoospermic subjects, either in the blood (173 +/- 184 +/- 53), or in the seminal plasma (21 +/- 12 versus 20 +/- 8). These data would seem to support the hypothesis under discussion.

  8. Cumulative Stress and Cortisol Disruption among Black and Hispanic Pregnant Women in an Urban Cohort.

    PubMed

    Suglia, Shakira Franco; Staudenmayer, John; Cohen, Sheldon; Enlow, Michelle Bosquet; Rich-Edwards, Janet W; Wright, Rosalind J

    2010-12-01

    While adult hypothalamic-pituitary-adrenocortical (HPA) axis functioning is thought to be altered by traumatic experiences, little data exist on the effects of cumulative stress on HPA functioning among pregnant women or among specific racial and ethnic groups. Individuals may be increasingly vulnerable to physiological alterations when experiencing cumulative effects of multiple stressors. These effects may be particularly relevant in urban poor communities where exposure to multiple stressors is more prevalent. The goal of this study was to explore the effects of multiple social stressors on HPA axis functioning in a sample of urban Black (n = 68) and Hispanic (n = 132) pregnant women enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS). Pregnant women were administered the Revised Conflict Tactics Scale (R-CTS) survey to assess interpersonal violence, the Experiences of Discrimination (EOD) survey, the Crisis in Family Systems-Revised (CRISYS-R) negative life events survey, and the My Exposure to Violence (ETV) survey, which ascertains exposure to community violence. A cumulative stress measure was derived from these instruments. Salivary cortisol samples were collected five times per day over three days to assess area under the curve (AUC), morning change, and basal awakening response in order to characterize diurnal salivary cortisol patterns. Repeated measures mixed models, stratified by race/ethnicity, were performed adjusting for education level, age, smoking status, body mass index and weeks pregnant at time of cortisol sampling. The majority of Hispanic participants (57%) had low cumulative stress exposure, while the majority of Black participants had intermediate (35%) or high (41%) cumulative stress exposure. Results showed that among Black but not Hispanic women, cumulative stress was associated with lower morning cortisol levels, including a flatter waking to bedtime rhythm. These analyses suggest that the combined

  9. 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

  10. 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.

  11. 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

  12. Cumulative Stress and Cortisol Disruption among Black and Hispanic Pregnant Women in an Urban Cohort.

    PubMed

    Suglia, Shakira Franco; Staudenmayer, John; Cohen, Sheldon; Enlow, Michelle Bosquet; Rich-Edwards, Janet W; Wright, Rosalind J

    2010-12-01

    While adult hypothalamic-pituitary-adrenocortical (HPA) axis functioning is thought to be altered by traumatic experiences, little data exist on the effects of cumulative stress on HPA functioning among pregnant women or among specific racial and ethnic groups. Individuals may be increasingly vulnerable to physiological alterations when experiencing cumulative effects of multiple stressors. These effects may be particularly relevant in urban poor communities where exposure to multiple stressors is more prevalent. The goal of this study was to explore the effects of multiple social stressors on HPA axis functioning in a sample of urban Black (n = 68) and Hispanic (n = 132) pregnant women enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS). Pregnant women were administered the Revised Conflict Tactics Scale (R-CTS) survey to assess interpersonal violence, the Experiences of Discrimination (EOD) survey, the Crisis in Family Systems-Revised (CRISYS-R) negative life events survey, and the My Exposure to Violence (ETV) survey, which ascertains exposure to community violence. A cumulative stress measure was derived from these instruments. Salivary cortisol samples were collected five times per day over three days to assess area under the curve (AUC), morning change, and basal awakening response in order to characterize diurnal salivary cortisol patterns. Repeated measures mixed models, stratified by race/ethnicity, were performed adjusting for education level, age, smoking status, body mass index and weeks pregnant at time of cortisol sampling. The majority of Hispanic participants (57%) had low cumulative stress exposure, while the majority of Black participants had intermediate (35%) or high (41%) cumulative stress exposure. Results showed that among Black but not Hispanic women, cumulative stress was associated with lower morning cortisol levels, including a flatter waking to bedtime rhythm. These analyses suggest that the combined

  13. Cumulative Stress and Cortisol Disruption among Black and Hispanic Pregnant Women in an Urban Cohort

    PubMed Central

    Suglia, Shakira Franco; Staudenmayer, John; Cohen, Sheldon; Enlow, Michelle Bosquet; Rich-Edwards, Janet W.; Wright, Rosalind J.

