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Sample records for analog induce cortisol

  1. Stress-Induced Hormones Cortisol and Epinephrine Impair Wound Epithelization.

    PubMed

    Stojadinovic, Olivera; Gordon, Katherine A; Lebrun, Elizabeth; Tomic-Canic, Marjana

    2012-02-01

    Stress-induced disruption of hormonal balance in animals and humans has a detrimental effect on wound healing. After the injury, keratinocytes migrate over the wound bed to repair a wound. However, their nonmigratory phenotype plays a role in pathogenesis of chronic wounds. Despite many therapeutic approaches, there is a dearth of treatments targeting the molecular mechanisms mediated by stress that prevent epithelization. Recent studies show that epidermal keratinocytes synthesize stress hormones. During acute wound healing, cortisol synthesis in the epidermis is tightly controlled. Further, a key intermediate molecule in the cholesterol synthesis pathway, farnesyl pyrophosphate (FPP), can bind glucocorticoid receptor (GR) and activate GR. Additionally, keratinocytes express beta-2-adrenergic-receptor (β2AR), a receptor for the stress hormone epinephrine. Importantly, migratory rates of keratinocytes are reduced by cortisol, FPP, epinephrine, and other β2AR agonists, thus indicating their role in the inhibition of epithelization. Topical inhibition of local glucocorticoid and FPP synthesis, as well as treatment with β2AR antagonists promotes wound epithelization. Modulation of local stress hormone production may represent an important therapeutic target for wound healing disorders. Topical administration of inhibitors of cortisol synthesis, statins, β2AR antagonists, and systemic beta-blockers can decrease cortisol synthesis, FPP, and epinephrine levels, respectively, thus restoring keratinocyte migration capacity. These treatment modalities could represent a novel therapeutic approach for wound healing disorders. Attenuation of the local stress-induced hormonal imbalance in epidermis may advance therapeutic modalities, thereby leading to enhanced epithelization and improved wound healing.

  2. Acute ACTH-induced elevations of circulating cortisol do not affect hair cortisol concentrations in calves.

    PubMed

    Tallo-Parra, O; Lopez-Bejar, M; Carbajal, A; Monclús, L; Manteca, X; Devant, M

    2017-01-01

    In recent times, the detection of cortisol in hair is intended to be used as an animal-based indicator for the assessment of chronic stress. However, the relationship between the ability to report average values of long-term circulating cortisol concentrations and the sensitivity to acute peaks of cortisol is still unclear. To gain insight into this relationship, 24 Holstein-Friesian bull calves under the same management conditions were used in this study. Two injections of ACTH (at D0 and D7) were administrated to twelve animals with the aim to create two acute increases of serum cortisol concentrations. Blood samples were taken in order to determine the duration of serum cortisol peaks and to confirm a mediated response by the administration of ACTH. Cortisol concentrations from 14-day-old white hair samples collected from forehead and hip were analysed separately by EIA and compared with those from the control group. Serum cortisol analyses revealed an acute increase of cortisol concentrations for approximately three hours after each ACTH administration. Concentrations of hair cortisol from forehead and hip locations showed no differences between ACTH-administrated and control animals. Hair cortisol concentrations from 14-day old samples were not altered by two acute elevations of serum cortisol suggesting that hair cortisol is not masked by short and non-recurrent moments of stress. These results are a step forward in the validation of hair cortisol detection as a robust integrative measure of serum cortisol concentrations from an extended period of time. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Stress-Induced Hormones Cortisol and Epinephrine Impair Wound Epithelization

    PubMed Central

    Stojadinovic, Olivera; Gordon, Katherine A.; Lebrun, Elizabeth; Tomic-Canic, Marjana

    2012-01-01

    Background Stress-induced disruption of hormonal balance in animals and humans has a detrimental effect on wound healing. The Problem After the injury, keratinocytes migrate over the wound bed to repair a wound. However, their nonmigratory phenotype plays a role in pathogenesis of chronic wounds. Despite many therapeutic approaches, there is a dearth of treatments targeting the molecular mechanisms mediated by stress that prevent epithelization. Basic/Clinical Science Advances Recent studies show that epidermal keratinocytes synthesize stress hormones. During acute wound healing, cortisol synthesis in the epidermis is tightly controlled. Further, a key intermediate molecule in the cholesterol synthesis pathway, farnesyl pyrophosphate (FPP), can bind glucocorticoid receptor (GR) and activate GR. Additionally, keratinocytes express beta-2-adrenergic-receptor (β2AR), a receptor for the stress hormone epinephrine. Importantly, migratory rates of keratinocytes are reduced by cortisol, FPP, epinephrine, and other β2AR agonists, thus indicating their role in the inhibition of epithelization. Topical inhibition of local glucocorticoid and FPP synthesis, as well as treatment with β2AR antagonists promotes wound epithelization. Clinical Care Relevance Modulation of local stress hormone production may represent an important therapeutic target for wound healing disorders. Topical administration of inhibitors of cortisol synthesis, statins, β2AR antagonists, and systemic beta-blockers can decrease cortisol synthesis, FPP, and epinephrine levels, respectively, thus restoring keratinocyte migration capacity. These treatment modalities could represent a novel therapeutic approach for wound healing disorders. Conclusion Attenuation of the local stress-induced hormonal imbalance in epidermis may advance therapeutic modalities, thereby leading to enhanced epithelization and improved wound healing. PMID:24527275

  4. 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.

  5. 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.

  6. 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.

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

    PubMed

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

    2014-04-01

    We evaluated the effect of increased plasma cortisol levels on fish antipredator behavior induced by conspecific chemical alarm cues. The experimental model for the study was the Frillfin goby Bathygobius soporator. We first confirmed that the alarm substance induces typical defensive antipredator responses in Frillfin gobies and described their alarm substance cells (epidermal 'club' cells). Second, we confirmed that intraperitoneal cortisol implants increase plasma cortisol levels in this species. We then demonstrated that exogenous cortisol administration and subsequent exposure to an alarm substance decreased swimming activity to a greater extent than the activity prompted by either stimulus alone. In addition, cortisol did not abolish the sheltering response to the alarm chemical cue even though it decreased activity. As predators use prey movements to guide their first contact with the prey, a factor that decreases swimming activity clearly increases the probability of survival. Consequently, this observation indicates that cortisol helps improve the antipredator response in fish. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Impact of experimentally induced serotonin deficiency by tryptophan depletion on saliva cortisol concentrations.

    PubMed

    Vielhaber, K; Riemann, D; Feige, B; Kuelz, A; Kirschbaum, C; Voderholzer, U

    2005-03-01

    Tryptophan depletion (TD) has been shown to induce a transient mood-lowering effect in psychiatric patients and susceptible healthy subjects. We investigated the effects of TD on cortisol secretion in psychiatric patients and healthy subjects based on the hypothesis that the potential mood-lowering effects may be associated with increased activity of the hypothalamic-pituitary-adrenal axis, thus leading to a rise of cortisol secretion. After TD at 18.00 h, salivary cortisol was sampled in the evening and on the following morning. The first study was a randomized, placebo-controlled, crossover study in healthy subjects. Two further open trials in patients with obsessive-compulsive disorder (OCD) and primary insomnia compared the effects of TD on cortisol with baseline conditions. In healthy subjects, TD significantly diminished cortisol the next morning compared with placebo. In OCD patients and primary insomniacs, cortisol the morning after TD was lowered compared with baseline. Evening cortisol was not affected by TD in any of the groups. Contrary to expectation, TD led to a comparable decrease of morning cortisol in all groups investigated. However, these findings are consistent with former studies analyzing the impact of antiserotonergic drugs on cortisol secretion. The results underline that the antiserotonergic effects caused by TD may influence cortisol secretion.

  9. Effects of cold environment exposure and cold acclimatization on exercise-induced salivary cortisol response.

    PubMed

    Izawa, Shuhei; Kim, Kijin; Akimoto, Takayuki; Ahn, Nayoung; Lee, Hoseong; Suzuki, Katsuhiko

    2009-01-01

    Considering the adverse effects of exercise-induced cortisol secretion on health in athletes, it is important to determine the environmental and individual factors that contribute to the variations in exercise-induced cortisol secretion. In this study, the effects of cold environment exposure and cold acclimatization on exercise-induced salivary cortisol responses were investigated. Short track skaters (n = 11), who usually practice under cold conditions, and inline skaters (n = 11), who usually practice under room temperature conditions, participated in a randomized crossover study. All participants cycled for 60 minutes at 65% Vo2 max under cold (ambient temperature: 5 +/- 1 degrees C, relative humidity 41% +/- 9%) and room temperature (ambient temperature: 21 +/- 1 degrees C, relative humidity 35% +/- 5%) conditions. The participants had a 120-minute bed rest recovery phase at room temperature after both exercise bouts. Cortisol levels were measured in saliva samples collected pre-exercise and postexercise at 1 minute, 30 minutes, 60 minutes, and 120 minutes. Both short track and inline skaters exhibited clear cortisol responses to exercise under cold and room temperature conditions. The magnitude of the cortisol response, however, was different between skaters and conditions. The inline skaters exhibited significantly higher cortisol values under cold conditions than under room temperature conditions (7.6 nmol/L and 4.2 nmol/L, respectively). However, the short track skaters exhibited significantly higher cortisol values under cold conditions compared to room temperature conditions (8.7 nmol/L and 5.4 nmol/L, respectively). The effects of cold environment exposure on exercise-induced cortisol response were different between skaters who usually practice under cold or room temperature conditions. These results can be interpreted as acclimatization to either cold or room temperature conditions attenuating the cortisol response, suggesting that acclimatization may

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Gender differences in the association between psychopathic personality traits and cortisol response to induced stress.

