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Sample records for analog induce cortisol

  1. Cortisol Induces Reactive Oxygen Species Through a Membrane Glucocorticoid Receptor in Rainbow Trout Myotubes.

    PubMed

    Espinoza, Marlen B; Aedo, Jorge E; Zuloaga, Rodrigo; Valenzuela, Cristian; Molina, Alfredo; Valdés, Juan A

    2017-04-01

    Cortisol is an essential regulator of neuroendocrine stress responses in teleosts. Cortisol predominantly affects target tissues through the genomic pathway, which involves interacting with cytoplasmic glucocorticoid receptors, and thereby, modulating stress-response gene expressions. Cortisol also produces rapid effects via non-genomic pathways, which do not involve gene transcription. Although cortisol-mediated genomic pathways are well documented in teleosts, non-genomic pathways are not fully understood. Moreover, no studies have focused on the contribution of non-genomic cortisol pathways in compensatory stress responses in fish. In this study, rainbow trout (Oncorhynchus mykiss) skeletal myotubes were stimulated with physiological concentrations of cortisol and cortisol-BSA, a membrane-impermeable agent, resulting in an early induction of reactive oxygen species (ROS). This production was not suppressed by transcription or translation inhibitors, suggesting non-genomic pathway involvement. Moreover, myotube preincubation with RU486 and NAC completely suppressed cortisol- and cortisol-BSA-induced ROS production. Subcellular fractionation analysis revealed the presence of cell membrane glucocorticoid receptors. Finally, cortisol-BSA induced a significant increase in ERK1/2 and CREB phosphorylation, as well as in CREB-dependent transcriptional activation of the pgc1a gene expression. The obtained results strongly suggest that cortisol acts through a non-genomic glucocorticoid receptor-mediated pathway to induce ROS production and contribute to ERK/CREB/PGC1-α signaling pathway activation as stress compensation mechanisms. J. Cell. Biochem. 118: 718-725, 2017. © 2016 Wiley Periodicals, Inc.

  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 interferes with the estradiol-induced surge of luteinizing hormone in the ewe.

    PubMed

    Wagenmaker, Elizabeth R; Breen, Kellie M; Oakley, Amy E; Pierce, Bree N; Tilbrook, Alan J; Turner, Anne I; Karsch, Fred J

    2009-03-01

    Two experiments were conducted to test the hypothesis that cortisol interferes with the positive feedback action of estradiol that induces the luteinizing hormone (LH) surge. Ovariectomized sheep were treated sequentially with progesterone and estradiol to create artificial estrous cycles. Cortisol or vehicle (saline) was infused from 2 h before the estradiol stimulus through the time of the anticipated LH surge in the artificial follicular phase of two successive cycles. The plasma cortisol increment produced by infusion was approximately 1.5 times greater than maximal concentrations seen during infusion of endotoxin, which is a model of immune/inflammatory stress. In experiment 1, half of the ewes received vehicle in the first cycle and cortisol in the second; the others were treated in reverse order. All ewes responded with an LH surge. Cortisol delayed the LH surge and reduced its amplitude, but both effects were observed only in the second cycle. Experiment 2 was modified to provide better control for a cycle effect. Four treatment sequences were tested (cycle 1-cycle 2): vehicle-vehicle, cortisol-cortisol, vehicle-cortisol, cortisol-vehicle. Again, cortisol delayed but did not block the LH surge, and this delay occurred in both cycles. Thus, an elevation in plasma cortisol can interfere with the positive feedback action of estradiol by delaying and attenuating the LH surge.

  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. Stress induced Salmonella Typhimurium recrudescence in pigs coincides with cortisol induced increased intracellular proliferation in macrophages.

    PubMed

    Verbrugghe, Elin; Boyen, Filip; Van Parys, Alexander; Van Deun, Kim; Croubels, Siska; Thompson, Arthur; Shearer, Neil; Leyman, Bregje; Haesebrouck, Freddy; Pasmans, Frank

    2011-12-07

    Salmonella Typhimurium infections in pigs often result in the development of carriers that intermittently excrete Salmonella in very low numbers. During periods of stress, for example transport to the slaughterhouse, recrudescence of Salmonella may occur, but the mechanism of this stress related recrudescence is poorly understood. Therefore, the aim of the present study was to determine the role of the stress hormone cortisol in Salmonella recrudescence by pigs. We showed that a 24 h feed withdrawal increases the intestinal Salmonella Typhimurium load in pigs, which is correlated with increased serum cortisol levels. A second in vivo trial demonstrated that stress related recrudescence of Salmonella Typhimurium in pigs can be induced by intramuscular injection of dexamethasone. Furthermore, we found that cortisol, but not epinephrine, norepinephrine and dopamine, promotes intracellular proliferation of Salmonella Typhimurium in primary porcine alveolar macrophages, but not in intestinal epithelial cells and a transformed cell line of porcine alveolar macrophages. A microarray based transcriptomic analysis revealed that cortisol did not directly affect the growth or the gene expression or Salmonella Typhimurium in a rich medium, which implies that the enhanced intracellular proliferation of the bacterium is probably caused by an indirect effect through the cell. These results highlight the role of cortisol in the recrudescence of Salmonella Typhimurium by pigs and they provide new evidence for the role of microbial endocrinology in host-pathogen interactions.

  7. Stress induced Salmonella Typhimurium recrudescence in pigs coincides with cortisol induced increased intracellular proliferation in macrophages

    PubMed Central

    2011-01-01

    Salmonella Typhimurium infections in pigs often result in the development of carriers that intermittently excrete Salmonella in very low numbers. During periods of stress, for example transport to the slaughterhouse, recrudescence of Salmonella may occur, but the mechanism of this stress related recrudescence is poorly understood. Therefore, the aim of the present study was to determine the role of the stress hormone cortisol in Salmonella recrudescence by pigs. We showed that a 24 h feed withdrawal increases the intestinal Salmonella Typhimurium load in pigs, which is correlated with increased serum cortisol levels. A second in vivo trial demonstrated that stress related recrudescence of Salmonella Typhimurium in pigs can be induced by intramuscular injection of dexamethasone. Furthermore, we found that cortisol, but not epinephrine, norepinephrine and dopamine, promotes intracellular proliferation of Salmonella Typhimurium in primary porcine alveolar macrophages, but not in intestinal epithelial cells and a transformed cell line of porcine alveolar macrophages. A microarray based transcriptomic analysis revealed that cortisol did not directly affect the growth or the gene expression or Salmonella Typhimurium in a rich medium, which implies that the enhanced intracellular proliferation of the bacterium is probably caused by an indirect effect through the cell. These results highlight the role of cortisol in the recrudescence of Salmonella Typhimurium by pigs and they provide new evidence for the role of microbial endocrinology in host-pathogen interactions. PMID:22151081

  8. Cross-Country Differences in Basal and Stress-Induced Cortisol Secretion in Older Adults

    PubMed Central

    Lupien, Sonia J.; Fiocco, Alexandra; Suchecki, Deborah

    2014-01-01

    Objective Several studies have emphasized the association between socioeconomic status (SES) and inadequate response of the biological stress system. However, other factors related to SES are rarely considered, such as cultural values, social norms, organization, language and communication skills, which raises the need to investigate cross-country differences in stress response. Although some studies have shown differences in cortisol levels between immigrants and natives, there is no cross-country evidence regarding cortisol levels in country-native elders. This is particularly important given the high prevalence of stress-related disorders across nations during aging. The current study examined basal diurnal and reactive cortisol levels in healthy older adults living in two different countries. Methods Salivary cortisol of 260 older adults from Canada and Brazil were nalyzed. Diurnal cortisol was measured in saliva samples collected at home throughout two working days at awakening, 30 min after waking, 1400 h, 1600 h and before bedtime. Cortisol reactivity was assessed in response to the Trier Social Stress Test (TSST) in both populations. Results Our results showed that even under similar health status, psychological and cognitive characteristics, Brazilian elders exhibited higher basal and stress-induced cortisol secretion compared to the Canadian participants. Conclusion These findings suggest that country context may modulate cortisol secretion and could impact the population health. PMID:25153322

  9. Low environmental humidity induces synthesis and release of cortisol in an epidermal organotypic culture system.

    PubMed

    Takei, Kentaro; Denda, Sumiko; Kumamoto, Junichi; Denda, Mitsuhiro

    2013-10-01

    Dry environmental conditions induce a variety of skin pathologies and a recent report indicating that cortisol synthesis in epidermis was increased during wound healing led us to hypothesize that environmental dryness might induce increased cortisol secretion in epidermis. Therefore, we incubated a skin equivalent model under dry (relative humidity: less than 10%) and humid (relative humidity: approximately 100%) conditions for 48 hours and evaluated cortisol secretion and mRNA levels of cortisol-synthesizing enzyme (steroid 11β-hydroxylase, CYP11B1) and IL-1β. Cortisol secretion was increased threefold, and CYP11B1 and IL-1β mRNAs were increased 38-fold and sixfold, respectively, in the dry condition versus the humid condition. Occlusion with a water-impermeable plastic membrane partially blocked the increases in cortisol secretion and CYP11B1 and IL-1β mRNA expression in the dry condition. Thus, environmental dryness might induce increased cortisol secretion in epidermis of diseased skin characterized by epidermal barrier dysfunction, potentially influencing mental state and systemic physiology.

  10. Differential Effects of Stress-induced Cortisol Responses on Recollection and Familiarity-based Recognition Memory

    PubMed Central

    McCullough, Andrew M.; Ritchey, Maureen; Ranganath, Charan; Yonelinas, Andrew

    2015-01-01

    Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol on the processes underlying recognition memory. Stress was induced with a cold-pressor test after incidental encoding of emotional and neutral pictures, and recollection and familiarity-based recognition memory were measured one day later. The relationship between stress-induced cortisol responses and recollection was non-monotonic, such that subjects with moderate stress-related increases in cortisol had the highest levels of recollection. In contrast, stress-related cortisol responses were linearly related to increases in familiarity. In addition, measures of cortisol taken at the onset of the experiment showed that individuals with higher levels of pre-learning cortisol had lower levels of both recollection and familiarity. The results are consistent with the proposition that hippocampal-dependent memory processes such as recollection function optimally under moderate levels of stress, whereas more cortically-based processes such as familiarity are enhanced even with higher levels of stress. These results indicate that whether post-encoding stress improves or disrupts recognition memory depends on the specific memory process examined as well as the magnitude of the stress-induced cortisol response. PMID:25930175

  11. Differential effects of stress-induced cortisol responses on recollection and familiarity-based recognition memory.

    PubMed

    McCullough, Andrew M; Ritchey, Maureen; Ranganath, Charan; Yonelinas, Andrew

    2015-09-01

    Stress-induced changes in cortisol can impact memory in various ways. However, the precise relationship between cortisol and recognition memory is still poorly understood. For instance, there is reason to believe that stress could differentially affect recollection-based memory, which depends on the hippocampus, and familiarity-based recognition, which can be supported by neocortical areas alone. Accordingly, in the current study we examined the effects of stress-related changes in cortisol on the processes underlying recognition memory. Stress was induced with a cold-pressor test after incidental encoding of emotional and neutral pictures, and recollection and familiarity-based recognition memory were measured one day later. The relationship between stress-induced cortisol responses and recollection was non-monotonic, such that subjects with moderate stress-related increases in cortisol had the highest levels of recollection. In contrast, stress-related cortisol responses were linearly related to increases in familiarity. In addition, measures of cortisol taken at the onset of the experiment showed that individuals with higher levels of pre-learning cortisol had lower levels of both recollection and familiarity. The results are consistent with the proposition that hippocampal-dependent memory processes such as recollection function optimally under moderate levels of stress, whereas more cortically-based processes such as familiarity are enhanced even with higher levels of stress. These results indicate that whether post-encoding stress improves or disrupts recognition memory depends on the specific memory process examined as well as the magnitude of the stress-induced cortisol response.

  12. Inhibition of MDMA-induced increase in cortisol does not prevent acute impairment of verbal memory

    PubMed Central

    Kuypers, KPC; Torre, R; Farre, M; Pujadas, M; Ramaekers, JG

    2013-01-01

    Background Ecstasy use is commonly linked with memory deficits in abstinent ecstasy users. Similar impairments are being found during ecstasy intoxication after single doses of ± 3,4 metylenedioxymethamphetamine (MDMA). The concordance of memory impairments during intoxication and abstinence suggests a similar neuropharmacological mechanism underlying acute and chronic memory impairments. The mechanism underlying this impairment is to date not known. We hypothesized that cortisol might play an important role in this mechanism as cortisol, implicated in the regulation of memory performance, can be brought out of balance by stressors like MDMA. Methods In the present study, we aimed to block the MDMA-induced acute memory defect by giving participants a cortisol synthesis inhibitor (metyrapone) together with a single dose of MDMA. Seventeen polydrug MDMA users entered this placebo-controlled within subject study with four treatment conditions. The treatments consisted of MDMA (75 mg) and metyrapone (750 mg), alone and in combination, and double placebo. Pre-treatment with metyrapone or Placebo occurred 1 h prior to MDMA or Placebo administration. Memory performance was tested at peak drug concentrations by means of several memory tests. Cortisol levels were determined in blood and oral fluid; this served as a control measure to see whether manipulations were effective. Results Main findings indicated that whereas treatment with metyrapone blocked the expected MDMA-induced increase in cortisol levels in blood, it did not prevent the MDMA-induced memory deficit from happening. Conclusion We therefore conclude that MDMA-induced increments in cortisol concentrations are not related to MDMA-induced memory impairments. PMID:22946487

  13. 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.

  14. 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

  15. 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.

  16. Cortisol mobilizes mineral stores from vertebral skeleton in the European eel: an ancestral origin for glucocorticoid-induced osteoporosis?

    PubMed

    Sbaihi, Miskal; Rousseau, Karine; Baloche, Sylvie; Meunier, François; Fouchereau-Peron, Martine; Dufour, Sylvie

    2009-05-01

    Endogenous excess cortisol and glucocorticoid (GC) therapy are a major cause of secondary osteoporosis in humans. Intense bone resorption can also be observed in other vertebrates such as migratory teleost fish at the time of reproductive migration and during fasting when large amounts of calcium and phosphate are required. Using a primitive teleost, the European eel, as a model, we investigated whether cortisol could play an ancestral role in the induction of vertebral skeleton demineralization. Different histological and histomorphometric methods were performed on vertebral samples of control and cortisol-treated eels. We demonstrated that cortisol induced a significant bone demineralization of eel vertebrae, as shown by significant decreases of the mineral ratio measured by incineration, and the degree of mineralization measured by quantitative microradiography of vertebral sections. Histology and image analysis of ultrathin microradiographs showed the induction by cortisol of different mechanisms of bone resorption, including periosteocytic osteolysis and osteoclastic resorption. Specificity of cortisol action was investigated by comparison with the effects of sex steroids. Whereas, testosterone had no effect, estradiol induced vertebral skeleton demineralization, an effect related to the stimulated synthesis of vitellogenin (Vg), an oviparous specific phospho-calcio-lipoprotein. By contrast, the cortisol demineralization effect was not related to any stimulation of Vg. This study demonstrates GC-induced bone demineralization in an adult non-mammalian vertebrate, which undergoes natural bone resorption during its life cycle. Our data suggest that the stimulatory action of cortisol on bone loss may represent an ancestral and conserved endocrine regulation in vertebrates.

  17. Pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium.

    PubMed

    Weng, Yi-Ming; Chang, Meng-Wei; Weng, Chia-Sui

    2008-11-01

    Pituitary apoplexy indicates pituitary adenoma hemorrhage, which could result in acute pituitary insufficiency and mortality. The typical symptoms are headache, visual disturbance, nausea, vomiting, altered mental status, and panhypopituitarism. However, cortisol-induced hyperglycemia and acute delirium could be an initial presentation of a pituitary adenoma hemorrhage with stormy release of the adrenocorticotrophic hormone. A 28-year-old woman presented with severe vomiting, irritable state, and delusion. She had medical history of irregular menstrual cycles and marked body weight gain after her second childbirth 8 years ago. She was diagnosed of diabetic ketoacidosis 2 days before this visiting at local medical department. On physical examination, Cushing appearance without definite neurological deficit was disclosed. Further blood tests revealed high blood sugar, cortisol, and adrenocorticotrophic hormone levels without evidence of diabetic ketoacidosis. The brain computed tomography and magnetic resonance imaging showed pituitary macroadenoma and pituitary hemorrhage. Cushing disease with pituitary apoplexy was then diagnosed. Conservative management with delayed neurosurgery was applied. The patient became clear with normalized cortisol and blood sugar levels soon after. Follow-up computed tomography scan of the brain revealed no progression of tumor bleeding or mass effect. To our knowledge, pituitary apoplexy associated with cortisol-induced hyperglycemia and acute delirium has never been reported before. This case reminds us of pituitary apoplexy and its rare manifestations.

  18. Stress, stress‐induced cortisol responses, and eyewitness identification performance

    PubMed Central

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

    2016-01-01

    Abstract 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

  19. 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.

  20. Changes in plasma adrenocorticotropic hormone and cortisol levels induced by intracerebroventricular injection of histamine and its related compounds in dogs.

    PubMed

    Tsujimoto, S; Kamei, C; Yoshida, T; Tasaka, K

    1993-08-01

    Changes in plasma adrenocorticotropic hormone (ACTH) and cortisol levels induced by intracerebroventricular injection of histamine (H(i)) were studied in dogs. Intracerebroventricular administration of Hi at doses of 5 and 10 micrograms/kg caused a significant increase in plasma ACTH, while more rapid and more marked increase in plasma cortisol was noticed after Hi injection at doses of 2-10 micrograms/kg. Similar results were obtained when 2-methylhistamine was injected; remarkable increases in both plasma ACTH and cortisol levels were observed at doses of 25 and 50 micrograms/kg. However, no such effect was elicited by 4-methylhistamine even at a dose of 50 micrograms/kg. The rate of plasma cortisol increase induced by either Hi or 2-methylhistamine was significantly faster than that of plasma ACTH. Simultaneous application of pyrilamine (intracerebroventricularly) with H(i) resulted in the significant inhibition of H(i)-induced hormone secretions, but in similar administration neither ACTH nor cortisol were affected by cimetidine. In hypophysectomized dogs, a significant increase in plasma cortisol level was also observed after H(i) injection at a dose of 5 micrograms/kg. Intravenous infusion of hexamethonium continued before and after H(i) injection failed to inhibit the increase in plasma ACTH and cortisol levels induced by H(i). From these findings, it can be concluded that intracerebroventricular injection of H(i) caused an increase in plasma ACTH and cortisol levels via H1-receptor, and it is suggested that to some extent, the cortisol release elicited by H(i) is certainly produced without participation of ACTH.

  1. Association of amphetamine-induced striatal dopamine release and cortisol responses to psychological stress.

    PubMed

    Wand, Gary S; Oswald, Lynn M; McCaul, Mary E; Wong, Dean F; Johnson, Elizabeth; Zhou, Yun; Kuwabara, Hiroto; Kumar, Anil

    2007-11-01

    Preclinical studies have shown that stress and glucocorticoids increase mesolimbic dopamine (DA) and thereby facilitate psychostimulant self-administration. The relationship between stress-induced cortisol and mesolimbic DA responses to psychostimulants has not been studied in humans. To test the hypotheses that glucocorticoid responses to psychological stress are correlated with DA and subjective responses to psychostimulants in humans, 25 healthy adults (18-29 years) completed the Trier Social Stress Test (TSST) and two positron emission tomography (PET) scans with high-specific [11C]raclopride. The first scan was preceded by intravenous saline and the second by amphetamine (AMPH). Findings showed that stress-induced cortisol levels were positively associated with AMPH-induced DA release in the ventral striatum and other striatal regions. Subjects with higher cortisol responses to stress also reported more positive subjective drug effects with AMPH than subjects with lower responses. The results are consistent with preclinical findings showing an interrelationship between glucocorticoids and mesolimbic DA dynamics, which may influence psychostimulant self-administration in humans.

  2. Stress eliminates retrieval-induced forgetting--does the oral application of cortisol?

    PubMed

    Koessler, Susanne; Steidle, Laura; Engler, Harald; Kissler, Johanna

    2013-01-01

    It is well established that stress and glucocorticoids can affect memory. Psychosocial stress has been reported to eliminate retrieval-induced forgetting (RIF), the phenomenon that repeated retrieval of a subset of previously learned material impairs later recall of related, but non-retrieved information. The stress-related reduction of RIF has been found correlated with an increase in salivary cortisol levels. Based on these findings, the current placebo-controlled study examined the effect of an oral dose of 25mg hydrocortisone on the RIF effect in 37 healthy men. Even though participants in the hydrocortisone group showed a marked increase in salivary cortisol, retrieval-induced forgetting was not affected by the pharmacological treatment. Thus, cortisol administration alone in contrast to stress experience does not impair the RIF effect. However, participants with high state anxiety during retrieval practice did not show RIF, whereas participants with low state anxiety did. This finding suggests a role for state anxiety in stress-related elimination of retrieval-induced forgetting, perhaps indicative of a memory-modulating sympathetic nervous system effect.

  3. Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

    PubMed

    Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

    2016-04-01

    Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress.

  4. 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.

  5. Effect of adrenergic receptor blockade on cortisol and GH response to insulin-induced hypoglycemia in man.

    PubMed

    Jezová-Repceková, D; Klimes, I; Jurcovicová, J; Vigas, M

    1979-02-01

    The effect of several drugs presumably influencing central catecholaminergic receptors on plasma cortisol and GH response to insulin-induced hypoglycemia was studied in healthy adult males. The intravenous infusion of alpha-adrenergic blocking agents tolazoline or phentolamine supressed plasma cortisol and GH response to insulin-induced hypoglycemia. After an infusion of beta-adrenergic antagonist propranolol both hypoglycemia and rise in plasma cortisol and GH were prolonged. Finally, the administration of dopaminergic blocker pimozide failed to affect the plasma cortisol response, but slightly suppressed the enhancement of GH release during hypoglycemia. Caution is recommended before making suggestions about neuroendocrine regulations from the data obtained after systemic administration of drugs. Nevertheless, it may be concluded that the hypothesis on the inhibitory role of the central alpha-adrenergic system on ACTH secretion suggested in rats and dogs was not confirmed by our results obtained in man.

  6. Body temperature, behavior, and plasma cortisol changes induced by chronic infusion of Staphylococcus aureus in goats.

    PubMed

    Mphahlele, Noko R; Fuller, Andrea; Roth, Joachim; Kamerman, Peter R

    2004-10-01

    Most experimentally induced fevers are acute, usually lasting approximately 6-12 h, and thus do not mimic chronic natural fevers, which can extend over several days or more. To produce a model of chronic natural fever, we infused eight goats (Capra hircus) intravenously with 2 ml of 2 x 10(11) cell walls of Staphylococcus aureus (S. aureus) for 6 days using osmotic infusion pumps (10 microl/h) while measuring changes in body temperature, behavior, and plasma cortisol concentration. Seven control animals were infused with sterile saline. Abdominal temperature-sensitive data loggers and osmotic infusion pumps were implanted under halothane anesthesia. To compare our new model with existing models of experimental fever, we also administered 2-ml bolus intravenous injections of 2 x 10(11) S. aureus cell walls, 0.1 microg/kg lipopolysaccharide (Escherichia coli, serotype 0111:B4), and sterile saline in random order to six other goats. Bolus injection of lipopolysaccharide and S. aureus induced typical acute phase responses, characterized by fevers lasting approximately 6 h, sickness behavior, and increased plasma cortisol concentration. Infusion of S. aureus evoked prolonged fevers, which lasted for approximately 3 days, starting on day 4 of infusion (ANOVA, P < 0.05), and did not disrupt the normal circadian rhythm of body temperature. However, pyrogen infusion did not cause plasma cortisol concentration to rise (ANOVA, P > 0.05) or the expression of sickness behavior. In conclusion, infusion of S. aureus produced a fever response resembling that of sustained natural fevers but did not elicit the cortisol and behavioral responses that often are described clinically and during short-term experimental fevers.

  7. 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.

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

    PubMed

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

    2009-05-01

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

  9. 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

  10. 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…

  11. Dyadic coping, insecure attachment, and cortisol stress recovery following experimentally induced stress.

    PubMed

    Meuwly, Nathalie; Bodenmann, Guy; Germann, Janine; Bradbury, Thomas N; Ditzen, Beate; Heinrichs, Markus

    2012-12-01

    Evidence for the stress-buffering effects of social support in intimate relationships raises important questions about whether partner support promotes recovery in physiological systems implicated in physical health. The present study examined (a) whether observed dyadic coping enhances cortisol stress recovery and (b) whether a stressed partner's self-reported attachment anxiety and avoidance moderate these effects. Stress was experimentally induced by asking either the man or woman in 123 heterosexual couples to participate in a standardized public speaking task. Stressed individuals recovered faster from stress the more positive dyadic coping they received from the partner, with women high in attachment anxiety benefiting less from these behaviors. Attachment avoidance did not moderate these associations. This study highlights the value of examining the interplay between partners' behaviors and attachment orientations in order to understand the impact of stress on close relationships and partners' health.

  12. Analogs of farnesylcysteine induce apoptosis in HL-60 cells.

    PubMed

    Pérez-Sala, D; Gilbert, B A; Rando, R R; Cañada, F J

    1998-04-24

    S-Farnesyl-thioacetic acid (FTA), a competitive inhibitor of isoprenylated protein methyltransferase, potently suppressed the growth of HL-60 cells and induced apoptosis, as evidenced by the development of increased annexin-V binding, decreased binding of DNA dyes and internucleosomal DNA degradation. FTA did not impair the membrane association of ras proteins, conversely, it brought about a decrease in the proportion of ras present in the cytosolic fraction. Farnesylated molecules which are weak inhibitors of the methyltransferase also induced DNA laddering and reduced the proportion of cytosolic ras. These findings suggest that neither inhibition of isoprenylated protein methylation nor impairment of ras membrane association are essential for apoptosis induced by farnesylcysteine analogs.

  13. 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.

  14. Classical analog of electromagnetically induced absorption in plasmonics.

    PubMed

    Taubert, Richard; Hentschel, Mario; Kästel, Jürgen; Giessen, Harald

    2012-03-14

    The ability to manipulate the phase shift between two resonantly coupled plasmonic oscillators in a controlled fashion has been unavailable up to now. Here we present a strategy to overcome this limitation by employing the benefits of near-field coupling on the one hand and retardation effects due to far-field coupling on the other hand. We theoretically and experimentally demonstrate that in the intermediate regime the coupling of a broad dipolar to a narrow dark quadrupolar plasmon resonance is possible while simultaneously allowing for a retardation-induced phase shift. This leads to constructive interference and enhanced absorption. The observed phenomenon can thus be termed a classical analog of electromagnetically induced absorption.

  15. 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.

  16. Cortisol Test

    MedlinePlus

    ... midnight. Cortisol is produced and secreted by the adrenal glands . Production of the hormone is regulated by the ... to produce ACTH (adrenocorticotropic hormone). ACTH stimulates the adrenal glands to produce and release cortisol. In order for ...

  17. Acyl Ghrelin Induces Insulin Resistance Independently of GH, Cortisol, and Free Fatty Acids

    PubMed Central

    Vestergaard, Esben T.; Jessen, Niels; Møller, Niels; Jørgensen, Jens Otto Lunde

    2017-01-01

    Ghrelin produced in the gut stimulates GH and ACTH secretion from the pituitary and also stimulates appetite and gastric emptying. We have shown that ghrelin also induces insulin resistance via GH-independent mechanisms, but it is unknown if this effect depends on ambient fatty acid (FFA) levels. We investigated the impact of ghrelin and pharmacological antilipolysis (acipimox) on insulin sensitivity and substrate metabolism in 8 adult hypopituitary patients on stable replacement with GH and hydrocortisone using a 2 × 2 factorial design: Ghrelin infusion, saline infusion, ghrelin plus short-term acipimox, and acipimox alone. Peripheral and hepatic insulin sensitivity was determined with a hyperinsulinemic euglycemic clamp in combination with a glucose tracer infusion. Insulin signaling was assayed in muscle biopsies. Peripheral insulin sensitivity was reduced by ghrelin independently of ambient FFA concentrations and was increased by acipimox independently of ghrelin. Hepatic insulin sensitivity was increased by acipimox. Insulin signaling pathways in skeletal muscle were not consistently regulated by ghrelin. Our data demonstrate that ghrelin induces peripheral insulin resistance independently of GH, cortisol, and FFA. The molecular mechanisms remain elusive, but we speculate that ghrelin is a hitherto unrecognized direct regulator of substrate metabolism. We also suggest that acipimox per se improves hepatic insulin sensitivity. PMID:28198428

  18. Role of estradiol in cortisol-induced reduction of luteinizing hormone pulse frequency.

    PubMed

    Oakley, Amy E; Breen, Kellie M; Tilbrook, Alan J; Wagenmaker, Elizabeth R; Karsch, Fred J

    2009-06-01

    Precise control of pulsatile GnRH and LH release is imperative to ovarian cyclicity but is vulnerable to environmental perturbations, like stress. In sheep, a sustained (29 h) increase in plasma cortisol to a level observed during stress profoundly reduces GnRH pulse frequency in ovariectomized ewes treated with ovarian steroids, whereas shorter infusion (6 h) is ineffective in the absence of ovarian hormones. This study first determined whether the ovarian steroid milieu or duration of exposure is the relevant factor in determining whether cortisol reduces LH pulse frequency. Prolonged (29 h) cortisol infusion did not lower LH pulse frequency in ovariectomized ewes deprived of ovarian hormones, but it did so in ovariectomized ewes treated with estradiol and progesterone to create an artificial estrous cycle, implicating ovarian steroids as the critical factor. Importantly, this effect of cortisol was more pronounced after the simulated preovulatory estradiol rise of the artificial follicular phase. The second experiment examined which component of the ovarian steroid milieu enables cortisol to reduce LH pulse frequency in the artificial follicular phase: prior exposure to progesterone in the luteal phase, low early follicular phase estradiol levels, or the preovulatory estradiol rise. Basal estradiol enabled cortisol to decrease LH pulse frequency, but the response was potentiated by the estradiol rise. These findings lead to the conclusion that ovarian steroids, particularly estradiol, enable cortisol to inhibit LH pulse frequency. Moreover, the results provide new insight into the means by which gonadal steroids, and possibly reproductive status, modulate neuroendocrine responses to stress.

  19. 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

  20. 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

    2015-07-28

    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.

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

    PubMed

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

    2003-10-03

    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.

  2. Haemodynamic characteristics of hypertension induced by prenatal cortisol exposure in sheep.

    PubMed

    Moritz, Karen M; Dodic, Miodrag; Jefferies, Andrew J; Wintour, E Marelyn; DeMatteo, Robert; Singh, Reetu R; Evans, Roger G

    2009-10-01

    1. Administration of glucocorticoids to ewes early in pregnancy results in offspring with hypertension in adulthood. The hypertension in female offspring exposed to dexamethasone is associated with increased cardiac output, but whether this is also true in cortisol-exposed offspring is unknown. 2. Systemic haemodynamic variables were measured under basal conditions in castrated male and female adult sheep exposed to cortisol (5 mg/h) or saline (0.19 mL/h) from 26 to 28 days of gestation. To examine the contribution of the autonomic nervous system to maintenance of basal arterial pressure in established hypertension in cortisol-exposed sheep, responses to adrenoceptor blockade (intravenous infusion of 0.15 mg/kg per h phentolamine plus 0.4 mg/kg per h propranolol) and ganglionic blockade (intravenous infusion of 125 mg/h hexamethonium) were examined in castrated male offspring. 3. Mean arterial pressure and calculated systemic vascular resistance were 9% and 17% greater, whereas cardiac output tended to be 8% less, in cortisol-compared with saline-exposed sheep. These effects were not sex dependent. The depressor response to ganglionic blockade and the initial phase of the depressor response to adrenoceptor blockade were greater in cortisol-compared with saline-exposed sheep. 4. These results indicate that hypertension in offspring exposed prenatally to cortisol is associated with increased total peripheral resistance, mimicking observations in human patients with chronic hypertension. Furthermore, the increased vascular resistance appears to be dependent, at least in part, on an increased effect of sympathetic vasomotor drive. Taken together with previous findings, the present observations suggest that prenatal cortisol and dexamethasone programme altered adult cardiovascular function via distinct mechanistic pathways.

  3. The role of salivary cortisol and DHEA-S in response to sexual, humorous, and anxiety-inducing stimuli

    PubMed Central

    Hamilton, Lisa Dawn; Meston, Cindy M.

    2011-01-01

    Stress and anxiety are commonly thought to be detrimental to sexual function. Several studies in both the human and animal literature, however, have found that inducing anxiety can enhance sexual function in women. The mechanisms that explain a negative relationship between physical and psychological stress and sexual functioning are well documented, but little is known about how stress or anxiety might have a facilitatory effect on sexual arousal. As an initial step in exploring the relationship between anxiety and sexual arousal, the present study examined the role of the autonomic nervous system, and the adrenal hormones cortisol and dehydroepiandrosterone-sulfate (DHEA-S) in response to a sexual film, an anxiety-inducing film, and a humorous film. Nineteen premenopausal women (mean age 24.4 years) who were free from sexual difficulties came into the lab on three separate days. At each session they were shown an anxiety-inducing, sexually arousing, or humorous (control) film while their physiological arousal was measured. They also provided saliva samples before and after each film. Cortisol significantly decreased, while DHEA-S increased in the sexual and humorous conditions. Neither hormone changed significantly in the anxiety-inducing condition. Autonomic nervous system activity measured by heart rate and heart rate variability did not change in response to the sexual or anxiety-inducing films, but heart rate variability increased significantly in response to the humorous film. The cortisol/DHEA-S ratio at the post-sexual film time point was significantly negatively correlated with genital arousal (measured by vaginal pulse amplitude). Anxiety-inducing films did not result in a physiological stress response, which can explain why they do not impair sexual function. PMID:21195074

  4. Ghrelin and GHRP-6-induced ACTH and cortisol release in thyrotoxicosis.

    PubMed

    Nascif, Sergio Oliva; Molica, Patrícia; Correa-Silva, Silvia Regina; Silva, Marcos Roberto; Lengyel, Ana-Maria Judith

    2009-01-01

    Thyrotoxicosis might alter the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated the effects of ghrelin and GHRP-6 on the HPA axis in 20 hyperthyroid patients and in 9 controls. Mean basal cortisol (microg/dl) and ACTH (pg/ml) levels were higher in hyperthyroidism (cortisol: 10.7 +/- 0.7; ACTH: 21.5 +/- 2.9) compared to controls (cortisol: 8.1 +/- 0.7; ACTH: 13.5 +/- 1.8). In thyrotoxicosis Delta AUC cortisol values (microg/dl.90 min) after ghrelin (484 +/- 80) and GHRP-6 (115 +/- 63) were similar to controls (ghrelin: 524 +/- 107; GHRP-6: 192 +/- 73). A significant increase in Delta AUC ACTH (pg/ml x 90 min) after ghrelin was observed in thyrotoxicosis (4,189 +/- 1,202) compared to controls (1,499 +/- 338). Delta AUC ACTH values after GHRP-6 were also higher, although not significantly (patients: 927 +/- 330; controls: 539 +/- 237). In summary, our results suggest that ghrelin-mediated pathways of ACTH release might be activated by thyroid hormone excess, but adrenocortical reserve is maintained.

  5. 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...

  6. 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

  7. Dairy Food Consumption and Meal-Induced Cortisol Response Interacted to Influence Weight Loss in Overweight Women Undergoing a 12-Week, Meal-Controlled, Weight Loss Intervention1234

    PubMed Central

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

    2013-01-01

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

  8. The corticotropin-releasing hormone test in normal short children: comparison of plasma adrenocorticotropin and cortisol responses to human corticotropin-releasing hormone and insulin-induced hypoglycemia.

    PubMed

    Goji, K

    1989-03-01

    The human corticotropin-releasing hormone (hCRH) tests were performed in twelve normal short children, and the responses of plasma ACTH and cortisol to iv administration of 1 micrograms/kg hCRH were compared with those to insulin-induced hypoglycemia. After administration of hCRH, the mean plasma ACTH level rose from a basal value of 3.3 +/- 0.4 pmol/l (mean +/- SEM) to a peak value of 9.2 +/- 0.8 pmol/l at 30 min, and the mean plasma cortisol level rose from a basal value of 231 +/- 25 nmol/l to a peak value of 546 +/- 30 nmol/l at 30 min. The ACTH response after insulin-induced hypoglycemia was greater than that after hCRH administration; the mean peak level (P less than 0.01), the percent maximum increment (P less than 0.01), and the area under the ACTH response curve (P less than 0.01) were all significantly greater after insulin-induced hypoglycemia than those after hCRH administration. Although the mean peak cortisol level after insulin-induced hypoglycemia was about 1.3-fold higher than that after hCRH administration (P less than 0.01), neither the percent maximum increment in plasma cortisol nor the area under the cortisol response curve after insulin-induced hypoglycemia was significantly different from that after hCRH administration. Consequently, the acute increases in plasma ACTH after the administration of 1 microgram/kg hCRH stimulated the adrenal gland to almost the same cortisol response as that obtained with a much greater increase in plasma ACTH after insulin-induced hypoglycemia. These results suggest that a plasma ACTH peak of 9-11 pmol/l produces near maximum acute stimulation of adrenal steroidogenesis.

  9. 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

  10. Cortisol - urine

    MedlinePlus

    ... the adrenal glands do not produce enough cortisol Hypopituitarism in which the pituitary gland does not signal ... Cushing syndrome Cushing syndrome due to adrenal tumor Hypopituitarism Review Date 10/28/2015 Updated by: Brent ...

  11. Cortisol level

    MedlinePlus

    ... the adrenal glands do not produce enough cortisol Hypopituitarism , in which the pituitary gland does not signal ... disease Cushing disease Cushing syndrome Ectopic Cushing syndrome Hypopituitarism Review Date 10/28/2015 Updated by: Brent ...