    2010-01-01

    While adult hypothalamic-pituitary-adrenocortical (HPA) axis functioning is thought to be altered by traumatic experiences, little data exist on the effects of cumulative stress on HPA functioning among pregnant women or among specific racial and ethnic groups. Individuals may be increasingly vulnerable to physiological alterations when experiencing cumulative effects of multiple stressors. These effects may be particularly relevant in urban poor communities where exposure to multiple stressors is more prevalent. The goal of this study was to explore the effects of multiple social stressors on HPA axis functioning in a sample of urban Black (n = 68) and Hispanic (n = 132) pregnant women enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS). Pregnant women were administered the Revised Conflict Tactics Scale (R-CTS) survey to assess interpersonal violence, the Experiences of Discrimination (EOD) survey, the Crisis in Family Systems-Revised (CRISYS-R) negative life events survey, and the My Exposure to Violence (ETV) survey, which ascertains exposure to community violence. A cumulative stress measure was derived from these instruments. Salivary cortisol samples were collected five times per day over three days to assess area under the curve (AUC), morning change, and basal awakening response in order to characterize diurnal salivary cortisol patterns. Repeated measures mixed models, stratified by race/ethnicity, were performed adjusting for education level, age, smoking status, body mass index and weeks pregnant at time of cortisol sampling. The majority of Hispanic participants (57%) had low cumulative stress exposure, while the majority of Black participants had intermediate (35%) or high (41%) cumulative stress exposure. Results showed that among Black but not Hispanic women, cumulative stress was associated with lower morning cortisol levels, including a flatter waking to bedtime rhythm. These analyses suggest that the combined

  14. Effects of the Higashi-Nihon earthquake: posttraumatic stress, psychological changes, and cortisol levels of survivors.

    PubMed

    Kotozaki, Yuka; Kawashima, Ryuta

    2012-01-01

    On March 11, 2011, the Pacific side of Japan's northeast was devastated by an earthquake and tsunami. For years, many researchers have been working on ways of examining the psychological effects of earthquakes on survivors in disaster areas who have experienced aftershocks, catastrophic fires, and other damage caused by the earthquake. The goal of this study is to examine scores on psychological measures and salivary cortisol level in these individuals both before and three months after the earthquake. The participants had been measured for these variables before the earthquake. After the earthquake, we carried out PTSD screening using CAPS for participants for another experiment, and then again conducted the aforementioned tests. We collected saliva samples from all survivors. Our results show that social relationship scores on the WHO-QOL26, negative mood scores of the WHO-SUBI, total GHQ score, POMS confusion scores, and CMI emotional status score after the earthquake showed scores indicating significantly decreased compared to before the earthquake. On the other hand, salivary cortisol levels after the earthquake was significantly increased compared to before the earthquake. Moreover, the result of a multiple regression analysis found that negative mood score on the WHO-SUBI and social relationship score on the WHO-QOL26 were significantly related to salivary cortisol levels. Our results thus demonstrate that several psychological stress induced by the earthquake was associated with an increase in salivary cortisol levels. These results show similar findings to previous study. We anticipate that this study will provide a better understanding of posttraumatic responses in the early stages of adaptation to the trauma and expand effective prevention strategies and countermeasures for PTSD. PMID:22558092

  15. Development of an LC-MS/MS method for the determination of endogenous cortisol in hair using (13)C3-labeled cortisol as surrogate analyte.

    PubMed

    Binz, Tina M; Braun, Ueli; Baumgartner, Markus R; Kraemer, Thomas

    2016-10-15

    Hair cortisol levels are increasingly applied as a measure for stress in humans and mammals. Cortisol is an endogenous compound and is always present within the hair matrix. Therefore, "cortisol-free hair matrix" is a critical point for any analytical method to accurately quantify especially low cortisol levels. The aim of this project was to modify current methods used for hair cortisol analysis to more accurately determine low endogenous cortisol concentrations in hair. For that purpose, (13)C3-labeled cortisol, which is not naturally present in hair (above 13C natural abundance levels), was used for calibration and comparative validation applying cortisol versus (13)C3-labeled cortisol. Cortisol was extracted from 20mg hair (standard sample amount) applying an optimized single step extraction protocol. An LC-MS/MS method was developed for the quantitative analysis of cortisol using either cortisol or (13)C3-cortisol as calibrators and D7-cortisone as internal standard (IS). The two methods (cortisol/(13)C3-labeled cortisol) were validated in a concentration range up to 500pg/mg and showed good linearity for both analytes (cortisol: R(2)=0.9995; (13)C3-cortisol R(2)=0.9992). Slight differences were observed for limit of detection (LOD) (0.2pg/mg/0.1pg/mg) and limit of quantification (LOQ) (1pg/mg/0.5pg/mg). Precision was good with a maximum deviation of 8.8% and 10% for cortisol and (13)C3-cortisol respectively. Accuracy and matrix effects were good for both analytes except for the quality control (QC) low cortisol. QC low (2.5pg/mg) showed matrix effects (126.5%, RSD 35.5%) and accuracy showed a deviation of 26% when using cortisol to spike. These effects are likely to be caused by the unknown amount of endogenous cortisol in the different hair samples used to determine validation parameters like matrix effect, LOQ and accuracy. No matrix effects were observed for the high QC (400pg/mg) samples. Recovery was good with 92.7%/87.3% (RSD 9.9%/6.2%) for QC low and

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

    Goldberg, Alexander A; Draz, Hossam; Montes-Grajales, Diana; Olivero-Verbél, Jesus; Safe, Stephen H; Sanderson, J Thomas

    2015-05-01

    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

  1. 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

  2. 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

  3. 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).