    PubMed

    O'Leary, Megan M; Loney, Bryan R; Eckel, Lisa A

    2007-02-01

    Blunted stress reactivity has been implicated in the development of psychopathic personality traits. Cortisol is a biological marker of stress reactivity that has received little attention in prior psychopathy studies. The current investigation proposed that inhibition of cortisol response to induced stress is a reliable marker for psychopathic personality traits. An extreme groups methodology was used to recruit a mixed-gender sample of 84 college students characterized by high and low scores on the Levenson Self-Report Psychopathy Scale. Participants provided saliva samples prior to and after a well-established stress induction procedure (i.e., Trier Social Stress Test). These samples were assessed for cortisol (microg/dL) using an enzyme immunoassay procedure. Consistent with prediction, male participants high in psychopathic personality traits lacked stress induced increases in cortisol displayed by males low in psychopathic personality traits. This effect was not present in female participants. These findings suggest that cortisol production is a gender-specific marker for psychopathic personality traits.

  20. 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

  1. Cardiac Corticosteroid Receptors Mediate the Enlargement of the Ovine Fetal Heart Induced by Chronic Increases in Maternal Cortisol

    PubMed Central

    Reini, Seth A.; Dutta, Garima; Wood, Charles E.; Keller-Wood, Maureen

    2009-01-01

    Previous studies have demonstrated that modest, physiologically relevant increases in maternal cortisol in late gestation result in enlargement of the fetal heart. In this study, we investigated the role of mineralocorticoid (MR) or glucocorticoid receptor (GR) in this enlargement. Ewes with single fetuses were randomly assigned at ~ 120d gestation to one of four groups: maternal cortisol infusion (1mg kg−1 day−1, cortisol); maternal cortisol infusion with fetal intrapericardial infusion of the MR antagonist potassium canrenoate (600µg day−1; cortisol + MRa); maternal cortisol infusion with fetal intrapericardial infusion of the GR antagonist mifepristone (50µg day−1, cortisol + GRa); and maternal saline infusion (control). At ~130 days gestation, fetal heart to body weight ratio and right (RV) and left ventricular (LV) free wall thickness were increased in the cortisol group compared to control group. Fetal hearts from the cortisol +MRa group weighed significantly less, with thinner LV, RV and interventricular septum walls, compared to the cortisol group. Fetal hearts from the cortisol + GRa group had significantly thinner RV walls than the cortisol group. Fetal arterial pressure and heart rate were not different among groups at 130 days. Picrosirius red staining of fetal hearts indicated that the increased size was not accompanied by cardiac fibrosis. These results suggest that physiologic increases in maternal cortisol late in gestation induce fetal cardiac enlargement via MR and, to a lesser extent, by GR, and indicate the enlargement is not secondary to an increase in fetal blood pressure or an increase in fibrosis within the fetal heart. PMID:18495945

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

    PubMed Central

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

    2014-01-01

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

  3. 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.

  4. 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.

  5. THE ROLE OF CORTISOL IN CHRONIC BINGE ALCOHOL-INDUCED CEREBELLAR INJURY: OVINE MODEL

    PubMed Central

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

    2012-01-01

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

  6. 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.

  7. Cortisol, high cortisol diseases and anti-cortisol therapy.

    PubMed

    Sapse, A T

    1997-01-01

    Elevated cortisol is found in many diseases, including infectious, aging-related, depression and depression-associated conditions; even in some with no known origin, and no known therapy. While it was initially thought that 'high cortisol' is the result of these diseases, there is mounting evidence to the contrary, namely, that high cortisol actually plays a major role in inducing them, opening the possibility that anti-cortisol drugs might represent a new beneficial therapy. Evidence is here presented, showing that the use of anti-cortisol drugs has already induced beneficial results in conditions ranging from AIDS to depression. A main reason for not realizing the major role played by cortisol is due to a defective interpretation of cortisol results. If cortisol is within normal range of 0800 h or 1700 h, it has been considered normal, without realizing that swings, sometimes at immunosuppressive levels, might occur during its 24 h circadian rhythm. We suggest that a first step toward unveiling the role of cortisol in diseases would be to develop a standardized cortisol circadian rhythm chart that would show normal levels at any time during a 24 h period, enabling a more accurate comparison with cortisol values obtained under pathological conditions.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Cortisol Test

    MedlinePlus

    ... cortisol, or to help diagnose adrenal insufficiency or Addison disease , conditions associated with deficient cortisol. Cortisol is a ... a low level of cortisol, adrenal insufficiency or Addison disease , such as: Weight loss Muscle weakness Fatigue Low ...

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

    PubMed Central

    Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

    2016-01-01

    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. PMID:26668010

  15. 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. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. 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.

  17. 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.

  18. 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.

  19. Feed efficiency and body composition are related to cortisol response to adrenocorticotropin hormone and insulin-induced hypoglycemia in rams.

    PubMed

    Knott, S A; Cummins, L J; Dunshea, F R; Leury, B J

    2010-08-01

    Metabolic rate and energy consumption increase through the activation of the hypothalamic-pituitary-adrenal axis when an animal is exposed to a stressor. Residual feed intake (RFI) as a measure of efficiency has been shown to be related to exogenous adrenocorticotropin hormone (ACTH)-stimulated cortisol concentrations, which is indicative of the relationship between an animal's response to stress and the efficiency with which the energy is used for growth and production. In this study, we tested the hypothesis that sheep with low post-ACTH serum cortisol concentration relative to the other sheep in the flock have lower RFI values and lower cortisol concentrations following insulin-induced hypoglycemia. Adrenocorticotropin hormone (2.0 microg/kg body weight)-stimulated cortisol concentrations were measured in 100 sheep. The extreme responders were selected (n = 12 high cortisol, n = 12 low cortisol), and feed efficiency and body composition parameters were measured. A second ACTH challenge and an insulin challenge were administered. More efficient sheep (more negative RFI value) were found to have lower (P < 0.05) cortisol concentrations following both an ACTH challenge and an insulin challenge. Low-cortisol sheep (low response to ACTH or insulin) were found to have a lower (P < 0.05) proportion of fat tissue in comparison to the high-cortisol animals. These data clearly indicate that an animal's response to exogenous ACTH or insulin-induced hypoglycemia as a stressor is related (P < 0.05) to efficiency of energy use when measured as RFI. These data have important implications in enabling identification of animals that are superior in terms of feed efficiency and for understanding the physiological mechanisms underlying efficiency of energy use. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Inhibition of cortisol production with metyrapone prevents mental stress-induced endothelial dysfunction and baroreflex impairment.

    PubMed

    Broadley, Andrew J M; Korszun, Ania; Abdelaal, Eltigani; Moskvina, Valentina; Jones, Christopher J H; Nash, Gerard B; Ray, Clare; Deanfield, John; Frenneaux, Michael P

    2005-07-19

    This study was designed to investigate the role of cortisol in stress-induced endothelial dysfunction and impaired baroreflex sensitivity (BRS) by blocking cortisol production with metyrapone before subjecting healthy volunteers to mental stress. Mental stress raises cortisol levels and is associated with increased coronary heart disease (CHD) morbidity and mortality, especially from sudden cardiac death. It also causes endothelial dysfunction and impaired BRS. We measured brachial artery flow-mediated dilation (FMD), a measure of endothelial function, and BRS in 36 subjects without CHD risk factors who were then randomized in a double-blind fashion to oral metyrapone 750 mg x 2 or placebo. Five hours later we subjected subjects to mental stress and then remeasured endothelial function and BRS. Prestress cortisol levels were significantly higher in the placebo group at 270.5 (30.9) nmol/l versus 89.1 (11.8) nmol/l (p = 0.01), and the increase with stress was higher at 57.9 (17.9) nmol/l versus 11.2 (2.2) nmol/l (p < 0.001). In the placebo group, compared to baseline, FMD and BRS fell significantly from 4.5% (0.7%) to 1.4% (1.1%) (p = 0.02) and 21.4 (2.3) ms/mmHg to 16.3 (1.5) ms/mmHg (p = 0.04), respectively. In the metyrapone group, FMD and BRS were unchanged from baseline: 4.3% (0.9%) versus 5.1% (0.8%) (p = 0.48) and 26.4 (2.9) ms/mmHg versus 24.9 (2.6) ms/mmHg (p = 0.62), respectively. Analysis of covariation showed a significant effect of metyrapone on change in both FMD (p = 0.009) and BRS (p = 0.024). Stress-related endothelial dysfunction and BRS impairment can be prevented by blocking cortisol production with metyrapone, demonstrating a direct or facilitative role for cortisol in these phenomena and suggesting mechanisms by which stress contributes to CHD and sudden cardiac death.