  12. Pathogen-induced chemokine secretion from model intestinal epithelium is inhibited by lipoxin A4 analogs.

    PubMed Central

    Gewirtz, A T; McCormick, B; Neish, A S; Petasis, N A; Gronert, K; Serhan, C N; Madara, J L

    1998-01-01

    Enteric pathogens induce intestinal epithelium to secrete chemokines that direct movement of polymorphonuclear leukocytes. Mechanisms that might downregulate secretion of these proinflammatory chemokines and thus contain intestinal inflammation have not yet been elucidated. The antiinflammatory activities exhibited by the arachidonate metabolite lipoxin A4 (LXA4) suggests that this eicosanoid, which is biosynthesized in vivo at sites of inflammation, might play such a role. We investigated whether chemokine secretion could be regulated by stable analogs of LXA4. Monolayers of T84 intestinal epithelial cells were infected with Salmonella typhimurium, which elicits secretion of distinct apical (pathogen-elicited epithelial chemoattractant) and basolateral (IL-8) chemokines. Stable analogs of LXA4 inhibited S. typhimurium-induced (but not phorbol ester-induced) secretion of both IL-8 and pathogen-elicited epithelial chemoattractant. LXA4 stable analogs did not alter bacterial adherence to nor internalization by epithelia, indicating that LXA4 stable analogs did not block all signals that Salmonella typhimurium activates in intestinal epithelia, but likely led to attenuation of signals that mediate chemokine secretion. Inhibition of S. typhimurium-induced IL-8 secretion by LXA4 analogs was concentration- (IC50 approximately 1 nM) and time-dependent (maximal inhibition approximately 1 h). As a result of these effects, LXA4 stable analogs inhibited the ability of bacteria-infected epithelia to direct polymorphonuclear leukocyte movement. These data suggest that LXA4 and its stable analogs may be useful in downregulating active inflammation at mucosal surfaces. PMID:9576749

  13. Vitamin C Prevents Sleep Deprivation-induced Elevation in Cortisol and Lipid Peroxidation in the Rat Plasma.

    PubMed

    Olayaki, L A; Sulaiman, S O; Anoba, N B

    2015-12-20

    Sleep deprivation (SD) is biological stressor that alters metabolic parameters, induced oxidative stress and lipid peroxidation. Previous studies have shown that antioxidants substances such as melatonin, tryptophan, vitamin E and vitamin C improved stress tolerance in laboratory animals. In this study, we examined the potential protective effects of administration of vitamin C on acute and chronic sleep deprivation-induced metabolic derangement. In addition, possible processes involved in vitamin C effects on acute and chronic sleep deprivation-induced metabolic derangement were determined. Thirty-five rats (120-250g) were used. The rats were divided into 7 groups of 5 rats each as Control (CTRL), Acute sleep deprived untreated with vitamin C (AC), Acute sleep deprived treated with vitamin C (AWC), Chronic sleep deprived untreated with vitamin C (CC), Chronic sleep deprived treated with vitamin C (CWC), Chronic sleep deprived + Recovery untreated with vitamin C (RC), and Chronic sleep deprived + Recovery treated with vitamin C (RWC). The SD was carried out for 20h for 1 day on the acute groups, and for 20h/day for 5 days on the chronic group, using the Multiple Modified Platforms (MMP) after oral administration of 300mg/kg of vitamin C to all vitamin C-treated groups. The recovery groups were further observed for five days after SD. The control group were treated with vitamin C and without stress in their home cages. At the end of the experiment, the animals were sacrificed and blood was collected for estimation of plasma glucose, insulin, cortisol and malondialdehyde (MDA). The results showed that acute and chronic SDs significantly  increased MDA and cortisol levels, while significantly reduced the levels of insulin. Treatment with vitamin C reversed the changes in the MDA, cortisol and plasma insulin levels. Additionally, allowing the rats to recover for 5 days after sleep deprivation corrected the observed changes. Plasma glucose was significantly

  14. 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.

  15. Acute and chronic stress-like levels of cortisol inhibit the oestradiol stimulus to induce sexual receptivity but have no effect on sexual attractivity or proceptivity in female sheep.

    PubMed

    Papargiris, M M; Rivalland, E T A; Hemsworth, P H; Morrissey, A D; Tilbrook, A J

    2011-09-01

    Stress-like levels of cortisol inhibit sexual receptivity in ewes but the mechanism of this action is not understood. One possibility is that cortisol interferes with the actions of oestradiol to induce sexual receptivity. We tested this hypothesis in 2 experiments with ovariectomised ewes that were artificially induced into oestrus by 12 days of i.m. injections of progesterone followed by an i.m. injection of oestradiol benzoate (ODB) 48 h later. In Experiment 1, ewes were randomly allocated to the following groups: saline infusion+25 μg ODB, saline infusion+50 μg ODB, cortisol infusion+25 μg ODB or cortisol infusion+50 μg ODB (n=5 per group). Saline or cortisol was infused i.v. for 40 h beginning at the ODB injection. In Experiment 2, ewes were infused with saline or cortisol (n=5 per group) for 5h beginning 1h before ODB injection. In both experiments, ewe sexual behaviour (attractivity, proceptivity and receptivity) was quantified every 6h. Blood samples were also collected. The cortisol infusion yielded plasma concentrations of cortisol similar to those seen during psychosocial stress. In both experiments, cortisol suppressed receptivity index (number of immobilisations by ewe/courtship displays by ram) and the number of times ewes were mounted but had no effect on attractivity or proceptivity, irrespective of the dose of ODB (Experiment 1). Cortisol also suppressed LH pulse amplitude. These results suggest that both an acute (5h) and chronic (40 h) infusion of cortisol inhibit oestradiol-induced sexual receptivity in ewes and that increasing the dose of ODB does not overcome the inhibitory effects of cortisol.

  16. True or false? Memory is differentially affected by stress-induced cortisol elevations and sympathetic activity at consolidation and retrieval.

    PubMed

    Smeets, Tom; Otgaar, Henry; Candel, Ingrid; Wolf, Oliver T

    2008-11-01

    Adrenal stress hormones released in response to acute stress may yield memory-enhancing effects when released post-learning and impairing effects at memory retrieval, especially for emotional memory material. However, so far these differential effects of stress hormones on the various memory phases for neutral and emotional memory material have not been demonstrated within one experiment. This study investigated whether, in line with their effects on true memory, stress and stress-induced adrenal stress hormones affect the encoding, consolidation, and retrieval of emotional and neutral false memories. Participants (N=90) were exposed to a stressor before encoding, during consolidation, before retrieval, or were not stressed and then were subjected to neutral and emotional versions of the Deese-Roediger-McDermott word list learning paradigm. Twenty-four hours later, recall of presented words (true recall) and non-presented critical lure words (false recall) was assessed. Results show that stress exposure resulted in superior true memory performance in the consolidation stress group and reduced true memory performance in the retrieval stress group compared to the other groups, predominantly for emotional words. These memory-enhancing and memory-impairing effects were strongly related to stress-induced cortisol and sympathetic activity measured via salivary alpha-amylase levels. Neutral and emotional false recall, on the other hand, was neither affected by stress exposure, nor related to cortisol and sympathetic activity following stress. These results demonstrate the importance of stress-induced hormone-related activity in enhancing memory consolidation and in impairing memory retrieval, in particular for emotional memory material.

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

    SciTech Connect

    Wood, C.E.; Silbiger, J.

    1987-03-01

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

  18. 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

    2015-07-10

    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.

  19. 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

  20. Cortisol-induced changes in oxygen consumption and ionic regulation in coastal cutthroat trout (Oncorhynchus clarki clarki) parr.

    PubMed

    Morgan, J D; Iwama, G K

    1996-11-01

    The influence of cortisol on oxygen consumption and osmoregulatory variables was examined in coastal cutthroat trout (Oncorhynchus clarki clarki) parr kept in fresh water (FW) and transferred to seawater (SW). Intraperitoneal implants containing cortisol (50 μg g(-1)) in vegetable oil resulted in elevated plasma cortisol titres similar to those observed in fish following a 24h SW exposure. Cortisol treatment significantly increased the oxygen consumption and plasma glucose levels of trout in FW, consistent with the glucocorticoid role of cortisol. Cortisol treatment did not cause any changes in plasma ion concentrations or gill Na(+),K(+)-ATPase activity in FW after 10 days. Cortisol-implanted fish exposed to SW for 24h showed slightly improved ion regulatory ability compare to non-implanted controls. The results of this study suggest that during SW transfer in juvenile salmonids, increases in cortisol may act as both a mineralocorticoid and a glucocorticoid, depending on the developmental state of the fish (e.g., smolt versus parr). Furthermore, the relative energetic costs of osmoregulation and that of the stress associated SW transfer cannot be discerned using whole-animal oxygen consumption rates.

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

    PubMed Central

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

    2015-01-01

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

  2. 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

  3. 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.

  4. Serum cortisol concentrations during induced hypothermia for perinatal asphyxia are associated with neurological outcome in human infants.

    PubMed

    Scaramuzzo, Rosa T; Giampietri, Matteo; Fiorentini, Erika; Bartalena, Laura; Fiori, Simona; Guzzetta, Andrea; Ciampi, Mariella; Boldrini, Antonio; Ghirri, Paolo

    2015-01-01

    Birth asphyxia is a cause of neonatal death or adverse neurological sequelae. Biomarkers can be useful to clinicians in order to optimize intensive care management and communication of prognosis to parents. During perinatal adverse events, increased cortisol secretion is due to hypothalamo-pituitary-adrenal axis activation. We aimed to investigate if cortisol variations during therapeutic hypothermia are associated with neurodevelopmental outcome. We compared 18 cases (neonates with birth asphyxia) with 18 controls (healthy term newborns) and confirmed increased serum cortisol concentrations following the peri-partum adverse event. Among cases, we stratified patients according to neurological outcome at 18 months (group A - good; group B - adverse) and found that after 24 h of therapeutic hypothermia serum cortisol concentration was significantly lower in group A vs group B (28.7 ng/mL vs 344 ng/mL, *p = 0.01). In group B serum, cortisol concentration decreased more gradually during therapeutic hypothermia. We conclude that monitoring serum cortisol concentration during neonatal therapeutic hypothermia can add information to clinical evaluation of neonates with birth asphyxia; cortisol values after the first 24 h of hypothermia can be a biomarker associated with neurodevelopmental outcome at 18 months of age.

  5. Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

    PubMed

    Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

    2016-12-01

    Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress.

  6. Prerequisites for ubiquinone analogs to prevent mitochondrial permeability transition-induced cell death.

    PubMed

    Belliere, Julie; Devun, Flavien; Cottet-Rousselle, Cécile; Batandier, Cécile; Leverve, Xavier; Fontaine, Eric

    2012-02-01

    The permeability transition pore (PTP) is a mitochondrial inner membrane channel involved in cell death. The inhibition of PTP opening has been proved to be an effective strategy to prevent cell death induced by oxidative stress. Several ubiquinone analogs are known to powerfully inhibit PTP opening with an effect depending on the studied cell line. Here, we have studied the effects of ubiquinone 0 (Ub(0)), ubiquinone 5 (Ub(5)) and ubiquinone 10 (Ub(10)) on PTP regulation, H(2)O(2) production and cell viability in U937 cells. We found that Ub(0) induced both PTP opening and H(2)O(2) production. Ub(5) did not regulate PTP opening yet induced H(2)O(2) production. Ub(10) potently inhibited PTP opening yet induced H(2)O(2) production. Both Ub(0) and Ub(5) induced cell death, whereas Ub(10) was not toxic. Moreover, Ub(10) prevented tert-butyl hydroperoxide-induced PTP opening and subsequent cell death. We conclude that PTP-inhibitor ubiquinone analogs are able to prevent PTP opening-induced cell death only if they are not toxic per se, which is the case when they have no or low pro-oxidant activity.

  7. Sequential multiphoton absorption enhancement induced by zinc complexation in functionalized distyrylbenzene analogs.

    PubMed

    Fabbrini, Graziano; Riccò, Raffaele; Menna, Enzo; Maggini, Michele; Amendola, Vincenzo; Garbin, Mattia; Villano, Massimo; Meneghetti, Moreno

    2007-02-07

    Functionalized distyrylbenzene analogs and , bearing a tris-(2-pyridylmethyl)amine-based receptor for Zn(2+), were synthesized by a Horner-Emmons-Wittig coupling reaction. It has been found that Zn(2+) complexation induces changes in the linear absorption spectrum that enhance a nonlinear sequential two-photon absorption of nanosecond pulses at 532 nm. This absorption was also found to depend on the nature of the substituent at the side benzene ring of the styrylbenzene structure.

  8. 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

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

    PubMed

    Tryon, M S; DeCant, Rashel; Laugero, K D

    2013-04-10

    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 visceral fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of chronic stress on eating behavior in humans is less understood, but it may be linked to HPA responsivity. The purpose of this study was to investigate the influence of chronic social stress and acute stress reactivity on food choice and food intake. Forty-one women (BMI=25.9±5.1 kg/m(2), age range=41 to 52 years) were subjected to the Trier Social Stress Test or a control task (nature movie) to examine HPA responses to an acute laboratory stressor and then invited to eat from a buffet containing low- and high-calorie snacks. Women were also categorized as high chronic stress or low chronic stress based on Wheaton Chronic Stress Inventory scores. Women reporting higher chronic stress and exhibiting low cortisol reactivity to the acute stress task consumed significantly more calories from chocolate cake on both stress and control visits. Chronic stress in the low cortisol reactor group was also positively related to total fat mass, body fat percentage, and stress-induced negative mood. Further, women reporting high chronic stress consumed significantly less vegetables, but only in those aged 45 years and older. Chronic stress in women within the higher age category was positively related to total calories consumed at the buffet, stress-induced negative mood and food craving. Our results suggest an increased risk for stress eating in persons with a specific chronic stress signature and imply that a habit of comfort food may link chronic social stress and acute stress-induced cortisol hyporesponsiveness.

  10. 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.

  11. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  13. Music therapy-induced changes in salivary cortisol level are predictive of cardiovascular mortality in patients under maintenance hemodialysis

    PubMed Central

    Hou, Yi-Chou; Lin, Yen-Ju; Lu, Kuo-Cheng; Chiang, Han-Sun; Chang, Chia-Chi; Yang, Li-King

    2017-01-01

    Background Music therapy has been applied in hemodialysis (HD) patients for relieving mental stress. Whether the stress-relieving effect by music therapy is predictive of clinical outcome in HD patients is still unclear. Methods We recruited a convenience sample of 99 patients on maintenance HD and randomly assigned them to the experimental (n=49) or control (n=50) group. The experimental group received relaxing music therapy for 1 week, whereas the control group received no music therapy. In the experimental group, we compared cardiovascular mortality in the patients with and without cortisol changes. Results The salivary cortisol level was lowered after 1 week of music therapy in the experimental group (−2.41±3.08 vs 1.66±2.11 pg/mL, P<0.05), as well as the frequency of the adverse reaction score (−3.35±5.76 vs −0.81±4.59, P<0.05), the severity of adverse reactions score (−1.93±2.73 vs 0.33±2.71, P<0.05), and hemodialysis stressor scale (HSS) score (−6.00±4.68 vs −0.877±7.08, P<0.05). The difference in salivary cortisol correlated positively with HD stress score scales (r=0.231, P<0.05), systolic blood pressure (r=0.264, P<0.05), and respiratory rates (r=0.369, P<0.05) and negatively with finger temperature (r=−0.235, P<0.05) in the total study population. The 5-year cardiovascular survival in the experimental group was higher in patients whose salivary cortisol lowered by <0.6 pg/mL than that in patients whose salivary cortisol lowered by >0.6 pg/mL (83.8% vs 63.6%, P<0.05). Conclusion Providing music during HD is an effective complementary therapy to relieve the frequency and severity of adverse reactions, as well as to lower salivary cortisol levels. Differences in salivary cortisol after music therapy may predict cardiovascular mortality in patients under maintenance HD. PMID:28260913

  14. Protective effect of central thyrotropin-releasing hormone analog on cerulein-induced acute pancreatitis in rats.

    PubMed

    Yoneda, Masashi; Goto, Manabu; Nakamura, Kimihide; Shimada, Tadahito; Hiraishi, Hideyuki; Terano, Akira; Haneda, Masakazu

    2005-02-15

    Central neuropeptides play a role in many physiological functions through the autonomic nervous system. We have recently demonstrated that central injection of a thyrotropin-releasing hormone (TRH) analog increases pancreatic blood flow through vagal and nitric oxide-dependent pathways. In this study, the central effect of a TRH analog on experimental acute pancreatitis was investigated in rats. Acute pancreatitis was induced by two intraperitoneal injections of cerulein (40 microg/kg) at 1-h interval. Either stable TRH analog, RX 77368 (5-100 ng), or saline was injected intracisternally 15 min before the first cerulein injection under ether anesthesia. Serum amylase level was measured before and 5 h after the first cerulein injection. Pancreatic wet/dry weight ratio and histological changes were also evaluated. Intracisternal TRH analog inhibited cerulean-induced elevation of serum amylase level, increase in pancreatic wet/dry weight ratio and pancreatic histological changes, such as interstitial edema, inflammation and vacuolization. The pancreatic cytoprotection induced by central TRH analog was abolished by subdiaphragmatic vagotomy and N(G)-nitro-L-arginine-methyl ester (L-NAME), but not by 6-hydroxydopamine (6-OHDA). Intravenous administration of the TRH analog did not influence cerulein-induced acute pancreatitis. These results indicate that the TRH analog acts in the central nervous system to protect against acute pancreatitis through vagal and nitric oxide-dependent pathways.

  15. A Phosphorylatable Sphingosine Analog Induces Airway Smooth Muscle Cytostasis and Reverses Airway Hyperresponsiveness in Experimental Asthma

    PubMed Central

    Gendron, David R.; Lecours, Pascale B.; Lemay, Anne-Marie; Beaulieu, Marie-Josée; Huppé, Carole-Ann; Lee-Gosselin, Audrey; Flamand, Nicolas; Don, Anthony S.; Bissonnette, Élyse; Blanchet, Marie-Renée; Laplante, Mathieu; Bourgoin, Sylvain G.; Bossé, Ynuk; Marsolais, David

    2017-01-01

    In asthma, excessive bronchial narrowing associated with thickening of the airway smooth muscle (ASM) causes respiratory distress. Numerous pharmacological agents prevent experimental airway hyperresponsiveness (AHR) when delivered prophylactically. However, most fail to resolve this feature after disease is instated. Although sphingosine analogs are primarily perceived as immune modulators with the ability to prevent experimental asthma, they also influence processes associated with tissue atrophy, supporting the hypothesis that they could interfere with mechanisms sustaining pre-established AHR. We thus assessed the ability of a sphingosine analog (AAL-R) to reverse AHR in a chronic model of asthma. We dissected the pharmacological mechanism of this class of agents using the non-phosphorylatable chiral isomer AAL-S and the pre-phosphorylated form of AAL-R (AFD-R) in vivo and in human ASM cells. We found that a therapeutic course of AAL-R reversed experimental AHR in the methacholine challenge test, which was not replicated by dexamethasone or the non-phosphorylatable isomer AAL-S. AAL-R efficiently interfered with ASM cell proliferation in vitro, supporting the concept that immunomodulation is not necessary to interfere with cellular mechanisms sustaining AHR. Moreover, the sphingosine-1-phosphate lyase inhibitor SM4 and the sphingosine-1-phosphate receptor antagonist VPC23019 failed to inhibit proliferation, indicating that intracellular accumulation of sphingosine-1-phosphate or interference with cell surface S1P1/S1P3 activation, are not sufficient to induce cytostasis. Potent AAL-R-induced cytostasis specifically related to its ability to induce intracellular AFD-R accumulation. Thus, a sphingosine analog that possesses the ability to be phosphorylated in situ interferes with cellular mechanisms that beget AHR. PMID:28270767

  16. 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.

  17. PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells.

    PubMed

    Haider, Dominik G; Bucek, Robert A; Giurgea, Aura G; Maurer, Gerald; Glogar, Helmut; Minar, Erich; Wolzt, Michael; Mehrabi, Mohammad R; Baghestanian, Mehrdad

    2005-11-01

    Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1-alpha (HIF-1alpha) are important regulators of endothelial function, which plays a role in the pathophysiology of heart failure (HF). PGE1 analog treatment in patients with HF elicits beneficial hemodynamic effects, but the precise mechanisms have not been investigated. We have investigated the effects of the PGE1 analog alprostadil on eNOS, VEGF, and HIF-1alpha expression in human umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under normoxic and hypoxic conditions. In addition, we studied protein expression by immunohistochemical staining in explanted hearts from patients with end-stage HF, treated or untreated with systemic alprostadil. Alprostadil causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1alpha. Hypoxia potently increased eNOS, VEGF, and HIF-1alpha synthesis. The alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was increased, and HIF-1alpha was reduced in failing hearts treated with alprostadil. The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process.

  18. Relaxation - Induced by Vibroacoustic Stimulation via a Body Monochord and via Relaxation Music - Is Associated with a Decrease in Tonic Electrodermal Activity and an Increase of the Salivary Cortisol Level in Patients with Psychosomatic Disorders.

    PubMed

    Sandler, Hubertus; Fendel, Uta; Buße, Petra; Rose, Matthias; Bösel, Rainer; Klapp, Burghard F

    2017-01-01

    Vibroacoustic stimulation by a Body Monochord can induce relaxation states of various emotional valence. The skin conductance level (SCL) of the tonic electrodermal activity is an indicator of sympathetic arousal of the autonomic nervous system and thus an indicator of the relaxation response. Salivary cortisol is considered to be a stress indicator of the HPA-axis. The effects of the treatment with a Body Monochord and listening to relaxation music (randomized chronological presentation) on SCL and salivary cortisol in relation to the emotional valence of the experience were examined in patients with psychosomatic disorders (N = 42). Salivary cortisol samples were collected immediately before and after the expositions. Subjective experience was measured via self-rating scales. Overall, both the exposure to the Body Monochord as well as the exposure to the relaxation music induced an improvement of patients' mood and caused a highly significant reduction of SCL. A more emotionally positive experience of relaxation correlated with a slightly stronger reduction of the SCL. Both treatment conditions caused a slight increase in salivary cortisol, which was significant after exposure to the first treatment. The increase of salivary cortisol during a relaxation state is contrary to previous findings. It is possible that the relaxation state was experienced as an emotional challenge, due to inner images and uncommon sensations that might have occurred.

  19. Relaxation – Induced by Vibroacoustic Stimulation via a Body Monochord and via Relaxation Music – Is Associated with a Decrease in Tonic Electrodermal Activity and an Increase of the Salivary Cortisol Level in Patients with Psychosomatic Disorders

    PubMed Central

    Sandler, Hubertus; Fendel, Uta; Buße, Petra; Rose, Matthias; Bösel, Rainer; Klapp, Burghard F.

    2017-01-01

    Vibroacoustic stimulation by a Body Monochord can induce relaxation states of various emotional valence. The skin conductance level (SCL) of the tonic electrodermal activity is an indicator of sympathetic arousal of the autonomic nervous system and thus an indicator of the relaxation response. Salivary cortisol is considered to be a stress indicator of the HPA-axis. The effects of the treatment with a Body Monochord and listening to relaxation music (randomized chronological presentation) on SCL and salivary cortisol in relation to the emotional valence of the experience were examined in patients with psychosomatic disorders (N = 42). Salivary cortisol samples were collected immediately before and after the expositions. Subjective experience was measured via self-rating scales. Overall, both the exposure to the Body Monochord as well as the exposure to the relaxation music induced an improvement of patients’ mood and caused a highly significant reduction of SCL. A more emotionally positive experience of relaxation correlated with a slightly stronger reduction of the SCL. Both treatment conditions caused a slight increase in salivary cortisol, which was significant after exposure to the first treatment. The increase of salivary cortisol during a relaxation state is contrary to previous findings. It is possible that the relaxation state was experienced as an emotional challenge, due to inner images and uncommon sensations that might have occurred. PMID:28114399

  20. 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

  1. 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.

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

    PubMed

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

    2013-07-16

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

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

    SciTech Connect

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

    2013-02-01

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

  4. 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

  5. beta-Endorphin-induced analgesia is inhibited by synthetic analogs of beta-endorphin.

    PubMed Central

    Nicolas, P; Hammonds, R G; Li, C H

    1984-01-01

    Competitive antagonism of human beta-endorphin (beta h-EP)-induced analgesia by synthetic beta h-EP analogs with high in vitro opiate receptor binding to in vivo analgesic potency ratio has been demonstrated. A parallel shift of the dose-response curve for analgesia to the right was observed when either beta h-EP or [ Trp27 ] -beta h-EP was coinjected with various doses of [Gln8, Gly31 ]-beta h-EP-Gly-Gly-NH2, [Arg9,19,24,28,29]-beta h-EP, or [ Cys11 ,26, Phe27 , Gly31 ]-beta h-EP. It was estimated that the most potent antagonist, [Gln8, Gly31 ]-beta h-EP-Gly-NH2, is at least 200 times more potent than naloxone. PMID:6328494

  6. 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.

  7. 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.

  8. Ketamine Analog Methoxetamine Induced Inflammation and Dysfunction of Bladder in Rats

    PubMed Central

    Wang, Qiang; Wu, Qinghui; Wang, Junpeng; Chen, Yang; Zhang, Guihao; Chen, Jiawei; Zhao, Jie; Wu, Peng

    2017-01-01

    The novel synthetic psychoactive ketamine analog methoxetamine is reportedly being used for recreational purposes. As ketamine use can result in urinary dysfunction, we conducted the present study to investigate how methoxetamine affects the bladder. A cystometry investigation showed that female Sprague-Dawley rats experienced increased micturition frequency bladder dysfunction after receiving a daily intraperitoneal injection of 30 mg/kg methoxetamine or ketamine for periods of 4 or 12 weeks. Histologic examinations of rat bladder tissue revealed damaged urothelium barriers, as well as evidence of inflammatory cell infiltration and matrix deposition. The drug-treated rats showed significantly upregulated levels of pro-inflammatory cytokines such as IL-1β, IL-6, CCL-2, CXCL-1, CXCL-10, NGF, and COX-2. In addition, interstitial fibrosis was confirmed by increased levels of collagen I, collagen III, fibronectin and TGF-β. Besides direct toxic effect on human urothelial cells, methoxetaminealso induced the upregulation related cytokines. Our results indicate that long term methoxetamine treatment can induce bladder dysfunction and inflammation in rats. Methoxetamine was confirmed to produce direct toxic and pro-inflammatory effects on human urothelial cells. Methoxetamine-associated bladder impairment may be similar to ketamine-induced cystitis. PMID:28106785

  9. 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

  10. Cortisol and finfish welfare.

    PubMed

    Ellis, Tim; Yildiz, Hijran Yavuzcan; López-Olmeda, Jose; Spedicato, Maria Teresa; Tort, Lluis; Øverli, Øyvind; Martins, Catarina I M

    2012-02-01

    Previous reviews of stress, and the stress hormone cortisol, in fish have focussed on physiology, due to interest in impacts on aquaculture production. Here, we discuss cortisol in relation to fish welfare. Cortisol is a readily measured component of the primary (neuroendocrine) stress response and is relevant to fish welfare as it affects physiological and brain functions and modifies behaviour. However, we argue that cortisol has little value if welfare is viewed purely from a functional (or behavioural) perspective-the cortisol response itself is a natural, adaptive response and is not predictive of coping as downstream impacts on function and behaviour are dose-, time- and context-dependent and not predictable. Nevertheless, we argue that welfare should be considered in terms of mental health and feelings, and that stress in relation to welfare should be viewed as psychological, rather than physiological. We contend that cortisol can be used (with caution) as a tractable indicator of how fish perceive (and feel about) their environment, psychological stress and feelings in fish. Cortisol responses are directly triggered by the brain and fish studies do indicate cortisol responses to psychological stressors, i.e., those with no direct physicochemical action. We discuss the practicalities of using cortisol to ask the fish themselves how they feel about husbandry practices and the culture environment. Single time point measurements of cortisol are of little value in assessing the stress level of fish as studies need to account for diurnal and seasonal variations, and environmental and genetic factors. Areas in need of greater clarity for the use of cortisol as an indicator of fish feelings are the separation of (physiological) stress from (psychological) distress, the separation of chronic stress from acclimation, and the interactions between feelings, cortisol, mood and behaviour.

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

    PubMed

    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.

  12. Effect of sub chronic tryptophan supplementation on stress-induced cortisol and appetite in subjects differing in 5-HTTLPR genotype and trait neuroticism.

    PubMed

    Capello, Aimée E M; Markus, C Rob

    2014-07-01

    Stress or negative effect often increases preference for, and intake of, palatable snack foods and this may be influenced by cognitive and genetic factors related to stress and 5-HT vulnerability. The short (S) compared to the long (L) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) has been associated (i) with decreased 5-HT transporter function and availability and hence, with 5-HT vulnerability, and (ii) with greater stress-responsiveness. Stress-proneness is furthermore promoted by cognitive stress-vulnerability, a key feature of trait neuroticism. Brain 5-HT function can be manipulated by dietary administration of its amino acid precursor tryptophan (Trp), and the beneficial effects of dietary Trp on stress experience and emotional eating may be greatest following repeated administration in both stress- and 5-HT-vulnerable subjects. The aim was to examine the influence of repeated Trp administration on stress responsiveness and emotional eating in homozygous 5-HTTLPR S-allele (N=60) and L-allele (N=58) carriers with high and low neuroticism. Following seven days of Trp or PLC intake, mood, cortisol and appetite were assessed before and after exposure to acute stress and snack intake and preference were measured post-stress. It was hypothesized that Trp would reduce stress experience and emotional eating particularly in S-allele carriers with high neuroticism. Results revealed Trp treatment caused a clear reduction in stress-induced cortisol levels in S/S-allele carriers exclusively, and prevented a stress-induced increase in appetite only in S/S-allele carriers with high trait neuroticism. The findings reveal an advantageous effect of sub chronic Trp treatment on stress experience and appetite depending on stress and (genetic) serotonergic vulnerability.

  13. Sex and stress: Men and women show different cortisol responses to psychological stress induced by the Trier social stress test and the Iowa singing social stress test.

    PubMed

    Reschke-Hernández, Alaine E; Okerstrom, Katrina L; Bowles Edwards, Angela; Tranel, Daniel

    2017-01-02

    Acute psychological stress affects each of us in our daily lives and is increasingly a topic of discussion for its role in mental illness, aging, cognition, and overall health. A better understanding of how such stress affects the body and mind could contribute to the development of more effective clinical interventions and prevention practices. Over the past 3 decades, the Trier Social Stress Test (TSST) has been widely used to induce acute stress in a laboratory setting based on the principles of social evaluative threat, namely, a judged speech-making task. A comparable alternative task may expand options for examining acute stress in a controlled laboratory setting. This study uses a within-subjects design to examine healthy adult participants' (n = 20 men, n = 20 women) subjective stress and salivary cortisol responses to the standard TSST (involving public speaking and math) and the newly created Iowa Singing Social Stress Test (I-SSST). The I-SSST is similar to the TSST but with a new twist: public singing. Results indicated that men and women reported similarly high levels of subjective stress in response to both tasks. However, men and women demonstrated different cortisol responses; men showed a robust response to both tasks, and women displayed a lesser response. These findings are in line with previous literature and further underscore the importance of examining possible sex differences throughout various phases of research, including design, analysis, and interpretation of results. Furthermore, this nascent examination of the I-SSST suggests a possible alternative for inducing stress in the laboratory. © 2016 Wiley Periodicals, Inc.

  14. Geldanamycin and its analog induce cytotoxicity in cultured human retinal pigment epithelial cells.

    PubMed

    Wu, Wen-Chuan; Wu, Meng-Hsien; Chang, Yo-Chen; Hsieh, Ming-Chu; Wu, Horng-Jiun; Cheng, Kai-Chun; Lai, Yu-Hung; Kao, Ying-Hsien

    2010-08-01

    Geldanamycin (GA), a benzoquinone ansamycin, was originally isolated as a natural product with anti-fungal activity. GA and its analogs, including 17-allylamino-demethoxy geldanamycin (17-AAG), are also known to block the function of a molecular chaperone, heat shock protein 90 (Hsp90). In light of their anti-tumor properties through direct cytotoxicity and anti-angiogenicity, GA has been previously demonstrated to suppress hypoxia-induced VEGF production in retinal pigment epithelium (RPE) cells, implicating its applicability in treating intraocular neovascularization. This study aimed at investigating the effectiveness of Hsp90 inhibitor treatment in suppressing proliferation of cultured human RPE cells and elucidating its underlying mechanism. Cultured RPE cells were treated with GA or 17-AAG and subjected for cell proliferation assay and cell cycle analysis. Expression of apoptotic regulators and survival signaling activity were monitored by Western blotting. The results showed that both GA and 17-AAG significantly inhibited RPE cell proliferation at micromolar levels. Treatment with GA and 17-AAG led to growth arrests in G1 and S phases, increased sub-G1 hypodipoid cell population, induced apoptotic cell death, and upregulated P53 and P21 expression, although the drug-induced Bcl-2 upregulation cannot prevent cell death. Additionally, GA and 17-AAG significantly suppressed constitutive contents of phosphorylated ERK1/2 and total Akt proteins, and completely abrogated wortmannin-sensitized Akt phosphorylation. In conclusion, GA and 17-AAG inhibit RPE cell proliferation and induce cytotoxicity, possibly through downregulating Akt- and ERK1/2-mediated signaling activities. They might potentially constitute a therapeutic agent for ocular disorders with RPE over proliferation, such as proliferative vitreoretinopathy.

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

    SciTech Connect

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

    1988-01-01

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

  16. 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

  17. Effect of curcumin analog on gamma-radiation-induced cellular changes in primary culture of isolated rat hepatocytes in vitro.

    PubMed

    Srinivasan, M; Sudheer, A Ram; Rajasekaran, K N; Menon, Venugopal P

    2008-10-22

    The present study was aimed to evaluate the radioprotective effect of curcumin analog, on gamma-radiation-induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The DNA damage was analysed by single cell gel electrophoresis (comet assay). An increase in the severity of DNA damage was observed with the increase in gamma-radiation dose at 1-4 Gy in cultured rat hepatocytes. The levels of lipid peroxidative indices like thiobarbituric acid reactive substances (TBARSs) were increased significantly, whereas the levels of reduced glutathione (GSH) and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4Gy gamma-irradiation. Pretreatment with different concentrations of curcumin analog (1.38, 6.91 and 13.82 microM) shows a significant decrease in the levels of TBARS and DNA damage. Pretreatment with curcumin analog prevents the loss of enzymic and non-enzymic antioxidants like GSH upon gamma-irradiation. The maximum protection of hepatocytes was observed at 6.91 microM of curcumin analog pretreatment. Thus, our result shows that pretreatment with curcumin analog protects the hepatocytes against gamma-radiation-induced cellular damage.

  18. Antitumor alkyl-lysophospholipid analog edelfosine induces apoptosis in pancreatic cancer by targeting endoplasmic reticulum.

    PubMed

    Gajate, C; Matos-da-Silva, M; Dakir, el-H; Fonteriz, R I; Alvarez, J; Mollinedo, F

    2012-05-24

    Pancreatic cancer remains as one of the most deadly cancers, and responds poorly to current therapies. The prognosis is extremely poor, with a 5-year survival of less than 5%. Therefore, search for new effective therapeutic drugs is of pivotal need and urgency to improve treatment of this incurable malignancy. Synthetic alkyl-lysophospholipid analogs (ALPs) constitute a heterogeneous group of unnatural lipids that promote apoptosis in a wide variety of tumor cells. In this study, we found that the anticancer drug edelfosine was the most potent ALP in killing human pancreatic cancer cells, targeting endoplasmic reticulum (ER). Edelfosine was taken up in significant amounts by pancreatic cancer cells and induced caspase- and mitochondrial-mediated apoptosis. Pancreatic cancer cells show a prominent ER and edelfosine accumulated in this subcellular structure, inducing a potent ER stress response, with caspase-4, BAP31 and c-Jun NH(2)-terminal kinase (JNK) activation, CHOP/GADD153 upregulation and phosphorylation of eukaryotic translation initiation factor 2 α-subunit that eventually led to cell death. Oral administration of edelfosine in xenograft mouse models of pancreatic cancer induced a significant regression in tumor growth and an increase in apoptotic index, as assessed by TUNEL assay and caspase-3 activation in the tumor sections. The ER stress-associated marker CHOP/GADD153 was visualized in the pancreatic tumor isolated from edelfosine-treated mice, indicating a strong in vivo ER stress response. These results suggest that edelfosine exerts its pro-apoptotic action in pancreatic cancer cells, both in vitro and in vivo, through its accumulation in the ER, which leads to ER stress and apoptosis. Thus, we propose that the ER could be a key target in pancreatic cancer, and edelfosine may constitute a prototype for the development of a new class of antitumor drugs targeting the ER.

  19. Loss of the pregnancy-induced rise in cortisol concentrations in the ewe impairs the fetal insulin-like growth factor axis

    PubMed Central

    Jensen, Ellen C.; Bennet, Laura; Wood, Charles; Vickers, Mark; Breier, Bernhard; Gunn, Alistair J.; Keller-Wood, Maureen

    2013-01-01

    Maternal cortisol levels increase during pregnancy. Although this change is important for optimal fetal growth, the mechanisms of the changes in growth remain unclear. We examined whether alterations in maternal plasma cortisol concentrations are associated with changes in the fetal insulin-like growth factor (IGF) axis. Pregnant ewes in late gestation (115 ± 0.4 days) were studied: six control animals, five ewes given 1 mg/kg/day cortisol (high cortisol), and five adrenalectomized ewes given 0.5-0.6 mg cortisol/kg/day (low cortisol). Blood samples were taken throughout the experiment and at necropsy (130 ± 0.2 days) and fetal liver was frozen for mRNA analysis. Fetal IGF-I and insulin plasma concentrations were lower and IGFBP-1 concentrations were higher in the low cortisol group compared with those in controls (p<0.05). Fetal liver IGF-II and IGFBP-3 (insulin-like growth factor binding protein 3) mRNA were decreased in low cortisol animals compared with those in controls (p<0.05). There were no significant changes in these parameters in the high cortisol group, and there were no changes in fetal liver IGF-I, growth hormone receptor, IGF-I receptor, IGF-II receptor, IGFBP-1 or IGFBP-2 mRNA levels between the groups. These data suggest that reduced fetal IGF availability contributes to reduced fetal growth when maternal cortisol secretion is impaired, but not during exposure to moderate increases in cortisol. PMID:21635815

  20. 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.