  4. 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

  5. The promise of analog computation

    NASA Astrophysics Data System (ADS)

    MacLennan, B. J.

    2014-10-01

    Future computing paradigms and technologies will have to be more like the physical processes by which they are realized, and because these processes are primarily continuous, post-Moore's law computing will involve an increased use of analog computation. Traditionally analog computers have computed ordinary differential equations of time, but analog field computation permits massively parallel temporal integration of partial differential equations. In principle many different physical media - not just electronics - can be exploited to implement the basic operations of analog computing, a small number of which are sufficient to approximate a wide variety of analog computations, thus providing a basis for universal analog computation and general-purpose analog computers. The contentious issue of the computational power of analog computers is addressed best on its own terms, rather by asking it within the context of Church-Turing computation, which distorts the relevant questions and their answers.

  6. 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.

  7. 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.

  8. Changes in Men's Salivary Testosterone and Cortisol Levels, and in Sexual Desire after Smelling Female Axillary and Vulvar Scents.

    PubMed

    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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Cortisol concentrations in follicular fluid of 'low responder' patients.

    PubMed

    Bider, D; Shine, S; Tur-Kaspa, I; Levron, J; Dor, J

    1998-01-01

    The study was undertaken to examine any differences existing in total cortisol concentrations in the follicular fluid (FF) of pre-ruptured follicles between 'low responder' patients (group 1, n = 20) and 'good responder' patients (group 2, n = 15). The groups were defined according to how many oocytes had been retrieved during the previous in-vitro fertilization procedure (group 1: three or fewer; group 2: more than three) and total oestradiol concentration at previous in-vitro fertilization (IVF) (group 1: < or = 500 pg/ml; group 2: > 500 pg/ml). All patients were aged 36-43 years (group 1 mean +/- SD: 38.2 +/- 4.7; group 2: 32.1 +/- 3.8 years) and were diagnosed with tubal or unexplained infertility. The total FF cortisol concentrations obtained in conjunction with an IVF procedure were assayed and related to oocyte fertilization. Follicular fluid was analysed for total cortisol content. Only follicles between 19 and 20 mm diameter were analysed in both groups. After aspiration of blood-free FF, total cortisol concentrations were measured by radioimmunoassay, designed for the quantitative measurement of cortisol, and related to oocyte fertilization. Total cortisol concentration in FF from fertilized oocytes was 9.7 +/- 0.6 microg/ml (mean +/- SD) in group 1 compared to 9.2 +/- 4.4 microg/ml in group 2 (not statistically significant). Total cortisol concentrations were not associated with oocyte fertilization and no difference between the groups was found in total cortisol concentrations in the FF of unfertilized oocytes or empty follicles.

  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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Utility of cerebrospinal fluid cortisol level in acute bacterial meningitis

    PubMed Central

    Mehta, Anish; Mahale, Rohan R.; Sudhir, Uchil; Javali, Mahendra; Srinivasa, Rangasetty

    2015-01-01

    Background: Meningitis remains a serious clinical problem in developing as well as developed countries. Delay in diagnosis and treatment results in significant morbidity and mortality. The role and levels of intrathecal endogenous cortisol is not known. Objective: To study the cerebrospinal fluid (CSF) cortisol levels and to evaluate its role as a diagnostic and therapeutic marker in acute bacterial meningitis. Materials and Methods: Thirty patients with acute bacterial meningitis with no prior treatment were evaluated. Cortisol levels were compared with 20 patients with aseptic (viral) meningitis and 25 control subjects. Results: Mean CSF cortisol level was 13.85, 3.47, and 1.05 in bacterial meningitis, aseptic meningitis, and controls, respectively. Mean CSF cortisol level in bacterial meningitis was significantly higher as compared to controls (P < 0.001). There was significant difference in CSFcortisol levels in bacterial and aseptic meningitis (P < 0.001). Conclusions: Cortisol levels in CSF are highly elevated in patients with acute bacterial meningitis. This suggests that intrathecalcortisol may serve as a valuable, rapid, relatively inexpensive diagnostic marker in discriminatingbetween bacterial and aseptic meningitis. This helps in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality. PMID:26019421