  1. 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.

  2. Catestatin, vasostatin, cortisol, temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale and visual analog scale for stress and pain behavior in dogs before and after ovariohysterectomy.

    PubMed

    Srithunyarat, Thanikul; Höglund, Odd V; Hagman, Ragnvi; Olsson, Ulf; Stridsberg, Mats; Lagerstedt, Anne-Sofie; Pettersson, Ann

    2016-08-02

    The stress reaction induced by surgery and associated pain may be detrimental for patient recovery and should be minimized. The neuropeptide chromogranin A (CGA) has shown promise as a sensitive biomarker for stress in humans. Little is known about CGA and its derived peptides, catestatin (CST) and vasostatin (VS), in dogs undergoing surgery. The objectives of this study were to investigate and compare concentrations of CGA epitopes CST and VS, cortisol, body temperature, heart rate, respiratory rate, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF) and visual analog scales (VAS) for stress and pain behavior in dogs before and after ovariohysterectomy. Thirty healthy privately owned female dogs admitted for elective ovariohysterectomy were included. Physical examination, CMPS-SF, pain behavior VAS, and stress behavior VAS were recorded and saliva and blood samples were collected before surgery, 3 h after extubation, and once at recall 7-15 days after surgery. Dogs were premedicated with morphine and received carprofen as analgesia for 7 days during the postoperative period. At 3 h after extubation, CMPS-SF and pain behavior VAS scores had increased (p < 0.0001) and stress behavior VAS scores, temperature, respiratory rate (p < 0.0001), plasma CST concentrations (p = 0.002) had decreased significantly compared to before surgery. No significant differences were observed in the subjective and physiological parameters between before surgery and at recall, but plasma CST (p = 0.04) and serum cortisol (p = 0.009) were significantly lower at recall. Plasma VS, saliva CST, and heart rate did not differ significantly at any observed time. Study parameters for evaluating surgery-induced stress and pain changed in dogs subjected to ovariohysterectomy. To further evaluate CST and VS usefulness as pain biomarkers, studies on dogs in acute painful situations are warranted.

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

    PubMed

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

    2016-03-01

    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. 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. 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. 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. 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.

  4. 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.

  5. 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…

  6. 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…

  7. 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

  8. 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.

  9. 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.

  10. The Relationship between naloxone-induced cortisol and mu opioid receptor availability in mesolimbic structures is disrupted in alcohol dependent subjects

    PubMed Central

    Wand, Gary S.; Weerts, Elise M.; Kuwabara, Hiroto; Wong, Dean F.; Xu, Xiaoqiang; McCaul, Mary E.

    2012-01-01

    The mu opioid receptor system is altered in alcohol dependent (AD) subjects. Cortisol responses to opioid receptor antagonists are assumed to impart information about opioid receptor activity. In the present study we examined naloxone-induced cortisol responses in 18 healthy control (HC) and 25 recently detoxified AD subjects and then correlated the cortisol response with mu opioid receptor availability across 15 brain regions using positron emission tomography (PET) and the mu opioid receptor selective ligand [11C] Carfentanil (CFN). On average the AD subjects required twice the dose of naloxone to induce a peak cortisol response compared to the HC subjects. Using the rising slope of the cortisol curve (placebo to peak) as a metric we then went on to examine the relationship between cortisol responses to naloxone and [11C]CFN BPND. There were significant negative relationships between cortisol and [11C]CFN binding potential (BPND) in multiple brain regions of HC subjects. However, cortisol responses did not correlate with [11C]CFN BPND across any brain region in AD subjects. In summary, naloxone imparts information about individual differences in mu opioid receptor availability throughout the mesolimbic system in healthy individuals. However pathways governing the relationship between naloxone-induced cortisol and mu opioid receptor availability are disrupted during early abstinence in AD subjects. PMID:22717196

  11. β-Glucan-induced cortisol levels improve the early immune response in matrinxã (Brycon amazonicus).

    PubMed

    Franco Montoya, Luz N; Martins, Talísia P; Gimbo, Rodrigo Y; Zanuzzo, Fábio S; Urbinati, Elisabeth C

    2017-01-01

    This study investigated the role of endogenous cortisol on the innate immune response in matrinxã (Brycon amazonicus) fed with β-glucan, prior to and after stressor exposure and bacterial challenge. For this, we evaluated the serum cortisol and plasma glucose levels, the serum lysozyme levels, the hemolytic activity of the complement system, and the respiratory activity of leukocytes, as well as the number of circulating erythrocytes and leukocytes of fish fed during 15 days with diets containing β-glucan 0.1% (β-G) or β-glucan 0.1% + metyrapone 30 mg kg(-1) fish (β-G + MTP). Dietary MTP was used to block cortisol production. After feeding, fish were air-exposed during 3 min, to endogenously increase the cortisol levels. Following that, they were challenged with intraperitoneal injection of Aeromonas hydrophila. Results were compared with a positive control group fed with a β-glucan-free diet. A negative control group, also fed with β-glucan-free diet but inoculated with PBS, was established to evaluate the effect of the handling during injection. Fish were sampled prior to the stressor exposure, 30 min after exposure, and 24 h post infection (hpi). Herein we observed that dietary β-G modulated the cortisol profile prior to and after the stressor, increasing the number and activity of leukocytes. Moreover, cortisol showed to be an efficient modulator of both humoral and cellular innate immune system by increasing lysozyme and complement activity, as well as neutrophil and monocyte populations. Our results suggest that β-glucan-induced cortisol increase is one important mechanism to improve the innate immune response in matrinxã. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Core temperature influences on the relationship between exercise-induced leukocytosis and cortisol or TNF-alpha.

    PubMed

    Cooper, Erica S; Berry, Mark P; McMurray, Robert G; Hosick, Peter A; Hackney, Anthony C

    2010-05-01

    The extent to which exercise in the heat modifies leukocytosis and the relationship between the leukocytosis and tumor necrosis factor-alpha (TNF-alpha) or cortisol is not well understood. Thus, this study attempted to determine the combined effect of exercise and differing elevations in core temperature on exercise-induced leukocytosis and to examine associations between any leukocytosis and cortisol orTNF-alpha. Eight male subjects completed two 40-min trials while immersed in 25 and 38.5 degrees C water. Leukocytes, TNF-alpha, and cortisol were determined at baseline, immediately post-, and 2 h post-exercise. Both trials resulted in significant 13-33% increases in total leukocytes, mostly driven by a 24-30% increase in neutrophils. A significant relationship was found between the change in core temperature (T(re)) during exercise and the increase in total leukocytes (r = 0.561). Similarly, the change in T(re) was related to the change in cortisol (r = 0.557) and TNF-alpha (r = 0.483). Yet the exercise-induced change in cortisol was not significantly correlated to any changes in leukocytes. There was a trend for the relationships between the exercise-induced change in TNF-alpha and the changes in total leukocytes (r = 0.491) and neutrophils (r = 0.479). These results suggest that although neither cortisol nor TNF-alpha are strong predictors of the leukocyte response during exercise or recovery, each factor may be one of many potential modifiers of the total leukocyte response.

  13. 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.

  14. Behavioral Adjustment in a Community Sample of Boys: Links with Basal and Stress-Induced Salivary Cortisol Concentrations

    PubMed Central

    Tyrka, Audrey R.; Kelly, Megan M.; Graber, Julia A.; DeRose, Laura; Lee, Janet K.; Warren, Michelle P.; Brooks-Gunn, Jeanne

    2010-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been observed in association with internalizing symptoms and is thought to be involved in the pathogenesis of depression and some anxiety disorders. This study examined basal and stress-induced cortisol concentrations in relation to internalizing and externalizing symptoms in a racially mixed community sample of 102 8–11 year-old boys. Afternoon basal cortisol concentrations were positively correlated with measures of internalizing behavior problems, social problems, and emotionality. Greater change in cortisol across a home-visit challenge task was also significantly associated with internalizing behaviors and social problems, as well as attention and thought problems. The implications of these findings and how they may relate to the pathogenesis of emotional and behavioral problems are discussed. PMID:20223598

  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. 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.