  1. High temperature induces cyp26b1 mRNA expression and delays meiotic initiation of germ cells by increasing cortisol levels during gonadal sex differentiation in Japanese flounder.

    PubMed

    Yamaguchi, Toshiya; Kitano, Takeshi

    2012-03-09

    The Japanese flounder (Paralichthys olivaceus) is a teleost fish with an XX/XY sex determination system. XX flounder can be induced to develop into phenotypic females or males, by rearing them at 18°C 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 cortisol, the major glucocorticoid produced by the interrenal cells in teleosts, causes female-to-male sex reversal by directly suppressing mRNA expression of ovary-type aromatase (cyp19a1), a steroidogenic enzyme responsible for the conversion of androgens to estrogens in the gonads. Furthermore, an inhibitor of cortisol synthesis prevented masculinization of XX flounder at 27°C, suggesting that masculinization by high temperature is due to the suppression of cyp19a1 mRNA expression by elevated cortisol levels during gonadal sex differentiation in the flounder. In the present study, we found that exposure to high temperature during gonadal sex differentiation upregulates the mRNA expression of retinoid-degrading enzyme (cyp26b1) concomitantly with masculinization of XX gonads and delays meiotic initiation of germ cells. We also found that cortisol induces cyp26b1 mRNA expression and suppresses specific meiotic marker synaptonemal complex protein 3 (sycp3) mRNA expression in gonads during the sexual differentiation. In conclusion, these results suggest that exposure to high temperature induces cyp26b1 mRNA expression and delays meiotic initiation of germ cells by elevating cortisol levels during gonadal sex differentiation in Japanese flounder.

  2. 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...

  3. 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.

  4. 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

  5. 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.

  6. A Metabolically-Stabilized Phosphonate Analog of Lysophosphatidic Acid Attenuates Collagen-Induced Arthritis

    PubMed Central

    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. PMID:23923032

  7. o-Amino Analogs of Green Fluorescence Protein Chromophore: Photoisomerization, Photodimerization and Aggregation-induced Emission.

    PubMed

    Huang, Guan-Jhih; Lin, Che-Jen; Liu, Yi-Hung; Peng, Shie-Ming; Yang, Jye-Shane

    2015-01-01

    The photochemical properties of three o-amino analogs of the green fluorescence protein chromophore O0, O1 and O8 (o-ABDIs) have been investigated and compared with those of the m- and p-amino isomers (m-ABDIs and p-ABDIs) in solutions, aggregates, and the solid state. In aprotic solvents, the fluorescence competes with the Z → E photoisomerization for all cases, and the o-ABDIs display a fluorescence quantum efficiency of 1-6%, lying between the m-ABDIs of 5-48% and the p-ABDIs of < 0.1%. The fluorescence of both the o- and m-ABDIs is nearly quenched in protic solvents, attributable to the solvent-solute hydrogen bonding (SSHB) interactions. The phenomenon of aggregation-induced emission observed for O8 in poor solvents resembles the behavior of M8 as a consequence of exclusion of the SSHB interactions and restriction of internal rotation for molecules located inside the aggregates. The occurrence of [2 + 2] photodimerization for O0 in the solid state is unique among the ABDIs, and the X-ray crystal structures of O0 and the photodimer OD reveal the head-to-tail syn-oriented stereochemistry. Analysis on the X-ray crystal structures of O0, O1, M0, M1 and P0 shows that not only the pairwise topochemical geometry but also the columnar packing mode is important in determining the photodimerization reactivity.

  8. 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).

  9. 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.

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

    PubMed

    Sandhu, Navdeep; Vijayan, Mathilakath M

    2011-05-01

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

  11. MPTP and MPTP analogs induced cell death in cultured rat hepatocytes involving the formation of pyridinium metabolites.

    PubMed

    Singh, Y; Swanson, E; Sokoloski, E; Kutty, R K; Krishna, G

    1988-11-01

    MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) which has been shown to produce a Parkinson-like syndrome in humans and monkeys also causes cell death in cultures of rat hepatocytes. Treatment of cells with MPTP or its metabolite MPP+ (1-methyl-4-phenyl pyridinium ion), resulted in leakage of lactic acid dehydrogenase and 14C-labeled adenine nucleotides, as well as marked depletion of ATP and glutathione. Deprenyl, a specific inhibitor of monoamine oxidase-B, the enzyme catalyzing the oxidation of MPTP into MPP+, blocked the lethal effect of MPTP, but gave no protection from MPP+-induced cell death. The 4'-fluoro and 4'-chloro analogs of MPTP evoked toxicities similar to that of the parent compound, while N-butyl-PTP, 4'-amino-MPTP, and 2'-methyl-MPTP were relatively less toxic. N-Acetylamino-MPTP was found virtually nontoxic. The cell death produced by these analogs was also associated with leakage of [14C]adenine nucleotides, which is an indicator of loss of ATP from cells. All these compounds except the N-acetylamino analog were converted to corresponding pyridinium metabolites by liver cells when analyzed by high-pressure liquid chromatography and plasma desorption mass spectrometry. MPTP and its analogs also served as substrates for rat liver mitochondrial monoamine oxidase to varying degrees. Toxicity of various analogs, with the noticeable exception of 2'-methyl-MPTP, was inhibited by deprenyl. These findings indicate that the conversion of MPTP and its analogs to corresponding pyridinium metabolites is essential for the expression of toxicity.

  12. Endocrine basis for disruptive effects of cortisol on preovulatory events.

    PubMed

    Breen, Kellie M; Billings, Heather J; Wagenmaker, Elizabeth R; Wessinger, Emily W; Karsch, Fred J

    2005-04-01

    Stress activates the hypothalamo-pituitary-adrenal axis leading to enhanced glucocorticoid secretion and concurrently inhibits gonadotropin secretion and disrupts ovarian cyclicity. Here we tested the hypothesis that stress-like concentrations of cortisol interfere with follicular phase endocrine events of the ewe by suppressing pulsatile LH secretion, which is essential for subsequent steps in the preovulatory sequence. Cortisol was infused during the early to midfollicular phase, elevating plasma cortisol concentrations to one third, one half, or the maximal value induced by isolation, a commonly used model of psychosocial stress. All cortisol treatments compromised at least some aspect of reproductive hormone secretion in follicular phase ewes. First, cortisol significantly suppressed LH pulse frequency by as much as 35%, thus attenuating the high frequency LH pulses typical of the preovulatory period. Second, cortisol interfered with timely generation of the follicular phase estradiol rise, either preventing it or delaying the estradiol peak by as much as 20 h. Third, cortisol delayed or blocked the preovulatory LH and FSH surges. Collectively, our findings support the hypothesis that stress-like increments in plasma cortisol interfere with the follicular phase by suppressing the development of high frequency LH pulses, which compromises timely expression of the preovulatory estradiol rise and LH and FSH surges. Moreover, the suppression of LH pulse frequency provides indirect evidence that cortisol acts centrally to suppress pulsatile GnRH secretion in follicular-phase ewes.

  13. 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

  14. 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.

  15. 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.

  16. Modulation of pain sensation by stress-related testosterone and cortisol.

    PubMed

    Choi, J C; Chung, M I; Lee, Y D

    2012-10-01

    Stress increases cortisol and decreases testosterone. It is not known whether pain is affected by stress-related testosterone. Therefore, we investigated whether stress can affect pain perception by decreasing testosterone and increasing cortisol. Pain thresholds, pain and anxiety ratings and salivary testosterone and cortisol levels were measured in 46 healthy men during resting and stressful conditions. Pain was induced by electrical stimulation. Stress was induced by having participants perform a medical test. Stress significantly increased anxiety ratings and salivary cortisol levels, but decreased salivary testosterone levels. Stress also increased pain ratings and decreased pain thresholds. During stress, cortisol levels were negatively correlated with pain thresholds and testosterone levels were positively correlated with pain thresholds. Results indicated that testosterone can decrease and cortisol can increase pain induced by electrical stimulation, suggesting that acute clinical pain may be relieved by controlling stress and managing consequent stress-related testosterone and cortisol.

  17. 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

  18. Inverse relation between cortisol and anger and their relation to performance and explicit memory.

    PubMed

    Kazén, Miguel; Kuenne, Thomas; Frankenberg, Heiko; Quirin, Markus

    2012-09-01

    Cortisol has been found to increase in response to social evaluative threat. However, little is known about the cortisol response to induced anger. Thus, in the present study, we investigated the cortisol response to anger induction and its effects on performance and explicit memory. A variant of the Montreal Stress Imaging Task (MIST; Dedovic et al., 2005) was used to induce anger in 17 male and 17 female students. Consistent with previous observations, a significant decrease in cortisol was found from pre to post manipulation which was inversely related to increases in subjective anger. Moreover, whereas anger increase was related to impairments in performance, cortisol reduction was inversely related to cognitive performance and explicit memory (recall and recognition of persons' features in a social memory task). The adaptive value of an increase in cortisol in response to fear or uncontrollability and of a decrease in cortisol in response to anger will be discussed.

  19. Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development.

    PubMed

    Schmidt, Kim L; Soma, Kiran K

    2008-07-01

    Glucocorticoids (GCs) have profound effects on the immune and nervous systems during development. However, circulating GC levels are low neonatally and show little response to stressors. This paradox could be resolved if immune and neural tissues locally synthesize GCs. Here, we measured baseline corticosterone and cortisol levels in plasma, immune organs, and brain regions of developing zebra finches. Steroids were extracted using solid phase-extraction and quantified using specific immunoassays. As expected, corticosterone was the predominant GC in plasma and increased with age. In contrast, cortisol was the predominant GC in immune tissues (bursa of Fabricius, thymus, spleen) and decreased with age. Cortisol levels in immune tissues were higher than cortisol levels in plasma. In the brain, corticosterone and cortisol levels were similarly low, providing little evidence for local synthesis of GCs in the brain. This is the first study to measure 1) cortisol in the plasma of songbirds, 2) corticosterone or cortisol in the brain of songbirds, and 3) corticosterone or cortisol in the immune system of any species. Despite the prevailing dogma that corticosterone is the primary GC in birds, these results indicate that cortisol is the predominant GC in the immune system of developing zebra finches. These results raise the hypothesis that cortisol is synthesized de novo from cholesterol in the immune system as an "immunosteroid," analogous to neurosteroids synthesized in the brain. Local production of GCs in immune tissues may allow GCs to regulate lymphocyte selection while avoiding the costs of high systemic GCs during development.

  20. 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

  1. EB 1089, a novel vitamin D analog with strong antiproliferative and differentiation-inducing effects on target cells.

    PubMed

    Hansen, C M; Mäenpää, P H

    1997-12-01

    The physiologically active form of vitamin D, 1alpha,25-dihydroxyvitamin D3, plays an important role not only in the establishment and maintenance of calcium metabolism, but also in regulating cell growth and differentiation. As the clinical usefulness of 1alpha,25-dihydroxyvitamin D3 is limited by its tendency to cause hypercalcemia, new analogs with a better therapeutic profile have been synthesized. One of these new synthetic vitamin D analogs is EB 1089, which is characterized by an altered side chain structure featuring 26,27-dimethyl groups and two double bonds. This analog has been shown to be more potent than 1,25-dihydroxyvitamin D3 in inhibiting proliferation, stimulating differentiation, and inducing apoptosis in a number of different cell types, including cancer cells. Despite being more potent than 1alpha,25-dihydroxyvitamin D3 with respect to its cell regulatory effects, EB 1089 displays weaker calcemic side-effects. These characteristics make EB 1089 a potentially useful compound for the treatment of a diversity of clinical disorders, including cancer and metabolic bone diseases. A promising phase I study with EB 1089 in patients with advanced breast and colon cancer has already been carried out, and more clinical trials evaluating the clinical effectiveness of EB 1089 in other types of cancer are in progress.

  2. 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.

  3. Reduced Cortisol Output during Public Speaking Stress in Ostracized Women

    PubMed Central

    Weik, Ulrike; Ruhweza, Jennifer; Deinzer, Renate

    2017-01-01

    Ostracism (being excluded or ignored) is experienced as unpleasant and distressing. In previous studies, an immediate pre-stress experience of ostracism induced by Cyberball, a virtual ball-tossing game, was found to inhibit cortisol reactivity to public speaking stress in female students. The present study examines whether the effect will persist when a 15-min time gap between the Cyberball experience and subsequent psychological stress is introduced. N = 84 women were randomly assigned to Cyberball ostracism vs. inclusion. 15 min after playing Cyberball, all women were subjected to public speaking stress. Salivary cortisol and mood were repeatedly assessed during the course of the experiment. These are the main findings of the study: Repeated measures ANCOVA revealed that public speaking stress resulted in a significant increase of cortisol in both groups (inclusion vs. ostracism). However, cortisol levels were significantly lower in the ostracism group. In earlier studies when Cyberball was played immediately before public speaking stress, the cortisol response to public speaking was completely suppressed in ostracized women. By introducing a waiting period between Cyberball and public speaking stress in the present study, the main effect of an ostracism induced reduction of cortisol remained, although both groups showed an increase of cortisol as a response to public speaking. These results again suggest that the experience of ostracism might inhibit hypothalamic-pituitary-adrenal (HPA) axis activity, thereby confirming previous results. The formerly observed total suppression of HPA axis responsiveness to public speaking, however, seems to be a rather short-term effect. PMID:28228738

  4. Reduced Cortisol Output during Public Speaking Stress in Ostracized Women.

    PubMed

    Weik, Ulrike; Ruhweza, Jennifer; Deinzer, Renate

    2017-01-01

    Ostracism (being excluded or ignored) is experienced as unpleasant and distressing. In previous studies, an immediate pre-stress experience of ostracism induced by Cyberball, a virtual ball-tossing game, was found to inhibit cortisol reactivity to public speaking stress in female students. The present study examines whether the effect will persist when a 15-min time gap between the Cyberball experience and subsequent psychological stress is introduced. N = 84 women were randomly assigned to Cyberball ostracism vs. inclusion. 15 min after playing Cyberball, all women were subjected to public speaking stress. Salivary cortisol and mood were repeatedly assessed during the course of the experiment. These are the main findings of the study: Repeated measures ANCOVA revealed that public speaking stress resulted in a significant increase of cortisol in both groups (inclusion vs. ostracism). However, cortisol levels were significantly lower in the ostracism group. In earlier studies when Cyberball was played immediately before public speaking stress, the cortisol response to public speaking was completely suppressed in ostracized women. By introducing a waiting period between Cyberball and public speaking stress in the present study, the main effect of an ostracism induced reduction of cortisol remained, although both groups showed an increase of cortisol as a response to public speaking. These results again suggest that the experience of ostracism might inhibit hypothalamic-pituitary-adrenal (HPA) axis activity, thereby confirming previous results. The formerly observed total suppression of HPA axis responsiveness to public speaking, however, seems to be a rather short-term effect.

  5. 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.

  6. Dissection of LPS-induced signaling pathways in murine macrophages using LPS analogs, LPS mimetics, and agents unrelated to LPS.

    PubMed

    Vogel, S N; Manthey, C L; Perera, P Y; Li, Z Y; Henricson, B E

    1995-01-01

    The model in Figure 3 summarizes the data presented above. Using the induction of the select panel of LPS-inducible genes and the phosphorylation on tyrosine of specific MAP kinases, we have been able to dissociate three signaling pathways shared by LPS and its analogs and mimetics: a pathway that leads to tyrosine phosphorylation, one that leads to the induction of a gene subset including TNF alpha, TNFR-2, and IL-1 beta, and a pathway that results in induction of IP-10, D3, and D8 gene expression. It is still unclear if macrophage activation by non-LPS products occurs entirely through distinct yet redundant pathways or if other signaling receptors ultimately tie into the same intermediate pathways. This approach may identify particular stimuli as tools to induce specific pathways leading to select gene subsets and/or tyrosine kinase activation and, perhaps, identify a pathway deficient in C3H/HeJ macrophages.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Oral Administration of Lactobacillus plantarum 299v Reduces Cortisol Levels in Human Saliva during Examination Induced Stress: A Randomized, Double-Blind Controlled Trial

    PubMed Central

    Andersson, Hannah; Tullberg, Cecilia; Ahrné, Siv; Hamberg, Kristina; Lazou Ahrén, Irini; Molin, Göran; Sonesson, Mikael

    2016-01-01

    Objective. To clarify the effect of Lactobacillus plantarum 299v on the salivary cortisol and salivary IgA levels in young adults under examination stress. Design. Forty-one students with an upcoming academic exam were included in a randomized double-blind, placebo-controlled study. The probiotic bacteria or the placebo product was administered in capsules once a day during 14 days. Saliva was collected and a perceived stress test was filled out at each sampling occasion. Saliva was collected for cortisol analysis by Electrochemiluminescence Immunoassay (ECLI) and salivary IgA was analysed by Enzyme-Linked Immunosorbent Assay (ELISA). Abundance of lactobacilli was evaluated by cultivation of saliva on selective medium and identification of L. plantarum 299v was done on randomly selected colonies by a random amplification of polymorphic DNA (RAPD) typing. Results. A significant difference in cortisol levels was found between the treatment group and the placebo group (P < 0.05), together with a significant increase in levels of lactobacilli in the treatment group compared with the placebo group (P < 0.001). No significant changes were found for salivary IgA. Conclusion. A probiotic bacterium with ability to reduce symptoms of irritable bowel syndrome (IBS) prohibited increased levels of the stress marker cortisol during the examination period. The registration number of the study is NCT02974894, and the study is registered at ClinicalTrials.gov. PMID:28101105

  9. 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

  10. Prenatal cortisol exposure predicts infant cortisol response to acute stress.

    PubMed

    O'Connor, Thomas G; Bergman, Kristin; Sarkar, Pampa; Glover, Vivette

    2013-03-01

    Experimental animal findings suggest that early stress and glucocorticoid exposure may program the function of the hypothalamic-pituitary-adrenal (HPA) axis in the offspring. The extension of these findings to human development is not yet clear. A prospective longitudinal study was conducted on 125 mothers and their normally developing children. Amniotic fluid was obtained at, on average, 17.2 weeks gestation; infant behavior and cortisol response to a separation-reunion stress was assessed at 17 months. Amniotic fluid cortisol predicted infant cortisol response to separation-reunion stress: infants who were exposed to higher levels of cortisol in utero showed higher pre-stress cortisol values and blunted response to stress exposure. The association was independent of prenatal, obstetric, and socioeconomic factors and child-parent attachment. The findings provide some of the strongest data in humans that HPA axis functioning in the child may be predicted from prenatal cortisol exposure.

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

    PubMed

    Steyn-Ross, M L; Steyn-Ross, D A; Sleigh, J W; Wilcocks, L 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.

  12. 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.

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

    PubMed

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

    2012-05-15

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

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

    PubMed Central

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

    2015-01-01

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

  15. 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.

  16. 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

  17. Hypoestrogenism does not mediate social suppression of cortisol in subordinate female marmosets.

    PubMed

    Saltzman, Wendy; Hogan, Brynn K; Allen, Amy J; Horman, Brian M; Abbott, David H

    2006-07-01

    Behaviorally subordinate female marmosets undergo social suppression of ovulation and hypoestrogenism, as well as chronic reductions in circulating basal cortisol concentrations. Because estrogen elevates hypothalamic-pituitary-adrenal axis activity and circulating glucocorticoid levels in other species, we tested the hypothesis that socially induced hypoestrogenism contributes to cortisol reductions in subordinate female marmosets. We characterized morning basal plasma cortisol levels, as well as cortisol responses to exogenous adrenocorticotropic hormone (ACTH; 0, 1, or 10 microg/kg), in seven anovulatory subordinate females and six ovariectomized, non-subordinate females under two conditions: during long-term treatment with estradiol (E2) and control. Circulating E2 and cortisol levels were compared to those of six dominant females undergoing ovulatory cycles. Basal cortisol concentrations in the control condition were significantly lower in subordinates than in both dominant and ovariectomized females. E2 treatment elevated circulating E2 levels of subordinate and ovariectomized females into the range seen in dominant females but did not increase either mean basal or ACTH-stimulated cortisol levels. To the contrary, E2 treatment caused a decline in basal cortisol levels over time, especially in ovariectomized animals. These results indicate that treatment with exogenous estrogen does not elevate circulating cortisol levels in previously hypoestrogenemic female marmosets and, correspondingly that socially induced hypoestrogenism does not diminish cortisol levels in subordinate females.

  18. Zidovudine induces downregulation of mitochondrial deoxynucleoside kinases: implications for mitochondrial toxicity of antiviral nucleoside analogs.

    PubMed

    Sun, Ren; Eriksson, Staffan; Wang, Liya

    2014-11-01

    Mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) catalyze the initial phosphorylation of deoxynucleosides in the synthesis of the DNA precursors required for mitochondrial DNA (mtDNA) replication and are essential for mitochondrial function. Antiviral nucleosides are known to cause toxic mitochondrial side effects. Here, we examined the effects of 3'-azido-2',3'-dideoxythymidine (AZT) (zidovudine) on mitochondrial TK2 and dGK levels and found that AZT treatment led to downregulation of mitochondrial TK2 and dGK in U2OS cells, whereas cytosolic deoxycytidine kinase (dCK) and thymidine kinase 1 (TK1) levels were not affected. The AZT effects on mitochondrial TK2 and dGK were similar to those of oxidants (e.g., hydrogen peroxide); therefore, we examined the oxidative effects of AZT. We found a modest increase in cellular reactive oxygen species (ROS) levels in the AZT-treated cells. The addition of uridine to AZT-treated cells reduced ROS levels and protein oxidation and prevented the degradation of mitochondrial TK2 and dGK. In organello studies indicated that the degradation of mitochondrial TK2 and dGK is a mitochondrial event. These results suggest that downregulation of mitochondrial TK2 and dGK may lead to decreased mitochondrial DNA precursor pools and eventually mtDNA depletion, which has significant implications for the regulation of mitochondrial nucleotide biosynthesis and for antiviral therapy using nucleoside analogs.

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

    PubMed

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

    2016-05-01

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

  20. 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.

  1. Effect of a novel neurotensin analog, NT69L, on nicotine-induced alterations in monoamine levels in rat brain.

    PubMed

    Liang, Yanqi; Boules, Mona; Shaw, Amanda M; Williams, Katrina; Fredrickson, Paul; Richelson, Elliott

    2008-09-22

    NT69L, is a novel neurotensin (8-13) analog that participates in the modulation of the dopaminergic pathways implicated in addiction to psychostimulants. NT69L blocks nicotine-induced hyperactivity as well as the initiation and expression of sensitization in rats. Recent evidence suggests that stimulation of mesocorticolimbic dopamine system, with influences from the other monoamine systems, e.g. norepinephrine and serotonin, is involved in nicotine's reinforcing properties. The aim of the present study was to investigate the effect of pretreatment with NT69L on nicotine-induced changes in monoamine levels in the rat brain using in vivo microdialysis. Acute or chronic (0.4 mg/kg, sc, once daily for 2 weeks) administration of nicotine elicited increases in extracellular levels of dopamine, dopamine metabolites, norepinephrine, or serotonin in medial prefrontal cortex, nucleus accumbens shell, and core of rats. Pretreatment with NT69L (1 mg/kg, intraperitoneally, ip) administered 40 min before nicotine injection significantly attenuated the acute nicotine-evoked increases in norepinephrine levels in medial prefrontal cortex, dopamine and serotonin in nucleus accumbens shell. After chronic nicotine administration, pretreatment of NT69L markedly reversed the increase in dopamine levels in the nucleus accumbens core. NT69L's attenuation of some of the biochemical effects of acute and chronic nicotine is consistent with this peptide's attenuation of nicotine-induced behavioral effects. These data further support a role for NT69L or other neurotensin receptor agonists to treat nicotine addiction.

  2. 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.

  3. 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.

  4. Hair cortisol concentrations and cortisol stress reactivity in generalized anxiety disorder, major depression and their comorbidity.

    PubMed

    Steudte-Schmiedgen, Susann; Wichmann, Susann; Stalder, Tobias; Hilbert, Kevin; Muehlhan, Markus; Lueken, Ulrike; Beesdo-Baum, Katja

    2017-01-01

    Studies investigating cortisol secretion in patients with generalized anxiety disorder (GAD) have reported heterogeneous findings. Further, current knowledge on the specificity of endocrine changes for GAD and/or comorbid major depression (MD) is limited. Hence, the current study investigated long-term integrated cortisol secretion, as indexed by hair cortisol concentrations (HCC), and experimentally-induced cortisol stress reactivity in relation to GAD, MD and their comorbidity. Carefully characterized groups of 17 GAD patients including 8 with comorbid MD (GAD-MD), 12 MD patients and 21 healthy controls were recruited. Alongside psychometric data, HCC (N = 43) and salivary cortisol stress reactivity in response to the Trier Social Stress Test (N = 45) were determined. Findings revealed that MD patients exhibited lower HCC compared to controls and GAD patients, with no differences between the latter two groups. Interestingly, when the GAD group was separated into two groups based on MD comorbidity, lower HCC in MD patients were found compared to controls and GAD-noMD patients, but did not show differences when compared to GAD-MD patients. No HCC differences were seen between GAD-MD or GAD-noMD patients and healthy controls. No TSST group differences emerged. Our findings suggest MD to be related to long-term attenuation in cortisol secretion. While no group differences emerged between patients with GAD, neither with nor without MD, and controls, the current results provide tentative evidence that MD determines long-term endocrine changes, with pure GAD showing a distinct pattern. Future studies are needed to confirm our findings in larger samples of pure and comorbid groups.

  5. Effects of long-term cortisol treatments on gonadal development, sex steroids levels and ovarian cortisol content in cultured great sturgeon Huso huso.

    PubMed

    Poursaeid, Samaneh; Falahatkar, Bahram; Mojazi Amiri, Bagher; Van Der Kraak, Glen

    2012-09-01

    C(50)-implanted fish, while the low cortisol dose had no effect on growth relative to the controls. These results indicated that chronic stress induced by cortisol implantation in great sturgeon suppressed gonadal steroidogenesis and somatic growth but had no effect on ovarian growth and development.

  6. 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

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

    SciTech Connect

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

    1986-01-01

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

  8. The analogous mechanisms of enzymatic inactivation induced by ascorbate and superoxide in the presence of copper.

    PubMed

    Shinar, E; Navok, T; Chevion, M

    1983-12-25

    protein, at the site of their formation, causing its inactivation. This mechanism is analogous to that previously proposed (Samuni, A., Chevion, M., and Czapski, G. (1981) J. Biol. Chem. 256, 12632-12635) for the enhancement of the biological damage caused by superoxide in the presence of copper.

  9. An Analog of the Antimicrobial Peptide CopA5 Inhibits Lipopolysaccharide-Induced Macrophage Activation.

    PubMed

    Yoon, I Na; Hong, Ji; Zhang, Peng; Hwang, Jae Sam; Kim, Ho

    2017-02-28

    We previously reported that the CopA3 peptide (LLCIALRKK, D-form) originally isolated from the Korean dung beetle has antimicrobial and immunosuppressive effects. However, the high cost of producing the synthetic peptide, especially the D-form, has limited the development of CopA3 for therapeutic purposes. Here, we investigated whether the CopA3 deletion derivative, CopA5, which is composed of only five amino acids (LLCIA) and has the L-form structure, could inhibit the lipopolysaccharide (LPS)-induced activation of macrophages. Peritoneal exudate macrophages (PEM) were isolated from mice and exposed to LPS in the presence or absence of CopA5, and biomarkers of macrophage activation were measured. Our results revealed that LPS-induced nitric oxide (NO) production, tumor necrosis factor (TNF)-α secretion, and phagocytic activity of PEM were significantly inhibited by CopA5 treatment. Similar to CopA3, the structurally modified CopA5 peptide had no cell toxicity (as assessed by measurement of cell viability loss and apoptosis) in PEM. Moreover, the LPS-induced upregulation of the activating phosphorylation of signal transducer and activator of transcription 1 (STAT1) was markedly inhibited by CopA5 treatment. These results suggest that, similar to CopA3, CopA5 inhibits macrophage activation by inhibiting STAT1 phosphorylation and blocking the release of NO and TNF-α. CopA5 may therefore prove therapeutically useful in the realm of immune suppression.

  10. Associations between basal cortisol levels and memory retrieval in healthy young individuals.

    PubMed

    Ackermann, Sandra; Hartmann, Francina; Papassotiropoulos, Andreas; de Quervain, Dominique J F; Rasch, Björn

    2013-11-01

    Cortisol is known to affect memory processes. On the one hand, stress-induced or pharmacologically induced elevations of cortisol levels enhance memory consolidation. On the other hand, such experimentally induced elevations of cortisol levels have been shown to impair memory retrieval. However, the effects of individual differences in basal cortisol levels on memory processes remain largely unknown. Here we tested whether individual differences in cortisol levels predict picture learning and recall in a large sample. A total of 1225 healthy young women and men viewed two different sets of emotional and neutral pictures on two consecutive days. Both sets were recalled after a short delay (10 min). On Day 2, the pictures seen on Day 1 were additionally recalled, resulting in a long-delay (20 hr) recall condition. Cortisol levels were measured three times on Days 1 and 2 via saliva samples before encoding, between encoding and recall as well as after recall testing. We show that stronger decreases in cortisol levels during retrieval testing were associated with better recall performance of pictures, regardless of emotional valence of the pictures or length of the retention interval (i.e., 10 min vs. 20 hr). In contrast, average cortisol levels during retrieval were not related to picture recall. Remarkably during encoding, individual differences in average cortisol levels as well as changes in cortisol did not predict memory recall. Our results support previous findings indicating that higher cortisol levels during retrieval testing hinders recall of episodic memories and extend this view onto interindividual changes in basal cortisol levels.

  11. Inhibition of inducible Nitric Oxide Synthase by a mustard gas analog in murine macrophages

    PubMed Central

    Qui, Min; Paromov, Victor M; Yang, Hongsong; Smith, Milton; Stone, William L

    2006-01-01

    Background 2-Chloroethyl ethyl sulphide (CEES) is a sulphur vesicating agent and an analogue of the chemical warfare agent 2,2'-dichlorodiethyl sulphide, or sulphur mustard gas (HD). Both CEES and HD are alkylating agents that influence cellular thiols and are highly toxic. In a previous publication, we reported that lipopolysaccharide (LPS) enhances the cytotoxicity of CEES in murine RAW264.7 macrophages. In the present investigation, we studied the influence of CEES on nitric oxide (NO) production in LPS stimulated RAW264.7 cells since NO signalling affects inflammation, cell death, and wound healing. Murine macrophages stimulated with LPS produce NO almost exclusively via inducible nitric oxide synthase (iNOS) activity. We suggest that the influence of CEES or HD on the cellular production of NO could play an important role in the pathophysiological responses of tissues to these toxicants. In particular, it is known that macrophage generated NO synthesised by iNOS plays a critical role in wound healing. Results We initially confirmed that in LPS stimulated RAW264.7 macrophages NO is exclusively generated by the iNOS form of nitric oxide synthase. CEES treatment inhibited the synthesis of NO (after 24 hours) in viable LPS-stimulated RAW264.7 macrophages as measured by either nitrite secretion into the culture medium or the intracellular conversion of 4,5-diaminofluorescein diacetate (DAF-2DA) or dichlorofluorescin diacetate (DCFH-DA). Western blots showed that CEES transiently decreased the expression of iNOS protein; however, treatment of active iNOS with CEES in vitro did not inhibit its enzymatic activity Conclusion CEES inhibits NO production in LPS stimulated macrophages by decreasing iNOS protein expression. Decreased iNOS expression is likely the result of CEES induced alteration in the nuclear factor kappa B (NF-κB) signalling pathway. Since NO can act as an antioxidant, the CEES induced down-regulation of iNOS in LPS-stimulated macrophages could elevate

  12. Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase-2 induction by capsaicin and related analogs in macrophages.

    PubMed

    Chen, Ching-Wen; Lee, Sho Tone; Wu, Wen Tung; Fu, Wen-Mei; Ho, Feng-Ming; Lin, Wan Wan

    2003-11-01

    1. Although capsaicin analogs might be a potential strategy to manipulate inflammation, the mechanism is still unclear. In this study, the effects and action mechanisms of vanilloid analogs on iNOS and COX-2 expression were investigated in RAW264.7 macrophages. 2. Capsaicin and resiniferatoxin (RTX) can inhibit LPS- and IFN-gamma-mediated NO production, and iNOS protein and mRNA expression with similar IC50 values of around 10 microm. 3. Capsaicin also transcriptionally inhibited LPS- and PMA-induced COX-2 expression and PGE2 production. However, this effect exhibited a higher potency (IC50: 0.2 microm), and RTX failed to elicit such responses at 10 microm. 4. Interestingly, we found that capsazepine, a competitive TRPV1 antagonist, did not prevent the inhibition elicited by capsaicin or RTX. Nevertheless, it mimicked vanilloids in inhibiting iNOS/NO and COX-2/PGE2 induction with an IC50 value of 3 microm. RT-PCR and immunoblotting analysis excluded the expression of TRPV1 in RAW264.7 macrophages. 5. The DNA binding assay demonstrated the abilities of vanilloids to inhibit LPS-elicited NF-kappaB and AP-1 activation and IFN-gamma-elicited STAT1 activation. The reporter assay of AP-1 activity also supported this action. 6. The kinase assay indicated that ERK, JNK, and IKK activation by LPS were inhibited by vanilloids. 7. In conclusion, vanilloids can modulate the expression of inflammatory iNOS and COX-2 genes in macrophages through interference with upstream signalling events of LPS and IFN-gamma. These findings provide new insights into the potential benefits of the active ingredient in hot chilli peppers in inflammatory conditions.

  13. 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.

  14. Tunable optical analog to electromagnetically induced transparency in graphene-ring resonators system

    PubMed Central

    Wang, Yonghua; Xue, Chenyang; Zhang, Zengxing; Zheng, Hua; Zhang, Wendong; Yan, Shubin

    2016-01-01

    The analogue of electromagnetically induced transparency in optical ways has shown great potential in optical delay and quantum-information technology due to its flexible design and easy implementation. The chief drawback for these devices is the bad tunability. Here we demonstrate a tunable optical transparency system formed by graphene-silicon microrings which could control the transparent window by electro-optical means. The device consists of cascaded coupled ring resonators and a graphene/graphene capacitor which integrated on one of the rings. By tuning the Fermi level of the graphene sheets, we can modulate the round-trip ring loss so that the transparency window can be dynamically tuned. The results provide a new method for the manipulation and transmission of light in highly integrated optical circuits and quantum information storage devices. PMID:27941895

  15. Analog electromagnetically induced transparency for circularly polarized wave using three-dimensional chiral metamaterials.

    PubMed

    Lin, Hai; Yang, Dong; Han, Song; Liu, Yangjie; Yang, Helin

    2016-12-26

    In this paper, we theoretically and experimentally demonstrate a three-dimensional metamaterial that can motivate electromagnetic induced transparency (EIT) by using circular polarized wave as stimulations. The unit cell consists of a pair of metallic strips printed on both sides of the printed circuit board (PCB), where a conductive cylinder junction is used to connect the metal strips by drilling a hole inside the substrate. When a right circularly polarized wave is incident, destructive interference is excited between meta-atoms of the 3D structure, the transmission spectrum demonstrates a sharp transparency window. A coupled oscillator model and an electrical equivalent circuit model are applied to quantitatively and qualitatively analyze the coupling mechanism in the EIT-like metamaterial. Analysis in detail shows the EIT window's amplitude and frequency are modulated by changing the degree of symmetry breaking. The proposed metamaterial may achieve potential applications in developing chiral slow light devices.

  16. Analog electromagnetically induced transparency for circularly polarized wave using three-dimensional chiral metamaterials

    NASA Astrophysics Data System (ADS)

    Lin, Hai; Yang, Dong; Han, Song; Liu, Yangjie; Yang, Helin

    2016-12-01

    In this paper, we theoretically and experimentally demonstrate a three dimensional metamaterial that can motivate electromagnetic induced transparency (EIT) by using circular polarized wave as stimulations. The unit cell consists of a pair of metallic strips printed on both sides of the printed circuit board (PCB), where a conductive cylinder junction is used to connect the metal strips by drilling a hole inside the substrate. When a right circularly polarized wave is incident, destructive interference is excited between meta-atoms of the 3D structure, the transmission spectrum demonstrates a sharp transparency window. A coupled oscillator model and an electrical equivalent circuit model are applied to quantitatively and qualitatively analyze the coupling mechanism in the EIT-like metamaterial. Analysis in detail shows the EIT window's amplitude and frequency are modulated by changing the degree of symmetry breaking. The proposed metamaterial may achieve potential applications in developing chiral slow light devices.

  17. 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

  18. Tunable optical analog to electromagnetically induced transparency in graphene-ring resonators system

    NASA Astrophysics Data System (ADS)

    Wang, Yonghua; Xue, Chenyang; Zhang, Zengxing; Zheng, Hua; Zhang, Wendong; Yan, Shubin

    2016-12-01

    The analogue of electromagnetically induced transparency in optical ways has shown great potential in optical delay and quantum-information technology due to its flexible design and easy implementation. The chief drawback for these devices is the bad tunability. Here we demonstrate a tunable optical transparency system formed by graphene-silicon microrings which could control the transparent window by electro-optical means. The device consists of cascaded coupled ring resonators and a graphene/graphene capacitor which integrated on one of the rings. By tuning the Fermi level of the graphene sheets, we can modulate the round-trip ring loss so that the transparency window can be dynamically tuned. The results provide a new method for the manipulation and transmission of light in highly integrated optical circuits and quantum information storage devices.

  19. Infant hair cortisol: associations with salivary cortisol and environmental context.

    PubMed

    Flom, Megan; St John, Ashley M; Meyer, Jerrold S; Tarullo, Amanda R

    2017-01-01

    Early chronic stress has enduring implications for physical and mental health outcomes. Hair cortisol concentration (HCC) has emerged as a marker of cumulative cortisol exposure, yet HCC in infants is not well understood. We examined how infant HCC relates to widely used basal salivary cortisol measures, maternal HCC, and environmental context in 111 infants assessed at 6 and 12 months of age. Maternal HCC at 6 and 12 months was correlated with infant HCC at 12 months. At 12 months, infant HCC was positively associated with waking salivary cortisol concentration (SCC), evening SCC, and area under the curve (AUC), but was independent of diurnal slope. Breastfeeding was associated with lower HCC, whereas increased sleep disruption was related to flatter slope. Reduced nighttime sleep duration was related both to higher HCC and to flatter slope. A person-focused analysis indicated that the combination of high HCC and flattened slope was associated with more environmental risks, highlighting the importance of investigating the interplay between HCC and diurnal cortisol slope. Results support the validity of HCC as a marker of cumulative cortisol exposure in infancy, while emphasizing the value of including multiple cortisol measures assessing distinct aspects of hypothalamic-pituitary-adrenal (HPA) function.