  20. 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

  1. Testosterone, cortisol and anxiety in elite field hockey players.

    PubMed

    Aguilar, Raúl; Jiménez, Manuel; Alvero-Cruz, José R

    2013-07-01

    The aim of the present study was to assess the change in the levels of testosterone and cortisol after victory and defeat in male field hockey players during an important tournament. In the beginning of the game series, the players were ranked very closely to achieve (for the first time) the championship rising to The Honor Division-A, the highest status national category. The first game resulted in a 7-4 victory, the second game resulted in a 6-1 victory, and the third game resulted in a 1-2 defeat. As expected, there were changes in testosterone levels after the competition, dropping in the game which ended in defeat, and rising slightly in the two games which ended in victory; there were also changes in cortisol levels, rising in the game which ended in defeat, and showing no variations in the games which ended in victory; correlational analyses congruently showed that defeat led to rises in cortisol whereas victory led to rises in testosterone; anticipatory somatic anxiety was related to cortisol levels prior to games, and physical exertion during competition was related to the change in testosterone levels (suggesting an inhibitory effect) but not to the change in cortisol levels. Hence, this pattern of hormonal responses to a real-life dominance challenge complied with Mazur's (1985) [16] biosocial model of status and dominance motivation, by showing that testosterone and cortisol are linked to victory and defeat in a theoretically predictable fashion.

  2. 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.

  3. Father contributions to cortisol responses in infancy and toddlerhood.

    PubMed

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

    2011-03-01

    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 of child age 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 the challenge conducted at 7 months of child age, 49.0% of the sample were girls; racial composition of the sample was 25.8% African American and 74.2% European American. At the challenge conducted at 24 months of child age 49.9% of the sample were girls; racial composition was 24.7% African American and 75.3% European American. We conducted analyses across assessment points 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

  4. Sleep disturbances are correlated with decreased morning awakening salivary cortisol.

    PubMed

    Backhaus, Jutta; Junghanns, Klaus; Hohagen, Fritz

    2004-10-01

    Morning and evening salivary cortisol levels were correlated with sleep parameters in 14 patients with primary insomnia and 15 healthy controls. Salivary cortisol was sampled immediately after awakening (T1), 15 min later (T2), and immediately before going to bed (T3) for 1 week at home. In parallel with this, subjects estimated parameters of sleep in a daily sleep log. Patients and controls were all non-smokers who did not differ regarding morning awakening time or bedtime. Cortisol after awakening was significantly decreased in primary insomnia. Salivary cortisol at the time of awakening correlated negatively with the subjective estimation of sleep quality, i.e. a low salivary cortisol level directly after awakening correlated with a higher frequency of nightly awakenings (r = -0.50), a diminished sleep quality (r = -0.34) and a decreased feeling of recovery after awakening (r = -0.35; all p < 0.05). Furthermore, awakening cortisol was negatively correlated with the Pittsburgh Sleep Quality Index (r = -0.43) and with a questionnaire on sleep-related cognitions with the subscales rumination in bed (r = -0.56 ) and focusing on sleep-related thoughts (r = -0.46; all p < 0.05).

  5. 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

  6. 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.

  7. Theta-Burst Stimulation of Hippocampal Slices Induces Network-Level Calcium Oscillations and Activates Analogous Gene Transcription to Spatial Learning

    PubMed Central

    O'Connor, John J.; Murphy, Keith J.

    2014-01-01

    Over four decades ago, it was discovered that high-frequency stimulation of the dentate gyrus induces long-term potentiation (LTP) of synaptic transmission. LTP is believed to underlie how we process and code external stimuli before converting it to salient information that we store as 'memories'. It has been shown that rats performing spatial learning tasks display theta-frequency (3–12 Hz) hippocampal neural activity. Moreover, administering theta-burst stimulation (TBS) to hippocampal slices can induce LTP. TBS triggers a sustained rise in intracellular calcium [Ca2+]i in neurons leading to new protein synthesis important for LTP maintenance. In this study, we measured TBS-induced [Ca2+]i oscillations in thousands of cells at increasing distances from the source of stimulation. Following TBS, a calcium wave propagates radially with an average speed of 5.2 µm/s and triggers multiple and regular [Ca2+]i oscillations in the hippocampus. Interestingly, the number and frequency of [Ca2+]i fluctuations post-TBS increased with respect to distance from the electrode. During the post-tetanic phase, 18% of cells exhibited 3 peaks in [Ca2+]i with a frequency of 17 mHz, whereas 2.3% of cells distributed further from the electrode displayed 8 [Ca2+]i oscillations at 33 mHz. We suggest that these observed [Ca2+]i oscillations could lead to activation of transcription factors involved in synaptic plasticity. In particular, the transcription factor, NF-κB, has been implicated in memory formation and is up-regulated after LTP induction. We measured increased activation of NF-κB 30 min post-TBS in CA1 pyramidal cells and also observed similar temporal up-regulation of NF-κB levels in CA1 neurons following water maze training in rats. Therefore, TBS of hippocampal slice cultures in vitro can mimic the cell type-specific up-regulations in activated NF-κB following spatial learning in vivo. This indicates that TBS may induce similar transcriptional changes to spatial learning

  8. 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

  9. The Association between Prenatal Exposure to Cigarettes and Cortisol Reactivity in 7-Month-Old Infants

    PubMed Central

    Schuetze, Pamela; Lopez, Francisco; Granger, Douglas A.; Eiden, Rina D.