  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. The endotoxin-induced increase of cytokines is followed by an increase of cortisol relative to dehydroepiandrosterone (DHEA) in healthy male subjects.

    PubMed

    Straub, R H; Schuld, A; Mullington, J; Haack, M; Schölmerich, J; Pollmächer, T

    2002-11-01

    Dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) inhibit T-helper lymphocyte type 2 immune reactions and exert anti-inflammatory effects in some chronic inflammatory diseases. Both DHEA and, in particular, DHEAS levels are dramatically decreased in chronic inflammatory diseases whereas cortisol levels remain stable or are elevated. However, the time course of cortisol relative to DHEA production is not known. We tested whether administration of endotoxin to healthy male subjects can induce an early predominance of cortisol relative to DHEA and DHEAS. It is demonstrated that endotoxin induces a dose-dependent increase of cortisol in relation to DHEA (no effect at 0.2 ng endotoxin/kg body weight (b.w.), clear effect at 0.4 and 0.8 ng/kg b.w., p<0.05) and DHEAS (tested at 0.4 ng/kg b.w., P=0.014). The increase of cortisol relative to DHEA appears 4 h after endotoxin injection and 2 h after a strong increase of interleukin (IL)-6 relative to tumour necrosis factor (TNF). In addition, an increase of cortisol relative to 17OH-progesterone was observed. The ratio of serum IL-6/TNF was positively correlated with the ratio of serum cortisol/DHEA (R(Rank)=0.472, P=0.041) and serum cortisol/17OH-progesterone (R(Rank)=0.514, P=0.048). In conclusion, dissociation of cortisol relative to DHEA, DHEAS or 17OH-progesterone appears very early during a systemic inflammatory response which is associated with an increase of IL-6 relative to TNF. As in chronic inflammatory diseases, during an acute inflammatory response with endotoxin, these physiological hormone changes are probably necessary to achieve adequate cortisol levels at the expense of adrenal androgens.

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

    PubMed

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

    2014-09-01

    The underlying cause of predisposition to obesity is complex but one marker is cortisol responsiveness. Selection of sheep for high (HR) or low (LR) cortisol responses to adrenocorticotropin shows that HR are more likely to become obese. Increased propensity to obesity is associated with reduced skeletal muscle thermogenesis. We sought to determine whether metabolic or behavioral responses to stress also contribute to altered propensity to obesity in LR and HR. Animals (n=5-10/group) were exposed to 3 stressors and we measured food intake and thermogenesis (recorded with dataloggers implanted into muscle). Stressors were hypoglycaemia (0.125 units/kg insulin, IV), a barking dog and immune challenge (200 ng/kg lipopolysaccharide--LPS, IV). LR animals showed a greater catabolic state in response to both immune and psychosocial stressors. LPS reduced (P<0.01) food intake in both groups but LR showed a greater (P<0.05) reduction in food intake and a more substantial (P<0.05) rise in muscle temperature. Introduction of the barking dog reduced (P<0.05) food intake in LR only. These metabolic differences coincided with differences in cortisol responsiveness, where HR animals had increased (P<0.05) cortisol in response to both immune and psychosocial stressors. We also assessed behavior in the following paradigms: 1, isolation in the open field test; 2, response to a human intruder; and 3, food competition. LR had greater (P<0.05) activity, reduced fearfulness and displayed a proactive coping style of behavior. Thus we demonstrate that high cortisol responsiveness identifies animals with stress-induced metabolic and behavioral traits that may contribute to susceptibility to obesity. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2015-07-28

    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.

  2. 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

  3. Sex differences in emotional memory consolidation: the effect of stress-induced salivary alpha-amylase and cortisol.

    PubMed

    Felmingham, Kim L; Tran, Thu Phuong; Fong, Wing Chee; Bryant, Richard A

    2012-03-01

    This study examined sex differences in the emotional memory consolidation, and the impact of stress-induced cortisol and salivary alpha amylase responses on emotional memory recall. Following baseline salivary measures, 39 healthy women and 41 men viewed 20 neutral and 20 negative arousing images, and then underwent either a cold pressor stress test or control condition, followed by further salivary measures. Participants returned two days later for a free recall test. The stress condition induced greater cortisol response, and negative images were better recalled than neutral. Whereas women displayed greater recall of negative images under stress than men, they recalled fewer negative images in the control condition. Stress-induced cortisol predicted recall of negative images in women, and neutral images in men. This suggests there is an enhanced consolidation of negative images under stress in women that may be a potential mechanism for the greater female prevalence for developing anxiety disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. High concentrate-induced subacute ruminal acidosis (SARA) increases plasma acute phase proteins (APPs) and cortisol in goats.

    PubMed

    Jia, Y Y; Wang, S Q; Ni, Y D; Zhang, Y S; Zhuang, S; Shen, X Z

    2014-09-01

    The aim of this study was to investigate changes of stress status in dairy goats induced to subacute ruminal acidosis (SARA). The level of acute phase proteins (APPs) including haptoglobin (HP) and serum amyloid A (SAA) in plasma and their mRNA expression in liver, as well as plasma cortisol and genes expression of key factors controlling cortisol synthesis in adrenal cortex were compared between SARA and control goats. SARA was induced by feeding high concentrate diet (60% concentrate of dry matter) for 3 weeks (SARA, n=6), while control goats (Con, n=6) received a low concentrate diet (40% concentrate of dry matter) during the experimental time. SARA goats showed ruminal pH below 5.8 for more than 3 h per day, which was significantly lower than control goats (pH>6.0). SARA goats demonstrated a significant increase of hepatic HP and SAA mRNA expression (P<0.05), and the level of HP but not SAA in plasma was markedly increased compared with control (P<0.05). The level of cortisol in plasma showed a trend to increase in SARA goats (0.050.05). These results suggested that SARA goats experienced a certain stress status, exhibiting an increase in HP production and cortisol secretion.

  5. 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

  6. 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.

  7. 15-Ketodihydro-PGF2alpha and cortisol plasma concentrations in newborn foals after spontaneous or oxytocin-induced parturition.

    PubMed

    Panzani, S; Villani, M; Govoni, N; Kindahl, H; Faustini, M; Romano, G; Veronesi, M C

    2009-03-15

    Hormonal changes during early neonatal life play a major role in the physiological processes underlying the maturation of several organs. Since prostaglandins and cortisol are associated with fetal organ system maturation, the aim of this study was to evaluate 15-ketodihydro-PGF(2alpha) (PGM) and cortisol plasma concentrations during the first 21 days after birth in foals born by either spontaneous (24 foals) or low-dose oxytocin (OT)-induced parturition performed after at least 320 gestational days (25 foals) since induction is often considered to be a cause of prematurity. After spontaneous birth, the PGM concentration was significantly (P<0.05) higher at 20 and 30min compared to samples taken several hours or days later, while induced foals showed significantly (P<0.05) higher concentrations at 10, 20, and 30min. Regarding differences between the two groups, the plasma concentration of PGM was significantly higher 10 (P<0.01), 20 (P<0.05), and 30 (P<0.05)min and 3h (P<0.05) after birth in induced foals compared to foals born by spontaneous parturition. It is difficult to determine whether the higher initial PGM concentrations in induced foals is related to higher uterine or fetal PGM release induced by exogenous OT stimulation. Cortisol plasma levels in both groups were higher at birth (P<0.05) compared to the later sampling times. No differences were observed between the two groups indicating that the induction protocol used does not seem to result in premature foals.

  8. 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

  9. Stress-induced cortisol level elevations are associated with reduced negative affect after stress: indications for a mood-buffering cortisol effect.

    PubMed

    Het, Serkan; Schoofs, Daniela; Rohleder, Nicolas; Wolf, Oliver T

    2012-01-01

    Stress is associated with increased negative affect and activation of the sympathetic nervous system and of the hypothalamic-pituitary-adrenal axis. However, the relationship between these stress systems and negative affect is incompletely understood. We therefore investigated positive and negative affects in relationship with salivary cortisol and salivary α-amylase (sAA) levels in a large sample of participants exposed to a psychosocial stressor or a control condition. Cortisol and sAA levels from five studies with a total sample size of 232 participants were reanalyzed using hierarchical linear modeling. In these studies, we measured affective responses to the Trier Social Stress Test (TSST) and its control condition (placebo TSST) with the Positive and Negative Affect Schedule. An inverse relationship between cortisol and negative affect was observed across all participants (β(06) = -0.13, p = .002). Higher level of negative affect was associated with lower mean cortisol levels 10 minutes after the TSST or the control condition. When the two conditions were tested separately, the effect was significant in the stress condition (β(06) = -0.05, p = .02) but not in the control condition (β(06) = -0.0008, p > .05). In contrast to the results for cortisol, a positive relationship was found between sAA and negative affect within the stress condition (β(06) = 0.10, p = .005). The present findings suggest that cortisol is associated with an attenuated negative emotional arousal in response to acute stress, whereas sAA levels seem to reflect the degree of negative emotional arousal. Together with previous pharmacological studies, these data seem to support the hypothesis of mood-buffering effects of cortisol.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  11. 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.