  20. Involvement of endogenous opioid peptides in the antinociception induced by the novel dermorphin tetrapeptide analog amidino-TAPA.

    PubMed

    Mizoguchi, Hirokazu; Watanabe, Chizuko; Watanabe, Hiroyuki; Moriyama, Kaori; Sato, Bunsei; Ohwada, Keiko; Yonezawa, Akihiko; Sakurada, Tsukasa; Sakurada, Shinobu

    2007-04-10

    The antinociceptive effect of i.t. administered N(alpha)-amidino-Tyr-d-Arg-Phe-beta-Ala (amidino-TAPA), an N-terminal tetrapeptide analog of dermorphin, was characterized in ddY mice. In the opioid receptor ligand-binding assays using mouse brain membranes, amidino-TAPA showed a very high affinity for mu-opioid receptors, a low affinity to delta-opioid receptors and no affinity for kappa-opioid receptors. In the mouse tail-flick test, i.t. treatment with amidino-TAPA produced a potent antinociception. The antinociception induced by amidino-TAPA was significantly attenuated by i.t. pretreatment with the mu-opioid receptor antagonist beta-funaltrexamine, the kappa-opioid receptor antagonist nor-binaltorphimine and the delta-opioid receptor antagonist naltrindole. Moreover, the antinociception induced by amidino-TAPA was significantly attenuated by i.t. pretreatment with antisera against the endogenous kappa-opioid peptides dynorphin A, dynorphin B and alpha-neo-endorphin; and the endogenous delta-opioid peptide [Leu(5)]enkephalin. In mice lacking prodynorphin, the precursor of the endogenous kappa-opioid peptides, the antinociceptive effect of amidino-TAPA was significantly attenuated compared to that in wild-type C57BL/6J mice. However, there was no difference in G-protein activation by amidino-TAPA in the spinal cord membranes from prodynorphin knockout mice and C57BL/6J mice. The present results suggest that the spinal antinociception induced by the mu-opioid receptor selective peptide amidino-TAPA is mediated in part by the release of endogenous opioid peptides in the spinal cord, which is caused by the direct stimulation of mu-opioid receptors.

  1. Associations between endogenous cortisol levels and emotional memory in young women: influence of encoding instructions.

    PubMed

    Preuss, Diana; Schoofs, Daniela; Wolf, Oliver T

    2009-09-01

    The stress hormone cortisol is known to influence memory. Elevated cortisol levels as a consequence of stress or as a consequence of cortisol administration have been repeatedly shown to enhance encoding and consolidation of (emotional) memory. Whether similar associations exist between basal cortisol levels and emotional memory remains to be established. The present study therefore evaluated if resting cortisol levels are correlated with memory for emotionally arousing and neutral pictures in a sample of young healthy females (n = 56). A second aim of the study was to explore if the relationship between basal cortisol levels and memory might be modulated by encoding instructions (intentional vs. incidental encoding). A significant positive correlation between basal salivary cortisol levels and memory for emotionally arousing pictures in a 24 h delayed free recall test was found. Further analyses revealed that this association only occurred in the group receiving intentional encoding instructions. Results indicate that basal cortisol levels, similarly to stress induced cortisol levels, are associated with emotional memory formation. Moreover this effect seems to be modulated by encoding instructions, suggesting a role of focussed attention or arousal induced by testing in this relationship.

  2. Morphological changes in Daphnia galeata induced by a crustacean terpenoid hormone and its analog.

    PubMed

    Oda, Shigeto; Kato, Yasuhiko; Watanabe, Hajime; Tatarazako, Norihisa; Iguchi, Taisen

    2011-01-01

    Terpenoid hormones in insects (i.e., juvenile hormones) have various effects on physiology, morphology, and behavior, producing a wide range of phenotypic variation. Recent studies have shown that sex determination in cladoceran crustaceans is under the strong control of a major terpenoid hormone of crustaceans, methyl farnesoatote (MF). It can be easily conceived that MF is also a major determinant of other traits in cladocerans. In the present study, morphological changes known as antipredatory responses in a cladoceran Daphnia galeata in response to exposure to MF and a juvenile hormone-mimicking pesticide, fenoxycarb, were investigated. Morphological change was studied using neonates less than 24 h old, exposed either to MF at the concentrations from 1.9 to 30 µg/L, or fenoxycarb at the concentrations from 13 to 200 ng/L, for 6 d. Animals developed a longer helmet at 1.9 µg/L of MF and 25 ng/L of fenoxycarb, and showed a concentration-dependent elongation. However, the tail spine was reduced in size in a concentration-dependent manner. Results of the present study not only give new insight into the mechanisms of inducible defenses in cladocerans, but also provide invaluable information to understand ecological and evolutionary consequences of endocrine disruption through the shift in biological interaction between predator and prey.

  3. 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.

  4. Changes in the social environment induce neurogenic plasticity predominantly in niches residing in sensory structures of the zebrafish brain independently of cortisol levels.

    PubMed

    Lindsey, Benjamin W; Tropepe, Vincent

    2014-11-01

    The social environment is known to modulate adult neurogenesis. Studies in mammals and birds have shown a strong correlation between social isolation and decreases in neurogenesis, whereas time spent in an enriched environment has been shown to restore these deficits and enhance neurogenesis. These data suggest that there exists a common adaptive response among neurogenic niches to each extreme of the social environment. We sought to further test this hypothesis in zebrafish, a social species with distinct neurogenic niches within primary sensory structures and telencephalic nuclei of the brain. By examining stages of adult neurogenesis, including the proliferating stem/progenitor population, their surviving cohort, and the resulting newly differentiated neuronal population, we show that niches residing in sensory structures are most sensitive to changes in the social context, and that social isolation or novelty are both capable of decreasing the number of proliferating cells while increasing the number of newborn neurons within a single niche. Contrary to observations in rodents, we demonstrate that social novelty, a form of enrichment, does not consistently rescue deficits in cell proliferation following social isolation, and that cortisol levels do not negatively regulate changes in adult neurogenesis, but are correlated with the social context. We propose that enhancement or suppression of adult neurogenesis in the zebrafish brain under different social contexts depends largely on the type of niche (sensory or telencephalic), experience from the preceding social environment, and occurs independently of changes in cortisol levels.

  5. Plasmalogen precursor analog treatment reduces levodopa-induced dyskinesias in parkinsonian monkeys.

    PubMed

    Grégoire, Laurent; Smith, Tara; Senanayake, Vijitha; Mochizuki, Asuka; Miville-Godbout, Edith; Goodenowe, Dayan; Di Paolo, Thérèse

    2015-06-01

    L-DOPA-induced dyskinesias (LID) remain a serious obstacle in the treatment of Parkinson's disease (PD). The objective of this study was to test a new target for treatment of dyskinesias, ethanolamine plasmalogens (PlsEtn). PlsEtn play critical roles in membrane structure mediated functions and as a storage depot of polyunsaturated fatty acids such as docosahexaenoic acid (DHA, omega-3) known to reduce dyskinesias. The motor effect of a daily treatment for 12 days of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Macaca fascicularis monkeys with DHA (100mg/kg) was compared to the DHA-PlsEtn precursor PPI-1011 (50mg/kg). PPI-1011 and DHA reduced LID while maintaining the antiparkinsonian activity of l-DOPA, however the PPI-1011 effect was observed at the first behavioral time point analyzed following drug administration (day 2) whereas the effect of DHA was not observed until after 10 days of administration. DHA treatment increased plasma DHA levels 2-3× whereas PPI-1011 had no effect. DHA and PPI-1011 increased DHA-PlsEtn levels by 1.5-2× while DHA-phosphatidylethanolamine (PtdEtn) levels remained unaffected. DHA treatment also elevated very long chain fatty acid containing PtdEtn and reduced non-DHA containing PtdEtn and PlsEtn levels. PPI-1011 had no effect on these systems. LID scores were inversely correlated with serum DHA-PlsEtn/total PlsEtn ratios levels in DHA and PPI-1011 treated monkeys. Hence, the antidyskinetic activity of DHA and PPI-1011 in MPTP monkeys appears to be associated with the increase of serum DHA-PlsEtn concentrations. This is the first study reporting an antidyskinetic response to augmentation of DHA-PlsEtn using a plasmalogen precursor thus providing a novel drug target for dyskinesias.

  6. 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

  7. 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…

  8. A novel vitamin D analog with two double bonds in its side chain. A potent inducer of osteoblastic cell differentiation.

    PubMed

    Mahonen, A; Jääskeläinen, T; Mäenpää, P H

    1996-04-12

    EB 1089 (1 alpha,25-dihydroxy-22,24-diene-24,26,27-trihomovitamin D3) is a novel, synthetic analog of calcitriol, characterized by two extra double bonds in its side chain. It is less potent than calcitriol in its calcemic action, but is an order of magnitude more potent in its antiproliferative action. The aim of this study was to determine the ability of EB 1089 to induce the well-known biological effects of calcitriol in MG-63 human osteosarcoma cells (i.e. by inhibiting cell proliferation and by induction of differentiation). Both calcitriol and EB 1089 significantly decreased cell growth after 2 days in culture. At 5 days, however, Eb 1089 was more potent than the natural hormone in inhibiting the proliferation of MG-63 cells. Potent effects of EB 1089 on cell differentiation were also seen in the stimulation of alkaline phosphatase activity, cellular vitamin D receptor mRNA levels, and medium osteocalcin synthesis. EB 1089 was clearly more effective than calcitriol in stimulating alkaline phosphatase activity and osteocalcin synthesis. In gel shift assays, the binding of vitamin D receptor to the composite AP-1 plus vitamin-D responsive promoter region of the human osteocalcin gene after EB 1089 treatment was stronger and longer-lasting than after calcitriol treatment.

  9. Cortisol Release in Response to UVB Exposure in Xiphophorus Fish

    PubMed Central

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

    2014-01-01

    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 assay of cortisol released into the water. Here, we present results from investigations of stress response during experimental treatment and UVB exposure in X. maculatus Jp 163 B, X. couchianus, and F1 interspecies hybrids produced from the mating X. maculatus Jp 163 B x X. couchianus. Overall, cortisol release rates for males and females after UVB exposure showed no statistical differences. At lower UVB doses (8 and 16 kJ/m2), X. couchianus exhibited 2 fold higher levels of DNA damage then either X. maculatus or the F1 hybrid. However, based on cortisol release rates, none of the fish types tested induced a primary stress response at the UVB lower doses (8 and 16 kJ/m2). In contrast, at a very high UVB dose (32 kJ/m2) both X. maculatus and the F1 hybrid showed a 5 fold increase in cortisol release rate. To determine the effect of pigmentation on UVB induced stress, wild type and albino X. hellerii were exposed to UVB (32 kJ/m2). Albino X. hellerii exhibited 3.7 fold increase in 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 tumour induction protocols do not induce a primary stress response in Xiphophorus fishes. PMID:24625568

  10. Effects of exogenous cortisol on the GH/IGF-I/IGFBP network in channel catfish.

    PubMed

    Peterson, Brian C; Small, Brian C

    2005-05-01

    Glucocorticoids are known to hinder somatic growth in a number of vertebrate species. In order to better understand the mechanisms through which they may act in channel catfish, we examined the effects of feeding cortisol on the growth hormone (GH)/insulin-like growth factor-I (IGF-I)/IGF-binding protein (IGFBP) network. Fish (30.6+/-3.0 g) were fed once daily for 4 weeks and treatments included: (1) High-cortisol (dietary cortisol provided at 400 mg/kg feed), (2) Low-cortisol (dietary cortisol provided at 200 mg/kg feed), and (3) Control (commercial catfish feed). Fish fed diets with cortisol weighed approximately 50% less than Controls. Feed intake was reduced by approximately 30% in both treatments of cortisol fed fish compared to Controls. A approximately 20-kDa IGFBP was observed in plasma from High- and Low-treated fish while it was not detected in Control fish plasma. High-cortisol treatment increased pituitary GH mRNA expression approximately 10-fold while liver IGF-I mRNA expression was not different between cortisol-treated fish and Controls. Cortisol treatments decreased plasma levels of IGF-I. These data indicate that feeding cortisol for 4 weeks reduces weight gain, feed intake, and plasma levels of IGF-I and induces a approximately 20-kDa IGFBP. One mechanism through which cortisol may impede growth of catfish is through an increase in a low molecular weight IGFBP which may lead to inhibitory effects on the action of IGF-I.

  11. 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.

  12. Effects of forskolin analogs, phosphodiesterase inhibitors and 8-bromo cyclic AMP on plasma exudations induced with bradykinin and prostaglandin E/sub 1/ in rat skin

    SciTech Connect

    Sugio, K.; Daly, J.W.

    1984-01-09

    The effects of forskolin analogs, phosphodiesterase inhibitors and 8-bromo cyclic AMP on plasma exudations induced with bradykinin and prostaglandin E/sub 1/ in rat skin were investigated using (/sup 125/I) bovine serum albumin (/sup 125/I-BSA). Forskolin, forskolin 7-ethyl carbonate and 7-desacetylforskolin, which are potent activators of adenylate cyclase, greatly potentiated the bradykinin-induced plasma exudation and inhibited the prostaglandin E/sub 1/-induced response. The phosphodiesterase inhibitors, ZK 627ll, dipyridamole, HL 725, and 3-isobutyl-1-methylxanthine potentiated the bradykinin-induced plasma exudation and inhibited and prostaglandin E/sub 1/-induced response. 8-Bromo cyclic AMP in the doses of 0.01 to 1 ..mu..g potentiated the bradykinin-induced plasma exudation, but had no effect at doses of 10 and 100 ..mu..g. 8-bromo cyclic AMP at all doses significantly inhibited the prostaglandin E/sub 1/-induced response. The results suggest that the effects of forskolin and its analogs on plasma exudations induced with bradykinin and prostaglandin E/sub 1/ in rat skin derive from activation of cyclic AMP-generating systems.

  13. 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.

  14. Effects of shallow scoop and deep scoop dehorning on plasma cortisol concentrations in calves.

    PubMed

    McMeekan, C M; Mellor, D J; Stafford, K J; Bruce, R A; Ward, R N; Gregory, N G

    1997-04-01

    Scoop dehorning is one method of horn amputation. Plasma cortisol concentrations were used to investigate the effects of wound depth caused by shallow scoop and deep scoop dehorning on the acute pain-induced distress experienced by 15 week-old calves during the first 9 hours following horn amputation. Shallow scoop and deep scoop dehorning caused a prolonged cortisol elevation which returned to control values within 8 hours and 6 hours, respectively. There were no significant differences between shallow and deep dehorning with regard to mean plasma cortisol concentrations and integrated cortisol responses during the 9 hours after dehorning. Linear regression analysis revealed no significant correlation between wound depth and integrated cortisol response. Hence, at the investigated scoop wound depths, there was no detectable benefit in implementing a shallow scoop strategy in order to reduce acute pain-induced distress caused by scoop dehorning in 15 week-old calves.

  15. Low cortisol levels and the balance between punishment sensitivity and reward dependency.

    PubMed

    van Honk, Jack; Schutter, Dennis J L G; Hermans, Erno J; Putman, Peter

    2003-10-27

    The neuro-endocrinological basis of psychopathy, a disorder characterized by lack of fear, is relatively unknown. However, low levels of cortisol may result in fearlessness and have been observed in individuals with psychopathic tendencies. Low fear models state that psychopaths are not motivated to avoid punishment, especially when reward is pending. In agreement, disadvantageous decision making on the IOWA gambling task in psychopaths and psychopathic analogous, indicates low punishment sensitivity and high reward dependency. Here, it was investigated whether low basal cortisol levels predicted the balance between punishment sensitivity and reward dependency in the same manner. As hypothesized, the most disadvantageous pattern of decision making was found in the subjects with the lowest cortisol levels. These findings suggest that low levels of cortisol may set the balance between the sensitivity for punishment and reward dependency towards a pre-disposition for psychopathy.

  16. 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

  17. 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.

  18. 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.

  19. Effect of 5-azacytidine and cortisol on the P1798 cortisol-sensitive and non-resistant lymphosarcoma

    SciTech Connect

    Chi, C.

    1986-01-01

    The P1798 lymphosarcoma is a tumor with both cortisol-sensitive (CS) and cortisol-resistant (CR) lines. Although differences between the CS and CR cells have been reported, none can fully explain the detailed mechanism of glucocorticoid resistance in CR tumors. Recently, it was shown that 5-azacytidine treatment could generate CS cells from CR SAK lymphoma cells in vitro. The present study examined the effect of combination treatment with 5-azacytidine and cortisol on the growth of the P1798 lymphosarcoma. 5-Azacytidine rendered the P1798 CR tumors partially cortisol-sensitive, and enhanced the cortisol-induced regression of the P1798 CS tumors. Survival of mice bearing both CS and CR P1798 tumors was increased by combination treatment. Similar whole cell and nuclear binding of /sup 3/H-TA were observed in both 5-azacytidine-treated and control P1798 tumors. However, CR nuclei retained 64% of the whole cell binding of /sup 3/H-TA compared to 25-29% nuclear retention in CS tumors. DNA methylation in tumors from 5-azacytidine-treated mice decreased to 53% (CS) and 42% (CR) of control. Since 5-azacytidine did not result in any change in thymidine labeling index or cell cycle distribution in P1798 tumors, it would appear to be cytostatic rather than cytotoxic to P1798 tumors. Three cell lines have been isolated from the P1798 lymphosarcoma: two are cortisol-sensitive both in vivo and in vitro, while the other is cortisol-resistant. Results from this study suggest that glucocorticoid resistance is a reversible process, and that the effect of 5-azacytidine on the P1798 CR tumor is at the gene expression level.

  20. 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.

  1. Exogenous cortisol facilitates responses to social threat under high provocation.

    PubMed

    Bertsch, Katja; Böhnke, Robina; Kruk, Menno R; Richter, Steffen; Naumann, Ewald

    2011-04-01

    Stress is one of the most important promoters of aggression. Human and animal studies have found associations between basal and acute levels of the stress hormone cortisol and (abnormal) aggression. Irrespective of the direction of these changes--i.e., increased or decreased aggressive behavior--the results of these studies suggest dramatic alterations in the processing of threat-related social information. Therefore, the effects of cortisol and provocation on social information processing were addressed by the present study. After a placebo-controlled pharmacological manipulation of acute cortisol levels, we exposed healthy individuals to high or low levels of provocation in a competitive aggression paradigm. Influences of cortisol and provocation on emotional face processing were then investigated with reaction times and event-related potentials (ERPs) in an emotional Stroop task. In line with previous results, enhanced early and later positive, posterior ERP components indicated a provocation-induced enhanced relevance for all kinds of social information. Cortisol, however, reduced an early frontocentral bias for angry faces and--despite the provocation-enhancing relevance--led to faster reactions for all facial expressions in highly provoked participants. The results thus support the moderating role of social information processing in the 'vicious circle of stress and aggression'.

  2. Maternal trait anxiety, emotional distress, and salivary cortisol in pregnancy.

    PubMed

    Pluess, Michael; Bolten, Margarete; Pirke, Karl-Martin; Hellhammer, Dirk

    2010-03-01

    Animal models suggest that stress-induced hormonal changes in the mother during pregnancy lead to enduring changes in the fetus and empirical links between prenatal maternal stress and negative child development have been discerned repeatedly in human studies. But the role of heritable personality traits has received little attention in the latter work. The goal of the current study was to investigate the relationship between maternal personality, psychological measures of maternal distress and maternal salivary cortisol during pregnancy. Maternal reports of personality (16 PF) and stress-related psychological measures (depression, pregnancy-related anxiety, perceived stress, negative life events) as well as salivary cortisol samples of 66 healthy pregnant women were collected in early and late pregnancy. Maternal trait anxiety proved related to all stress-related psychological measures and high anxiety predicted low baseline cortisol awakening levels in early pregnancy. Maternal trait anxiety is related to both psychological and biological stress measures during pregnancy.

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

    PubMed

    Engert, Veronika; Smallwood, Jonathan; Singer, Tania

    2014-12-01

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

  4. ATLa, an aspirin-triggered lipoxin A4 synthetic analog, prevents the inflammatory and fibrotic effects of bleomycin-induced pulmonary fibrosis.

    PubMed

    Martins, Vanessa; Valença, Samuel S; Farias-Filho, Francisco A; Molinaro, Raphael; Simões, Rafael L; Ferreira, Tatiana P T; e Silva, Patrícia M R; Hogaboam, Cory M; Kunkel, Steven L; Fierro, Iolanda M; Canetti, Claudio; Benjamim, Claudia F

    2009-05-01

    Despite an increase in the knowledge of mechanisms and mediators involved in pulmonary fibrosis, there are no successful therapeutics available. Lipoxins (LX) and their 15-epimers, aspirin-triggered LX (ATL), are endogenously produced eicosanoids with potent anti-inflammatory and proresolution effects. To date, few studies have been performed regarding their effect on pulmonary fibrosis. In the present study, using C57BL/6 mice, we report that bleomycin (BLM)-induced lung fibrosis was prevented by the concomitant treatment with an ATL synthetic analog, ATLa, which reduced inflammation and matrix deposition. ATLa inhibited BLM-induced leukocyte accumulation and alveolar collapse as evaluated by histology and morphometrical analysis. Moreover, Sirius red staining and lung hydroxyproline content showed an increased collagen deposition in mice receiving BLM alone that was decreased upon treatment with the analog. These effects resulted in benefits to pulmonary mechanics, as ATLa brought to normal levels both lung resistance and compliance. Furthermore, the analog improved mouse survival, suggesting an important role for the LX pathway in the control of disease establishment and progression. One possible mechanism by which ATLa restrained fibrosis was suggested by the finding that BLM-induced myofibroblast accumulation/differentiation in the lung parenchyma was also reduced by both simultaneous and posttreatment with the analog (alpha-actin immunohistochemistry). Interestingly, ATLa posttreatment (4 days after BLM) showed similar inhibitory effects on inflammation and matrix deposition, besides the TGF-beta level reduction in the lung, reinforcing an antifibrotic effect. In conclusion, our findings show that LX and ATL can be considered as promising therapeutic approaches to lung fibrotic diseases.

  5. 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…

  6. Frontal lobe activation mediates the relation between sensation seeking and cortisol increases.

    PubMed

    Freeman, Hani D; Beer, Jennifer S

    2010-10-01

    Low sensation seekers are theorized to avoid risk more often because risk is emotionally more costly for them (in comparison to high sensation seekers). Therefore, individual differences in sensation seeking should predict differences in risk task-induced cortisol changes. Furthermore, the neural mediation that accounts for the relation between sensation seeking and cortisol changes has not been studied. The current study tested whether individual differences in sensation seeking predicted cortisol changes in relation to a risk task and whether this relation was mediated by frontal lobe activation. Participants (N=17) who varied in sensation seeking completed an fMRI study in which they rated the likelihood they would take various risks. Cortisol was measured from saliva samples collected prior to and after the fMRI procedure. The findings show that low sensation seekers showed the greatest rise in cortisol after the risk procedure, and this relation was partially mediated by increased orbitofrontal cortex activity.

  7. Application of a pore-scale reactive transport model to a natural analog for reaction-induced pore alterations

    DOE PAGES

    Yoon, Hongkyu; Major, Jonathan; Dewers, Thomas; ...

    2017-01-05

    Dissolved CO2 in the subsurface resulting from geological CO2 storage may react with minerals in fractured rocks, confined aquifers, or faults, resulting in mineral precipitation and dissolution. The overall rate of reaction can be affected by coupled processes including hydrodynamics, transport, and reactions at the (sub) pore-scale. In this work pore-scale modeling of coupled fluid flow, reactive transport, and heterogeneous reactions at the mineral surface is applied to account for permeability alterations caused by precipitation-induced pore-blocking. This paper is motivated by observations of CO2 seeps from a natural CO2 sequestration analog, Crystal Geyser, Utah. Observations along the surface exposure ofmore » the Little Grand Wash fault indicate the lateral migration of CO2 seep sites (i.e., alteration zones) of 10–50 m width with spacing on the order of ~100 m over time. Sandstone permeability in alteration zones is reduced by 3–4 orders of magnitude by carbonate cementation compared to unaltered zones. One granular porous medium and one fracture network systems are used to conceptually represent permeable porous media and locations of conduits controlled by fault-segment intersections and/or topography, respectively. Simulation cases accounted for a range of reaction regimes characterized by the Damköhler (Da) and Peclet (Pe) numbers. Pore-scale simulation results demonstrate that combinations of transport (Pe), geochemical conditions (Da), solution chemistry, and pore and fracture configurations contributed to match key patterns observed in the field of how calcite precipitation alters flow paths by pore plugging. This comparison of simulation results with field observations reveals mechanistic explanations of the lateral migration and enhances our understanding of subsurface processes associated with the CO2 injection. In addition, permeability and porosity relations are constructed from pore-scale simulations which account for a range of

  8. Behavioral reactivity to emotion challenge is associated with cortisol reactivity and regulation at 7, 15, and 24 months of age.

    PubMed

    Ursache, Alexandra; Blair, Clancy; Granger, Douglas A; Stifter, Cynthia; Voegtline, Kristin

    2014-04-01

    Emotionally arousing stimuli have been largely unsuccessful in eliciting cortisol responses in young children. Whether or not emotion challenge will elicit a cortisol response, however, may in part be determined by the extent to which the tasks elicit behavioral reactivity and regulation. We examined relations of behavioral reactivity and regulation to emotional arousal in the context of fear and frustration to the cortisol response at 7, 15, and 24 months of age in a low income, rural population based sample of 1,292 families followed longitudinally from birth. At each age, children participated in fear and frustration inducing tasks, and cortisol samples were taken at three time points (before the tasks began, 20 min following peak emotional arousal or after the series of tasks ended, and 40 min after peak arousal or the tasks ended) in order to capture both increases (reactivity) and subsequent decreases (regulation) in the cortisol response. Using multilevel models, we predicted the cortisol response from measures of behavioral reactivity and regulation. At 7 months of age, cortisol reactivity and recovery were related to behavioral reactivity during a frustration-eliciting task and marginally related to behavioral reactivity during a fear-eliciting task. At 15 and 24 months of age, however, cortisol reactivity and recovery were related only to behavioral reactivity during a fear-eliciting task. Results indicate that while behavioral reactivity is predictive of whether or not infants and young children will exhibit a cortisol response to emotionally arousing tasks, behavioral and cortisol reactivity are not necessarily coupled.

  9. 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.

  10. 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

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

    PubMed

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

    2013-10-01

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

  12. Cushing, cortisol, and cardiovascular disease.

    PubMed

    Whitworth, J A; Mangos, G J; Kelly, J J

    2000-11-01

    Cushing's syndrome of glucocorticoid excess is named after the eminent Boston neurosurgeon Harvey W. Cushing (1869-1939). The recognition that glucocorticoid excess produces hypertension led to examination of the role of cortisol in essential hypertension, but it is only over the last decade that evidence has emerged to support the concept. Despite the widespread assumption that cortisol raises blood pressure as a consequence of renal sodium retention, there are few data consistent with the notion. Although it has a plethora of actions on brain, heart and blood vessels, kidney, and body fluid compartments, precisely how cortisol elevates blood pressure is unclear. Candidate mechanisms currently being examined include inhibition of the vasodilator nitric oxide system and increases in vasoconstrictor erythropoietin concentration.

  13. Associations between circadian and stress response cortisol in children.

    PubMed

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

    2017-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the cortisol circadian rhythm is associated with cortisol stress responses in 6-year-old children. To this end, 149 normally developing children (Mage = 6.09 years; 70 girls) participated in an innovative social evaluative stress test that effectively provoked increases in cortisol. To determine the cortisol stress response, six cortisol saliva samples were collected and two cortisol stress response indices were calculated: total stress cortisol and cortisol stress reactivity. To determine children's cortisol circadian rhythm eight cortisol circadian samples were collected during two days. Total diurnal cortisol and diurnal cortisol decline scores were calculated as indices of the cortisol circadian rhythm. Hierarchical regression analyses indicated that higher total diurnal cortisol as well as a smaller diurnal cortisol decline, were both uniquely associated with higher total stress cortisol. No associations were found between the cortisol circadian rhythm indices and cortisol stress reactivity. Possible explanations for the patterns found are links with children's self-regulatory capacities and parenting quality.

  14. Regulation of estrogenic and nuclear factor kappa B functions by polyamines and their role in polyamine analog-induced apoptosis of breast cancer cells.

    PubMed

    Shah, N; Thomas, T J; Lewis, J S; Klinge, C M; Shirahata, A; Gelinas, C; Thomas, T

    2001-03-29

    The natural polyamines -putrescine, spermidine, and spermine- are essential for cell growth and differentiation. Polyamines are involved in several gene regulatory functions, although their mechanism(s) of action has not been elucidated. We investigated the role of polyamines in the function of NF-kappa B and estrogen receptor-alpha (ER alpha), two transcription factors implicated in breast cancer cell proliferation and cell survival, using MCF-7 breast cancer cells. We found that spermine facilitated the binding of ER alpha and NF-kappa B to estrogen response element (ERE)- and NF-kappa B response element (NRE), respectively, and enhanced ER alpha-mediated transcriptional activation in transient transfection experiments. We also found that the association of the co-regulatory protein CBP/p300 with ER alpha and NF-kappa B was increased by spermine treatment of MCF-7 cells. Spermine also increased the nuclear translocation of NF-kappa B compared to the control. In contrast, treatment of MCF-7 cells with polyamine analogs, BE-3-4-3 and BE-3-3-3, resulted in transcriptional inhibition of both ERE- and NRE-driven reporter plasmids. In addition, polyamine analogs inhibited the association of ER alpha and NF-kappa B with CBP/p300 and were unable to facilitate nuclear translocation of NF-kappa B. APO-BRDU assay demonstrated that polyamine analogs induced apoptosis, with a loss of the anti-apoptotic protein Bcl-2. These data show a gene regulatory function of polyamines involving transcriptional activation of ER alpha and NF-kappa B, potentially leading to the up-regulation of genes involved in breast cancer cell proliferation. Our results with BE-3-4-3 and BE-3-3-3 suggest that down-regulation of ER alpha- and NF-kappa B-regulated genes is a possible mechanism for the action of polyamine analogs in inducing apoptosis of breast cancer cells.

  15. Cyber Analogies

    DTIC Science & Technology

    2014-02-28

    including the time for reviewing instructions , searching existing data sources, gathering and maintaining the data needed, and completing and reviewing... CONTENTS 1 Introduction Emily O. Goldman & John Arquilla 7 The Cyber Pearl Harbor James J. Wirtz 15 Applying the Historical Lessons of Surprise Attack...As H.G. Wells put it, “History is a race between education and catastrophe.” SURPRISE ATTACK The primarily history- based analogies contained herein

  16. Antifeedant Activity and High Mortality in the Pea Aphid Acyrthosiphon pisum (Hemiptera: Aphidae) Induced by Biostable Insect Kinin Analogs

    DTIC Science & Technology

    2010-01-01

    this core Aib analog mimicked the amylase (carbohy- drase) release inhibition activity of natural insect kinins, specifi- cally demonstrating 1.1- and...3,4,28,29,33], inhibit the in vitro release of the digestive enzyme amylase in the midgut [13,14], and inhibit in vivo larvalweightgain [26,33,41...Nachman RJ. In vitro release of amylase by culekinins in two insects: Opsinia arenosella (Lepidoptera) and Rhynchophorus ferrugineus (Coleoptera). Trends

  17. 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

  18. Effects of cortisol on pregnancy rate and corpus luteum function in heifers: an in vivo study.

    PubMed

    Duong, Hai Thanh; Piotrowska-Tomala, Katarzyna Karolina; Acosta, Tomas Javier; Bah, Mamadou Mousa; Sinderewicz, Emilia; Majewska, Magdalena; Jankowska, Katarzynna; Okuda, Kiyoshi; Skarzynski, Dariusz Jan

    2012-01-01

    To determine whether glucocorticoids affect the function of the bovine corpus luteum (CL) during the estrous cycle and early pregnancy, we examined the effects of exogenous cortisol or reduced endogenous cortisol on the secretion of progesterone (P4) and on pregnancy rate. In preliminary experiments, doses of cortisol and metyrapone (an inhibitor of cortisol synthesis) were established (n=33). Cortisol in effective doses of 10 mg blocked tumor necrosis factor-induced prostaglandin F(2α) secretion as measured by its metabolite (PGFM) concentrations in the blood. Metyrapone in effective doses of 500 mg increased the P4 concentration. Thus, both reagents were then intravaginally applied in the chosen doses daily from Day 15 to 18 after estrus (Day 0) in noninseminated heifers (n=18) or after artificial insemination (n=36). Pregnancy was confirmed by transrectal ultrasonography between Days 28-30 after insemination. Plasma concentrations of P4 were lower in cortisol-treated heifers than in control heifers on Days 17 and 18 of the estrous cycle (P<0.05). However, the interestrus intervals were not different between control and cortisol-treated animals (P>0.05). Moreover, metyrapone increased P4 and prolonged the CL lifespan in comparison to control animals (P<0.05). Interestingly, in inseminated heifers, cortisol increased the pregnancy rate (75%) compared with control animals (58%), whereas metyrapone reduced the pregnancy rate to 16.7% (P<0.05). The overall results suggest that cortisol, depending on the physiological status of heifers (pregnant vs. nonpregnant), modulates CL function by influencing P4 secretion. Cortisol may have a positive influence on CL function during early pregnancy, leading to support of embryo implantation and resulting in higher rates of pregnancy in heifers.

  19. 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.

  20. Plasma cortisol response to stress in juvenile rainbow trout is influenced by their life history during early development and by egg cortisol content.

    PubMed

    Auperin, B; Geslin, M

    2008-09-15

    In this study, the consequences of the exposure of rainbow trout (Oncorhynchus mykiss) to a brief stress during early development were explored on the later response of fingerlings to stress. Firstly, we analyzed the ontogeny of cortisol production and that of the initial cortisol response to stress in developing fish. It is only at the eyed stage that the embryos started to produce some basal cortisol. The HPI (hypothalamic-pituitary-interrenal axis) was however not functional before hatching, as exposure of the embryos to a stress did not trigger any cortisol response. A cortisol response to an acute stress was detected 9 days after hatching. In a second set of experiments, we showed that a very brief stress applied at 3 different early stages (eyed, hatching, and yolk resorption) reduced the later cortisol response to stress of 5-month-old fingerlings. This reduction is not likely to be due to alterations in the fish interrenal sensitivity because the 5-month-old fingerlings responded to ACTH treatment (only one dose tested) within the same magnitude as the fish that were not stressed during early development. An experimentally induced increase in egg cortisol just after fertilization also induced a reduction in stress sensitivity of 5 month old fingerlings, which was dose-dependent This study shows for the first time that the responsiveness of the corticotrope axis in 5-6 months old rainbow trout was influenced both by early stress exposure and by initial egg cortisol levels. Whether the HPI was functional or not at the time the initial stress was applied only had a small influence on the later unambiguous effect of early stress exposure.

  1. Effects of ipsapirone on plasma cortisol and body temperature in major depression.

    PubMed

    Meltzer, H Y; Maes, M

    1995-10-01

    Major depressed patients have been reported to exhibit significantly attenuated hypothermic responses to ipsapirone, a serotonin (5-HT)-1A partial agonist, compared to normal controls. This study further investigated the cortisol and temperature responses to ipsapirone (0.5 mg/kg orally) and placebo in 20 normal volunteers and 12 major depressed patients. Both plasma cortisol and temperature were measured every 30 min before ipsapirone or placebo administration until 180 min post administration. Ipsapirone administration produced a significant increase in plasma cortisol levels as well as hypothermia. Major depressed patients showed significantly blunted ipsapirone-induced cortisol responses compared to normal controls. No significant differences in ipsapirone-induced hypothermic responses were found between major depressed patients and normal controls.

  2. Mathematical problem solving by analogy.

    PubMed

    Novick, L R; Holyoak, K J

    1991-05-01

    We report the results of 2 experiments and a verbal protocol study examining the component processes of solving mathematical word problems by analogy. College students first studied a problem and its solution, which provided a potential source for analogical transfer. Then they attempted to solve several analogous problems. For some problems, subjects received one of a variety of hints designed to reduce or eliminate the difficulty of some of the major processes hypothesized to be involved in analogical transfer. Our studies yielded 4 major findings. First, the process of mapping the features of the source and target problems and the process of adapting the source solution procedure for use in solving the target problem were clearly distinguished: (a) Successful mapping was found to be insufficient for successful transfer and (b) adaptation was found to be a major source of transfer difficulty. Second, we obtained direct evidence that schema induction is a natural consequence of analogical transfer. The schema was found to co-exist with the problems from which it was induced, and both the schema and the individual problems facilitated later transfer. Third, for our multiple-solution problems, the relation between analogical transfer and solution accuracy was mediated by the degree of time pressure exerted for the test problems. Finally, mathematical expertise was a significant predictor of analogical transfer, but general analogical reasoning ability was not. The implications of the results for models of analogical transfer and for instruction were considered.

  3. 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

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

    PubMed

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

    2016-01-01

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

  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. 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.

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

    PubMed

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

    2013-04-01

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

  8. 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.

  9. Changes in plasma cortisol concentrations in bitches in response to different combinations of halothane and butorphanol, with or without ovariohysterectomy.