    2008-01-01

    We examined the association between prenatal exposure to cigarettes and adrenocortical responses to stress in 7-month old infants. Cortisol levels were assessed twice prior to and twice following affect-eliciting procedures in 111 (59 exposed and 52 nonexposed) infants. Cortisol reactivity was defined as the difference between the peak poststressor cortical level and the pretask cortisol level. Higher values indicated higher cortisol reactivity. Exposed infants had higher peak cortisol reactivity than non exposed infants. There were no differences in pretask cortisol levels. Maternal hostility mediated the association between cigarette exposure and peak cortisol reactivity. Furthermore, infant gender moderated this association such that exposed boys had significantly higher peak cortisol reactivity than nonexposed infants or exposed girls. These findings provide additional evidence that prenatal cigarette exposure is associated with dysregulation during infancy and that early adverse, non-social experiences may have relatively long-lasting effects on cortisol reactivity in infants. PMID:18690653

  10. Transtensional tectonics induced by oblique reactivation of previous lithospheric anisotropies during the Late Triassic to Early Jurassic rifting in the Neuquén basin: Insights from analog models

    NASA Astrophysics Data System (ADS)

    Bechis, Florencia; Cristallini, Ernesto O.; Giambiagi, Laura B.; Yagupsky, Daniel L.; Guzmán, Cecilia G.; García, Víctor H.

    2014-09-01

    The goal of this study was to determine the main factors that controlled the kinematic evolution and the structural architecture developed during the Late Triassic to Early Jurassic rifting that led to the opening of the Neuquén basin in the southwestern sector of Gondwana. We carried out a series of analog models to simulate an extensional system with a bent geometry similar to the northeastern border of the basin. In different experiments, we varied the extension direction between NNE (N10°E) and NE (N45°E) orientations, inducing rift systems with different degrees of obliquity in each sector of the extended area. We compared the kinematic evolution and the final structural architecture observed in the experiments with data from two selected representative areas of the basin: (1) the Atuel depocenter, situated in the northern Andean sector, and (2) the Entre Lomas area, situated in the northeastern Neuquén Embayment. In both cases, the good match between the field and subsurface data and the results of the analog models supports a NNE orientation of the regional extension (N30°E-N20°E) during the synrift stage. Our experimental results suggest that lithospheric weakness zones of NNW to NW trend could have controlled and localized the extension in the Neuquén basin. These previous anisotropies were linked to the sutures and rheological contrasts generated during the collision of terranes against the southwestern margin of Gondwana during the Paleozoic, as well as further modifications of the thermo-mechanical state of the lithosphere during the Late Paleozoic to Early Mesozoic evolution.

  11. 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.

  12. Correlation between maternal and infant cortisol varies by breastfeeding status

    PubMed Central

    Benjamin Neelon, Sara E.; Stroo, Marissa; Mayhew, Meghan; Maselko, Joanna; Hoyo, Cathrine

    2015-01-01

    Objective The objective of this study was to examine associations of mother and infant salivary cortisol, measured three times over the course of a day, and assess whether these varied by breastfeeding status. Methods We conducted a cross-sectional study of 54 mothers and their infants aged 4–11 months. Mothers collected their own saliva and that of their infants upon awakening, 30 min after waking and at bedtime. Breastfeeding status was reported by mothers and cortisol level was measured in saliva in μg/dl using standard techniques. We used generalized linear models to evaluate relationships between maternal and infant cortisol levels, and assessed whether the relationship differed by breastfeeding status: formula only compared to partial and full breastfeeding, adjusting for infant sex, race, age, maternal education, and family income. Results Thirty-four infants received formula only and 20 were either partially or fully breastfed. Breastfeeding was associated with higher household income, higher maternal education, and white race. Cortisol levels were higher among breastfed infants at all three time points. After adjustment, maternal cortisol levels were related with infant cortisol at bedtime only (regression estimate 0.06; 95% CI: 0.10, 1.1; p = 0.02). The adjusted association between bedtime maternal and infant cortisol was stronger among breastfeeding dyads than among formula-feeding dyads (regression estimate 1.0; 95% CI: 0.1, 2.0; p = 0.04 vs. 0.6; CI: −0.1,1.3; p = 0.10). In addition, we assessed the influence of maternal education and household income in our adjusted model; income strengthened the observed association, whereas maternal education did not change the estimate. Conclusions Breastfeeding mothers and infants had significant correlations for cortisol at bedtime, while formula-feeding dyads did not. These data suggest that several factors may contribute to cortisol synchrony observed in mother/infant dyads, including the transfer of

  13. Stress-Immune-Growth Interactions: Cortisol Modulates Suppressors of Cytokine Signaling and JAK/STAT Pathway in Rainbow Trout Liver.