  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. 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

  14. 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

  15. 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.

  16. 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 ...

  17. 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 ...

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

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

    PubMed

    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(2)SO(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(50)>2000mg/L). RT cells were more sensitive (EC(50)=8.7mg/L) to selenite than BT cells (EC(50)=90.4mg/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. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. 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.

  6. Synthesis of the rosette-inducing factor RIF-1 and analogs.

    PubMed

    Beemelmanns, Christine; Woznica, Arielle; Alegado, Rosanna A; Cantley, Alexandra M; King, Nicole; Clardy, Jon

    2014-07-23

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

  7. 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

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

    PubMed

    Kori, Rohini Sharanappa; Aladakatti, Ravindranath H; Desai, S D; Das, Kusal Kanti

    2016-08-01

    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. To investigate the effect of alprazolam on restrained stress induced alteration of serum cortisol, and antioxidant vitamin levels in male albino rats. 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. 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. Results indicate a possible antioxidant effect of alprazolam on restrained stress induced alteration of serum cortisol and antioxidant vitamin levels.

  9. Naloxone decreases the inhibitory effect of alprazolam on the release of adrenocorticotropin/cortisol induced by physical exercise in man

    PubMed Central

    Coiro, Vittorio; Volpi, Riccardo; Casti, Amos; Maffei, Maria Ludovica; Stella, Adriano; Volta, Elio; Chiodera, Paolo

    2011-01-01

    AIMS To establish the possible involvement of alprazolam (ALP) and/or opiates in the mechanism underlying the ACTH/cortisol response to physical exercise. METHODS Tests were carried out under basal conditions (exercise control test), exercise plus ALP (50 µg at time −90 min), naloxone (10 mg at time 0) or ALP plus naloxone. Plasma ACTH and serum cortisol concentrations were evaluated in blood samples taken before, during and after the bicycle ergometer tests. RESULTS ACTH and cortisol concentrations rose significantly after physical exercise. Maximum peak at time 15 min (P≤ 0.01 vs. baseline) for ACTH and at time 30 min (P≤ 0.01 vs. baseline) for cortisol. In the presence of naloxone, the ACTH and cortisol responses were significantly increased (maximum peak at time 20 min, P≤ 0.02 vs. control test for ACTH, and at time 30 min (P≤ 0.01 vs. baseline) for cortisol) whereas they were abolished by ALP. When ALP and naloxone were given together, the inhibitory effect of ALP was partial. CONCLUSIONS These data demonstrate an inhibitory effect of ALP in the regulation of the ACTH/cortisol response to physical exercise in man and suggest that GABAergic receptor activating benzodiazepines and opioids interact in the neuroendocrine secretion of ACTH/cortisol. PMID:21564163

  10. 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.

  11. The impact of semantic distance and induced stress on analogical reasoning: a neurocomputational account.

    PubMed

    Vendetti, Michael; Knowlton, Barbara J; Holyoak, Keith J

    2012-12-01

    In a study of reasoning with four-term verbal analogy problems, we explored the relationship between the effects of an acute, mild stressor and the complexity of the reasoning process. Participants judged whether analogy problems in the form A:B :: C:D were valid or invalid, on the basis of whether the relation in the A:B term matched that in the C:D term. Half of the problems contained a C:D pair semantically near the A:B pair (e.g., NOSE:SCENT :: TONGUE:TASTE), and the other half contained ones semantically far from A:B (e.g., NOSE:SCENT :: ANTENNA:SIGNAL). After an initial block without stress, participants were randomly assigned to count backward by 13 s from 1,000 while being told to go faster, or to count forward by 1 s from 0. The stress-induced participants reported a significant increase in state anxiety as compared to controls immediately after the mental arithmetic task. Stressed participants performed less accurately (as measured by d') on both near and far analogy problems, mainly due to an increase in false alarms. We were able to model the influence of semantic distance using the "learning and inference with schemas and analogies" (LISA) model. Our findings indicated that even mild increases in stress impair analogical reasoning. However, the decrement does not seem to directly involve the integration of relations, but rather is due to a shift in decision strategy: Under stress, people show an increased tendency to endorse analogies as valid when the terms in the individual pairs are semantically related to each other, even if the overall analogical relationship is not valid.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Salivary Cortisol: A Psychophysiological Marker for PTSD

    DTIC Science & Technology

    2011-04-01

    Department of Behavioral Sciences and Leadership West Point Resilience Project (WPRP) Research Report PL488E5 Salivary Cortisol : A...valid OMB control number. 1. REPORT DATE APR 2011 2. REPORT TYPE 3. DATES COVERED 4. TITLE AND SUBTITLE Salivary Cortisol : A...lab-induced trauma-related stressor. Our research is aimed at analyzing the validity of measuring baseline salivary cortisol levels of Soldiers as a

  18. 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.

  19. "Picolog," a synthetically-available bryostatin analog, inhibits growth of MYC-induced lymphoma in vivo.

    PubMed

    DeChristopher, Brian A; Fan, Alice C; Felsher, Dean W; Wender, Paul A

    2012-01-01

    Bryostatin 1 is a naturally occurring complex macrolide with potent anti-neoplastic activity. However, its extremely low natural occurrence has impeded clinical advancement. We developed a strategy directed at the design of simplified and synthetically more accessible bryostatin analogs. Our lead analog, "picolog", can be step-economically produced. Picolog, compared to bryostatin, exhibited superior growth inhibition of MYC-induced lymphoma in vitro. A key mechanism of picolog's (and bryostatin's) activity is activation of PKC. A novel nano-immunoassay (NIA) revealed that picolog treatment increased phospho-MEK2 in the PKC pathway. Moreover, the inhibition of PKC abrogated picolog's activity. Finally, picolog was highly potent at 100 micrograms/kg and well tolerated at doses ranging from 100 micrograms/kg to 1 milligram/kg in vivo for the treatment of our aggressive model of MYC-induced lymphoma. We provide the first in vivo validation that the bryostatin analog, picolog, is a potential therapeutic agent for the treatment of cancer and other diseases.

  20. 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.

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

    PubMed

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

    2016-07-29

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

  2. 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.

  3. 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

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

    PubMed

    Yokawa, Ken; Kagenishi, Tomoko; Kawano, Tomonori

    2011-04-01

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

  5. 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

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

    PubMed

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

    2014-01-01

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

  7. 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.

  8. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  10. Liposomes Containing Monophosphoryl Lipid A: A Potent Adjuvant System For Inducing Antibodies To Heroin Hapten Analogs

    PubMed Central

    Matyas, Gary R.; Mayorov, Alexander V.; Rice, Kenner C.; Jacobson, Arthur E.; Cheng, Kejun; Iyer, Malliga R.; Li, Fuying; Beck, Zoltan; Janda, Kim D.; Alving, Carl R.

    2014-01-01

    In order to create an effective immunization approach for a potential vaccine to heroin, liposomes containing monophosphoryl lipid A [L(MPLA)] were tested as an adjuvant system to induce antibodies to heroin hapten analogs. Four synthetic haptens and two immunization strategies were employed. In the first strategy, a hydrophobic 23 amino acid immunogenic peptide derived from the membrane proximal external region of gp41 from HIV-1 envelope protein was embedded as a carrier in the outer surface of L(MPLA), to which was conjugated a 15 amino acid universal T cell epitope and a terminal heroin hapten analog. In the second strategy, tetanus toxoid (TT) carrier protein was decorated with haptens by conjugation, and the hapten-conjugated protein was mixed with L(MPLA). After immunization of mice, each of the immunization strategies was effective for induction of IgG anti-hapten antibodies. The first immunization strategy induced a mean end-point IgG titer against one of two haptens tested of approximately 12,800; however, no detectable antibodies were induced against the liposome-associated HIV-1 carrier peptide. In the second immunization strategy, depending on the hapten used for decorating the TT, end-point IgG titers ranged from 100,000 to 6,500,000. In this strategy, in which hapten was conjugated to the TT, end-point IgG titers of 400,000 to the TT carrier were observed with each conjugate. However, upon mixing unconjugated TT with L(MPLA), anti-TT titers of 6,500,000 were observed. We conclude that L(MPLA) serves as a potent adjuvant for inducing antibodies to candidate heroin haptens. However, antibodies to the carrier peptide or protein were partly or completed inhibited by the presence of conjugated hapten. PMID:23624097

  11. Liposomes containing monophosphoryl lipid A: a potent adjuvant system for inducing antibodies to heroin hapten analogs.