    PubMed

    Fox, S M; Mellor, D J; Lawoko, C R; Hodge, H; Firth, E C

    1998-01-01

    Changes in plasma cortisol concentrations were assessed in bitches in response to nine treatments: control, anaesthesia, analgesia, analgesia followed by anaesthesia, anaesthesia followed by analgesia at intubation, anaesthesia followed by analgesia at extubation, anaesthesia plus surgery, analgesia followed by anaesthesia plus surgery, and anaesthesia plus surgery followed by analgesia. The anaesthetic was halothane, the analgesic was butorphanol (0.4 mg kg(-1)) and the surgery was ovariohysterectomy. Blood samples, for plasma cortisol assays, were taken regularly from before treatment for five hours and then again after 24 hours. A small transient rise in plasma cortisol concentration in the control group was attributed to mild distress associated with novel experiences. A more pronounced and protracted rise in cortisol concentration in the analgesia group was ascribed to a dysphoric state of bitches under the influence of the agonist-antagonist butorphanol. Halothane anaesthesia alone resulted in no change in plasma cortisol concentration. When butorphanol was given after anaesthesia was induced or while the animal was still under the influence of anaesthesia (immediately after tracheal extubation), there was no immediate rise in plasma cortisol concentration and low concentrations were maintained for up to 60 minutes after halothane withdrawal. A marked rise in plasma cortisol concentration, which was sustained above pretreatment values for at least five hours, occurred in all surgery groups. Giving intravenous butorphanol 30 minutes prior to surgery had no effect on the surgically-induced rise in plasma cortisol concentration and no effect on the postsurgical plasma cortisol concentration. In contrast, butorphanol given at extubation did reduce plasma cortisol concentrations during the postsurgical period. These observations did not support the hypothesis that preoperative use of butorphanol would reduce the cortisol response after surgery under halothane

  10. 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...

  11. Aldosterone-cortisol imbalance immediately after fontan operation with implications for abnormal fluid homeostasis.

    PubMed

    Saiki, Hirofumi; Kuwata, Seiko; Kurishima, Clara; Iwamoto, Yoichi; Ishido, Hirotaka; Masutani, Satoshi; Senzaki, Hideaki

    2014-11-15

    Abnormal water metabolism is frequently observed after Fontan surgery. We hypothesized that patients' adrenal hormones show unique responses immediately after Fontan operation and that such a hormonal profile is related to postoperative hemodynamics and water imbalance. Twenty-eight patients who underwent a Fontan operation (n = 16) or a non-Fontan type operation (n = 12; controls) under cardiopulmonary bypass were studied. Postoperative urine cortisol and aldosterone levels were measured daily to minimize the influence of circadian rhythms and temporal hemodynamic variations. Cortisol excretion was markedly elevated on postoperative day (POD) 0 in controls, consistent with a stress-induced cortisol response. Cortisol excretion was not high on POD 0 in Fontan patients and was markedly lower than that in the controls (444 ± 150 vs 34 ± 6 μg/m(2)/day, p <0.05), indicating an adrenal insufficiency status. Conversely, aldosterone levels were significantly higher in Fontan patients than in controls immediately after surgery and remained so thereafter. The cortisol-to-aldosterone ratio was significantly lower in Fontan patients on POD 0 (p <0.05 vs controls); low cortisol-to-aldosterone ratios were associated with a longer pleural drainage duration and intensive care unit stay. Daily cortisol and aldosterone levels were significantly associated with postoperative hemodynamics; low cortisol levels correlated with low cardiac and urine outputs, whereas high aldosterone levels correlated with low cardiac output and increased blood pressure and central venous pressure. Thus, aldosterone-to-cortisol imbalance occurred specifically after the Fontan operation. This unique hormonal profile significantly affected patients' postoperative water balance and hemodynamics. Modulation of the adrenal hormone could be useful for reducing postoperative complications after the Fontan operation.

  12. Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation

    PubMed Central

    McCracken, Alison N.; McMonigle, Ryan J.; Tessier, Jérémie; Fransson, Rebecca; Perryman, Michael S.; Chen, Bin; Keebaugh, Andrew; Selwan, Elizabeth; Barr, Sarah A.; Kim, Seong M.; Roy, Saurabh G.; Liu, Gang; Fallegger, Daniel; Sernissi, Lorenzo; Brandt, Cordelia; Moitessier, Nicolas; Snider, Ashley J.; Clare, Simon; Müschen, Markus; Huwiler, Andrea; Kleinman, Michael T.; Hanessian, Stephen; Edinger, Aimee L.

    2016-01-01

    The frequency of poor outcomes in relapsed leukemia patients underscores the need for novel therapeutic approaches. The FDA-approved immunosuppressant FTY720 limits leukemia progression by activating protein phosphatase 2A and restricting nutrient access. Unfortunately, FTY720 cannot be re-purposed for use in cancer patients due to on-target toxicity associated with S1P receptor activation at the elevated, anti-neoplastic dose. Here we show that the constrained azacyclic FTY720 analog SH-RF-177 lacks S1P receptor activity but maintains anti-leukemic activity in vitro and in vivo. SH-RF-177 was not only more potent than FTY720, but killed via a distinct mechanism. Phosphorylation is dispensable for FTY720’s anti-leukemic actions. However, chemical biology and genetic approaches demonstrated that the sphingosine kinase 2- (SPHK2) mediated phosphorylation of SH-RF-177 led to engagement of a pro-apoptotic target and increased potency. The cytotoxicity of membrane-permeant FTY720 phosphonate esters suggests that the enhanced potency of SH-RF-177 stems from its more efficient phosphorylation. The tight inverse correlation between SH-RF-177 IC50 and SPHK2 mRNA expression suggests a useful biomarker for SH-RF-177 sensitivity. In summary, these studies indicate that FTY720 analogs that are efficiently phosphorylated but fail to activate S1P receptors may be superior anti-leukemic agents compared to compounds that avoid cardiotoxicity by eliminating phosphorylation. PMID:27573555

  13. Delayed effects of cortisol enhance fear memory of trace conditioning.

    PubMed

    Cornelisse, Sandra; van Ast, Vanessa A; Joëls, Marian; Kindt, Merel

    2014-02-01

    Corticosteroids induce rapid non-genomic effects followed by slower genomic effects that are thought to modulate cognitive function in opposite and complementary ways. It is presently unknown how these time-dependent effects of cortisol affect fear memory of delay and trace conditioning. This distinction is of special interest because the neural substrates underlying these types of conditioning may be differently affected by time-dependent cortisol effects. Delay conditioning is predominantly amygdala-dependent, while trace conditioning additionally requires the hippocampus. Here, we manipulated the timing of cortisol action during acquisition of delay and trace fear conditioning, by randomly assigning 63 men to one of three possible groups: (1) receiving 10mg hydrocortisone 240 min (slow cort) or (2) 60 min (rapid cort) before delay and trace acquisition, or (3) placebo at both times, in a double-blind design. The next day, we tested memory for trace and delay conditioning. Fear potentiated startle responses, skin conductance responses and unconditioned stimulus expectancy scores were measured throughout the experiment. The fear potentiated startle data show that cortisol intake 240 min before actual fear acquisition (slow cort) uniquely strengthened subsequent trace conditioned memory. No effects of cortisol delivery 60 min prior to fear acquisition were found on any measure of fear memory. Our findings emphasize that slow, presumably genomic, but not more rapid effects of corticosteroids enhance hippocampal-dependent fear memories. On a broader level, our findings underline that basic experimental research and clinically relevant pharmacological treatments employing corticosteroids should acknowledge the timing of corticosteroid administration relative to the learning phase, or therapeutic intervention.

  14. 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.

  15. Positive upshots of cortisol in everyday life.

    PubMed

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

    2016-06-01

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

  16. Inhibition of mitogen activated protein kinases increases the sensitivity of A549 lung cancer cells to the cytotoxicity induced by a kava chalcone analog.

    PubMed

    Warmka, Janel K; Solberg, Eric L; Zeliadt, Nicholette A; Srinivasan, Balasubramanian; Charlson, Aaron T; Xing, Chengguo; Wattenberg, Elizabeth V

    2012-08-03

    We are interested in investigating the biological activity of chalcones, a major class of compounds found in the beverage kava, in order to develop potent and selective chemopreventive candidates. Consumption of kava in the South Pacific Islands is inversely correlated with cancer incidence, even among smokers. Accordingly, chalcones have anti-cancer activities in animal and cell culture models. To investigate signaling pathways that affect chalcone action we studied a potent analog, (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (chalcone-24). Chalcone-24 was selected from a series of chalcone analogs that were synthesized based on the structures derived from flavokawain compounds found in kava, and screened in A549 lung cancer cells for induction of cytotoxicity and inhibition of NF-κB, a transcription factor associated with cell survival. Incubation of A549 cells with chalcone-24 resulted in a dose-dependent inhibition of cell viability, inhibition of NF-κB, activation of caspases, and activation of extracellular signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK); ERK1/2 and JNK are mitogen activated protein kinases that play central roles in regulating cell fate. Pharmacological inhibitors of ERK1/2 or JNK increased the sensitivity of A549 cells to chalcone-24-induced cytotoxicity, without affecting NF-κB or caspase activity. These results will help refine the synthesis of chalcone analogs to maximize the combination of actions required to prevent and treat cancer.

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

    PubMed

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

    2016-04-01

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

  18. 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).

  19. Optomechanical analog of two-color electromagnetically induced transparency: Photon transmission through an optomechanical device with a two-level system

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Gu, Xiu; Liu, Yu-xi; Miranowicz, Adam; Nori, Franco

    2014-08-01

    Some optomechanical systems can be transparent to a probe field when a strong driving field is applied. These systems can provide an optomechanical analog of electromagnetically induced transparency (EIT). We study the transmission of a probe field through a hybrid optomechanical system consisting of a cavity and a mechanical resonator with a two-level system (qubit). The qubit might be an intrinsic defect inside the mechanical resonator, a superconducting artificial atom, or another two-level system. The mechanical resonator is coupled to the cavity field via radiation pressure and to the qubit via the Jaynes-Cummings interaction. We find that the dressed two-level system and mechanical phonon can form two sets of three-level systems. Thus, there are two transparency windows in the discussed system. We interpret this effect as an optomechanical analog of two-color EIT (or double EIT). We demonstrate how to switch between one and two EIT windows by changing the transition frequency of the qubit. We show that the absorption and dispersion of the system are mainly affected by the qubit-phonon coupling strength and the transition frequency of the qubit.

  20. 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.

  1. 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

  2. Is afternoon cortisol more reliable than waking cortisol in association studies of children with an ASD?

    PubMed

    Sharpley, Christopher F; Bitsika, Vicki; Andronicos, Nicholas M; Agnew, Linda L

    2016-03-01

    Salivary cortisol may be used as a biomarker of stress and anxiety in children with an Autism Spectrum Disorder (ASD) and is particularly valuable in studies of the association between stress-related cortisol concentrations and other factors such as comorbid disorders or aspects of the ASD phenotype. Although protocols for the collection of cortisol shortly after waking are often based on the assumption of the presence of a diurnal rhythm in cortisol, that rhythm may not be as reliable in children with an ASD as in non-ASD children. Alternatively, collecting cortisol during the afternoon may represent a more reliable procedure with less inter-participant variability.

  3. Benzimidazole Analogs as Potent Hypoxia Inducible Factor Inhibitors: Synthesis, Biological Evaluation, and Profiling Drug-like Properties

    PubMed Central

    Chen, Jianjun; Wang, Jin; Schwab, Luciana P.; Park, Kyung-Tae; Seagroves, Tiffany N.; Jennings, Lisa K.; Miller, Duane D.; Li, Wei

    2017-01-01

    Aim To develop potent HIF-1α inhibitors for potential treatment of cancer. Materials and Methods Chemical synthesis, HIF-luciferase assay, cytotoxic assay, platelet aggregation assay, western blot analysis, quantitative real-time PCR, aqueous solubility, protein binding, metabolic stability, and metabolic pathways. Results Thirteen novel benzimidazole analogs were synthesized. Compounds 3a and 3k showed the highest anti-HIF-1α activity. They are significantly more effective than YC-1 in the suppression of HIF-1α protein expression based on western blot assay. They show comparable potency in inhibition of cancer cell migration. They are less potent in the inhibition of platelet aggregation. 3k had the most favorable drug-like properties, including long half-life in human liver microsomes, medium protein binding level and reasonable aqueous solubility. Conclusion The potent anti-HIF-1α activity and favorable drug-like properties of compound 3k suggest that it may hold great potential as an adjuvant therapy for cancer treatment through repression of HIF-1α protein expression. PMID:25075010

  4. The mechanism of oxidation-induced low-density lipoprotein aggregation: an analogy to colloidal aggregation and beyond?

    PubMed Central

    Xu, S; Lin, B

    2001-01-01

    Atherosclerosis is a disease initiated by lipoprotein aggregation and deposition in artery walls. In this study, the de novo low-density lipoprotein aggregation process was examined. Nine major intermediates were identified in two stages of the aggregation process. In the aggregation stage, low-density lipoprotein molecules aggregate and form nucleation units. The nucleation units chain together and form linear aggregates. The linear aggregates branch and interact with one another, forming fractals. In the fusion stage, spatially adjacent nucleation units in the fractal fuse into curved membrane surfaces, which, in turn, fuse into multilamellar or unilamellar vesicles. Alternatively, some adjacent nucleation units in the fractals assemble in a straight line and form rods. Subsequently, the rods flatten out into rough and then into smooth ribbons. Occasionally, tubular membrane vesicles are formed from the fractals. The aggregation stage seems to be analogous to colloidal aggregation and amyloid fiber formation. The fusion stage seems to be characteristic of the lipid-rich lipoproteins and is beyond colloidal aggregation and amyloid fiber formation. PMID:11566810

  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. 19-nor vitamin-D analogs: a new class of potent inhibitors of proliferation and inducers of differentiation of human myeloid leukemia cell lines.

    PubMed

    Asou, H; Koike, M; Elstner, E; Cambell, M; Le, J; Uskokovic, M R; Kamada, N; Koeffler, H P

    1998-10-01

    We have studied the in vitro biological activities and mechanisms of action of 1,25-dihydroxyvitamin D3 (1,25D3) and nine potent 1,25D3 analogs on proliferation and differentiation of myeloid leukemia cell lines (HL-60, retinoic acid-resistant HL-60 [RA-res HL-60], NB4 and Kasumi-1). The common novel structural motiff for almost all the analogs included removal of C-19 (19-nor); each also had unsaturation of the side chain. All the compounds were potent; for example, the concentration of analogs producing a 50% clonal inhibition (ED50) ranged between 1 x 10(-9) to 4 x 10(-11) mol/L when using the HL-60 cell line. The most active compound [1, 25(OH)2-16,23E-diene-26-trifluoro-19-nor-cholecalciferol (Ro 25-9716)] had an ED50 of 4 x 10(-11) mol/L; in contrast, the 1,25D3 produced an ED50 of 10(-9) mol/L with the HL-60 target cells. Ro 25-9716 (10(-9) mol/L, 3 days) was a strong inducer of myeloid differentiation because it caused 92% of the HL-60 cells to express CD11b and 75% of these cells to reduce nitroblue tetrazolium (NBT). This compound (10(-8) mol/L, 4 days) also caused HL-60 cells to arrest in the G1 phase of the cell cycle (88% cells in G1 v 48% of the untreated control cells). The p27(kip-1), a cyclin-dependent kinase inhibitor which is important in blocking the cell cycle, was induced more quickly and potently by Ro 25-9716 (10(-7) mol/L, 0 to 5 days) than by 1,25D3, suggesting a possible mechanism by which these analogs inhibit proliferation of leukemic growth. The NB4 promyelocytic leukemia cells cultured with the Ro 25-9716 were also inhibited in their clonal proliferation (ED50, 5 x 10(-11) mol/L) and their expression of CD11b was enhanced (80% positive [10(-9) mol/L, 4 days] v 27% untreated NB4 cells). Moreover, the combination of Ro 25-9716 (10(-9) mol/L) and all-trans retinoic acid (ATRA, 10(-7) mol/L) induced 92% of the NB4 cells to reduce NBT, whereas only 26% of the cells became NBT positive after a similar exposure to the combination of 1,25D3

  7. 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.

  8. 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.

  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. 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.

  11. A low cortisol response to acute stress is related to worse basal memory performance in older people

    PubMed Central

    Almela, Mercedes; Hidalgo, Vanesa; van der Meij, Leander; Pulopulos, Matías M.; Villada, Carolina; Salvador, Alicia

    2014-01-01

    Age-related memory decline has been associated with a faulty regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis). The aim of this study was to investigate whether the magnitude of the stress-induced cortisol increase is related to memory performance when memory is measured in non-stressful conditions. To do so, declarative and working memory performance were measured in 31 men and 35 women between 55 and 77 years of age. On a different day, the magnitude of their cortisol response to acute psychosocial stress was measured. The relationship between the cortisol response and memory performance was U shaped: a low cortisol response to stress was related to poorer declarative and working memory performance, whereas those who did not increase their cortisol levels and those who had the largest cortisol increase had better declarative and working memory capabilities. Sex did not moderate these relationships. These results suggest that a low cortisol response to stress could reflect a defective HPA-axis response to stressors that is accompanied by poorer memory performance. Conversely, a high cortisol response seems to reflect a correct functioning of the HPA-axis and may protect against memory deficits in the later stages of human life. PMID:25076903

  12. 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

  13. Induction of progesterone receptor A form attenuates the induction of cytosolic phospholipase A2alpha expression by cortisol in human amnion fibroblasts.

    PubMed

    Guo, Chunming; Ni, Xiaotian; Zhu, Ping; Li, Wenjiao; Zhu, Xiaoou; Sun, Kang

    2010-05-01

    Cytosolic phospholipase A2alpha (cPLA(2alpha), now known as PLA2G4A) is the enzyme catalyzing the formation of the rate-limiting substrate, arachidonic acid, for prostaglandin (PG) synthesis. The increasing expression of PLA2G4A toward term gestation in human amnion fibroblasts is believed to be the crucial event in parturition. Human amnion fibroblasts produce cortisol, progesterone and express glucocorticoid receptor (GR), progesterone receptor A (PGRA) form at term. The roles of progesterone and PGRA in the induction of PLA2G4A by cortisol via GR in the amnion fibroblasts remain largely unknown. Using cultured human term amnion fibroblasts, we found that cortisol induced the expression of PGRA, which was attenuated by inhibiting PG synthesis with indomethacin. Knockdown of PGRA expression or inhibition of endogenous progesterone production with trilostane significantly enhanced the induction of PLA2G4A by cortisol, whereas overexpression of PGRA attenuated the induction of PLA2G4A by cortisol. Although exogenous progesterone did not alter PLA2G4A expression under basal conditions, it attenuated cortisol-induced PLA2G4A expression at concentrations about tenfold higher, which might be achieved by competition with cortisol for GR. In conclusion, PGRA in the presence of endogenous progesterone is a transdominant repressor of the induction of PLA2G4A by cortisol. High level of progesterone may compete with cortisol for GR, thus further inhibiting the induction of PLA2G4A by cortisol. Moreover, increased PG synthesis by cortisol may feed back on the expression of PGRA leading to attenuation of cortisol-induced PLA2G4A expression. The above findings may be pertinent to the inconsistent effects of glucocorticoids on parturition in humans.

  14. 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

  15. Effects of head down tilt upon cortisol and sex hormones

    NASA Astrophysics Data System (ADS)

    Strollo, Felice; Pecorelli, Lia; Uva, Bianca Maria; Masini, Maria Angela; More, Massimo; Strollo, Giovanna; Riondino, Giuseppe

    2005-08-01

    Real and modelled μG conditions seem to induce reversible testicular failure. Suitable onground simulation methods are anyway needed in order to better aim further studies in humans in space. A 5- hour head down tilt (5h-HDT) was therefore performed in 22 male and female healthy volunteers looking at adrenal and gonadal hormones as compared to 12 age- and gender- matched controls. Cortisol and A decreased significantly in both genders, being cortisol decrease less pronounced in women, while leptin, LH, testosterone, estradiol and estrone failed to do so. The authors conclude that a 5h-HDT is only acceptable for adrenal adaptation studies whole longer duration HDT protocols are needed for gonadal investigations.

  16. VMY-1-103, a dansylated analog of purvalanol B, induces caspase-3-dependent apoptosis in LNCaP prostate cancer cells.

    PubMed

    Ringer, Lymor; Sirajuddin, Paul; Yenugonda, Venkata Mahidhar; Ghosh, Anup; Divito, Kyle; Trabosh, Valerie; Patel, Yesha; Brophy, Amanda; Grindrod, Scott; Lisanti, Michael P; Rosenthal, Dean; Brown, Milton L; Avantaggiati, Maria Laura; Rodriguez, Olga; Albanese, Chris

    2010-08-15

    The 2,6,9-trisubstituted purine group of cyclin dependent kinase inhibitors have the potential to be clinically relevant inhibitors of cancer cell proliferation. We have recently designed and synthesized a novel dansylated analog of purvalanol B, termed VMY-1-103, that inhibited cell cycle progression in breast cancer cell lines more effectively than did purvalanol B and allowed for uptake analyses by fluorescence microscopy. ErbB-2 plays an important role in the regulation of signal transduction cascades in a number of epithelial tumors, including prostate cancer (PCa). Our previous studies demonstrated that transgenic expression of activated ErbB-2 in the mouse prostate initiated PCa and either the overexpression of ErbB-2 or the addition of the ErbB-2/ErbB-3 ligand, heregulin (HRG), induced cell cycle progression in the androgen-responsive prostate cancer cell line, LNCaP. In the present study, we tested the efficacy of VMY-1-103 in inhibiting HRG-induced cell proliferation in LNCaP prostate cancer cells. At concentrations as low as 1 μM, VMY-1-103 increased both the proportion of cells in G(1) and p21(CIP1) protein levels. At higher concentrations (5 μM or 10 μM), VMY-1-103 induced apoptosis via decreased mitochondrial membrane polarity and induction of p53 phosphorylation, caspase-3 activity and PARP cleavage. Treatment with 10 μM Purvalanol B failed to either influence proliferation or induce apoptosis. Our results demonstrate that VMY-1-103 was more effective in inducing apoptosis in PCa cells than its parent compound, purvalanol B, and support the testing of VMY-1-103 as a potential small molecule inhibitor of prostate cancer in vivo.

  17. 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.

  18. 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

  19. The effect of free and carrier-bound cortisol on equine neutrophil function.

    PubMed

    Fratto, Melanie A; Hart, Kelsey A; Norton, Natalie A; Barton, Michelle H; Giguère, Steeve; Hurley, David J

    2017-01-01

    Cortisol is a key anti-inflammatory hormone that increases in bacterial sepsis and circulates predominantly bound to cortisol binding globulin (CBG). Only unbound cortisol was believed to be biologically active, but recent evidence suggests that CBG-bound cortisol also regulates inflammation. The objective of this study was to evaluate the effects of free and CBG-bound cortisol on equine neutrophil function ex vivo. We hypothesized that CBG would enhance cortisol-mediated suppression of neutrophil pro-inflammatory responses. Neutrophils isolated from 8 foals and 6 adult horses were exposed to Staphylococcus aureus antigen (SAA) alone and with hydrocortisone (HC), CBG, or both (CBG+HC). Inflammatory cytokine (TNF-α, IL-8) and reactive oxygen species (ROS) production were measured and compared among stimulants and between ages with linear mixed-effects models. CBG and CBG+HC inhibited ROS production induced by SAA in both foal and horse neutrophils, maintaining it at levels comparable to baseline production (P≤0.060-0.907). TNF-α production was not significantly different among stimulants (P=0.284). CBG+HC significantly (P≤0.016) increased IL-8 production by neutrophils in response to SAA in both foals and adults, although the response of foals was significantly greater than that of adults (P<0.001). These findings suggest that CBG directly modulates equine neutrophil responses, but the effects are cytokine- and age-specific.

  20. 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

  1. Effects of Elevated Circulating Cortisol Concentrations on Maternal Behavior in Common Marmoset Monkeys (Callithrix jacchus)

    PubMed Central

    Saltzman, Wendy; Abbott, David H.

    2009-01-01

    Summary Both acute and chronic stress can impair maternal behavior and increase rates of infant abuse in several species. The mechanisms inducing these effects are unknown, but experimental manipulation of circulating corticosterone levels alters maternal behavior in rats, and circulating or excreted cortisol concentrations have been found to correlate either positively or negatively with maternal behavior in humans and nonhuman primates. In this study, therefore, we experimentally tested the hypothesis that both acute and chronic treatment with exogenous glucocorticoids would alter maternal behavior in a primate, the common marmoset (Callithrix jacchus). Multiparous females, approximately 3−5 weeks postpartum, received daily injections of either cortisol (hydrocortisone sodium succinate and hydrocortisone acetate; N = 7) or vehicle (N = 7) for 8 days, and maternal behavior was characterized under baseline conditions as well as during exposure to a noise stressor. Cortisol treatment successfully elevated both morning and afternoon plasma cortisol concentrations and suppressed circulating levels of adrenocorticotropic hormone. In home-cage observations, cortisol-treated females carried their infants significantly less than control mothers, and in noise-stressor tests, several hours after the first cortisol or vehicle treatment, cortisol-treated mothers inspected their infants significantly more often than controls. Aggression towards infants was infrequent and mild, and did not differ between treatment groups. These findings provide the first experimental evidence that cortisol elevations can alter maternal behavior in primates. As these effects were limited in scope, however, they suggest that other stress-responsive hormones or neuropeptides may additionally play a role in mediating the effects of stress on maternal behavior. PMID:19362777

  2. Obatoclax analog SC-2001 inhibits STAT3 phosphorylation through enhancing SHP-1 expression and induces apoptosis in human breast cancer cells.

    PubMed

    Liu, Chun-Yu; Su, Jung-Chen; Ni, Mei-Huei; Tseng, Ling-Ming; Chu, Pei-Yi; Wang, Duen-Shian; Tai, Wei-Tien; Kao, Yuan-Ping; Hung, Man-Hsin; Shiau, Chung-Wai; Chen, Kuen-Feng

    2014-07-01

    Interfering oncogenic STAT3 signaling is a promising anti-cancer strategy. We examined the efficacy and drug mechanism of an obatoclax analog SC-2001, a novel STAT3 inhibitor, in human breast cancer cells. Human breast cancer cell lines were used for in vitro studies. Apoptosis was examined by both flow cytometry and western blot. Signaling pathways were assessed by western blot. In vivo efficacy of SC-2001 was tested in xenograft nude mice. SC-2001 inhibited cell growth and induced apoptosis in association with downregulation of p-STAT3 (Tyr 705) in breast cancer cells. STAT3-regulated proteins, including Mcl-1, survivin, and cyclin D1, were repressed by SC-2001. Over-expression of STAT3 in MDA-MB-468 cells protected cells from SC-2001-induced apoptosis. Moreover, SC-2001 enhanced the expression of protein tyrosine phosphatase SHP-1, a negative regulator of STAT3. Furthermore, the enhanced SHP-1 expression, in conjunction with increased SHP-1 phosphatase activity, was mediated by upregulated transcription by RFX-1. Chromatin immunoprecipitation assay revealed that SC-2001 increased the binding capacity of RFX-1 to the SHP-1 promoter. Knockdown of either RFX-1 or SHP-1 reduced SC-2001-induced apoptosis, whereas ectopic expression of RFX-1 increased SHP-1 expression and enhanced the apoptotic effect of SC-2001. Importantly, SC-2001 suppressed tumor growth in association with enhanced RFX-1 and SHP-1 expression and p-STAT3 downregulation in MDA-MB-468 xenograft tumors. SC-2001 induced apoptosis in breast cancer cells, an effect that was mediated by RFX-1 upregulated SHP-1 expression and SHP-1-dependent STAT3 inactivation. Our study indicates targeting STAT3 signaling pathway may be a useful approach for the development of targeted agents for anti-breast cancer.

  3. Ethacrynic acid oxadiazole analogs induce apoptosis in malignant hematologic cells through downregulation of Mcl-1 and c-FLIP, which was attenuated by GSTP1-1.

    PubMed

    Liu, Guyue; Wang, Rui; Wang, Yuetong; Li, Pengzhan; Zhao, Guisen; Zhao, Linxiang; Jing, Yongkui

    2013-09-01

    Ethacrynic acid, a diuretic, inhibits glutathione S-transferase P1-1 (GSTP1-1) activity and induces cell death in malignant cells at high concentrations. To improve ethacrynic acid activity, ethacrynic acid oxadiazole analogs 6s and 6u were synthesized. Although both compounds have greater antiproliferative effects than ethacrynic acid in human HL-60 cells, 6u has a reduced ability to inhibit GSTP1-1 activity. The mechanisms of both 6s- and 6u-induced cell death as well as the role of GSTP1-1 in their actions were studied. Both 6s and 6u equally induced apoptosis in HL-60 cells due to the activation of caspase-3, -9, and -8, which was correlated with the downregulation of antiapoptotic proteins c-FLIP, Mcl-1, and XIAP. The caspase inhibitor Z-VAD-FMK blocked the reduction of XIAP, but not of c-FLIP and Mcl-1, in 6s-treated cells. The reduction of c-FLIP and Mcl-1 by 6s was not blocked by the proteasomal inhibitor MG132, but was correlated with inhibition of the phosphorylation of extracellular signal-regulated kinase (ERK) and eIF4E. Both 6s and 6u decreased the intracellular glutathione (GSH) levels. N-acetylcysteine blocked reduction in the levels of Mcl-1, c-FLIP, and intracellular GSH as well as apoptosis in HL-60 cells treated by either compound. Silencing of GSTP1-1 in K562 cells sensitized, but overexpression of GSTP1-1 in Raji cells blocked, apoptosis induction by either compound. GSH conjugation at the methylene group abrogated the ability of inducing apoptosis. These data suggest that the methylene group plays an important role in the downregulation of c-FLIP and Mcl-1 proteins and apoptosis induction, which is inactivated by GSTP1-1 by forming GSH conjugates.

  4. 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.

  5. Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer.

    PubMed

    Stocke, Nathanael A; Sethi, Pallavi; Jyoti, Amar; Chan, Ryan; Arnold, Susanne M; Hilt, J Zach; Upreti, Meenakshi

    2017-03-01

    Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles or magnetic nanocomposites (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/mL) caused significant increase in cellular death/damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies.

  6. Cortisol Response to an Induction of Negative Affect among Adolescents with and without Loss of Control Eating

    PubMed Central

    Kelly, Nichole R.; Pickworth, Courtney K.; Thompson, Katherine A.; Brady, Sheila M.; Demidowich, Andrew; Galescu, Ovidiu; Altschul, Anne M.; Shank, Lisa M.; Yanovski, Susan Z.; Tanofsky-Kraff, Marian; Yanovski, Jack A.

    2015-01-01

    Background Adults with binge-eating disorder may have an exaggerated or blunted cortisol response to stress. Yet, limited data exist among youth who report loss of control (LOC) eating, a developmental precursor to binge-eating disorder. Methods We studied cortisol reactivity among 178 healthy adolescents with and without LOC eating. Following a buffet lunch meal adolescents were randomly assigned to watch a neutral or sad film clip. After, they were offered snacks from a multi-item array to assess eating in the absence of hunger. Salivary cortisol was collected at −80, 0, 30, and 50 minutes relative to film administration, and state mood ratings were reported before and after the film. Results Adolescents with LOC had greater increases in negative affect during the experimental paradigm in both conditions (ps>.05). Depressive symptoms, but not LOC, related to a greater cortisol response in the sad film condition (ps>.05). Depressive symptoms and state LOC were related to different aspects of eating behavior, independent of film condition or cortisol response (ps>.05). Conclusions A film clip that induced depressed state affect increased salivary cortisol only in adolescents with more elevated depressive symptoms. Adolescents with and without LOC were differentiated by greater increases in state depressed affect during laboratory test meals, but had no difference in cortisol reactivity. Future studies are required to determine if adolescents with LOC manifest alterations in stress reactivity to alternative stress-inducing situations. PMID:26667312

  7. Seasonal changes in CRF-I and urotensin I transcript levels in masu salmon: correlation with cortisol secretion during spawning.

    PubMed

    Westring, Christian G; Ando, Hironori; Kitahashi, Takashi; Bhandari, Ramji Kumar; Ueda, Hiroshi; Urano, Akihisa; Dores, Robert M; Sher, Anna A; Danielson, Phillip B

    2008-01-01

    Pacific salmon employ a semelparous reproductive strategy where sexual maturation is followed by rapid senescence and death. Cortisol overproduction has been implicated as the central physiologic event responsible for the post-spawning demise of these fish. Cortisol homeostasis is regulated through the action of hormones of the hypothalamus-pituitary-interrenal (HPI) axis. These include corticotropin-releasing factor (CRF) and urotensin-I (UI). In the present study, masu salmon (Oncorhynchus masou) were assayed for changes in the levels CRF-I and UI mRNA transcripts by quantitative real-time PCR (qRT-PCR). These results were compared to plasma cortisol levels in juvenile, adult, and spawning masu salmon to identify specific regulatory factors that appear to be functionally associated with changes in cortisol levels. Intramuscular implantation of GnRH analog (GnRHa) capsules was also used to determine whether GnRH influences stress hormone levels. In both male and female masu salmon, spawning fish experienced a 5- to 7-fold increase in plasma cortisol levels relative to juvenile non-spawning salmon. Changes in CRF-I mRNA levels were characterized by 1-2 distinctive short-term surges in adult masu salmon. Conversely, seasonal changes in UI mRNA levels displayed broad and sustained increases during the pre-spawning and spawning periods. The increases in UI mRNA levels were positively correlated (R(2)=0.21 male and 0.26 female, p<0.0001) with levels of plasma cortisol in the pre-spawning and spawning periods. Despite the importance of GnRH in sexual maturation and reproduction, the administration of GnRHa to test animals failed to produce broad changes in CRF-I, UI or plasma cortisol levels. These findings suggest a more direct role for UI than for CRF-I in the regulation of cortisol levels in spawning Pacific salmon.

  8. 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.

  9. 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.

  10. Interaction between cortisol and cortisol-binding protein in silver foxes (Vulpes fulvus).

    PubMed

    Oskina, I N; Tinnikov, A A

    1992-04-01

    1. Selection of silver foxes for domestic behaviour resulted in the parallel lowering of both cortisol and cortisol-binding protein (CBP) levels in the blood plasma. 2. During seasonal cycles (summer-winter) and after stress an increase in cortisol levels is followed by a decrease in CBP activity. 3. It is concluded that there are two types of interaction between cortisol and CBP in silver foxes: parallel changes in the process of domestication and opposite changes under the influence of environmental factors.

  11. Effects of chronic cortisol administration on global expression of GR and the liver transcriptome in Sparus aurata.

    PubMed

    Teles, Mariana; Boltaña, Sebastian; Reyes-López, Felipe; Santos, Maria Ana; Mackenzie, Simon; Tort, Lluis

    2013-02-01

    The present work was designed to assess the effects of artificially increased high plasma cortisol levels induced by slow-release cortisol implants on the mRNA abundance of the glucocorticoid receptor (GR) in different organs of Sparus aurata (Gilthead sea bream), as well as to evaluate global transcriptional changes in the liver, using the Aquagenomics S. aurata oligo-nucleotide microarray technology. For that purpose, groups of fish were intraperitoneally injected with implants containing two different concentrations of cortisol (50 or 200 μg/g body weight). Blood and organs were sampled after 7 and 14 days of cortisol implantation. Only fish with 200 μg/g implants exhibited a significant rise in plasma cortisol. Thus, we evaluated the expression of the GR in different organs in these fish 7 and 14 days post-implantation. GR mRNA abundance was upregulated in head kidney and heart of fish at both sampling times. In liver and muscle, GR mRNA abundance was upregulated after 14 days, whereas in gills, the GR mRNA transcript was upregulated earlier, at day 7. These results suggest that increased plasma cortisol induced by a slow-release implant of cortisol mimics the overall effects of stress and affects the expression of GR mRNA in a time- and organ-specific manner. Data obtained with the Aquagenomics S. aurata oligo-nucleotide microarray allowed the identification of a total of 491 cortisol-responsive transcripts and highlight the strong intensity of transcriptional modulation in liver of fish implanted with cortisol after 7 days, in contrast to that observed at day 14. Transcriptional remodeling highlighted a significant activity in carbohydrate metabolism mainly in the gluconeogenic pathway linked to downregulation of inflammatory and immune response processes in implanted fish.

  12. Porcine induced pluripotent stem cells analogous to naïve and primed embryonic stem cells of the mouse.

    PubMed

    Telugu, Bhanu Prakash V L; Ezashi, Toshihiko; Roberts, R Michael

    2010-01-01

    Authentic or naïve embryonic stem cells (ESC) have probably never been derived from the inner cell mass (ICM) of pig blastocysts, despite over 25 years of effort. Recently, several groups, including ours, have reported induced pluripotent stem cells (iPSC) from swine by reprogramming somatic cells with a combination of four factors, OCT4 (POU5F1)/SOX2/KLF4/c-MYC delivered by retroviral transduction. The porcine (p) iPSC resembled human (h) ESC and the mouse "Epiblast stem cells" (EpiSC) in their colony morphology and expression of pluripotent genes, and are likely dependent on FGF2/ACTIVIN/NODAL signaling, therefore representing a primed ESC state. These cells are likely to advance swine as a model in biomedical research, since grafts could potentially be matched to the animal that donated the cells for re-programming. The objective of the present work has been to develop naïve piPSC. Employing a combination of seven reprogramming factors assembled on episomal vectors, we successfully reprogrammed porcine embryonic fibroblasts on a modified LIF-medium supplemented with two kinase inhibitors; CHIR99021, which inhibits GSK-3beta, and PD0325901, a MEK inhibitor. The derived piPSC bear a striking resemblance to naïve mESC in colony morphology, are dependent on LIF to maintain an undifferentiated phenotype, and express markers consistent with pluripotency. They exhibit high telomerase activity, a short cell cycle interval, and a normal karyotype, and are able to generate teratomas. Currently, the competence of these lines for contributing to germ-line chimeras is being tested.

  13. 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.

  14. New approach for monitoring fish stress: A novel enzyme-functionalized label-free immunosensor system for detecting cortisol levels in fish.