    PubMed

    Philip, Anju M; Vijayan, Mathilakath M

    2015-01-01

    Chronic stress is a major factor in the poor growth and immune performance of salmonids in aquaculture. However, the molecular mechanisms linking stress effects to growth and immune dysfunction is poorly understood. The suppressors of cytokine signaling (SOCS), a family of genes involved in the inhibition of JAK/STAT pathway, negatively regulates growth hormone and cytokine signaling, but their role in fish is unclear. Here we tested the hypothesis that cortisol modulation of SOCS gene expression is a key molecular mechanism leading to growth and immune suppression in response to stress in fish. Exposure of rainbow trout (Oncorhynchus mykiss) liver slices to cortisol, mimicking stress level, upregulated SOCS-1 and SOCS-2 mRNA abundance and this response was abolished by the glucocorticoid receptor antagonist mifepristone. Bioinformatics analysis confirmed the presence of putative glucocorticoid response elements in rainbow trout SOCS-1 and SOCS-2 promoters. Prior cortisol treatment suppressed acute growth hormone (GH)-stimulated IGF-1 mRNA abundance in trout liver and this involved a reduction in STAT5 phosphorylation and lower total JAK2 protein expression. Prior cortisol treatment also suppressed lipopolysaccharide (LPS)-induced IL-6 but not IL-8 transcript levels; the former but not the latter cytokine expression is via JAK/STAT phosphorylation. LPS treatment reduced GH signaling, but this was associated with the downregulation of GH receptors and not due to the upregulation of SOCS transcript levels by this endotoxin. Collectively, our results suggest that upregulation of SOCS-1 and SOCS-2 transcript levels by cortisol, and the associated reduction in JAK/STAT signaling pathway, may be a novel mechanism leading to growth reduction and immune suppression during stress in trout.

  14. Cortisol is not the primary mediator for augmented CXCR4 expression on natural killer cells after acute exercise.

    PubMed

    Okutsu, Mitsuharu; Ishii, Kenji; Niu, Kaijun; Nagatomi, Ryoichi

    2014-08-01

    CXC-chemokine receptor 4 (CXCR4) and its ligand, stromal-derived factor 1α (SDF-1α; also known as CXCL12), are crucial for the redistribution of immune cells after acute exercise. We investigated the relationships between acute exercise and CXCR4 expression on natural killer (NK) cells. Peripheral blood mononuclear cells (PBMCs) were cultured with cortisol and analyzed for CXCR4 expression on CD3(-)/CD56(+) NK cells and NK cell migration activity. To determine the effect of exercise, we isolated PBMCs from subjects before and after a 90-min exercise at 70% peak O2 uptake (V̇o2peak) and determined the changes in CXCR4 expression on NK cells after exercise. We cultured PBMCs with plasma obtained before and after exercise and with the glucocorticoid antagonist RU-486 to determine NK cell migration activity and the effects of cortisol on CXCR4 expression in vitro. Cortisol treatment increased CXCR4 expression (P < 0.05) and migration activity (P < 0.05) of NK cells. Exercise did not affect CXCR4 expression on NK cells, whereas incubating them with postexercise plasma significantly increased CXCR4 expression (P < 0.05) and migration activity (P < 0.05). RU-486 blocked cortisol-induced CXCR4 upregulation on NK cells, but only partially blocked (7%) CXCR4 upregulation when PMBCs were incubated with postexercise plasma. Thus acute exercise increases CXCR4 expression on NK cells and their migration activity and may contribute to NK cell redistribution after acute exercise; however, cortisol did not appear to be the primary mediator of augmented CXCR4 expression.

  15. 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

  16. 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

  17. GH and cortisol responses following an acute session of respiratory muscle endurance training in severely obese patients.

    PubMed

    Sartorio, A; Agosti, F; Patrizi, A; Gattico, A; Tringali, G; Giunta, M; Muller, E E; Rigamonti, A E

    2013-03-01

    It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age±SEM: 22.8±1.6 years, body mass index, BMI: 39.9±1.1 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n=7, 4 M/3 F, age: 26.1±3.1 years, BMI: 22.4±0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normal-weighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Cancer-induced bone loss and associated pain-related behavior is reduced by risedronate but not its phosphonocarboxylate analog NE-10790.