    PubMed

    Matyas, Gary R; Mayorov, Alexander V; Rice, Kenner C; Jacobson, Arthur E; Cheng, Kejun; Iyer, Malliga R; Li, Fuying; Beck, Zoltan; Janda, Kim D; Alving, Carl R

    2013-06-10

    In order to create an effective immunization approach for a potential vaccine to heroin, liposomes containing monophosphoryl lipid A [L(MPLA)] were tested as an adjuvant system to induce antibodies to heroin hapten analogs. Four synthetic haptens and two immunization strategies were employed. In the first strategy, a hydrophobic 23 amino acid immunogenic peptide derived from the membrane proximal external region of gp41 from HIV-1 envelope protein was embedded as a carrier in the outer surface of L(MPLA), to which was conjugated a 15 amino acid universal T cell epitope and a terminal heroin hapten analog. In the second strategy, tetanus toxoid (TT) carrier protein was decorated with haptens by conjugation, and the hapten-conjugated protein was mixed with L(MPLA). After immunization of mice, each of the immunization strategies was effective for induction of IgG anti-hapten antibodies. The first immunization strategy induced a mean end-point IgG titer against one of two haptens tested of approximately 12,800; however, no detectable antibodies were induced against the liposome-associated HIV-1 carrier peptide. In the second immunization strategy, depending on the hapten used for decorating the TT, end-point IgG titers ranged from 100,000 to 6,500,000. In this strategy, in which hapten was conjugated to the TT, end-point IgG titers of 400,000 to the TT carrier were observed with each conjugate. However, upon mixing unconjugated TT with L(MPLA), anti-TT titers of 6,500,000 were observed. We conclude that L(MPLA) serves as a potent adjuvant for inducing antibodies to candidate heroin haptens. However, antibodies to the carrier peptide or protein were partly or completed inhibited by the presence of conjugated hapten. Published by Elsevier Ltd.

  12. 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

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

    PubMed

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

    2017-01-01

    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. 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. 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). 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.

  14. Reduced Cortisol Metabolism during Critical Illness

    PubMed Central

    Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E.; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J.; Perre, Sarah Vander; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R.; Van den Berghe, Greet

    2015-01-01

    BACKGROUND Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically

  15. Reduced cortisol metabolism during critical illness.

    PubMed

    Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J; Vander Perre, Sarah; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R; Van den Berghe, Greet

    2013-04-18

    Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic-pituitary-adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the

  16. 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.

  17. The characterization of a non-Newtonian blood analog in natural- and shear-layer-induced transitional flow.

    PubMed

    Li, Lin; Walker, Andrew M; Rival, David E

    2014-01-01

    Although a blood analog of aqueous glycerol and xanthan gum was found to replicate the viscoelastic behavior of blood, measurements were restricted to laminar flow. To expand the characterization of a non-Newtonian blood analog of aqueous glycerol and xanthan gum to transitional Reynolds numbers to quantify its behavior as a function of both natural and shear-layer-induced mechanisms. A Newtonian analog and a shear-thinning aqueous glycerol, xanthan gum solution were circulated through an in vitro flow loop replicating both a straight and obstructed artery where transition was initiated through natural and shear-layer-induced mechanisms respectively. Steady and pulsatile pressure drop measurements for both fluids were acquired across a range of Reynolds numbers up to 7600 and Womersley numbers of 4 and 6. In steady and pulsatile straight flow, the non-Newtonian analog presented with reduced pressure drops and prolonged laminar flow to Reynolds numbers of 3200 and 3800 respectively. Upon blockage inclusion, non-Newtonian minor losses were comparable to Newtonian in steady flow and greater in pulsatile flow suggesting an elongation of downstream non-Newtonian recirculation. Although non-Newtonian total system pressure drops in both straight and obstructed flows were lower, the ratio of pressure drop difference between the two fluids decreased through shear-layer-induced transition. These findings not only demonstrated the suitability of using a xanthan gum analog to model blood flow in transitional regimes, but also presented the respective differences in analog behavior as a function of transition mechanism.

  18. 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.

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

    PubMed Central

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

    2013-01-01

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

  20. 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.

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

    PubMed

    Osada, Kazumi; Miyazono, Sadaharu; Kashiwayanagi, Makoto

    2015-01-01

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

  2. 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

  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. 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.

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

    PubMed

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

    2015-01-01

    Arsenic (As) exerts oxidative stress with depletion of body selenium in monogastric animals. But in ruminants this fact is not yet verified. Vitamin E is an effective dietary antioxidant. Thus, in this experiment, the protective effect of vitamin E against arsenic toxicity induced by sodium arsenite (60mg As/kg diet) was investigated in goat kids. For this, 21 male kids were divided into three equal groups and fed either basal diet as such (control), or supplemented with 60mg As/kg diet and 60mg As/kg diet+250IU vitamin E/kg diet for 180 days. Vitamin E supplementation alleviated the toxic effects caused by arsenic on serum alanine aminotransferase and aspartate aminotransferase and lipid peroxidation. It also prevented the depletion of reduced glutathione content and reduction in activity of catalase, superoxide dismutase and glutathione-s-transferase in erythrocytes resulted from arsenic intoxication. The elevated levels of arsenic and reduced levels of selenium in the serum and tissues in arsenic treated animals were attenuated by vitamin E supplementation, though not completely. However, serum cortisol level was not affected by arsenic. It was concluded that arsenic exerts cortisol independent stressor mechanism and supplementation of vitamin E at a level of 250IU/kg diet was partially effective in reducing tissue accumulation of arsenic in the body and protect the kids from oxidative stress induced by arsenic. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. 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.

  8. Naloxone-induced cortisol predicts mu opioid receptor binding potential in specific brain regions of healthy subjects

    PubMed Central

    Wand, Gary S.; Weerts, Elise M.; Kuwabara, Hiroto; Frost, J. James; Xu, Xiaoqiang; McCaul, Mary E.

    2011-01-01

    Investigators have administered the opioid receptor antagonist, naloxone, to interrogate the hypothalamic-pituitary-adrenal (HPA) axis response under the assumption that this technique provides a measure of endogenous opioid activity. However it has never been tested whether provocation of the HPA axis with naloxone provides a surrogate marker for direct measurement of endogenous opioid activity using PET imaging as the gold standard. To test this hypothesis, eighteen healthy subjects underwent a PET scan with the mu-opioid receptor (MOR) selective ligand [11C]carfentanil (CFN). The following day ACTH and cortisol responses were assessed using a technique which allows administration of 5 incremental doses of naloxone (0, 25, 50, 100 and 250 µg/kg) in a single session. Relationships between ACTH and cortisol responses and [11C]CFN binding potential (BPND) were examined in 5 brain regions involved in the regulation of the HPA axis and/or regions with high concentrations of MOR. All subjects mounted graded ACTH and cortisol responses to naloxone administrations. There were significant negative relationships between cortisol response to naloxone and [11C]CFN BPND in ventral striatum, putamen and caudate. When sex and smoking were added as covariates to the model, these correlations were strengthened and there was a significant correlation with the hypothalamus. There were no significant correlations between ACTH and any volumes of interest. The opioid receptor antagonist naloxone is not merely a non-specific pharmacologic activator of the HPA axis; it provides information about individual differences in opioid receptor availability. PMID:21549509

  9. MADP, a salidroside analog, protects hippocampal neurons from glutamate induced apoptosis.

    PubMed

    Xian, Hua; Zhao, Jing; Zheng, Yuan; Wang, Meihong; Huang, Jun; Wu, Bingxin; Sun, Cheng; Yang, Yumin

    2014-05-08

    To investigate the anti-apoptotic effect of MADP, an analog of salidroside, against glutamate induced apoptosis in the cultured rat hippocampal neurons. Cytotoxicity was determined by the MTT method and lactate dehydrogenase release to the medium. Cell apoptosis was evaluated by Hoechst 33342 staining, TUNEL assay and flow cytometric analysis. Western blotting was applied for detecting protein levels of cellular signaling molecules. Our results showed that glutamate exposure significantly induces cell apoptosis, whereas the pretreatment of salidroside or MADP remarkably improves cell viability. Most importantly, the anti-apoptotic effect of MADP against glutamate insult is superior to salidroside. To explore the involved mechanisms, we measured some pro-apoptotic and anti-apoptotic protein levels, and several cell survival signaling pathways were analyzed as well. No visible alterations in Bcl-2 and Bax protein levels were observed by MADP or salidroside. Akt and JNK phosphorylation was robustly stimulated by MADP in the glutamate-treated neurons. Salidroside treatment results in a slight activation in Akt, while no significant alteration in JNK activity was observed. MADP exhibits higher capacity to attenuate glutamate induced cell apoptosis in the cultured rat hippocampal neurons, suggesting that MADP might be a better candidate than salidroside for developing novel drugs treating neuron loss associated disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

    Huang, Tom Tao; Wages, John M

    2016-04-01

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

  11. 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

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

    PubMed

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

    2017-01-18

    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.