    PubMed

    Wu, Haiyun; Ohnuki, Hitoshi; Ota, Shirei; Murata, Masataka; Yoshiura, Yasutoshi; Endo, Hideaki

    2017-07-15

    Fishes display a wide variation in their physiological responses to stress, which is clearly evident in the plasma corticosteroid changes, chiefly cortisol levels in fish. As a well-known indicator of fish stress, a simple and rapid method for detecting cortisol changes especially sudden increases is desired. In this study, we describe an enzyme-functionalized label-free immunosensor system for detecting fish cortisol levels. Detection of cortisol using amperometry was achieved by immobilizing both anti-cortisol antibody (selective detection of cortisol) and glucose oxidase (signal amplification and non-toxic measurement) on an Au electrode surface with a self-assembled monolayer. This system is based on the maximum glucose oxidation output current change induced by the generation of a non-conductive antigen-antibody complex, which depends on the levels of cortisol in the sample. The immunosensor responded to cortisol levels with a linear decrease in the current in the range of 1.25-200ngml(-1) (R=0.964). Since the dynamic range of the sensor can cover the normal range of plasma cortisol in fish, the samples obtained from the fish did not need to be diluted. Further, electrochemical measurement of one sample required only ~30min. The sensor system was applied to determine the cortisol levels in plasma sampled from Nile tilapia (Oreochromis niloticus), which were then compared with levels of the same samples determined using the conventional method (ELISA). Values determined using both methods were well correlated. These findings suggest that the proposed label-free immunosensor could be useful for rapid and convenient analysis of cortisol levels in fish without sample dilution. We also believe that the proposed system could be integrated in a miniaturized potentiostat for point-of-care cortisol detection and useful as a portable diagnostic in fish farms in the future.

  15. Zymosan-induced immune challenge modifies the stress response of hypoxic air-breathing fish (Anabas testudineus Bloch): Evidence for reversed patterns of cortisol and thyroid hormone interaction, differential ion transporter functions and non-specific immune response.

    PubMed

    Simi, S; Peter, Valsa S; Peter, M C Subhash

    2016-11-18

    Fishes have evolved physiological mechanisms to exhibit stress response, where hormonal signals interact with an array of ion transporters and regulate homeostasis. As major ion transport regulators in fish, cortisol and thyroid hormones have been shown to interact and fine-tune the stress response. Likewise, in fishes many interactions have been identified between stress and immune components, but the physiological basis of such interaction has not yet delineated particularly in air-breathing fish. We, therefore, investigated the responses of thyroid hormones and cortisol, ion transporter functions and non-specific immune response of an obligate air-breathing fish Anabas testudineus Bloch to zymosan treatment or hypoxia stress or both, to understand how immune challenge modifies the pattern of stress response in this fish. Induction of experimental peritonitis in these fish by zymosan treatment (200ngg(-1)) for 24h produced rise in respiratory burst and lysozomal activities in head kidney phagocytes. In contrast, hypoxia stress for 30min in immune-challenged fish reversed these non-specific responses of head kidney phagocytes. The decline in plasma cortisol in zymosan-treated fish and its further suppression by hypoxia stress indicate that immune challenge suppresses the cortisol-driven stress response of this fish. Likewise, the decline in plasma T3 and T4 after zymosan-treatment and the rise in plasma T4 after hypoxia stress in immune-challenged fish indicate a critical role for thyroid hormone in immune-stress response due to its differential sensitivity to both immune and stress challenges. Further, analysis of the activity pattern of ion-dependent ATPases viz. Na(+)/K(+)-ATPase, H(+)/K(+)-ATPase and Na(+)/NH4(+)-ATPase indicates a functional interaction of ion transport system with the immune response as evident in its differential and spatial modifications after hypoxia stress in immune-challenged fish. The immune-challenge that produced differential pattern

  16. Salivary cortisol and α-amylase: subclinical indicators of stress as cardiometabolic risk

    PubMed Central

    Cozma, S.; Dima-Cozma, L.C.; Ghiciuc, C.M.; Pasquali, V.; Saponaro, A.; Patacchioli, F.R.

    2017-01-01

    Currently, the potential for cardiovascular (CV) stress-induced risk is primarily based on the theoretical (obvious) side effects of stress on the CV system. Salivary cortisol and α-amylase, produced respectively by the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic-adrenomedullary (SAM) system during stress response, are still not included in the routine evaluation of CV risk and require additional and definitive validation. Therefore, this article overviews studies published between 2010 and 2015, in which salivary cortisol and α-amylase were measured as stress biomarkers to examine their associations with CV/CMR (cardiometabolic risk) clinical and subclinical indicators. A comprehensive search of PubMed, Web of Science and Scopus electronic databases was performed, and 54 key articles related to the use of salivary cortisol and α-amylase as subclinical indicators of stress and CV/CMR factors, including studies that emphasized methodological biases that could influence the accuracy of study outcomes, were ultimately identified. Overall, the biological impact of stress measured by salivary cortisol and α-amylase was associated with CV/CMR factors. Results supported the use of salivary cortisol and α-amylase as potential diagnostic tools for detecting stress-induced cardiac diseases and especially to describe the mechanisms by which stress potentially contributes to the pathogenesis and outcomes of CV diseases. PMID:28177057

  17. High temperature causes masculinization of genetically female medaka by elevation of cortisol.

    PubMed

    Hayashi, Yuki; Kobira, Hiroshi; Yamaguchi, Toshiya; Shiraishi, Eri; Yazawa, Takashi; Hirai, Toshiaki; Kamei, Yasuhiro; Kitano, Takeshi

    2010-08-01

    In poikilothermic vertebrates, sex determination is sometimes influenced by environmental factors such as temperature. However, little is known about the molecular mechanisms underlying environmental sex determination. The medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. Recently, it was reported that XX medaka can be sex-reversed into phenotypic males by high water temperature (HT; 32-34 degrees C) treatment during the sex differentiation period. Here we report that cortisol caused female-to-male sex reversal and that metyrapone (an inhibitor of cortisol synthesis) inhibited HT-induced masculinization of XX medaka. HT treatment caused elevation of whole-body levels of cortisol, while metyrapone suppressed the elevation by HT treatment during sexual differentiation. Moreover, cortisol and 33 degrees C treatments inhibited female-type proliferation of germ cells as well as expression of follicle-stimulating hormone receptor (fshr) mRNA in XX medaka during sexual differentiation. These results strongly suggest that HT induces masculinization of XX medaka by elevation of cortisol level, which, in turn, causes suppression of germ cell proliferation and of fshr mRNA expression.

  18. Salivary Cortisol: A Psychophysiological Marker for PTSD

    DTIC Science & Technology

    2011-04-01

    focused on the effects of pain killers ( morphine ) and the development of PTSD. The results indicated that for Soldiers who received morphine ... hippocampus and prevent neurogenesis in the same regions, both of which can interfere with cognition and the future adaptation to stress (Ganzel, Morris...cortisol can damage areas of the hippocampus . The damage caused by the cortisol then causes a lack of ability to cope with stress in the future. This

  19. 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.

  20. 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.

  1. 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.

  2. Changes in numbers of leukocytes in immune organs of juvenile coho salmon after acute stress or cortisol treatment

    USGS Publications Warehouse

    Maule, Alec G.; Schreck, Carl B.

    1990-01-01

    We examined the effects of acute stress and cortisol treatment on the number of leukocytes (normalized for fish body weight) in the blood, thymus, spleen, and anterior kidney of juvenile coho salmon Oncorhynchus kisutch. In acutely stressed or cortisol-fed fish, the numbers of leukocytes increased significantly in the thymus and anterior kidney, and decreased significantly in blood and spleen within 1 d after treatment. Numbers of cells in the anterior kidney, blood, and spleen returned to control levels by 3 d after treatment, but cell numbers in the thymus remained significantly greater than control values until 3–7 d after acute stress. Although dietary cortisol resulted in increased plasma cortisol titers and caused the same changes in leukocyte distribution as those caused by acute stress, the magnitude or duration of elevated cortisol levels and leukocyte numbers were not correlated. These results suggest that, although increased plasma cortisol titers induced by stress may be involved in the change in number of cells in various immune organs, factors other than cortisol are involved as well.

  3. 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.

  4. 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.

  5. 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.

  6. Learning by Analogy: Discriminating between Potential Analogs

    ERIC Educational Resources Information Center

    Richland, Lindsey E.; McDonough, Ian M.

    2010-01-01

    The ability to successfully discriminate between multiple potentially relevant source analogs when solving new problems is crucial to proficiency in a mathematics domain. Experimental findings in two different mathematical contexts demonstrate that providing cues to support comparative reasoning during an initial instructional analogy, relative to…

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

    PubMed

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

    2014-01-01

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

  8. 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

  9. NSC666715 and Its Analogs Inhibit Strand-Displacement Activity of DNA Polymerase β and Potentiate Temozolomide-Induced DNA Damage, Senescence and Apoptosis in Colorectal Cancer Cells.

    PubMed

    Jaiswal, Aruna S; Panda, Harekrushna; Law, Brian K; Sharma, Jay; Jani, Jitesh; Hromas, Robert; Narayan, Satya

    2015-01-01

    Recently approved chemotherapeutic agents to treat colorectal cancer (CRC) have made some impact; however, there is an urgent need for newer targeted agents and strategies to circumvent CRC growth and metastasis. CRC frequently exhibits natural resistance to chemotherapy and those who do respond initially later acquire drug resistance. A mechanism to potentially sensitize CRC cells is by blocking the DNA polymerase β (Pol-β) activity. Temozolomide (TMZ), an alkylating agent, and other DNA-interacting agents exert DNA damage primarily repaired by a Pol-β-directed base excision repair (BER) pathway. In previous studies, we used structure-based molecular docking of Pol-β and identified a potent small molecule inhibitor (NSC666715). In the present study, we have determined the mechanism by which NSC666715 and its analogs block Fen1-induced strand-displacement activity of Pol-β-directed LP-BER, cause apurinic/apyrimidinic (AP) site accumulation and induce S-phase cell cycle arrest. Induction of S-phase cell cycle arrest leads to senescence and apoptosis of CRC cells through the p53/p21 pathway. Our initial findings also show a 10-fold reduction of the IC50 of TMZ when combined with NSC666715. These results provide a guide for the development of a target-defined strategy for CRC chemotherapy that will be based on the mechanisms of action of NSC666715 and TMZ. This combination strategy can be used as a framework to further reduce the TMZ dosages and resistance in CRC patients.

  10. Immunosensor with fluid control mechanism for salivary cortisol analysis.

    PubMed

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

    2013-03-15

    The purpose of this research is to demonstrate a new design for a cortisol immunosensor for the noninvasive and quantitative analysis of salivary cortisol. We propose a cortisol immunosensor with a fluid control mechanism which has both a vertical flow and a lateral flow. The detected current resulting from a competitive reaction between the sample cortisol and a glucose oxidase (GOD)-labeled cortisol conjugate was found to be inversely related to the concentration of cortisol in the sample solution. A calibration curve using the relative detected current showed a R(2)=0.98 and CV=14% for a range of standard cortisol solutions corresponding to the concentrations of native salivary cortisol (0.1-10 ng/ml). The measurement could be accomplished within 35 min and the cortisol immunosensor could be reused. These results show promise for realizing an on-site and easy-to-use biosensor for cortisol. Used for evaluation of human salivary cortisol levels, the cortisol immunosensor measurement corresponded closely with commercially available ELISA method (R(2)=0.92). Our results indicate the promise of the new cortisol immunosensor for noninvasive, point of care measurement of human salivary cortisol levels.

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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

  14. Acute psychological stress increases plasma levels of cortisol, prolactin and TSH.

    PubMed

    Schedlowski, M; Wiechert, D; Wagner, T O; Tewes, U

    1992-01-01

    The effects of acute stress during a parachute jump on hormonal responses were studied in 12 experienced and 11 inexperienced military parachutists. Each subject performed two jumps. Prior to and immediately after each jump blood samples were drawn and analysed for plasma levels of cortisol, prolactin, thyrotropin (TSH), somatotropin (STH), and luteinizing hormone (LH). While there was a significant increase in cortisol, prolactin and TSH levels after both jumps, no alterations could be observed in STH and LH levels. Stress-induced hormonal responses were not affected by jump experience. There was also no association between the endocrine variables and anxiety scores.

  15. Cortisol increases growth hormone-receptor expression in human osteoblast-like cells.

    PubMed

    Swolin-Eide, D; Nilsson, A; Ohlsson, C

    1998-01-01

    It is well known that high levels of glucocorticoids cause osteoporosis and that physiologic levels of growth hormone (GH) are required for normal bone remodeling. It has been suggested that glucocorticoids regulate GH-responses via the regulation of GH-receptor expression. The aim of the present study was to investigate whether cortisol plays a role in the regulation of GH-receptor expression in cultured human osteoblasts. The effect of serum starvation and cortisol on GH-receptor expression was tested in human osteoblast (hOB)-like cells. Serum starvation for 24 h resulted in an increase in GH-receptor mRNA levels (90 +/- 1% over control culture). Cortisol increased GH-receptor mRNA levels in a dose-dependent manner with a maximal effect at 10(-6)M. The stimulating effect of cortisol on GH-receptor mRNA levels was time-dependent, reaching a peak 12 h after the addition of cortisol (126 +/- 29% over control culture) and remaining up to 12 h later. The increase in GH-receptor mRNA levels was accompanied by an increase in 125I-GH binding which reached a maximum at 24 h (196 +/- 87% over control culture). In conclusion, glucocorticoids increase GH-receptor expression in hOB-like cells. Further studies are needed to clarify whether glucocorticoid-induced regulation of the GH-receptor is important in human bone physiology.

  16. Saliva Cortisol and Exposure to Aircraft Noise in Six European Countries

    PubMed Central

    Selander, Jenny; Bluhm, Gösta; Theorell, Töres; Pershagen, Göran; Babisch, Wolfgang; Seiffert, Ingeburg; Houthuijs, Danny; Breugelmans, Oscar; Vigna-Taglianti, Federica; Antoniotti, Maria Chiara; Velonakis, Emmanuel; Davou, Elli; Dudley, Marie-Louise; Järup, Lars

    2009-01-01

    Background Several studies show an association between exposure to aircraft or road traffic noise and cardiovascular effects, which may be mediated by a noise-induced release of stress hormones. Objective Our objective was to assess saliva cortisol concentration in relation to exposure to aircraft noise. Method A multicenter cross-sectional study, HYENA (Hypertension and Exposure to Noise near Airports), comprising 4,861 persons was carried out in six European countries. In a subgroup of 439 study participants, selected to enhance the contrast in exposure to aircraft noise, saliva cortisol was assessed three times (morning, lunch, and evening) during 1 day. Results We observed an elevation of 6.07 nmol/L [95% confidence interval (CI), 2.32–9.81 nmol/L] in morning saliva cortisol level in women exposed to aircraft noise at an average 24-hr sound level (LAeq,24h) > 60 dB, compared with women exposed to LAeq,24h ≤ 50 dB, corresponding to an increase of 34%. Employment status appeared to modify the response. We found no association between noise exposure and saliva cortisol levels in men. Conclusions Our results suggest that exposure to aircraft noise increases morning saliva cortisol levels in women, which could be of relevance for noise-related cardiovascular effects. PMID:20049122

  17. 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.

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

    PubMed Central

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

    2015-01-01

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

  19. Adaptive Appraisals of Anxiety Moderate the Association between Cortisol Reactivity and Performance in Salary Negotiations

    PubMed Central

    Fridman, Ilona; Mor, Shira; Morris, Michael W.; Crum, Alia J.

    2016-01-01

    Prior research suggests that stress can be harmful in high-stakes contexts such as negotiations. However, few studies actually measure stress physiologically during negotiations, nor do studies offer interventions to combat the potential negative effects of heightened physiological responses in negotiation contexts. In the current research, we offer evidence that the negative effects of cortisol increases on negotiation performance can be reduced through a reappraisal of anxiety manipulation. We experimentally induced adaptive appraisals by randomly assigning 97 male and female participants to receive either instructions to appraise their anxiety as beneficial to the negotiation or no specific instructions on how to appraise the situation. We also measured participants’ cortisol responses prior to and following the negotiation. Results revealed that cortisol increases were positively related to negotiation performance for participants who were told to view anxiety as beneficial, and not detrimental, for negotiation performance (appraisal condition). In contrast, cortisol increases were negatively related to negotiation performance for participants given no instructions on appraising their anxiety (control condition). These findings offer a means through which to combat the potentially deleterious effects of heightened cortisol reactivity on negotiation outcomes. PMID:27992484

  20. Validation of a radioimmunoassay for measuring fecal cortisol metabolites in the hystricomorph rodent, Octodon degus.

    PubMed

    Soto-Gamboa, Mauricio; Gonzalez, Sandra; Hayes, Loren D; Ebensperger, Luis A

    2009-08-01

    Determination of fecal steroid metabolites is a noninvasive technique that characterizes the physiological state of organisms without the physiological and psychological stress of handling. Although this technique has many applications in the study of wildlife and/or captive animals without the necessity of capturing individuals, it requires a species-specific validation before use. A complete validation includes an analytical and a physiological one. In the latter changes in fecal hormone metabolites are induced by previous manipulations of the respective plasma hormones. Here we validated a method for measuring fecal cortisol metabolites (FCM) in the hystricomorph rodent Octodon degus. We extracted feces with 80% ethanol and quantified steroids using a commercial available cortisol radioimmunoassay. We first compared baseline levels of blood cortisol and FCM, and then performed a challenge test with adrenocorticotropic hormone (ACTH) to demonstrate that FCM accurately reflect adrenocortical activity. We found a significantly positive relationship between concentrations of blood cortisol and its fecal metabolites. During the ACTH challenge test, blood cortisol levels peaked 30 min after injection, and FCM mirrored this peak with a delay of about 6 hr. Our successfully validated noninvasive method provides new opportunities for studies assessing the influence of social and ecological factors on degus under natural conditions.

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

    PubMed

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

    2015-04-01

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

  2. 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

  3. 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.

  4. 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)

  5. The Analogical Mind.

    ERIC Educational Resources Information Center

    Holyoak, Keith J.; Thagard, Paul

    1997-01-01

    The use of analogy in human thinking is examined from the perspective of a multiconstraint theory that postulates similarity, structure, and purpose as three kinds of constraints. The theory has been implemented in computational simulations of the analogical human mind using the Analogical Mapping by Constraint Satisfaction (ACME) model. (SLD)

  6. 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.

  7. The ribavirin analog ICN 17261 demonstrates reduced toxicity and antiviral effects with retention of both immunomodulatory activity and reduction of hepatitis-induced serum alanine aminotransferase levels.

    PubMed

    Tam, R C; Ramasamy, K; Bard, J; Pai, B; Lim, C; Averett, D R

    2000-05-01

    The demonstrated utility of the nucleoside analog ribavirin in the treatment of certain viral diseases can be ascribed to its multiple distinct properties. These properties may vary in relative importance in differing viral disease conditions and include the direct inhibition of viral replication, the promotion of T-cell-mediated immune responses via an enhanced type 1 cytokine response, and a reduction of circulating alanine aminotransferase (ALT) levels associated with hepatic injury. Ribavirin also has certain known toxicities, including the induction of anemia upon chronic administration. To determine if all these properties are linked, we compared the D-nucleoside ribavirin to its L-enantiomer (ICN 17261) with regard to these properties. Strong similarities were seen for these two compounds with respect to induction of type 1 cytokine bias in vitro, enhancement of type 1 cytokine responses in vivo, and the reduction of serum ALT levels in a murine hepatitis model. In contrast, ICN 17261 had no in vitro antiviral activity against a panel of RNA and DNA viruses, while ribavirin exhibited its characteristic activity profile. Importantly, the preliminary in vivo toxicology profile of ICN 17261 is significantly more favorable than that of ribavirin. Administration of 180 mg of ICN 17261 per kg of body weight to rats by oral gavage for 4 weeks generated substantial serum levels of drug but no observable clinical pathology, whereas equivalent doses of ribavirin induced a significant anemia and leukopenia. Thus, structural modification of ribavirin can dissociate its immunomodulatory properties from its antiviral and toxicologic properties, resulting in a compound (ICN 17261) with interesting therapeutic potential.

  8. 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).

  9. Homocysteine, Cortisol, Diabetes Mellitus, and Psychopathology

    PubMed Central

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

    2015-01-01

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

  10. Effects of the Adult Attachment Projective Picture System on Oxytocin and Cortisol Blood Levels in Mothers.

    PubMed

    Krause, Sabrina; Pokorny, Dan; Schury, Katharina; Doyen-Waldecker, Cornelia; Hulbert, Anna-Lena; Karabatsiakis, Alexander; Kolassa, Iris-Tatjana; Gündel, Harald; Waller, Christiane; Buchheim, Anna

    2016-01-01

    Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the "hormone of affiliation" and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP) as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in n = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post in the significant majority of 73% participants (p = 0.004) and cortisol decreased in the significant majority of 73% participants (p = 0.004). Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should investigate non-lactating healthy females as well as

  11. Effects of the Adult Attachment Projective Picture System on Oxytocin and Cortisol Blood Levels in Mothers

    PubMed Central

    Krause, Sabrina; Pokorny, Dan; Schury, Katharina; Doyen-Waldecker, Cornelia; Hulbert, Anna-Lena; Karabatsiakis, Alexander; Kolassa, Iris-Tatjana; Gündel, Harald; Waller, Christiane; Buchheim, Anna

    2016-01-01

    Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the “hormone of affiliation” and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP) as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in n = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post in the significant majority of 73% participants (p = 0.004) and cortisol decreased in the significant majority of 73% participants (p = 0.004). Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should investigate non-lactating healthy females as

  12. 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.

  13. Suppression of tumor necrosis factor-α-induced nuclear factor κB activation and aromatase activity by capsaicin and its analog capsazepine.

    PubMed

    Luqman, Suaib; Meena, Abha; Marler, Laura E; Kondratyuk, Tamara P; Pezzuto, John M

    2011-11-01

    Target-specific drugs, including natural products, offer promise for the amelioration of cancer and other human ailments. Capsaicin, the pungent ingredient present in chilies (Capsicum annuum L.), and capsazepine, a synthetic analog of capsaicin (collectively referred to as vanilloids), are known to possess a variety of pharmacological and physiological properties. In our continuous effort to discover and characterize cancer chemopreventive agents from natural products, we investigated the effect of vanilloids on nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) activation using stably transfected 293/NFκB-Luc human embryonic kidney cells induced by treatment with tumor necrosis factor-α (TNFα) and on aromatase activity. Capsaicin and capsazepine blocked TNFα-induced NFκB activation in a dose-dependent manner with 50% inhibitory concentration (IC(50)) values of 0.68 and 4.2 μM, respectively. No significant cytotoxicity was observed at the highest concentrations tested (53.1 μM for capsazepine and 65.5 μM for capsaicin). In addition, these vanilloids inhibited aromatase activity with IC(50) values of 13.6 and 8.8 μM, respectively. Computer-aided molecular docking studies showed docking scores indicative of good binding affinity of vanilloids with aromatase and NFκB. The highly conserved residues for capsaicin and capsazepine binding with NFκB p50 were Ser299 and Ile278 (H-bond 2.81Å) and with NFκB p100 were Ser6, Arg82, Val86, Arg90 (H-bond 2.89Å), Gly4, and Ser2 (H-bond 2.81Å). The amino acids Trp224, Arg435, and Val373 (H-bond 2.80Å) were found to be important for the binding of capsaicin and capsazepine with aromatase. Based on these findings, aromatase and NFκB are suggested as valid targets for these compounds; additional investigation of chemopreventive or chemotherapeutic potential is required.

  14. 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.

  15. High and low emotion events influence emotional stress perceptions and are associated with salivary cortisol response changes in a consecutive stress paradigm.

    PubMed

    Nejtek, Vicki A

    2002-04-01

    Numerous studies over the last few decades have successfully utilized "psychological" stressors to examine stress-induced cortisol release as a function of the hypothalamic-pituitary-adrenal (HPA) cascade. In contrast, research examining the effect emotionally-laden stressors may have on cortisol release is scarce. Moreover, the results from the few studies that have examined subjective perceptions of emotional stress and their relationship to cortisol release are mixed. Thus, little is known about the impact an emotionally-charged stressor may have on cortisol responsivity and even less is understood about the relationship between cortisol release and perceived emotional stress. The primary goal of the present research was to investigate the effect of consecutive, emotionally stressful events on cortisol release. The secondary goal was to examine the influence perceptions about emotionally stressful events might have on cortisol responsivity. This is the first study to identify two distinct patterns of cortisol release that were significantly reversed (P=0.006) in response to high and low emotion events presented in a consecutive stress paradigm that were associated with perceptions of emotional stress.

  16. Increased testosterone to cortisol ratio in psychopathy

    PubMed Central

    Glenn, Andrea L.; Raine, Adrian; Schug, Robert A.; Gao, Yu; Granger, Douglas A.

    2011-01-01

    Only a few studies have examined hormones in psychopathy and results have been mixed. It has been suggested that since hormone systems are highly interconnected, it may be important to examine multiple systems simultaneously to gain a clearer picture of how hormones work together to predispose for a certain construct. In the present study, we attempt to clarify the role of the hormones cortisol and testosterone in psychopathy by examining both hormones in a community sample of 178 adults demonstrating a wide range of psychopathy scores. Results showed that psychopathy scores were associated with an increased ratio of testosterone (baseline) to cortisol responsivity to a stressor. Psychopathy was not associated with either of these measures independently, or with baseline cortisol levels. These findings suggest that these highly interconnected hormone systems may work in concert to predispose to psychopathy. PMID:21133509

  17. A physiological increase in maternal cortisol alters uteroplacental metabolism in the pregnant ewe

    PubMed Central

    Davies, K. L.; Ward, J. W.; de Blasio, M. J.; Fowden, A. L.

    2016-01-01

    Key points Fetal nutrient supply is dependent, in part, upon the transport capacity and metabolism of the placenta.The stress hormone, cortisol, alters metabolism in the adult and fetus but it is not known whether cortisol in the pregnant mother affects metabolism of the placenta.In this study, when cortisol concentrations were raised in pregnant sheep by infusion, proportionately more of the glucose taken up by the uterus was consumed by the uteroplacental tissues while less was transferred to the fetus, despite an increased placental glucose transport capacity. Concomitantly, the uteroplacental tissues produced lactate at a greater rate.The results show that maternal cortisol concentrations regulate uteroplacental glycolytic metabolism, producing lactate for use in utero.Prolonged increases in placental lactate production induced by cortisol overexposure may contribute to the adverse effects of maternal stress on fetal wellbeing. Abstract Fetal nutrition is determined by maternal availability, placental transport and uteroplacental metabolism of carbohydrates. Cortisol affects maternal and fetal metabolism, but whether maternal cortisol concentrations within the physiological range regulate uteroplacental carbohydrate metabolism remains unknown. This study determined the effect of maternal cortisol infusion (1.2 mg kg−1 day−1 i.v. for 5 days, n = 20) on fetal glucose, lactate and oxygen supplies in pregnant ewes on day ∼130 of pregnancy (term = 145 days). Compared to saline infusion (n = 21), cortisol infusion increased maternal, but not fetal, plasma cortisol (P < 0.05). Cortisol infusion also raised maternal insulin, glucose and lactate concentrations, and blood pH, PCO2 and HCO3 − concentration. Although total uterine glucose uptake determined by Fick's principle was unaffected, a greater proportion was consumed by the uteroplacental tissues, so net fetal glucose uptake was 29% lower in cortisol‐infused than control ewes (P < 0

  18. 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

  19. Stress and salivary cortisol during pregnancy.

    PubMed

    Obel, C; Hedegaard, M; Henriksen, T B; Secher, N J; Olsen, J; Levine, S

    2005-08-01

    The purpose of this study was to determine whether exposure to stressful life events was associated with changes in levels of circulating cortisol during pregnancy in a population of 603 pregnant women. The participating pregnant women filled out a questionnaire and collected a morning and evening sample of saliva in early pregnancy (median 14th gestational week) and in late pregnancy (median and 30th gestational week). They were asked to report the number of life events experienced during first and second trimester, respectively, and were asked to rate the intensity of the experienced events. Complications related to the pregnancy such as vaginal bleeding and suspected growth retardation were registered and the women were asked about concerns about their pregnancy. The salivary samples were analyzed for cortisol and the levels were higher in late than in early pregnancy. In late pregnancy women exposed to more than one life event or were concerned about pregnancy complications during second trimester had a higher evening cortisol level, whereas morning values were unaffected. After adjustment for smoking women who experienced more than one very stressful life event had 27% higher evening cortisol concentrations (95% confidence intervals: 1-59%). Women with worries about pregnancy complications had 27% (95% confidence intervals: 2-57%) higher levels. In early pregnancy women reporting stressful life events did not have higher evening cortisol levels, but tended to have a blunted morning HPA response. In conclusion, we found differences in the associations between chronic stress in early and late pregnancy and cortisol levels indicating that the response to chronic stress is dependent on the stage of the pregnancy.

  20. Children's Diurnal Cortisol Activity during the First Year of School

    ERIC Educational Resources Information Center

    Yang, Pei-Jung; Lamb, Michael E.; Kappler, Gregor; Ahnert, Lieselotte

    2017-01-01

    The present study examined 4- to 5-year-old British children's diurnal cortisol activity during their first year of school. The children's cortisol was measured before enrollment (baseline), upon enrollment, and both 3 and 6 months after enrollment. On each day, cortisol was sampled four times, providing information about the diurnal amount of…

  1. Altered "set-point" of the hypothalamus determines effects of cortisol on food intake, adiposity, and metabolic substrates in sheep.

    PubMed

    Henry, B A; Blache, D; Dunshea, F R; Clarke, I J

    2010-01-01

    Chronic elevation of glucocorticoid concentrations is detrimental to health. We investigated effects of chronic increase in plasma cortisol concentrations on energy balance and endocrine function in sheep. Because food intake and reproduction are regulated by photoperiod, we performed experiments in January (JAN) and August (AUG), when appetite drive is either high or low, respectively. Ovariectomized ewes were treated (intramuscularly) daily with 0.5mg Synacthen Depot(R) (synthetic adrenocorticotropin: ACTH) or saline for 4 wk. Blood samples were taken to measure plasma concentrations of cortisol, luteinising hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), leptin, insulin, and glucose. Adrenocorticotropin treatment increased concentrations of cortisol. During JAN, treatment reduced food intake transiently, but increased food intake in AUG. Leptin concentrations were reduced and glucose concentrations were greater in AUG, and insulin concentrations were similar throughout the year. Treatment with ACTH increased leptin concentrations in AUG only, whereas insulin concentrations increased in JAN only. Synacthen treatment increased glucose concentrations, with a greater effect in JAN. Changes in truncal adiposity and ACTH-induced cortisol secretion were positively correlated in JAN and negatively correlated in AUG. Treatment reduced the plasma LH pulse frequency in JAN and AUG, with an effect on pulse amplitude in JAN only. Treatment did not affect plasma GH or FSH concentrations. We conclude that chronically elevated cortisol concentrations can affect food intake, adiposity, and reproductive function. In sheep, effects of chronically elevated cortisol concentrations on energy balance and metabolism depend upon metabolic setpoint, determined by circannual rhythms.

  2. 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.

  3. 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

  4. Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population

    PubMed Central

    Kamba, Aya; Daimon, Makoto; Murakami, Hiroshi; Otaka, Hideyuki; Matsuki, Kota; Sato, Eri; Tanabe, Jutaro; Takayasu, Shinobu; Matsuhashi, Yuki; Yanagimachi, Miyuki; Terui, Ken; Kageyama, Kazunori; Tokuda, Itoyo; Takahashi, Ippei; Nakaji, Shigeyuki

    2016-01-01

    Glucocorticoids (GCs) are well known to induce insulin resistance. However, the effect of GCs on insulin secretion has not been well characterized under physiological conditions in human. We here evaluated the effect of GCs on insulin secretion/ß-cell function precisely in a physiological condition. A population-based study of 1,071 Japanese individuals enrolled in the 2014 Iwaki study (390 men, 681 women; aged 54.1 ± 15.1 years), those excluded individuals taking medication for diabetes or steroid treatment, were enrolled in the present study. Association between serum cortisol levels and insulin resistance/secretion assessed by homeostasis model assessment using fasting blood glucose and insulin levels (HOMA-R and HOMA-ß, respectively) were examined. Univariate linear regression analyses showed correlation of serum cortisol levels with HOMA-ß (ß = -0.134, p <0.001) but not with HOMA-R (ß = 0.042, p = 0.172). Adjustments for age, gender, and the multiple clinical characteristics correlated with HOMA indices showed similar results (HOMA-ß: ß = -0.062, p = 0.025; HOMA-R: ß = -0.023, p = 0.394). The correlation between serum cortisol levels and HOMA-ß remained significant after adjustment for HOMA- R (ß = -0.057, p = 0.034). When subjects were tertiled based on serum cortisol levels, the highest tertile was at greater risk of decreased insulin secretion (defined as lower one third of HOMA-ß (≤70)) than the lowest tertile, after adjustment for multiple factors including HOMA- R (odds ratio 1.26, 95% confidence interval 1.03–1.54). In conclusion, higher serum cortisol levels are significantly associated with decreased insulin secretion in the physiological cortisol range in a Japanese population. PMID:27861636

  5. Cortisol Stress Response Variability in Early Adolescence: Attachment, Affect and Sex.

    PubMed

    Cameron, Catherine Ann; McKay, Stacey; Susman, Elizabeth J; Wynne-Edwards, Katherine; Wright, Joan M; Weinberg, Joanne

    2017-01-01

    Attachment, affect, and sex shape responsivity to psychosocial stress. Concurrent social contexts influence cortisol secretion, a stress hormone and biological marker of hypothalamic-pituitary-adrenal axis activity. Patterns of attachment, emotion status, and sex were hypothesized to relate to bifurcated, that is, accentuated and attenuated, cortisol reactivity. The theoretical framework for this study posits that multiple individual differences mediate a cortisol stress response. The effects of two psychosocial stress interventions, a modified Trier Social Stress Test for Teens and the Frustration Social Stressor for Adolescents were developed and investigated with early adolescents. Both of these protocols induced a significant stress reaction and evoked predicted bifurcation in cortisol responses; an increase or decrease from baseline to reactivity. In Study I, 120 predominantly middle-class, Euro-Canadian early adolescents with a mean age of 13.43 years were studied. The girls' attenuated cortisol reactivity to the public performance stressor related significantly to their self-reported lower maternal-attachment and higher trait-anger. In Study II, a community sample of 146 predominantly Euro-Canadian middle-class youth, with an average age of 14.5 years participated. Their self-reports of higher trait-anger and trait-anxiety, and lower parental attachment by both sexes related differentially to accentuated and attenuated cortisol reactivity to the frustration stressor. Thus, attachment, affect, sex, and the stressor contextual factors were associated with the adrenal-cortical responses of these adolescents through complex interactions. Further studies of individual differences in physiological responses to stress are called for in order to clarify the identities of concurrent protective and risk factors in the psychosocial stress and physiological stress responses of early adolescents.

  6. [Evaluation of hypothalamic-pituitary-adrenal axis recovery after corticotherapy by using basal cortisol secretion].

    PubMed

    Silva, Ivani N; Cunha, Cristiane F; Finch, Francisca L; Colosimo, Enrico A

    2006-02-01

    The glucocorticoid-induced inhibition that occurs after discontinuation of treatment is the most frequent cause of adrenal insufficiency. There are yet some doubts about the best way of evaluating the hypothalamic-pituitary-adrenal (HPA) axis in those patients. The main objective of this study was to evaluate the utility of basal cortisol in diagnosing adrenal insufficiency. Thirty-five children with acute lymphoid leukemia (ALL) receiving glucocorticoid therapy (median age of 6.9 years) were evaluated. A stimulus test with corticotropin releasing hormone (CRH-1 mcg/kg) was performed before the introduction of dexamethasone (6 mg/m2/day, for 28 days), in the 8th and the 28th days of glucocorticoid therapy, and 48 hours and one month after discontinuation of therapy. Suppression of the basal secretion as well as the maximum concentration of cortisol (post-CRH) occurred during glucocorticoid therapy, which persisted for 48 hours after the steroid was removed from treatment (p< 0.01 and p< 0.0001, respectively, for the three tests). One month after ceasing the administration of the glucocorticoid, the basal secretion, as well as the maximum concentration of cortisol, were similar to that before glucocorticoid therapy. There was a positive and statistically significant correlation between basal secretion and maximum concentration of cortisol in all tests. We observed 95% of specificity for the diagnosis of adrenal insufficiency when the inferior limit of basal cortisol was 8.5 mcg/dl. According to these results we concluded that basal secretion of cortisol is a good marker of supra-renal function in evaluating children after discontinuation of glucocorticoid therapy.

  7. Minireview: Stress-related psychiatric disorders with low cortisol levels: a metabolic hypothesis.

    PubMed

    Yehuda, Rachel; Seckl, Jonathan

    2011-12-01

    Several stress-associated neuropsychiatric disorders, notably posttraumatic stress disorder and chronic pain and fatigue syndromes, paradoxically exhibit somewhat low plasma levels of the stress hormone cortisol. The effects appear greatest in those initially traumatized in early life, implying a degree of developmental programming, perhaps of both lower cortisol and vulnerability to psychopathology. In these conditions, lowered cortisol is not due to any adrenal or pituitary insufficiency. Instead, two processes appear involved. First, there is increased target cell sensitivity to glucocorticoid action, notably negative feedback upon the hypothalamic-pituitary-adrenal (stress) axis. Altered density of the glucocorticoid receptor is inferred, squaring with much preclinical data showing early life challenges can permanently program glucocorticoid receptors in a tissue-specific manner. These effects involve epigenetic mechanisms. Second, early life trauma/starvation induces long-lasting lowering of glucocorticoid catabolism, specifically by 5α-reductase type 1 (predominantly a liver enzyme) and 11β-hydroxysteroid dehydrogenase type 2 (in kidney), an effect also seen in model systems. These changes reflect a plausible early-life adaptation to increase the persistence of active cortisol in liver (to maximize fuel output) and kidney (to increase salt retention) without elevation of circulating levels, thus avoiding their deleterious effects on brain and muscle. Modestly lowered circulating cortisol and increased vulnerability to stress-associated disorders may be the outcome. This notion implies a vulnerable early-life phenotype may be discernable and indicates potential therapy by modest glucocorticoid replacement. Indeed, early clinical trials with cortisol have shown a modicum of promise.

  8. 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

  9. Analog without fear

    NASA Technical Reports Server (NTRS)

    Delagrange, A. D.

    1977-01-01

    Analog circuitry, also referred to as Linear, has been nearly run over by the digital/computer bandwagon. This is unfortunate because tremendous advances are being made in the field of analog integrated circuitry. Each year's progress raises the state-of-the-art, bringing achievements not possible even the year before. Many of the traditional prejudices against analog circuitry are no longer valid. This report attempts to summarize what is available now and what can (and can't) be done with analog integrated circuitry.