    PubMed

    Hald, Andreas; Hansen, Rikke R; Thomsen, Mette W; Ding, Ming; Croucher, Peter I; Gallagher, Orla; Ebetino, Frank H; Kassem, Moustapha; Heegaard, Anne-Marie

    2009-09-01

    Prostate, breast and lung cancers readily develop bone metastases which lead to fractures, hypercalcemia and pain. Malignant growth in the bones depends on osteoclast-mediated bone resorption and in this regard bisphosphonate compounds, which have high-bone affinity and inhibit osteoclast activity, have been found to alleviate bone cancer symptoms. In this study, the bisphosphonate risedronate and its phosphonocarboxylate derivative NE-10790 was tested in a murine bone cancer pain model. Risedronate decreased bone cancer-related bone destruction and pain-related behavior and decreased the spinal expression of glial fibrillary acidic protein, whereas NE-10790 had no effect on these parameters. Furthermore, risedronate but not NE-10790 induced dose-dependent toxicity in NCTC-2472 cells in vitro. Furthermore, the direct toxic effect of risedronate on tumor cells observed in vitro opens the possibility that a direct toxic effect on tumor cells may also be present in vivo and be related to the efficacy of bisphosphonate compounds. In conclusion, these results suggest that risedronate treatment may lead to an increased life quality, in patient suffering from bone cancer, in terms of decreased osteolysis and pain, and merits further study.

  4. 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

  5. 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.

  6. 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 ...

  7. 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...

  8. Behavior of testosterone and cortisol during an intensity-controlled high-volume training period measured by a training task-specific test in men rowers.

    PubMed

    Rämson, Raul; Jürimäe, Jaak; Jürimäe, Toivo; Mäestu, Jarek

    2009-03-01

    The aim of this study was to investigate changes in the stress hormones testosterone and cortisol after a task-specific exercise during a high-volume endurance training cycle in men rowers. Eight highly trained men rowers were investigated during a high-volume, low-intensity training period. A 2-hour, low-intensity, long-distance rowing (LDT) test was conducted at baseline, after a high-volume period, and after the recovery period. Training and performance intensities were obtained at the graded incremental test, were preset individually, and were the same during all LDTs. Fasting blood samples were taken during the same days as the LDTs. Exercise-induced blood samples were taken before, 5 minutes after, and 30 minutes after (post 30') the completion of each LDT. There were no significant changes in fasting cortisol and testosterone values during the whole study period, and there were no significant changes in cortisol and testosterone concentrations during the LDT. However, testosterone concentration was significantly decreased at post 30' compared with posttest values during the second LDT that was held after the 2-week high-training-volume period, and, during the second LDT, post 30' values of cortisol tended to be decreased compared with posttest values (p = 0.063). In conclusion, changes in the concentrations of testosterone and cortisol after long-distance rowing indicate decreased adaptivity after the training-specific performance test.

  9. Concerns regarding hair cortisol as a biomarker of chronic stress in exercise and sport science.

    PubMed

    Gerber, Markus; Brand, Serge; Lindwall, Magnus; Elliot, Catherine; Kalak, Nadeem; Herrmann, Christian; Pühse, Uwe; Jonsdottir, Ingibjörg H

    2012-12-01

    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.

  10. Development of the cortisol circadian rhythm in the light of stress early in life.

    PubMed

    Simons, Sterre S H; Beijers, Roseriet; Cillessen, Antonius H N; de Weerth, Carolina

    2015-12-01

    The secretion of the stress hormone cortisol follows a diurnal circadian rhythm. There are indications that this rhythm is affected by stress early in life. This paper addresses the development of the cortisol circadian rhythm between 1 and 6 years of age, and the role of maternal stress and anxiety early in the child's life on this (developing) rhythm. Participants were 193 healthy mother-child dyads from a community sample. Self-reported maternal stress and anxiety and physiological stress (saliva cortisol), were assessed prenatally (gestational week 37). Postnatally, self-reported maternal stress and anxiety were measured at 3, 6, 12, 30, and 72 months. Saliva cortisol samples from the children were collected on two days (four times each day) at 12, 30, and 72 months of age. The total amount of cortisol during the day and the cortisol decline over the day were determined to indicate children's cortisol circadian rhythm. Multilevel analyses showed that the total amount of cortisol decreased between 1 and 6 years. Furthermore, more maternal pregnancy-specific stress was related to higher total amounts of cortisol in the child. Higher levels of early postnatal maternal anxiety were associated with flatter cortisol declines in children. Higher levels of early postnatal maternal daily hassles were associated with steeper child cortisol declines over the day. These results indicated developmental change in children's cortisol secretion from 1 to 6 years and associations between maternal stress and anxiety early in children's lives and children's cortisol circadian rhythm in early childhood.

  11. Hair Analysis Provides a Historical Record of Cortisol Levels in Cushing’s Syndrome

    PubMed Central

    Thomson, S.; Koren, G.; Fraser, L.-A.; Rieder, M.; Friedman, T. C.; Van Uum, S. H. M.