  13. Intermittently-induced endotoxaemia has no effect on post-challenge plasma metabolites, but increases body temperature and cortisol concentrations in periparturient dairy cows.

    PubMed

    Zebeli, Q; Sivaraman, S; Dunn, S M; Ametaj, B N

    2013-12-01

    This study evaluated the responses of plasma cortisol, metabolites and body temperature to intermittently-induced endotoxaemia in periparturient cows. Sixteen Holstein cows were randomly allocated to one of the two treatment groups. Cows were infused intravenously either with saline solution (control) or with the same solution containing 3 increasing doses of lipopolysaccharide (LPS) for 3 consecutive weeks around parturition as follows: 0.01 μg LPS/kg body weight (BW) on d -14 and -10 prepartum, 0.05 μg LPS/kg BW on d -7 and -3 prepartum, and 0.1 μg LPS/kg BW on d 3 and 7 postpartum. Blood samples were measured shortly before and in 8 time-points after (up to 6h) the challenges on d -14, -7, 3, and 7 to evaluate the post-challenge plasma profile. Results showed greater concentrations of plasma cortisol, in particular after the second and third LPS challenge. An increase in body temperature was recorded after administration of the greatest LPS dose, but this effect diminished during the very last LPS challenge. A biphasic response of glucose was observed; a linear increase up to 60 min after the second LPS challenge followed by a rapid decrease thereafter. Other plasma variables like lactate, cholesterol, non-esterified fatty acids, and beta-hydroxybutyrate were not affected by treatment. In conclusion, LPS administrations did not notably affect post-challenge metabolic responses in periparturient dairy cows but increased the level of plasma cortisol and the body temperature after the highest LPS challenge. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Salivary cortisol and cortisone in the clinical setting.

    PubMed

    Blair, Joanne; Adaway, Jo; Keevil, Brian; Ross, Richard

    2017-06-01

    A resurgence of interest in salivary biomarkers has generated evidence for their value in assessing adrenal function. The advantages of salivary measurements include only free hormone is detected, samples can be collected during normal daily routines and stress-induced cortisol release is less likely to occur than during venepuncture. We review the use of salivary biomarkers to diagnose and monitor patients for conditions of cortisol excess and deficiency and discuss the value of measuring salivary cortisone versus salivary cortisol. Developments in laboratory techniques have enabled the measurement of salivary hormones with a high level of sensitivity and specificity. In states of altered cortisol binding, salivary biomarkers are more accurate measures of adrenal reserve than serum cortisol. Salivary cortisone is a superior marker of serum cortisol compared with salivary cortisol, specifically when serum cortisol is low and during hydrocortisone therapy when contamination of saliva may result in misleading salivary cortisol concentrations. Salivary cortisol and cortisone can be used to assess cortisol excess, deficiency and hydrocortisone replacement, with salivary cortisone having the advantage of detection when serum cortisol levels are low and there is no interference from oral hydrocortisone.

  15. Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity.

    PubMed

    Pražienková, Veronika; Holubová, Martina; Pelantová, Helena; Bugáňová, Martina; Pirník, Zdenko; Mikulášková, Barbora; Popelová, Andrea; Blechová, Miroslava; Haluzík, Martin; Železná, Blanka; Kuzma, Marek; Kuneš, Jaroslav; Maletínská, Lenka

    2017-01-01

    Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys11 (analogs 1 and 2), but not with analog modified both at the N-terminus and Lys11 (analog 3) decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders.

  16. Impact of novel palmitoylated prolactin-releasing peptide analogs on metabolic changes in mice with diet-induced obesity

    PubMed Central

    Pelantová, Helena; Bugáňová, Martina; Pirník, Zdenko; Mikulášková, Barbora; Popelová, Andrea; Blechová, Miroslava; Haluzík, Martin; Železná, Blanka; Kuzma, Marek; Kuneš, Jaroslav; Maletínská, Lenka

    2017-01-01

    Analogs of anorexigenic neuropeptides, such as prolactin-releasing peptide (PrRP), have a potential as new anti-obesity drugs. In our previous study, palmitic acid attached to the N-terminus of PrRP enabled its central anorexigenic effects after peripheral administration. In this study, two linkers, γ-glutamic acid at Lys11 and a short, modified polyethylene glycol at the N-terminal Ser and/or Lys11, were applied for the palmitoylation of PrRP31 to improve its bioavailability. These analogs had a high affinity and activation ability to the PrRP receptor GPR10 and the neuropeptide FF2 receptor, as well as short-term anorexigenic effect similar to PrRP palmitoylated at the N-terminus. Two-week treatment with analogs that were palmitoylated through linkers to Lys11 (analogs 1 and 2), but not with analog modified both at the N-terminus and Lys11 (analog 3) decreased body and liver weights, insulin, leptin, triglyceride, cholesterol and free fatty acid plasma levels in a mouse model of diet-induced obesity. Moreover, the expression of uncoupling protein-1 was increased in brown fat suggesting an increase in energy expenditure. In addition, treatment with analogs 1 and 2 but not analog 3 significantly decreased urinary concentrations of 1-methylnicotinamide and its oxidation products N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide, as shown by NMR-based metabolomics. This observation confirmed the previously reported increase in nicotinamide derivatives in obesity and type 2 diabetes mellitus and the effectiveness of analogs 1 and 2 in the treatment of these disorders. PMID:28820912

  17. 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

  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. 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.

  1. Antimutagenic effects of dehydrozingerone and its analogs on UV-induced mutagenesis in Escherichia coli.

    PubMed

    Motohashi, N; Ashihara, Y; Yamagami, C; Saito, Y

    1997-06-09

    Antimutagenic activities of dehydrozingerone, benzalacetone and its analogs substituted with the hydroxyl, methoxyl or methyl group on the benzene ring were investigated by the post-treatment for UV-induced mutagenesis in Escherichia coli WP2s (uvrA). In this assay, dehydrozingerone was a poor antimutagen. Among the test compounds except for 2-hydroxybenzalacetone, benzalacetone was the most strong antimutagen, showing that the ring substitutions decrease the antimutagenic activities. 2-Hydroxybenzalacetone was, however, more effective than benzalacetone. The antimutagenicity of 2-hydroxybenzalacetone might be dependent on the property that is known to associate inter-molecularly by hydrogen bonding between the hydroxyl group and the carbonyl group. The effects of the side chain, single, double or triple bond and its adjacent carbonyl group, were further investigated using benzylacetone with saturated carbonyl chain, benzalacetone with double-bonded carbonyl chain, 4-phenyl-3-butyn-2-one with triple-bonded carbonyl chain and trans-beta-methyl styrene with only double bond. Benzalacetone and 4-phenyl-3-butyn-2-one suppressed the UV-induced mutagenesis, but benzylacetone and trans-beta-methyl styrene scarcely inhibited the mutagenesis: an alpha, beta-double or triple-bonded carbonyl system was necessary for the antimutagenic activity. 4-Phenyl-3-butyn-2-one showed the potent antimutagenicity at one order lower concentrations than that of benzalacetone. Benzalacetone, 2-hydroxybenzalacetone and 4-phenyl-3-butyn-2-one that were effective on the UV-induced mutagenesis also decreased the gamma-induced mutagenesis in Salmonella typhimurium TA2638.

  2. 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.