  10. 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.

  11. 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.

  12. Cortisol Awakening Response and Acute Stress Reactivity in First Nations People

    PubMed Central

    Berger, Maximus; Leicht, Anthony; Slatcher, Angela; Kraeuter, Ann Katrin; Ketheesan, Sarangan; Larkins, Sarah; Sarnyai, Zoltán

    2017-01-01

    First Nations people globally have a higher incidence of mental disorders and non-communicable diseases. These health inequalities are partially attributed to a complex network of social and environmental factors which likely converge on chronic psychosocial stress. We hypothesized that alterations in stress processing and the regulation of the hypothalamic-pituitary-adrenal axis might underlie health disparities in First Nations people. We assessed the cortisol awakening response and the dynamic response to a laboratory induced psychosocial stress of young Indigenous tertiary students (n = 11, mean age 23.82 years) and non-Indigenous students (n = 11) matched for age and gender. Indigenous participants had a blunted cortisol awakening response (27.40 (SD 35.00) vs. 95.24 (SD 55.23), p = 0.002), which was differentially associated with chronic experience of stress in Indigenous (r = −0.641, p = 0.046) and non-Indigenous (r = 0.652, p = 0.03) participants. The cortisol response to the laboratory induced psychosocial stress did not differ between groups. Self-reported racial discrimination was strongly associated with flattened cortisol response to stress (r = −0676, p = 0.022) and with heart rate variability (r = 0.654, p = 0.040). Our findings provide insight into potential biological factors underlying health discrepancies in ethnic minority groups. PMID:28139727

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

    PubMed

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

    1985-12-01

    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. 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.

  15. CSF cortisol in Alzheimer's disease and mild cognitive impairment.

    PubMed

    Popp, Julius; Schaper, Karsten; Kölsch, Heike; Cvetanovska, Gabriela; Rommel, Fatima; Klingmüller, Dietrich; Dodel, Richard; Wüllner, Ullrich; Jessen, Frank

    2009-03-01

    Hypercortisolaemia occurs in Alzheimer's disease (AD) and may be involved in the AD related neurodegenerative process. In order to determine whether brain structures are exposed to high cortisol concentrations early in AD, we measured cerebrospinal fluid (CSF) cortisol in 66 subjects with AD, 33 subjects with mild cognitive impairment (MCI) and 34 control subjects. CSF cortisol concentrations were higher in AD subjects compared to controls (p<0.001) and to MCI subjects (p=0.002). There was no significant increase of cortisol in MCI subjects compared with controls suggesting that the increase of CSF cortisol is not an early event in the course of AD.

  16. GHRP-6 is able to stimulate cortisol and ACTH release in patients with Cushing's disease: comparison with DDAVP.

    PubMed

    Oliveira, J H A; Vieira, J G H; Abucham, J; Lengyel, A M J

    2003-03-01

    It has been shown that hexarelin stimulates ACTH and cortisol secretion in patients with Cushing's disease. The ACTH release induced by this peptide is 7-fold greater than that obtained by hCRH. The mechanism of action of hexarelin on the hypothalamic-pituitary-adrenal axis has not been fully elucidated. Although controversial, there is evidence that it might be mediated by arginine vasopressin (AVP). The aim of this study was to evaluate the ACTH and cortisol releasing effects of GHRP-6 in patients with Cushing's disease and to compare them with those obtained with DDAVP administration. We studied 10 patients with Cushing's disease (8 female, 2 male; age: 36.7 +/- 4.2 yr), 9 with microadenomas, who were submitted to both GHRP-6 (2 microg/kg iv) and DDAVP (10 micro g i.v.) in bolus administration on 2 separate occasions. ACTH was measured by immunochemiluminometric assay and cortisol by radioimmunoassay. The sensitivities of the assays are 0.2 pmol/l for ACTH, and 11 nmol/l for cortisol. GHRP-6 was able to increase significantly both ACTH (pmol/l, mean +/- SE; basal: 15.5 +/- 1.7 vs peak: 45.1 +/- 9.3) and cortisol values (nmol/l, basal: 583.0 +/- 90.8 vs peak: 1013.4 +/- 194.6). ACTH AUC (pmol/l min(-1)) and cortisol AUC (nmol/l min(-1)) values were 1235.4 and 20577.2, respectively. After DDAVP administration there was a significant increase in ACTH (basal: 13.0 +/- 1.4 vs peak: 50.5 +/- 16.2) and cortisol levels (basal: 572.5 +/- 112.7 vs peak: 860.5 +/- 102.8. AUC values for ACTH and cortisol were 1627.6 +/- 639.8 and 18364.7 +/- 5661.4, respectively. ACTH and cortisol responses to GHRP-6 and DDAVP did not differ significantly (peak: 45.1 +/- 9.3 vs 50.5 +/- 16.2; AUC: 1235.4 +/- 424.8 vs 1627.6 +/- 639.8). There was a significant positive correlation between peak cortisol values after GHRP-6 and DDAVP administration (r = 0.87, p = 0.001). Our results show that GHRP-6 is able to stimulate ACTH and cortisol release in patients with Cushing's disease. These

  17. Cortisol Response to Embarrassment and Shame.

    ERIC Educational Resources Information Center

    Lewis, Michael; Ramsay, Douglas

    2002-01-01

    This study examined individual differences in 4-year-old children's expression of the self-conscious emotions of embarrassment and shame and their relation to differences in cortisol response to stress. Results indicated the presence of two different types of embarrassment--one that reflected negative evaluation of the self, and the other a…

  18. Cortisol extraction through human skin by reverse iontophoresis.

    PubMed

    Ventura, Stephanie A; Heikenfeld, Jason; Brooks, Tiffany; Esfandiari, Leyla; Boyce, Steven; Park, Yoonjee; Kasting, Gerald B

    2017-04-01

    Continuous monitoring of cortisol at the surface of the skin would advance the diagnosis and treatment of cortisol-related diseases, or of elevated cortisol levels related to stress in otherwise healthy populations. Reliable and accurate detection of cortisol at the skin surface remains a limiting factor in real-time monitoring of cortisol. To address this limitation, cortisol extraction through excised human skin by reverse iontophoresis was studied in vitro in side-by-side diffusion cells using a radiolabeled probe. The skin was subjected to four direct current regimens (0, 28, 56, 113μAcm(-2)) with the anode in the donor chamber and the cumulative cortisol concentrations recorded in the receiver chamber. The 56 and 113μAcm(-2) regimens significantly increased transport of (3)H-cortisol through the skin, and current density correlated directly with transcutaneous transport of (3)H-cortisol. The threshold of detection of electroosmotic versus passive diffusion of cortisol through the skin was between 28 and 56μAcm(-2). The results of this study are significant in examining how lipophilic analytes found in the bloodstream respond to reverse iontophoresis across the skin. In addition, a device integration technique is presented which illustrates how continuous cortisol extraction and sensing could potentially be achieved in a conventional wearable format.

  19. Accelerated trace eyeblink conditioning after cortisol IV-infusion.

    PubMed

    Kuehl, Linn K; Lass-Hennemann, Johanna; Richter, Steffen; Blumenthal, Terry D; Oitzl, Melly; Schachinger, Hartmut

    2010-11-01

    Impairing effects of cortisol on learning performance have been shown in human trace eyeblink conditioning. As the effect is observed from 30 min to hours after administration, a genomic action of cortisol is assumed. Here we report rapid cortisol effects that were observed during the first 10 min after cortisol administration in humans. Young healthy males (n=24) received the cortisol synthesis inhibitor metyrapone (1.5 g per os) to avoid interference of the endogenous pulsatile secretion of cortisol. Next, 2mg cortisol or placebo was infused intravenously, immediately before the trace conditioning task. The probability of the conditioned eyeblink responses was assessed electromyographically during the trace eyeblink conditioning task (unconditioned stimulus: corneal air puff, 10 psi, 50 ms; conditioned stimulus: binaural pure tone, 7 dB, 1000 Hz, 400 ms; empty interval between CS and US: 550 ms). Cortisol resulted in a faster increase of conditioning (p=.02), reaching a comparable level to placebo later on. This result extends the well-known effects of stress on the quality and amount of learning by showing that cortisol also affects the speed of learning. We propose that cortisol accelerates trace eyeblink conditioning via a fast, non-genomic mechanism. This fast action of cortisol is part of the adaptive strategy during the early stress response.

  20. 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 ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. Cortisol stress responses and children's behavioral functioning at school

    PubMed Central

    Cillessen, Antonius H.N.; de Weerth, Carolina

    2016-01-01

    The present study investigated whether cortisol stress responses of 6‐year‐olds were associated with their behavioral functioning at school. Additionally, the moderating role of stress in the family environment was examined. To this end, 149 healthy children (M age = 6.09 years; 70 girls) participated in an age‐appropriate innovative social evaluative stress test. Saliva cortisol samples were collected six times during the stress test to calculate two indices of the cortisol stress response: cortisol stress reactivity and total stress cortisol. Teachers assessed children's internalizing, externalizing, and prosocial behaviors. Stress in the family environment was operationalized as maternally reported parenting stress. Results indicated a significant increase in cortisol concentrations in response to the stressor. No significant associations were found between cortisol stress responses and behavioral functioning at school and there was no evidence for moderation by maternal parenting stress. Potential theoretical and methodological explanations for these results are discussed. PMID:27774583

  3. 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…

  4. Analogies for Avogadro's Number.

    ERIC Educational Resources Information Center

    Poskozim, Paul S.; And Others

    1986-01-01

    Reviews analogies used to try to capture the concept of the magnitude of Avogadro's number, including analogies related to small/tiny objects, counting, people, water, and money. Also presents several new ones which are based on modern computers and printers. (JN)

  5. 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…

  6. Analog pulse processor

    DOEpatents

    Wessendorf, Kurt O.; Kemper, Dale A.

    2003-06-03

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

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

    PubMed Central

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

    2013-01-01

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

  8. 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

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

    PubMed

    Vainikka, Anssi; Kortet, Raine; Taskinen, Jouni

    2004-09-08

    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.

  10. 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.

  11. 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

  12. The burden of conscientiousness? Examining brain activation and cortisol response during social evaluative stress.

    PubMed

    Dahm, Anne-Sophie; Schmierer, Phöbe; Veer, Ilya M; Streit, Fabian; Görgen, Anna; Kruschwitz, Johann; Wüst, Stefan; Kirsch, Peter; Walter, Henrik; Erk, Susanne

    2017-04-01

    Although conscientiousness has for a long time been considered generally adaptive, there are findings challenging this view, suggesting that conscientiousness might be less advantageous during uncontrollable stress. We here examined the impact of conscientiousness on brain activation during and the cortisol response following an uncontrollable social evaluative stress task in order to test this hypothesis. Brain activation and cortisol levels were measured during an fMRI stress task, where subjects (n=86) performed cognitive tasks containing preprogrammed failure under time pressure, while being monitored by a panel of experts inducing social-evaluative threat. The degree of conscientiousness was measured using the NEO-FFI. We observed a positive correlation between conscientiousness and salivary cortisol levels in response to the stressful task in male subjects only. In male subjects conscientiousness correlated positively with activation in right amygdala and left insula, and, moreover, mediated the influence of amygdala and insula activation on cortisol output. This pattern of brain activation can be interpreted as a disadvantageous response to uncontrollable stress to which highly conscientious individuals might be predisposed. This is the first study showing the effect of conscientiousness on physiology and brain activation to an uncontrollable psychosocial stressor. Our results provide neurobiological evidence for the hypothesis that conscientiousness should not just be seen as beneficial, but rather as a trait associated with either costs or benefits depending on the extent to which one is in control of the situation.

  13. 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.

  14. Stress and emotional memory retrieval: effects of sex and cortisol response.

    PubMed

    Buchanan, Tony W; Tranel, Daniel

    2008-02-01

    In some situations, memory is enhanced by stressful experience, while in others, it is impaired. The specific components of the stress-response that may result in these differing effects remain unclear, and the current study sought to address this knowledge gap. Forty healthy participants (20 women, 20 men) were exposed to emotionally arousing and neutral pictures. Twenty-four hours later, 20 participants underwent a social stressor (speech and math tests), and 20 underwent a control reading task, both followed by a delayed free recall task. Cortisol responders to the stress condition (5 men and 1 woman) showed reduced memory retrieval for both neutral and emotionally arousing pictures. Men and women in the stress condition who did not produce a cortisol response showed increased retrieval of unpleasant pictures compared to controls. The results provide further evidence that cortisol is a primary effector in the stress-induced memory retrieval deficit. At the same time, stress can enhance memory retrieval performance, especially for emotional stimuli, when the cortisol response is absent.

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. Huggable communication medium decreases cortisol levels.

    PubMed

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

    2013-10-23

    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.

  20. The role of anxiety in cortisol stress response and cortisol recovery in boys with oppositional defiant disorder/conduct disorder.

    PubMed

    Schoorl, Jantiene; Rijn, Sophie van; Wied, Minet de; van Goozen, Stephanie; Swaab, Hanna

    2016-11-01

    Children with antisocial and aggressive behaviors have been found to show abnormal neurobiological responses to stress, specifically impaired cortisol stress reactivity. The role of individual characteristics, such as comorbid anxiety, in the stress response is far less studied. Furthermore, this study extended previous studies in that not only baseline and reactivity to a psychosocial stressor were examined, but also recovery from a stressor. These three phases of cortisol could be impacted differentially in boys with oppositional defiant disorder/conduct disorder (ODD/CD) with (+ANX) and without anxiety (-ANX). The results revealed that cortisol patterns in response to psychosocial stress were different for boys with ODD/CD+ANX (n=32), ODD/CD-ANX (n=22) and non-clinical controls (NC) (n=34), with age range of 7.8-12.9 years. The ODD/CD-ANX group showed lower overall cortisol levels than the NC group. When considering the three phases of cortisol separately, the ODD/CD-ANX group had lower baseline cortisol levels relative to the other groups, whereas the ODD/CD+ANX showed an impaired cortisol recovery response. Within those with ODD/CD, callous-unemotional traits were predictive of high baseline cortisol levels. Also, anxiety predicted high baseline and recovery cortisol levels, whereas a high number of CD symptoms predicted reduced cortisol stress reactivity. These results clearly indicate that comorbid anxiety is an important factor in explaining differences in stress response profiles in boys with ODD/CD; although boys with CD/ODD are generally characterized by an impaired cortisol stress response, we found that those with comorbid anxiety showed impaired cortisol recovery, whereas those without anxiety showed reduced baseline cortisol levels.

  1. Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder.

    PubMed

    Meltzer, H; Bastani, B; Jayathilake, K; Maes, M

    1997-07-01

    It has been suggested that the clinical efficacy of chronic treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and perhaps all antidepressants is due to their ability to enhance serotonergic activity. The effects of chronic treatment with fluoxetine or tricyclic antidepressants on the L-5-hydroxytryptophan (200 mg, L-5-HTP; PO)-induced increases in plasma cortisol and prolactin (PRL) concentrations were studied in patients with major depression or obsessive compulsive disorder (OCD). Administration of L-5-HTP increased plasma cortisol and PRL levels in medicated and unmedicated patients with major depression or OCD. The L-5-HTP-induced cortisol and PRL responses were significantly higher in fluoxetine-treated than in tricyclic-treated or unmedicated major depressed patients. The latter two groups did not differ significantly in their cortisol or PRL responses to L-5-HTP. The L-5-HTP-induced increases in cortisol and PRL in fluoxetine-treated patients with major depression or OCD were not significantly different. The results suggest that fluoxetine, but not tricyclic antidepressants, potentiates 5-HT receptor-mediated stimulation of cortisol and PRL secretion in humans, consistent with available evidence that fluoxetine treatment, but not tricyclic antidepressants, increases central serotonergic activity in patients with MD or OCD by a presynaptic mechanism.

  2. 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.

  3. 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.

  4. The stress hormone cortisol blocks perceptual learning in humans.

    PubMed

    Dinse, Hubert R; Kattenstroth, J C; Lenz, M; Tegenthoff, M; Wolf, O T

    2017-03-01

    Cortisol, the primary glucocorticoid (GC) in humans, influences neuronal excitability and plasticity by acting on mineralocorticoid and glucocorticoid receptors. Cellular studies demonstrated that elevated GC levels affect neuronal plasticity, for example through a reduction of hippocampal long-term potentiation (LTP). At the behavioural level, after treatment with GCs, numerous studies have reported impaired hippocampal function, such as impaired memory retrieval. In contrast, relatively little is known about the impact of GCs on cortical plasticity and perceptual learning in adult humans. Therefore, in this study, we explored the impact of elevated GC levels on human perceptual learning. To this aim, we used a training-independent learning approach, where lasting changes in human perception can be induced by applying passive repetitive sensory stimulation (rss), the timing of which was determined from cellular LTP studies. In our placebo-controlled double-blind study, we used tactile LTP-like stimulation to induce improvements in tactile acuity (spatial two-point discrimination). Our results show that a single administration of hydrocortisone (30mg) completely blocked rss-induced changes in two-point discrimination. In contrast, the placebo group showed the expected rss-induced increase in two-point discrimination of over 14%. Our data demonstrate that high GC levels inhibit rss-induced perceptual learning. We suggest that the suppression of LTP, as previously reported in cellular studies, may explain the perceptual learning impairments observed here.

  5. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    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.

  6. Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age.

    PubMed

    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

  7. Gains in fluid ability performance and their relationship to cortisol.

    PubMed

    Kelly, K S; Hayslip, B

    2000-01-01

    The present analyses examined the relationship between cortisol and performance gains in crystallized (Gc) and fluid (Gf) ability, as well as the relationship to measures of everyday cognitive functioning in a sample of 73 older adults. The analyses were part of a larger study examining the impact of anxiety-reduction training on everyday tasks. Cortisol was assessed via urine sampling. Results indicated that there was a significant negative correlation between cortisol and performance gains for Gf, replicating earlier findings reported by our laboratory. These findings also extend the relationship to cortisol measured in urine; previous analyses were conducted using serum-based cortisol. Cortisol was also significantly related to performance gains in some measures of everyday cognitive functioning.

  8. 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.

  9. 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)

  10. 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.

  11. 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.

  12. Development of a modified cortisol extraction procedure for intermediately sized fish not amenable to whole-body or plasma extraction methods.

    PubMed

    Guest, Taylor W; Blaylock, Reginald B; Evans, Andrew N

    2016-02-01

    The corticosteroid hormone cortisol is the central mediator of the teleost stress response. Therefore, the accurate quantification of cortisol in teleost fishes is a vital tool for addressing fundamental questions about an animal's physiological response to environmental stressors. Conventional steroid extraction methods using plasma or whole-body homogenates, however, are inefficient within an intermediate size range of fish that are too small for phlebotomy and too large for whole-body steroid extractions. To assess the potential effects of hatchery-induced stress on survival of fingerling hatchery-reared Spotted Seatrout (Cynoscion nebulosus), we developed a novel extraction procedure for measuring cortisol in intermediately sized fish (50-100 mm in length) that are not amenable to standard cortisol extraction methods. By excising a standardized portion of the caudal peduncle, this tissue extraction procedure allows for a small portion of a larger fish to be sampled for cortisol, while minimizing the potential interference from lipids that may be extracted using whole-body homogenization procedures. Assay precision was comparable to published plasma and whole-body extraction procedures, and cortisol quantification over a wide range of sample dilutions displayed parallelism versus assay standards. Intra-assay %CV was 8.54%, and average recovery of spiked samples was 102%. Also, tissue cortisol levels quantified using this method increase 30 min after handling stress and are significantly correlated with blood values. We conclude that this modified cortisol extraction procedure provides an excellent alternative to plasma and whole-body extraction procedures for intermediately sized fish, and will facilitate the efficient assessment of cortisol in a variety of situations ranging from basic laboratory research to industrial and field-based environmental health applications.

  13. 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.

  14. 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.

  15. Responses of cortisol and prolactin to sexual excitement and stress in stallions and geldings.

    PubMed

    Colborn, D R; Thompson, D L; Roth, T L; Capehart, J S; White, K L

    1991-06-01

    Sexual stimulation induces rapid secretion of cortisol and prolactin (PRL) in stallions. Experiment 1 was designated to determine whether stallions associated location and(or) procedure with previous sexual stimulation in that location. After a control period on d 1, four stallions were exposed to an estrous mare for 5 min on d 2. On d 3, 4, 5, and 6, the same procedure was followed with no mare present. Concentrations of PRL and cortisol increased (P less than .05) after mare exposure on d 2 but did not vary (P greater than .05) on d 1, 3, 4, 5, or 6. In Exp. 2, six stallions were used to determine the short-term effects of 1) sexual stimulation, 2) acute physical exercise, 3) restraint via a twitch (twitching), 4) epinephrine administration, and 5) no stimulation on plasma concentrations of PRL and cortisol. Stallions received one treatment per day separated by 2 d of no treatment. Concentrations of cortisol increased (P less than .05) within 10 min after sexual stimulation, exercise, twitching, and epinephrine administration but not during control bleedings. Concentrations of PRL increased (P less than .05) immediately after sexual stimulation, exercise, and twitching but not after epinephrine administration or during control bleeding. In Exp. 3, the same five treatments were administered to six geldings. Concentrations of cortisol increased (P less than .05) after epinephrine administration, exercise, and twitching but not after sexual stimulation or during control bleedings. Concentrations of PRL increased (P less than .05) after exercise and sexual stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Effects of IL-6 and cortisol fluctuations in post-stroke depression.

    PubMed

    Zhang, Xiao-Fan; Zou, Wei; Yang, Yuan

    2016-10-01

    Depression is an important post-stroke sequela with negative impact on mortality, functional outcome and quality of life. Changes in cytokines have been hypothesized to be associated with the etiology of post-stroke depression (PSD). The altere dhypothalamic-pituitary-adrenal (HPA) functioning is associated with the onset of depression. The activity of HPA could induce the fluctuations of cortisol levels. In this study, we prospectively checked interleukin 6 (IL-6) and cortisol levels in patients with early ischemic stroke. It was hypothesized that early serum IL-6 and cortisol fluctuations in stroke patients were the predictions of PSD. Totally, 100 participants were selected from stroke inpatients consecutively admitted to the Department of Neurology, Tongji Hospital from July 2014 to December 2015. Fifty health people served as the controls. The serum of all the patients was collected at 8:00 am and 4:00 pm respectively one week after stroke. The serum of controls was collected only at 8:00 am. The levels of IL-6 were analyzed by enzyme-linked immunosorbent assay kit, and those of cortisol were detected by chemiluminescence immunoassay. On the 3rd week after stroke, the patients were enrolled to the PSD group and non-PSD group based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and The Hamilton Depression Rating Scale (HAMD-21, score>7). The IL-6 level (13.24±2.89 ng/L) was elevated significantly in PSD groups as compared with that in non-PSD group and control group respectively (P<0.05 for both), but there was no significant difference in the IL-6 level between non-PSD group and control group. The patients in both PSD group and non-PSD group had significantly elevated morning cortisol levels in comparison with those in the control group (P<0.05; for PSD, non-PSD and control: 508.86±119.51, 420.83±70.04 and 340.40±76.30 nmol/L respectively). Moreover, afternoon cortisol levels in PSD group were significantly higher than those in non

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

    PubMed Central

    2010-01-01

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

  18. Use of Salivary Cortisol Measurements in Young Infants: A Note of Caution.

    ERIC Educational Resources Information Center

    Magnano, Catherine L.; And Others

    1989-01-01

    Findings indicate that high cortisol levels and interfering substances in formula and breast milk could contaminate salivary cortisol measurements in young infants. To insure accurate results, appropriate controls should be taken for salivary cortisol measurements of young infants. (RH)

  19. A piezoelectric immunosensor for the detection of cortisol.

    PubMed

    Attili, B S; Suleiman, A A

    1995-01-01

    A piezoelectric crystal immunosensor has been developed for the detection and determination of cortisol. Cortisol antibody was layered onto the gold electrodes of a 10 MHz piezoelectric crystal which was pre-coated with either protein A or gluteraldehyde. Crystals pre-coated with protein A showed the best results with respect to stability and sensitivity. The sensor was successfully used for the determination of cortisol in standard solutions from 36-3628 micrograms/L (part per billion). The advantages of the proposed sensor include simplicity, short analysis time, cost effectiveness and selectivity. The results demonstrate the feasibility of cortisol assay in clinical testing and in drug monitoring.

  20. Cortisol levels in hair of East Greenland polar bears.

    PubMed

    Bechshøft, T Ø; Sonne, C; Dietz, R; Born, E W; Novak, M A; Henchey, E; Meyer, J S

    2011-01-15

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

  1. Born to yawn? Cortisol linked to yawning: a new hypothesis.

    PubMed

    Thompson, Simon B N

    2011-11-01

    Yawning has become an interesting and curious scientific conundrum. Links between several neurological disorders can be found through the commonality of yawning episodes and contagious yawning. However, the reasons why we yawn are uncertain. Cortisol levels are known to rise during stress and fatigue; yawning may occur when we are under stress or tired. We do not know whether cortisol levels fluctuate during yawning. Potentially, yawning and cortisol levels may provide a valuable diagnostic tool and warning of untoward underlying neurological problems. A new hypothesis is proposed that links cortisol levels with yawning episodes.

  2. Alteration of cartilage glycosaminoglycan protein acceptor by somatomedin and cortisol.

    PubMed

    Kilgore, B S; McNatt, M L; Meador, S; Lee, J A; Hughes, E R; Elders, M J

    1979-02-01

    The effect of somatomedin and cortisol on embryonic chick cartilage in vitro indicates that somatomedin stimulates 35SO4 uptake while cortisol decreases it with no effect on glycosaminoglycan turnover. Xylosyltransferase activity is increased in crude fractions of somatomedin-treated cartilage but decreased in cortisol-treated cartilage. By using a Smith-degraded proteoglycan as an exogenous acceptor, xylosyltransferase activities from both treatments were equivalent, suggesting that the enzyme was not rate limiting. The results of xylosyltransferase assays conducted by mixing enzyme and endogenous acceptor from control, cortisol-treated and somatomedin-treated cartilage, suggest both effects to be at the level of the acceptor protein.

  3. 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.

  4. Cell contacts are required for induction by cortisol of glutamine synthetase gene transcription in the retina.

    PubMed Central

    Vardimon, L; Fox, L L; Degenstein, L; Moscona, A A

    1988-01-01

    In embryonic neural retina the enzyme glutamine synthetase [GS; L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] is a glia-specific differentiation marker inducible with cortisol. We show that cortisol elicits GS mRNA accumulation by stimulating transcription of the GS gene and that this stimulation requires cell contacts: in dissociated and separated retina cells GS gene transcription was not induced; when the separated cells were reassembled into multicellular aggregates, restoring cell contacts, accumulation of GS mRNA was again inducible. In cells dissociated from retina tissue that had been preinduced with cortisol, GS gene transcription rapidly declined, despite continued hormone availability. In the separated cells transcription of the histone H3.3 gene and accumulation of carbonic anhydrase II mRNA were unaffected; therefore, cell separation selectively precluded induction of the GS gene. These findings provide direct evidence for the regulatory role of cell contacts in hormonal control of gene transcription. Images PMID:2901094

  5. 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

  6. Cortisol and IGF-1 synergistically up-regulate taurine transport by the rat skeletal muscle cell line, L6.

    PubMed

    Park, Sung-Hee; Lee, Haemi; Park, Taesun

    2004-01-01

    This study was undertaken to evaluate effects of exercise-induced hormones, cortisol, IGF-1, and beta-endorphin, on the regulation of taurine transport activity in rat skeletal myoblasts, L6 cells. Challenge of L6 cells with cortisol (100 nM) for 24 hrs resulted in a 165% increase in taurine transport activity, 220% increase in Vmax of the taurine transporter, and 55% increase in taurine transporter/ beta-actin mRNA level compared with untreated control cells. Neither IGF-1 (1 approximately 100 nM) nor beta-endorphin (1 approximately 20 nM), added in the incubation medium separately for 24 hrs, affected taurine uptake by L6 cells. However, when cells were co-treated with IGF-1 (10 nM) plus cortisol (100 nM), taurine transport activity (37% increase, p < 0.05), Vmax of the transporter (54%, p < 0.05), and taurine transporter/ beta-actin mRNA level were further increased compared to the value for cells treated with cortisol alone. These results suggest that taurine transport by skeletal muscle cells appear to be synergistically up-regulated during a prolonged exercise via elevated levels of cortisol and IGF-1 in muscle.

  7. Psychosocial stress inhibits amplitude of gonadotropin-releasing hormone pulses independent of cortisol action on the type II glucocorticoid receptor.

    PubMed

    Wagenmaker, Elizabeth R; Breen, Kellie M; Oakley, Amy E; Tilbrook, Alan J; Karsch, Fred J

    2009-02-01

    Our laboratory has developed a paradigm of psychosocial stress (sequential layering of isolation, blindfold, and predator cues) that robustly elevates cortisol secretion and decreases LH pulse amplitude in ovariectomized ewes. This decrease in LH pulse amplitude is due, at least in part, to a reduction in pituitary responsiveness to GnRH, caused by cortisol acting via the type II glucocorticoid receptor (GR). The first experiment of the current study aimed to determine whether this layered psychosocial stress also inhibits pulsatile GnRH release into pituitary portal blood. The stress paradigm significantly reduced GnRH pulse amplitude compared with nonstressed ovariectomized ewes. The second experiment tested if this stress-induced decrease in GnRH pulse amplitude is mediated by cortisol action on the type II GR. Ovariectomized ewes were allocated to three groups: nonstress control, stress, and stress plus the type II GR antagonist RU486. The layered psychosocial stress paradigm decreased GnRH and LH pulse amplitude compared with nonstress controls. Importantly, the stress also lowered GnRH pulse amplitude to a comparable extent in ewes in which cortisol action via the type II GR was antagonized. Therefore, we conclude that psychosocial stress reduces the amplitude of GnRH pulses independent of cortisol action on the type II GR. The present findings, combined with our recent observations, suggest that the mechanisms by which psychosocial stress inhibits reproductive neuroendocrine activity at the hypothalamic and pituitary levels are fundamentally different.

  8. 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.

  9. The effects of cortisol increase on long-term memory retrieval during and after acute psychosocial stress.

    PubMed

    Tollenaar, Marieke S; Elzinga, Bernet M; Spinhoven, Philip; Everaerd, Walter A M

    2008-03-01

    In this study the effects of stress-induced cortisol increases on long-term memory retrieval during and after acute psychosocial stress were examined. Seventy male students were exposed to either a psychosocial stress task or to a non-stressful control task. During and after this task, retrieval was tested for idiosyncratic emotionally negative and neutral word pair associations that were learned 1 day or 5 weeks earlier. Within the stress condition, retrieval of negative words, 5 weeks after learning, was impaired both during and after the stress task compared to the control group. Further, during the stress task, when sympathetic activity was enhanced, impaired retrieval of both neutral and emotional words was significantly related to enhanced cortisol response. In contrast, after the stress task, when cortisol levels were still increased but sympathetic activity was low again, no association was found between cortisol increase and retrieval of either neutral or emotional material. These results are in line with the previous animal research showing that when arousal is high, cortisol increase can impair memory retrieval.

  10. Plasma concentrations of cortisol, testosterone, glucose and blood gases in male goats during anaesthesia with pentobarbitone sodium.

    PubMed

    Sanhouri, A A; Jones, R S; Dobson, H

    1990-01-01

    Fasting for 24 h had no statistically significant effect on cortisol, glucose or testosterone concentrations. A dose of pentobarbitone sodium which induced light anaesthesia resulted in an immediate decrease in cortisol values from 5.0-11.1 ng/ml to 2.2-3.6 ng/ml until waking-this latter event was accompanied by an excessive release of cortisol (up to 16.6 ng/ml). In two out of three goats testosterone concentrations decreased from 4.0-9.0 ng/ml to less than 0.5 ng/ml after pentobarbitone; low values were maintained for 4.5-6 hours. Glucose concentrations were unaffected. Precise doses of pentobarbitone (20 mg/kg or 30 mg/kg) resulted in similar cortisol profiles as above but with higher concentrations achieved upon waking from the higher dose of pentobarbitone. On two out of nine occasions increased PCO2 values were recorded concurrently with increased cortisol concentrations during the period of anaesthesia, suggesting that a sufficiently strong stressful stimulus can break through the pentobarbitone blockade.

  11. Relationship between the cortisol awakening response and other features of the diurnal cortisol rhythm: the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Golden, Sherita Hill; Sánchez, Brisa N; Wu, Meihua; Champaneri, Shivam; Diez Roux, Ana V; Seeman, Teresa; Wand, Gary S

    2013-11-01

    Cumulative cortisol burden is known to influence neuropsychiatric and metabolic disorders. To better understand the relationship between daily cortisol exposure and measures of the diurnal circadian cortisol rhythm, we examined the cross-sectional association of the cortisol awakening response (CAR) with wake-up cortisol, bedtime cortisol, diurnal slope, and total cortisol area under the curve (AUC). Up to 18 salivary cortisol samples were collected over 3 days from 935 White, Hispanic, and Black individuals (mean age 65 ± 9.8 years) in the Multi-Ethnic Study of Atherosclerosis. Outcome measures included awakening cortisol, CAR (awakening to 30 min post-awakening), early decline (30 min to 2h post-awakening), late decline (2h post-awakening to bedtime), and the corresponding AUCs. Total cortisol AUC was a summary measure of cumulative cortisol exposure. Higher CAR was associated with significantly lower wake-up cortisol (β=-0.56; 95% CI: -0.59 to -0.53) and a higher early decline AUC (β=0.38; 95% CI: 0.34-0.42) but was not associated with total cortisol AUC (β=0.04; 95% CI: -0.01 to 0.09), or other diurnal cortisol curve components following multivariable adjustment. Total cortisol AUC was significantly and positively associated with wake-up cortisol (β=0.36; 95% CI: 0.32-0.40), bedtime cortisol (β=0.61; 95% CI: 0.58-0.64), and other AUC measures, following multivariable adjustment. Associations were similar by sex, race/ethnicity, and age categories. We conclude that bedtime cortisol showed the strongest correlation with total cortisol AUC, suggesting it may be a marker of daily cortisol exposure.

  12. Methodological Considerations for Hair Cortisol Measurements in Children

    PubMed Central

    Slominski, Radomir; Rovnaghi, Cynthia R.; Anand, Kanwaljeet J. S.

    2015-01-01

    Background Hair cortisol levels are used increasingly as a measure for chronic stress in young children. We propose modifications to the current methods used for hair cortisol analysis to more accurately determine reference ranges for hair cortisol across different populations and age groups. Methods The authors compared standard (finely cutting hair) vs. milled methods for hair processing (n=16), developed a 4-step extraction process for hair protein and cortisol (n=16), and compared liquid chromatography-mass spectrometry (LCMS) vs. ELISA assays for measuring hair cortisol (n=28). The extraction process included sequential incubations in methanol and acetone, repeated twice. Hair protein was measured via spectrophotometric ratios at 260/280 nm to indicate the hair dissolution state using a BioTek® plate reader and dedicated software. Hair cortisol was measured using an ELISA assay kit. Individual (n=13), pooled hair samples (n=12) with high, intermediate, and low cortisol values and the ELISA assay internal standards (n=3) were also evaluated by LCMS. Results Milled and standard methods showed highly correlated hair cortisol (rs=0.951, p<0.0001) and protein values (rs=0.902, p=0.0002), although higher yields of cortisol and protein were obtained from the standard method in 13/16 and 14/16 samples respectively (p<0.05). Four sequential extractions yielded additional amounts of protein (36.5%, 27.5%, 30.5%, 3.1%) and cortisol (45.4%, 31.1%, 15.1%, 0.04%) from hair samples. Cortisol values measured by LCMS and ELISA were correlated (rs=0.737; p<0.0001), although cortisol levels (median [IQR]) detected in the same samples by LCMS (38.7 [14.4, 136] ng/ml) were lower than by ELISA (172.2 [67.9, 1051] ng/ml). LCMS also detected cortisone, which comprised 13.4% (3.7%, 25.9%) of the steroids detected. Conclusion Methodological studies suggest that finely cutting hair with sequential incubations in methanol and acetone, repeated twice, extracts greater yields of cortisol

  13. Cortisol plays a role in the high environmental ammonia associated suppression of the immune response in zebrafish.

    PubMed

    Gonçalves, A F; Neves, J V; Coimbra, J; Rodrigues, P; Vijayan, M M; Wilson, J M

    2017-03-02

    Exposure to high environmental ammonia (HEA) levels increases the vulnerability of fishes to parasitic, viral and bacterial diseases. We tested the hypothesis that elevated plasma cortisol levels play a role in the HEA-mediated immunosuppression in fishes. To this end, we tested the effect of exogenous cortisol treatment on the lipopolysaccharide (LPS)-induced immune response in zebrafish (Danio rerio). Also, to test whether glucocorticoid receptor (GR) signaling is involved in HEA-mediated immunosuppression, zebrafish were treated with mifepristone, a GR antagonist, and the LPS-induced immune response assessed after HEA exposure. We evaluated a panel of important immunity-related genes including interleukin 1β (il1b) and suppressor of cytokine signaling (socs-1a, 2, 3) and acute phase response genes [serum amyloid A (saa), transferrin (tfa), leukocyte cell-derived chemotaxin 2-like (lect2l), haptoglobin (hp), hepcidin (=hepatic anti-microbial peptide hamp), and complement component 3b (c3b)] by real-time quantitative PCR. Our results demonstrate that exogenous cortisol administration as well as elevated cortisol levels in response to HEA exposure modulate mRNA transcript levels of key mediators of the innate immune response in zebrafish. Mifepristone treatment reduced whole body cortisol levels and eliminated the HEA-mediated changes in transcript abundance of socs1a, il1b, as well as APR genes. Together, these results suggest that the HEA effect on the innate immune response is in part mediated by cortisol signaling, while the mode of action, including the receptors involved remains to be elucidated.

  14. 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.

  15. 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.

  16. 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…

  17. 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.

  18. 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.