    2010-01-01

    The severity of Cushing’s Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids. Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism. We attempted to measure cortisol in hair in relation to clinical course in six female patients with CS and in 32 healthy volunteers in 1 cm hair sections. Hair cortisol content was measured using a commercially available salivary cortisol immune assay with a protocol modified for use with hair. Hair cortisol levels were higher in patients with CS than in controls, the medians (ranges) were 679 (279–2500) and 116 (26–204) ng/g respectively (P <0.001). Segmental hair analysis provided information for up to 18 months before time of sampling. Hair cortisol concentrations appeared to vary in accordance with the clinical course. Based on these data, we suggest that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol, and that more research is required to fully understand the utility and limits of this technique. PMID:19609841

  12. 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

  13. 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

  14. Salivary Alpha Amylase-Cortisol Asymmetry in Maltreated Youth

    PubMed Central

    Gordis, Elana B.; Granger, Douglas A.; Susman, Elizabeth J.; Trickett, Penelope K.

    2008-01-01

    Background Maltreatment represents a major stressor in the lives of many youth. Given the known effects of stress exposure on subsequent biological stress response systems, researchers have been interested in the effects of maltreatment on the functioning of these systems. Experimental studies reveal that previous exposure to stress affects the symmetry between components of the physiological stress response to subsequent stress. The present study examined asymmetry between salivary alpha amylase (sAA), a sympathetic indicator, and cortisol reactivity to a social stressor among maltreated and comparison youth age 9 to 14 years. Consistent with earlier studies suggesting that stress leads to asymmetry between hypothalamic-pituitary-adrenal axis and sympathetic nervous system activity, we expected that maltreated youth would exhibit greater sAA-cortisol asymmetry than would comparison youth. Methods Forty-seven maltreated and 37 comparison youth visited the lab and engaged in a social stress protocol. We collected 2 saliva samples before the stressor and 4 after, at 0 minutes post stress and every 10 minutes for 30 minutes. Results Maltreatment status moderated the relation between sAA and cortisol activity in response to the stressor. Comparison youth showed significant links between the sAA and cortisol responses; maltreated youth had no significant associations between responses in the two biomarkers. Conclusion The data were consistent with sAA-cortisol asymmetry among maltreated youth. Further research should seek to replicate this finding and investigate its implication for developmental trajectories. PMID:17945232

  15. 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

  16. Trait and state perseverative cognition and the cortisol awakening response.

    PubMed

    Zoccola, Peggy M; Dickerson, Sally S; Yim, Ilona S

    2011-05-01

    Perseverative cognition (i.e., rumination, worry) may amplify or maintain cortisol stress responses. The present study examined the effects of trait and state perseverative cognition (PC) on the cortisol awakening response (CAR). We hypothesized that trait PC and state (prior day's) PC would be associated with greater CARs. Undergraduates scoring high (N=77) and low (N=42) on trait PC were included. Participants reported worries about upcoming events and ruminations on past events that occurred throughout the day as a measure of state PC. The next morning, saliva samples were collected 0, 30, 45, and 60min after awakening to assess the CAR. Area under the curve (AUC) and 30-min increase (30-min Inc) were calculated to capture the salivary cortisol total output and increase relative to baseline in the hour after awakening. There was no effect of trait PC on the CAR. In contrast, reports of worrying and/or ruminating the night before predicted greater increases in cortisol concentration and total cortisol output compared to those who neither ruminated nor worried the night before. These effects were not accounted for by depressed mood, anxiety, sleep, or recent stressors. Findings suggest differential effects of trait and state PC on the CAR and highlight the importance of using proximal measures in examining individual differences in the CAR.

  17. 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.

  18. 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.

  19. Mars inflatable greenhouse analog.

    PubMed

    Sadler, Philip D; Giacomelli, Gene A

    2002-01-01

    Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design.

  20. Mars inflatable greenhouse analog.

    PubMed

    Sadler, Philip D; Giacomelli, Gene A

    2002-01-01

    Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design. PMID:11987303

  1. 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

  2. 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

  3. 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.

  4. 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...

  5. Interplay between plasma oxidative status, cortisol and coping styles in wild alpine marmots, Marmota marmota.

    PubMed

    Costantini, David; Ferrari, Caterina; Pasquaretta, Cristian; Cavallone, Elena; Carere, Claudio; von Hardenberg, Achaz; Réale, Denis

    2012-01-15

    Variation in how individuals cope behaviourally and physiologically with stressors is widespread and can have a significant impact on life-history traits and fitness. Individual coping styles are characterised by differential behavioural and adrenocortical reactivity to various challenges. As stress hormones can affect the production of reactive chemical species and the antioxidant status, individuals with different coping styles may differ also in oxidative status. Field studies on wild mammalian populations are few in number and none so far has simultaneously tested the relationship between coping style, adrenocortical reactivity and oxidative status in the same individuals. We measured individual variation in coping styles along a proactive-reactive continuum together with variation in baseline and stress-induced plasma oxidative damage, plasma non-enzymatic antioxidant capacity and cortisol in wild alpine marmots, Marmota marmota. Confirmatory path analysis revealed that different coping styles are accompanied by different baseline and stress-induced plasma oxidative statuses. Our findings also highlight the potential role of cortisol as a mediator of such differences.

  6. 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

  7. 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 glucocort