  19. Analog Optical Links

    NASA Astrophysics Data System (ADS)

    Cox, Charles H., III

    2004-05-01

    Unlike books that focus on the devices used in links, such as lasers and photodiodes, among others, this text focuses on the next level. It covers the collection of devices that form a link, how the individual device performance affects the link performance, or the reverse. Analog links are used for the distribution of cable TV signals, and in conveying the signals to and from antennas (so called antenna remoting). The design of analog links differs significantly from digital links which are primarily used in telecommunications.

  20. 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.

  1. Inadequate cortisol synthesis in prophyria cutanea tarda.

    PubMed

    Pereţianu, D; Sava, D; Giurcăneanu, C; Grigorie, D

    1991-01-01

    Many common clinical features suggest that between corticosuprarenal insufficiency (CSRI) and porphyria cutanea tarda (PCT) there may be some pathogenic relationships. In order to further understand these relations we have performed the ACTH-depot stimulation test (1 mg, i.m.) in 9 patients (from 13 males) with PCT. In 8 patients cortisolemia was assayed 1, 2, (12) and 24 hours post-stimulation. In all 13 cases the basal eliminations of cortisol metabolite (17-OH-corticosteroids) were under normal limits: 2.88 mg/24 h/g creatinine vs 15 controls with 7.06 mg/24h/g creatinine. After ACTH four cases showed lack of stimulation, considered on the second day for 17-OH-corticosteroids. In one case, after one year of PCT treatment, the early post-stimulation level is only moderately decreased. In one case, the test was normal. In four cases the ACTH stimulation was over-normal, i.e., greater than on the first day, suggesting supraphysiological responses. In this group 2 patients showed unexpectedly low early stimulation slopes on cortisolemia (at 1 and 2 hours) associated with concordant high late stimulation levels. This later phenomenon suggests a functional impaired secretion of cortisol in PCT, which seems to be similar to that of insulinemia after glucose in NIDDM, as a receptor lesion. The lesions of cortisol secretion in PCT could have been made by porphyrin storage, impaired hem-enzyme synthesis (cyt P-450) and as a new and attractive hypothesis, could be due to mitochondrial porphyrin receptor decreased activity.

  2. 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…

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  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. Role of glucocorticoid receptor and CCAAT/enhancer-binding protein alpha in the feed-forward induction of 11beta-hydroxysteroid dehydrogenase type 1 expression by cortisol in human amnion fibroblasts.

    PubMed

    Yang, Zhen; Guo, Chunming; Zhu, Ping; Li, Wenjiao; Myatt, Leslie; Sun, Kang

    2007-11-01

    The amount of cortisol available to its receptors is increased by the pre-receptor enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) which converts cortisone to cortisol. We examined the molecular mechanisms of the feedback effect of cortisol on 11beta-HSD1 mRNA expression in human amnion fibroblasts. Our data showed that cortisol-induced 11beta-HSD1 mRNA expression dose dependently in amnion fibroblasts, which could be completely blocked both by the mRNA transcription inhibitor 5,6-dichlorobenzimidazole riboside and by the glucocorticoid receptor (GR) antagonist RU486, and partially blocked by global inhibition of CCAAT/enhancer-binding proteins (C/EBPs) with transfection of C/EBP-specific dominant-negative expression CMV500 plasmid (AC/EBP) into the cells. Likewise, the induction of the promoter activity by cortisol could also be completely blocked by RU486 and partially by AC/EBP transfection. Progressive 5' deletion of the 11beta-HSD1promoter located the region responsible for cortisol's induction within -204 bp upstream to the transcription start site. Specific nucleotide mutations of the putative glucocorticoid responsive element or CCAAT in this promoter region attenuated the induction by cortisol. Moreover, chromatin immunoprecipitation assay and electrophoretic mobility shift assay showed that GR and C/EBPalpha but not C/EBPbeta could bind this promoter region upon cortisol stimulation of amnion fibroblasts. In conclusion, we demonstrated that GR and C/EBPalpha were involved in cortisol-induced 11beta-HSD1 mRNA expression via binding to 11beta-HSD1 promoter in amnion fibroblasts, which may cast a feed-forward production of cortisol in the fetal membranes at the end of gestation.

  11. 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.

  12. Claudin tight junction proteins in rainbow trout (Oncorhynchus mykiss) skin: Spatial response to elevated cortisol levels.

    PubMed

    Gauberg, Julia; Kolosov, Dennis; Kelly, Scott P

    2017-01-01

    This study examined regional distribution and corticosteroid-induced alterations of claudin (cldn) transcript abundance in teleost fish skin. Regional comparison of mRNA encoding 20 Cldns indicated that 12 exhibit differences in abundance along the dorsoventral axis of skin. However, relative abundance of cldns (i.e. most to least abundant) remained similar in different skin regions. Several cldns appear to be present in the epidermis and dermal vasculature whereas others are present only in the epidermis. Increased circulating cortisol levels significantly altered mRNA abundance of 10 cldns in a region specific manner, as well as corticosteroid receptors and 11β-hydroxysteroid dehydrogenase (type 2). Epidermis and epidermal mucous cell morphometrics also altered in response to cortisol, exhibiting changes that appear to enhance skin barrier properties. Taken together, data provide a first look at spatial variation in the molecular physiology of the teleost fish integument TJ complex and region-specific sensitivity to an endocrine factor.

  13. Delayed adrenal insufficiency long after unilateral adrenalectomy: prolonged glucocorticoid therapy reduced reserved secretory capacity of cortisol.

    PubMed

    Kazama, Itsuro; Komatsu, Yasuhiro; Ohiwa, Takafumi; Sanayama, Kyo; Nagata, Mikio

    2005-06-01

    A 51-year-old woman with Cushing's syndrome underwent unilateral adrenalectomy for left adrenal adenoma. After 7 years of prednisolone treatment (with some interruptions), followed by 4 years of total withdrawal from prednisolone treatment, she presented with hypotension, weight loss, general fatigue, nausea, hyponatremia and hypoglycemia. These clinical features together with a low response in the rapid adrenocorticotropic hormone test led to the diagnosis of acute adrenal insufficiency. Relatively low serum adrenocorticotropic hormone levels in the face of increased demand for cortisol during adrenal crisis suggested a disordered hypothalamic-pituitary function, indicating secondary adrenal insufficiency. This patient demonstrated the etiology of acute adrenal insufficiency long after unilateral adrenalectomy in association with subsequent glucocorticoid therapy. A reduction in the reserved secretory capacity of cortisol after prolonged prednisolone treatment was considered to have induced secondary adrenal insufficiency, even after 4 years of total withdrawal from prednisolone.

  14. 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

  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. 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…

  17. An Interesting Analogy

    ERIC Educational Resources Information Center

    Pacheco, Jose M.; Fernandez, Isabel

    2002-01-01

    The aim of this note is to give some insight into the formal unity of a very applicable area of mathematics by showing an interesting analogy between the weak part of the Rouche-Frobenius theorem and the existence result for the initial value problem for the general first-order linear two-dimensional PDE.

  18. Analogy, explanation, and proof.

    PubMed

    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.

  19. 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.

  20. Are Scientific Analogies Metaphors?

    DTIC Science & Technology

    1981-02-01

    psychospiritual processes. A more modern example of unclarified analogy is Freud’s (1973; reprinted from 1955) discussion of anal- eroticism , in which...299-304. Freud, S. On transformations of instinct as exemplified in anal eroticism . In J. Strachey (Ed.), The standard 37 edition of the complete

  1. 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

  2. Cortisol secretion in children with symptoms of reactive attachment disorder.

    PubMed

    Kočovská, Eva; Wilson, Philip; Young, David; Wallace, Alan Michael; Gorski, Charlotta; Follan, Michael; Smillie, Maureen; Puckering, Christine; Barnes, James; Gillberg, Christopher; Minnis, Helen

    2013-08-30

    Maltreated children with reactive attachment disorder (RAD) have severe problems with social relationships and affect regulation. An association between early maltreatment and changes in the daily rhythm of cortisol secretion has already been reported for maltreated toddlers. We sought to find out whether such changes were apparent in school-age children with symptoms of RAD, who had experienced early maltreatment but were currently adopted in well-functioning families. We recruited 66 children: 34 adopted children, aged 5-12 years, with an early history of maltreatment and with social difficulties such as indiscriminate friendliness; and 32 age- and sex-matched comparison children with no history of maltreatment or social difficulties. Daily rhythms of cortisol production were determined from saliva samples collected over 2 days. The adopted group had significantly lower absolute levels of cortisol compared to the control group, but a typical profile of cortisol secretion. There was no association between cortisol secretion and symptom scores for psychopathology.

  3. Enhanced cortisol response to stress in children in autism.

    PubMed

    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 novel environment; and (3) in response to a blood draw stressor. A significantly higher serum cortisol response was found in the group of children with autism. Analysis showed significantly higher peak cortisol levels and prolonged duration and recovery of cortisol elevation following the blood-stick stressor in children with autism. This study suggests increased reactivity of the HPA axis to stress and novel stimuli in children with autism.

  4. Work stress models and diurnal cortisol variations: The SALVEO study.

    PubMed

    Marchand, Alain; Juster, Robert-Paul; Durand, Pierre; Lupien, Sonia J

    2016-04-01

    The objective of this study was to assess components, subscales, and interactions proposed by the popular Job Demand-Control (JDC), Job Demand-Control-Support (JDCS), and Effort-Reward Imbalance (ERI) work stress models in relation to diurnal variation of the stress hormone cortisol. Participants included 401 day-shift workers employed from a random sampling of 34 Canadian workplaces. Questionnaires included the Job Content Questionnaire to measure psychological demands, decision latitude, and social support as well as the Effort-Reward Imbalance Questionnaire to measure effort, reward, and overcommitment. Salivary cortisol was collected on 2 working days at awaking, +30 min after awaking, 1400h, 1600h, and bedtime. Multilevel regressions with 3 levels (time of day, workers, workplaces) were performed. Results revealed that JDC, JDCS and ERI interactions were not statistically associated with variations in diurnal cortisol concentrations. By contrast when assessing specific work stress subscales, increased psychological demands were linked to decreased bedtime cortisol, increased job recognition was linked to increased cortisol +30 min after waking and at bedtime, and finally increased overcommitment was linked to increased awakening cortisol and decreased cortisol at 1400h, 1600h, and bedtime. Sex moderation effects principally among men were additionally detected for psychological demands, total social support, and supervisor support. Our findings suggest that components and subsubscales of these popular work stress models rather than theorized interactions are more meaningful in explaining diurnal cortisol variations. In particular, psychological demands, job recognition, overcommitment, and to a lesser extent social support at work are the most significant predictors of diurnal cortisol variation in this large sample of Canadian workers. Importantly, the overall effect sizes of these subscales that explained diurnal cortisol concentrations were weak.

  5. 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.

  6. Motivation, stress, and cortisol responses in skydiving.

    PubMed

    Thatcher, Joanne; Reeves, Sue; Dorling, Debbie; Palmer, Anna

    2003-12-01

    This study examined metamotivational dominance, metamotivational states, and cortisol responses in skydiving participants. Data were obtained from 23 experienced skydivers 15 min. prior to and following a skydive. Respondents were mainly paratelic-conformist dominant and most occupied the conformist and arousal-seeking states prior to skydiving, assessed respectively, with Apter, et al.'s Motivational Style Profile and Cook, et al.'s measure of metamotivational states. Paratelic-conformist dominance indicates a predisposition towards conformity and a desire to be spontaneous, and the conformist and arousal seeking states reported prior to completing the skydive represent a desire to conform to expected norms but also to seek arousal. There was no significant change in scores for metamotivational state or stress following skydiving. Contrary to expectations, cortisol level prior to skydiving was negatively associated with external stress. These results support the paratelic, but not the negativistic, dominance found in previous samples of risk sport participants (no skydivers). The conformist dominance and pre-dive conformist metamotivational state scores of this sample may be fundamental for adhering to safety regulations imposed on skydivers. To obtain better understanding of this phenomenon, researchers should attempt to measure these variables during, rather than prior to and after, participation in risk sports.

  7. Now you see it, now you don't: Testing environments modulate the association between hippocampal volume and cortisol levels in young and older adults.

    PubMed

    Sindi, Shireen; Fiocco, Alexandra J; Juster, Robert-Paul; Lord, Catherine; Pruessner, Jens; Lupien, Sonia J

    2014-12-01

    The hypothalamic pituitary adrenal axis production of the stress hormone cortisol interacts with the hippocampal formation and impacts memory function. A growing interest is to determine whether hippocampal volume (HV) predicts basal and/or reactive cortisol levels in young and older adults. Recent evidence shows that contextual features in testing environments might be stressful and inadvertently induce a stress response in young and/or older populations. This latter result suggests that variations in testing environments might influence associations between HV and cortisol levels in young and older adults. To this end, we investigated 28 healthy young adults (ages 18-35) and 32 healthy older adults (ages 60-75) in two different environments constructed to be more or less stressful for each age group (Favoring-Young versus Favoring-Old conditions). Cortisol levels were repeatedly assessed in each environment, and young and older participants underwent an anatomical magnetic resonance imaging scan for subsequent assessment of HV. Results in both age groups showed that HV was significantly associated with cortisol levels only in the unfavorable stressful testing conditions specific for each age group. This association was absent when testing environments were designed to decrease stress for each age group. These findings are fundamental in showing that unless the nature of the testing environment is taken into consideration, detected associations between HV and cortisol levels in both young and older populations might be confounded by environmental stress.

  8. 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.

  9. 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.

  10. 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.

  11. Social isolation affects partner-directed social behavior and cortisol during pair formation in marmosets, Callithrix geoffroyi

    PubMed Central

    Smith, Adam S.; Birnie, Andrew K.; French, Jeffrey A.

    2011-01-01

    Pair-bonded relationships form during periods of close spatial proximity and high sociosexual contact. Like other monogamous species, marmosets form new social pairs after emigration or ejection from their natal group resulting in periods of social isolation. Thus, pair formation often occurs following a period of social instability and a concomitant elevation in stress physiology. Research is needed to assess the effects that prolonged social isolation has on the behavioral and cortisol response to the formation of a new social pair. We examined the sociosexual behavior and cortisol during the first 90-days of cohabitation in male and female Geoffroy's tufted-ear marmosets (Callithrix geoffroyi) paired either directly from their natal group (Natal-P) or after a prolonged period of social isolation (ISO-P). Social isolation prior to pairing seemed to influence cortisol levels, social contact, and grooming behavior; however, sexual behavior was not affected. Cortisol levels were transiently elevated in all paired marmosets compared to natal-housed marmosets. However, ISO-P marmosets had higher cortisol levels throughout the observed pairing period compared to Natal-P marmoset. This suggests that the social instability of pair formation may lead to a transient increase in hypothalamic-pituitary-adrenal (HPA) axis activity while isolation results in a prolonged HPA axis dysregulation. In addition, female social contact behavior was associated with higher cortisol levels at the onset of pairing; however, this was not observed in males. Thus, isolation-induced social contact with a new social partner may be enhanced by HPA axis activation, or a moderating factor. PMID:21712050

  12. N-terminal 5-mer peptide analog P165 of amyloid precursor protein inhibits UVA-induced MMP-1 expression by suppressing the MAPK pathway in human dermal fibroblasts.

    PubMed

    Wang, Ying; Chen, Hui; Wang, Wen; Wang, Rong; Liu, Zi-Lian; Zhu, Wei; Lian, Shi

    2014-07-05

    Exposure to ultraviolet (UV) radiation leads to a progressive increase in dermal damage through the degradation of collagen, which is mediated by matrix metalloproteinases (MMPs). UV radiation alters the intracellular signaling events that regulate the elaboration of MMPs. Our previous study showed that P165, the N-terminal 5-mer peptide analog of amyloid precursor protein, exerts a protective effect on ultraviolet A (UVA)-induced loss of collagen type I in human dermal fibroblasts (HDFs) by inhibiting the generation of intracellular reactive oxygen species and MMP-1. In this study, we focused on specific signal transduction pathways to elucidate the possible photoprotective mechanisms of P165 in controlling MMP-1 inhibition. Results from western blot analyses indicated that pretreatment with P165 dose-dependently inhibited UVA-induced phosphorylation of extracellular regulated protein kinases (ERK), c-Jun N-terminal kniase (JNK), p38 mitogen-activated protein kinases (MAPKs), and the phosphorylation of their downstream targets c-Jun and c-Fos. The photoprotective effects of P165 were further demonstrated in collagen type I secretion and cellular senescence induced by UVA irradiation. These findings suggest that P165 exerts photoprotective activity in UVA-treated HDFs by regulating MMP-1 generation. This activity may be mediated by inhibiting the MAPK signaling pathways. Thus, P165 is a potential agent for the prevention of skin photoaging.

  13. Analogy Construction versus Analogy Solution, and Their Influence on Transfer

    ERIC Educational Resources Information Center

    Harpaz-Itay, Yifat; Kaniel, Shlomo; Ben-Amram, Einat

    2006-01-01

    This study compares transfer performed by subjects trained to solve verbal analogies, with transfer by subjects trained to construct them. The first group (n = 57) received instruction in a strategy to solve verbal analogies and the second group (n = 66) was trained in strategies for constructing such analogies. Before and after intervention, all…

  14. 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.

  15. VIIP Bedrest Analog Roadmap

    NASA Technical Reports Server (NTRS)

    Villarreal, Jennifer D.

    2014-01-01

    The objective is to define successive bed rest campaigns leading to a potential VIIP (Vision Impairment and Intracranial Pressure) countermeasure. To determine if the analog is successful, changes need to occur in the following outcome measures (dependent variables): Intracranial pressure; Retinal nerve fiber layer; Choroidal engorgement; Globe flattening; Axial biometry; Optic nerve sheath diameter distention; Cycloplegic refraction; Visual acuity. Study parameters (independent variables) to include: CO2; Sodium; Exercise (resistive & aerobic); Strict tilt angle.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Violence exposure and cortisol responses in urban youth.

    PubMed

    Kliewer, Wendy

    2006-01-01

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

  1. Social isolation and diurnal cortisol patterns in an ageing cohort☆

    PubMed Central

    Stafford, Mai; Gardner, Mike; Kumari, Meena; Kuh, Diana; Ben-Shlomo, Yoav

    2013-01-01

    Summary Background Social isolation may operate as a psychosocial stressor which disrupts functioning of the hypothalamic–pituitary–adrenocortical axis. Methods Using data from the MRC National Survey of Health and Development, we tested whether living alone, not being married and social network size were associated with diurnal cortisol patterns at 60–64 years. We hypothesised that recent onset compared with long-term isolation would be more strongly associated with cortisol awakening response, cortisol decline over the day and evening cortisol. Models were adjusted for sex, smoking, body mass index, alcohol intake, psychological distress and financial difficulties. Results Those widowed within the last three years had a 36% (95%CI 6%, 73%) higher night time cortisol than those who were currently married. Those newly living alone also had a higher night time cortisol and flatter diurnal slope than those living with others. Conclusion Independently of multiple behavioural and psychosocial correlates, recent onset of social isolation is related to diurnal cortisol patterns that increase the risk of morbidity and mortality. PMID:23920224

  2. Outcomes after resection of cortisol-secreting adrenocortical carcinoma

    PubMed Central

    Margonis, Georgios Antonios; Kim, Yuhree; Tran, Thuy B.; Postlewait, Lauren M.; Maithel, Shishir K.; Wang, Tracy S.; Glenn, Jason A.; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E.; Keplinger, Kara; Fields, Ryan C.; Jin, Linda X.; Weber, Sharon M.; Salem, Ahmed; Sicklick, Jason K.; Gad, Shady; Yopp, Adam C.; Mansour, John C.; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C.; Kiernan, Colleen M.; Votanopoulos, Konstantinos I.; Levine, Edward A.; Poultsides, George A.; Pawlik, Timothy M.

    2016-01-01

    BACKGROUND We sought to define the impact of cortisol-secreting status on outcomes after surgical resection of adrenocortical carcinoma (ACC). METHODS The U.S ACC group database was queried to identify patients who underwent ACC resection between 1993 and 2014. The short-term and long-term outcomes were assessed. RESULTS The incidence of all functional and cortisol-secreting tumors was 40.6% and 22.6%, respectively. On multivariable analysis, cortisol secretion remained associated with an increased risk of postoperative complications (odds ratio = 2.25, 95 % confidence interval = 1.04 to 4.88; P = .04). At a median follow-up of 17.6 months, 118 patients (50.4%) had developed a recurrence. On multivariable analysis, after adjusting for patient and disease-related factors cortisol secretion independently predicted shorter recurrence-free survival (Hazard ratio = 2.05, 95% confidence interval = 1.16 to 3.60; P = .01). CONCLUSIONS Cortisol secretion was associated with an increased risk of postoperative morbidity. Recurrence remains high among patients with ACC after surgery; cortisol secretion was independently associated with a shorter recurrence-free survival. Tailoring postoperative surveillance of ACC patients based on their cortisol secreting status may be important. PMID:26810939

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

    PubMed Central

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

    2015-01-01

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

  4. Role of shame and body esteem in cortisol stress responses

    PubMed Central

    Lupis, Sarah B.; Sabik, Natalie J.

    2016-01-01

    Studies assessing the role of shame in HPA axis reactivity report mixed findings. Discrepancies may be due to methodological difficulties and inter-individual differences in the propensity to experience shame in a stressful situation. Hence, the current study combined self-report of shame and facial coding of shame expressions and assessed the role of body esteem as a moderator of the shame–stress link. For this, 44 healthy students (24F, age 20.5 ± 2.1 years) were exposed to an acute psychosocial stress paradigm (Trier Social Stress Test: TSST). Salivary cortisol levels were measured throughout the protocol. Trait shame was measured before the stress test, and state shame immediately afterwards. Video recordings of the TSST were coded to determine emotion expressions. State shame was neither associated with cortisol stress responses nor with body esteem (self-report: all ps ≥ .24; expression: all ps ≥ .31). In contrast, higher trait shame was associated with both negative body esteem (p = .049) and stronger cortisol stress responses (p = .013). Lastly, having lower body esteem predicted stronger cortisol stress responses (p = .022); however, it did not significantly moderate the association between shame indices and cortisol stress responses (all ps ≥ .94). These findings suggest that body esteem and trait shame independently contribute to strength of cortisol stress responses. Thus, in addition to trait shame, body esteem emerged as an important predictor of cortisol stress responses and as such, a potential contributor to stress-related negative health outcomes. PMID:26577952

  5. Role of shame and body esteem in cortisol stress responses.

    PubMed

    Lupis, Sarah B; Sabik, Natalie J; Wolf, Jutta M

    2016-04-01

    Studies assessing the role of shame in HPA axis reactivity report mixed findings. Discrepancies may be due to methodological difficulties and inter-individual differences in the propensity to experience shame in a stressful situation. Hence, the current study combined self-report of shame and facial coding of shame expressions and assessed the role of body esteem as a moderator of the shame-stress link. For this, 44 healthy students (24F, age 20.5 ± 2.1 years) were exposed to an acute psychosocial stress paradigm (Trier Social Stress Test: TSST). Salivary cortisol levels were measured throughout the protocol. Trait shame was measured before the stress test, and state shame immediately afterwards. Video recordings of the TSST were coded to determine emotion expressions. State shame was neither associated with cortisol stress responses nor with body esteem (self-report: all ps ≥ .24; expression: all ps ≥ .31). In contrast, higher trait shame was associated with both negative body esteem (p = .049) and stronger cortisol stress responses (p = .013). Lastly, having lower body esteem predicted stronger cortisol stress responses (p = .022); however, it did not significantly moderate the association between shame indices and cortisol stress responses (all ps ≥ .94). These findings suggest that body esteem and trait shame independently contribute to strength of cortisol stress responses. Thus, in addition to trait shame, body esteem emerged as an important predictor of cortisol stress responses and as such, a potential contributor to stress-related negative health outcomes.

  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. Assessing salivary cortisol in large-scale, epidemiological research.

    PubMed

    Adam, Emma K; Kumari, Meena

    2009-11-01

    Salivary cortisol measures are increasingly being incorporated into large-scale, population-based, or epidemiological research, in which participants are selected to be representative of particular communities or populations of interest, and sample sizes are in the order of hundreds to tens of thousands of participants. These approaches to studying salivary cortisol provide important advantages but pose a set of challenges. The representative nature of sampling, and large samples sizes associated with population-based research offer high generalizability and power, and the ability to examine cortisol functioning in relation to: (a) a wide range of social environments; (b) a diverse array individuals and groups; and (c) a broad set of pre-disease and disease outcomes. The greater importance of high response rates (to maintain generalizability) and higher costs associated with this type of large-scale research, however, requires special adaptations of existing ambulatory cortisol protocols. These include: using the most efficient sample collection protocol possible that still adequately address the specific cortisol-related questions at hand, and ensuring the highest possible response and compliance rates among those individuals invited to participate. Examples of choices made, response rates obtained, and examples of results obtained from existing epidemiological cortisol studies are offered, as are suggestions for the modeling and interpretation of salivary cortisol data obtained in large-scale epidemiological research.

  8. 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.

  9. Approaches to salivary cortisol collection and analysis in infants.

    PubMed

    Tryphonopoulos, Panagiota D; Letourneau, Nicole; Azar, Rima

    2014-10-01

    Salivary cortisol is becoming more commonly utilized as a biologic marker of stress in observational studies and intervention research. However, its use with infants (12 months of age or younger) is less widespread and poses some special challenges to researchers. In order to decide on the most suitable collection procedure for salivary cortisol in infants, a number of criteria should be considered. This article will aid investigators interested in integrating salivary cortisol measurement into their research studies by presenting (1) an overview of the patterns of cortisol secretion in infancy including the development of diurnal rhythm and response to stress; (2) a comparison of the most commonly used approaches for collecting salivary cortisol samples in infants including cotton rope, syringe aspiration technique, filter paper, hydrocellulose microsponge, and the Salimetrics children's swab; (3) a discussion of the factors contributing to heightened cortisol variability in infancy and how these can be limited; (4) analytical issues associated with cortisol measurement; and (5) examples of criteria to consider when choosing a saliva sampling method and lab for conducting assays.

  10. A Transiting Jupiter Analog

    NASA Astrophysics Data System (ADS)

    Kipping, D. M.; Torres, G.; Henze, C.; Teachey, A.; Isaacson, H.; Petigura, E.; Marcy, G. W.; Buchhave, L. A.; Chen, J.; Bryson, S. T.; Sandford, E.

    2016-04-01

    Decadal-long radial velocity surveys have recently started to discover analogs to the most influential planet of our solar system, Jupiter. Detecting and characterizing these worlds is expected to shape our understanding of our uniqueness in the cosmos. Despite the great successes of recent transit surveys, Jupiter analogs represent a terra incognita, owing to the strong intrinsic bias of this method against long orbital periods. We here report on the first validated transiting Jupiter analog, Kepler-167e (KOI-490.02), discovered using Kepler archival photometry orbiting the K4-dwarf KIC-3239945. With a radius of (0.91+/- 0.02) {R}{{J}}, a low orbital eccentricity ({0.06}-0.04+0.10), and an equilibrium temperature of (131+/- 3) K, Kepler-167e bears many of the basic hallmarks of Jupiter. Kepler-167e is accompanied by three Super-Earths on compact orbits, which we also validate, leaving a large cavity of transiting worlds around the habitable-zone. With two transits and continuous photometric coverage, we are able to uniquely and precisely measure the orbital period of this post snow-line planet (1071.2323 ± 0.0006d), paving the way for follow-up of this K = 11.8 mag target.

  11. 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

  12. 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.

  13. Correlates and Consequences of Toddler Cortisol Reactivity to Fear

    PubMed Central

    Kiel, Elizabeth J.; Kalomiris, Anne E.

    2015-01-01

    Cortisol reactivity to fear-eliciting stimuli in toddlerhood may represent an indicator of risk for anxiety-spectrum problems and other maladjustment. Thus, it is important to understand factors that may contribute to cortisol reactivity as well as those that determine its predictive relation to early emerging anxiety. In this vein, the current study investigated maternal comforting behaviors, both solicited and unsolicited by the toddler, as correlates of cortisol reactivity at age 2. Further, we investigated maternal comforting behaviors and behavioral indicators of fear in both a low-threat and a high-threat context as moderators of the relation between cortisol reactivity at age 2 and change in anxiety from age 2 to age 3. The sample comprised 99 2-year-old toddlers and their mothers. Toddlers provided saliva samples at baseline and after a fear-eliciting stimulus that were assayed for cortisol. Mothers were observed for comforting behavior while interacting with their toddlers in laboratory tasks and completed questionnaires about their toddlers’ anxiety. Results indicated that unsolicited (spontaneous) comforting behavior related to toddler cortisol reactivity above and beyond solicited comforting and the level of fear toddlers displayed in the same task. Moreover, fear in a low-threat, but not high-threat, context moderated the relation between cortisol reactivity and change in anxiety, such that cortisol reactivity had a positive relation to anxiety at extreme levels of low-threat fear. Results suggest the importance of considering the caregiving environment and context-specific fear in understanding the nature of cortisol reactivity in the toddler years. PMID:26410395

  14. Correlates and consequences of toddler cortisol reactivity to fear.

    PubMed

    Kiel, Elizabeth J; Kalomiris, Anne E

    2016-02-01

    Cortisol reactivity to fear-eliciting stimuli during toddlerhood may represent an indicator of risk for anxiety spectrum problems and other maladjustment. Thus, it is important to understand factors that may contribute to cortisol reactivity as well as those that determine its predictive relation to early emerging anxiety. In this vein, the current study investigated maternal comforting behaviors, both solicited and unsolicited by the toddler, as correlates of cortisol reactivity at 2years of age. Furthermore, we investigated maternal comforting behaviors and behavioral indicators of fear in both a low-threat and a high-threat context as moderators of the relation between cortisol reactivity at age 2 and change in anxiety from age 2 to age 3. The sample comprised 99 2-year-old toddlers and their mothers. Toddlers provided saliva samples at baseline and after a fear-eliciting stimulus that were assayed for cortisol. Mothers were observed for comforting behavior while interacting with their toddlers in laboratory tasks and completed questionnaires about their toddlers' anxiety. Results indicated that unsolicited (spontaneous) comforting behavior related to toddler cortisol reactivity above and beyond solicited comforting and the level of fear toddlers displayed in the same task. Moreover, fear in a low-threat context, but not in a high-threat context, moderated the relation between cortisol reactivity and change in anxiety, such that cortisol reactivity had a positive relation to anxiety at extreme levels of low-threat fear. Results suggest the importance of considering the caregiving environment and context-specific fear in understanding the nature of cortisol reactivity during the toddler years.

  15. 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

  16. 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.

  17. Cortisol reduces plasticity in the kitten visual cortex.

    PubMed

    Daw, N W; Sato, H; Fox, K; Carmichael, T; Gingerich, R

    1991-03-01

    We investigated the effect of elevated levels of cortisol on plasticity in the visual cortex of the cat. Animals were given daily injections of cortisol i.m. for 20 days starting around 35 days of age. After 10 days they were monocularly deprived, and after an additional 10 days recordings were made from the visual cortex to construct an ocular dominance histogram. The results were compared with those from normal animals of the same age, and with animals monocularly deprived for the same period but not treated with cortisol. Cortisol reduced the ocular dominance shift in a dose-dependent manner, but did not totally abolish it even at the highest doses used. Two other series of animals were recorded, one slightly later in the critical period and one slightly earlier, with care taken to give cortisol before the animals were exposed to light in the morning. In both cases, cortisol reduced the ocular dominance shift but did not abolish it. To interpret these results, we measured levels of plasma cortisol in normal cats of various ages. Average levels were fairly constant between birth and 12 months of age (0.5-1 microgram/dl), and increased slightly after that, but there was a large variation between animals. Thus elevated levels of cortisol can have a substantial effect on plasticity in the visual cortex of the cat, but the decline of the critical period for plasticity between 6 weeks and 3-5 months of age does not seem to be due to a rise in cortisol levels during this time.

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

    PubMed

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

    2014-01-01

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

  19. Interventions to improve cortisol regulation in children: a systematic review.

    PubMed

    Slopen, Natalie; McLaughlin, Katie A; Shonkoff, Jack P

    2014-02-01

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

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

    PubMed Central

    McLaughlin, Katie A.; Shonkoff, Jack P.

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    Adrenal tumors autonomously producing cortisol cause Cushing syndrome1–4. Exome sequencing of 25 tumor-normal pairs revealed two groups. Eight tumors (including 3 carcinomas) had many somatic copy number variants (CNV+) with frequent deletion of CDC42 and CDKN2A, amplification of 5q31.2, and protein-altering mutations in TP53 and RB1. Seventeen (all adenomas) had no CNVs (CNV-), TP53 or RB1 mutations. Six of these had known gain of function mutations in CTNNB15,6 (beta-catenin) or GNAS7,8 (Gαs), Six others had somatic p.Leu206Arg mutations in PRKACA (protein kinase A (PKA) catalytic subunit). Further sequencing identified this mutation in 13 of 63 tumors (35% of adenomas with overt CS). PRKACA, GNAS and CTNNB1 mutations were mutually exclusive. Leu206 directly interacts with PKA’s regulatory subunit, PRKAR1A9,10. PRKACAL206R loses PRKAR1A binding, increasing phosphorylation of downstream targets. PKA activity induces cortisol production and cell proliferation11–15, providing a mechanism for tumor development. These findings define distinct mechanisms underlying adrenal cortisol-producing tumors. PMID:24747643

  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. 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

  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. Effect of nanosilver on cortisol release and morphometrics in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Murray, Laura; Rennie, Michael D; Enders, Eva C; Pleskach, Kerri; Martin, Jonathan D

    2016-11-17

    Nanosilver (nAg) is a nanoparticle commonly incorporated into consumer products for its antimicrobial properties that has been detected in aquatic environments. Toxic effects of nAg on fish have been observed, and nAg may induce a stress response in fish in the form of increased blood plasma cortisol. Effects of nAg exposure on rainbow trout (Oncorhynchus mykiss) were investigated over a 28-d period using blood plasma cortisol concentrations as an indicator of stress. Several morphometric measures (growth, Fulton's condition factor, and hepatosomatic index [HSI]) were also taken during the experiment to investigate potential whole-body effects of exposure, and concentrations of nAg in fish muscle tissue were measured. Fish were exposed to environmentally relevant (average 0.28 μg/L) and higher (average 47.60 μg/L) exposure concentrations of nAg. The results showed a significant increase in blood plasma cortisol for both exposure treatments. A significant effect on HSI by treatment dependent on exposure time was also observed, although no obvious trend was detected, whereas other morphometric measures were not affected by nAg exposure. In addition, Ag was detected in fish muscle tissue. The results indicate that although nAg did engage the stress response in fish, it did not affect growth or condition under the experimental conditions and time frame investigated. Environ Toxicol Chem 2017;9999:1-8. © 2016 SETAC.

  6. Cortisol Responses to Mental Stress and the Progression of Coronary Artery Calcification in Healthy Men and Women

    PubMed Central

    Hamer, Mark; Endrighi, Romano; Venuraju, Shreenidhi M.; Lahiri, Avijit; Steptoe, Andrew

    2012-01-01

    Background Psychosocial stress is a risk factor for coronary heart disease (CHD). The mechanisms are incompletely understood, although dysfunction of the hypothalamic pituitary adrenal (HPA) axis might be involved. We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification (CAC). Methods and Results Participants were 466 healthy men and women (mean age = 62.7±5.6 yrs), without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. At the baseline assessment salivary cortisol was measured in response to mental stressors, consisting of a 5-min Stroop task and a 5-min mirror tracing task. CAC was measured at baseline and at 3 years follow up using electron beam computed tomography. CAC progression was defined as an increase >10 Agatston units between baseline and follow up. 38.2% of the sample demonstrated CAC progression over the 3 years follow up. There was considerable variation in the cortisol stress response, with approximately 40% of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l. There was an association between cortisol stress reactivity (per SD) and CAC progression (odds ratio = 1.27, 95% CI, 1.02–1.60) after adjustments for age, sex, pre-stress cortisol, employment grade, smoking, resting systolic BP, fibrinogen, body mass index, and use of statins. There was no association between systolic blood pressure reactivity and CAC progression (odds ratio per SD increase = 1.03, 95% CI, 0.85–1.24). Other independent predictors of CAC progression included age, male sex, smoking, resting systolic blood pressure, and fibrinogen. Conclusion Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression. These data support the notion that cortisol reactivity, an index of HPA function, is one of the possible mechanisms through which psychosocial stress may

  7. 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.

  8. 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.

  9. 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

  10. Differentiating anticipatory from reactive cortisol responses to psychosocial stress.

    PubMed

    Engert, Veronika; Efanov, Simona I; Duchesne, Annie; Vogel, Susanne; Corbo, Vincent; Pruessner, Jens C

    2013-08-01

    Most psychosocial stress studies assess the overall cortisol response without further identifying the temporal dynamics within hormone levels. It has been shown, however, that the amplitude of anticipatory cortisol stress levels has a unique predictive value for psychological health. So far, no "best practice" in how to investigate the anticipatory cortisol stress response has emerged. The goal of the current research was to develop a protocol that would allow for a sensitive and easy-to-implement laboratory-based investigation into anticipatory cortisol stress levels. We initially tested 26 healthy men in either an anticipation- or stress-only condition of the Trier Social Stress Test (TSST) to map the distinct timelines of anticipatory and reactive cortisol release profiles (study 1). Subsequently, we administered the TSST to 50 healthy men such that the cortisol responses to anticipatory and reactive stress components could be dissociated (study 2). In both studies we sampled saliva cortisol at high frequency (at baseline, during 10min of anticipation and during and after 10min of acute stress) and the current mood state pre- and post-stress. We found anticipatory responder rates of 20% and 40%, with peak anticipatory cortisol levels between 14 and 20min after onset of anticipation. Visible changes in reactive cortisol levels occurred only after the termination of the acute stressor. We conclude that the best practice to detect a maximum number of anticipatory responders in the TSST would be to extend the anticipation phase to 15min. In doing so, the anticipatory cortisol peak could be captured at a time-point of the actual stressor that is uninfluenced by reactive cortisol levels. Overall, we could reveal several features of anticipatory responders. Most importantly, there was a positive correlation between anticipatory and reactive stress responses. There was no association between anticipatory cortisol and alpha-amylase as well as subjective

  11. 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

  12. 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

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

    PubMed Central

    Horvath, PJ; Kazial, KA

    2015-01-01

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

  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.

  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) app