  3. The epoxyeicosatrienoic acid analog PVPA ameliorates cyclosporine-induced hypertension and renal injury in rats.

    PubMed

    Yeboah, Michael M; Hye Khan, Md Abdul; Chesnik, Marla A; Sharma, Amit; Paudyal, Mahesh P; Falck, John R; Imig, John D

    2016-09-01

    The introduction of calcineurin inhibitors (CNI) into clinical practice in the late 1970s transformed organ transplantation and led to significant improvement in acute rejection episodes. However, despite their significant clinical utility, the use of these agents is hampered by the development of hypertension and nephrotoxicity, which ultimately lead to end-stage kidney disease and overt cardiovascular outcomes. There are currently no effective agents to treat or prevent these complications. Importantly, CNI-free immunosuppressive regimens lack the overall efficacy of CNI-based treatments and put patients at risk of allograft rejection. Cytochrome P-450 epoxygenase metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), have potent vasodilator and antihypertensive properties in addition to many cytoprotective effects, but their effects on CNI-induced nephrotoxicity have not been explored. Here, we show that PVPA, a novel, orally active analog of 14,15-EET, effectively prevents the development of hypertension and ameliorates kidney injury in cyclosporine-treated rats. PVPA treatment reduced proteinuria and renal dysfunction induced by cyclosporine. PVPA inhibited inflammatory cell infiltration into the kidney and decreased renal fibrosis. PVPA also reduced tubular epithelial cell apoptosis, attenuated the generation of reactive oxygen species, and modulated the unfolded protein response that is associated with endoplasmic reticulum stress. Consistent with the in vivo data, PVPA attenuated cyclosporine-induced apoptosis of NRK-52E cells in vitro. These data indicate that the cytochrome P-450/EET system offers a novel therapeutic strategy to treat or prevent CNI-induced nephrotoxicity. Copyright © 2016 the American Physiological Society.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  12. 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. © 2016 Wiley Periodicals, Inc.

  13. 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.

  14. Salivary cortisol in two professions: daily cortisol profiles in school teachers and firefighters.

    PubMed

    Susoliakova, Olga; Smejkalova, Jindra; Bicikova, Marie; Potuznikova, Dana; Hodacova, Lenka; Grimby-Ekman, Anna; Fiala, Zdenek

    2014-01-01

    It's indicated negative-perceived stress could induce worse health status and change of cortisol secretion. To assess salivary cortisol levels in two occupations with a high psychosocial workload, but different features, teachers and firefighters. The study population consisted of 142 school teachers and 136 firefighters. Four saliva samples were collected from pedagogical participants during their busiest workday. The cortisol measures used were: morning values, evening values, slope of decline, ratio (evening value divided by morning value), and area under the curve (AUC). The salivary cortisol measurements in both genders were almost equal regarding morning values, slope, and AUC increase. Evening values were lower and the relative reactivity was higher (lower ratio) for female teachers, compared to male teachers. There was a tendency of a lower total daytime output of cortisol (AUC ground) among female teachers. Firefighters had lower levels of cortisol, lower total daytime output, and higher relative reactivity (lower ratio), but lower absolute reactivity, regarding both slope and AUC increase. Overall, male teachers might be the group most affected by stress in this study, even if some of their cortisol values were almost equal to the female teachers' values. Male teachers also seemed to be more affected by stress, according to salivary cortisol, compared to male firefighters, even if there were some inconsistencies.

  15. 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.

  16. 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.

  17. 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).

  18. 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

  19. 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.

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

    PubMed

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

    2016-04-15

    Multiple myeloma is an aggressive hematopoietic cancer of plasma cells. The recent emergence of three effective FDA-approved proteasome-inhibiting drugs, bortezomib (Velcade®), carfilzomib (Kyprolis®), and ixazomib (Ninlaro®), confirms that proteasome inhibitors are therapeutically useful against neoplastic disease, in particular refractory multiple myeloma and mantle cell lymphoma. This study describes the synthesis, computational affinity assessment, and preclinical evaluation of TIR-199, a natural product-derived syrbactin structural analog. Molecular modeling and simulation suggested that TIR-199 covalently binds each of the three catalytic subunits (β1, β2, and β5) and revealed key interaction sites. In vitro and cell culture-based proteasome activity measurements confirmed that TIR-199 inhibits the proteasome in a dose-dependent manner and induces tumor cell death in multiple myeloma and neuroblastoma cells as well as other cancer types in the NCI-60 cell panel. It is particularly effective against kidney tumor cell lines, with >250-fold higher anti-tumor activities than observed with the natural product syringolin A. In vivo studies in mice revealed a maximum tolerated dose of TIR-199 at 25 mg/kg. The anti-tumor activity of TIR-199 was confirmed in hollow fiber assays in mice. Adverse drug reaction screens in a kidney panel revealed no off-targets of concern. This is the first study to examine the efficacy of a syrbactin in animals. Taken together, the results suggest that TIR-199 is a potent new proteasome inhibitor with promise for further development into a clinical drug for the treatment of multiple myeloma and other forms of cancer. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    PubMed Central

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

    2016-01-01

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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  8. 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.

  9. “Picolog,” a Synthetically-Available Bryostatin Analog, Inhibits Growth of MYC-Induced Lymphoma In Vivo

    PubMed Central

    Felsher, Dean W.; Wender, Paul A.

    2012-01-01

    Bryostatin 1 is a naturally occurring complex macrolide with potent anti-neoplastic activity. However, its extremely low natural occurrence has impeded clinical advancement. We developed a strategy directed at the design of simplified and synthetically more accessible bryostatin analogs. Our lead analog, “picolog”, can be step-economically produced. Picolog, compared to bryostatin, exhibited superior growth inhibition of MYC-induced lymphoma in vitro. A key mechanism of picolog's (and bryostatin's) activity is activation of PKC. A novel nano-immunoassay (NIA) revealed that picolog treatment increased phospho-MEK2 in the PKC pathway. Moreover, the inhibition of PKC abrogated picolog's activity. Finally, picolog was highly potent at 100 micrograms/kg and well tolerated at doses ranging from 100 micrograms/kg to 1 milligram/kg in vivo for the treatment of our aggressive model of MYC-induced lymphoma. We provide the first in vivo validation that the bryostatin analog, picolog, is a potential therapeutic agent for the treatment of cancer and other diseases. PMID:22308267

  10. Exercise-induced responses in salivary testosterone, cortisol, and their ratios in men: a meta-analysis.

    PubMed

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

    2015-05-01

    Testosterone, cortisol and their ratios may be indicators of anabolic status, but technical issues surrounding blood sampling has limited wider application. The advent of salivary testosterone (sal-T) analysis simplified sample acquisition, resulting in a subsequent rapid increase in the number of published research articles. The objective of this study was to undertake a meta-analysis to determine the effect of acute exercise bouts on post exercise sal-T and salivary cortisol (sal-C) concentrations and their ratio (sal-T:C). Relevant databases such as PubMed, Web of Science, Science Direct and SPORTDiscus were searched up to and including 31 December 2013 for the term 'saliva AND testosterone AND exercise'. Studies (n = 21) selected from the 933 identified included randomised controlled trials (RCTs; n = 2), uncontrolled trials (UCTs; n = 18) and control trials (CTs; n = 1), all of which had an exercise component characterised as either aerobic, resistance or power training, each with acute sal-T and sal-C measurement obtained within 30 min of exercise bout completion. A meta-analysis was conducted on change in sal-T, sal-C and the sal-T:C ratio following exercise using standard difference in means (SDM) and a random effects model. For aerobic, resistance and power exercise, the overall SDMs for sal-T were 0.891, 1.061 and 0.509, respectively; for sal-C, the SDMs were 3.041, 0.773 and 1.200, respectively. For sal-T:C, the SDMs were -2.014, 0.027 and -0.968, respectively. RCTs, UCTs and CTs were separated by subgroup analysis. There were significant differences in overall weighted SDM values for sal-T between RCTs, UCTs and CTs within exercise modes. When examining aerobic exercise interventions, a quantitative interaction of study design was observed. RCTs resulted in a greater SDM than UCTs (1.337 vs. 0.446). Power interventions displayed a qualitative interaction with study design. UCTs where baseline measures were obtained 24 h before exercise had an SDM of -1

  11. Cortisol shifts financial risk preferences

    PubMed Central

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

    2014-01-01

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

  12. Cortisol shifts financial risk preferences.

    PubMed

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

    2014-03-04

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

  13. 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

  14. 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

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

    NASA Technical Reports Server (NTRS)

    Belcastro, C. M.

    1984-01-01

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

  16. 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.

  17. Allopregnanolone and its analog BR 297 rescue neuronal cells from oxidative stress-induced death through bioenergetic improvement.

    PubMed

    Lejri, Imane; Grimm, Amandine; Miesch, Michel; Geoffroy, Philippe; Eckert, Anne; Mensah-Nyagan, Ayikoe-Guy

    2017-03-01

    Allopregnanolone (AP) is supposed to exert beneficial actions including anxiolysis, analgesia, neurogenesis and neuroprotection. However, although mitochondrial dysfunctions are evidenced in neurodegenerative diseases, AP actions against neurodegeneration-induced mitochondrial deficits have never been investigated. Also, the therapeutic exploitation of AP is limited by its difficulty to pass the liver and its rapid clearance after sulfation or glucuronidation of its 3-hydroxyl group. Therefore, the characterization of novel potent neuroprotective analogs of AP may be of great interest. Thus, we synthesized a set of AP analogs (ANS) and investigated their ability to counteract APP-overexpression-evoked bioenergetic deficits and to protect against oxidative stress-induced death of control and APP-transfected SH-SY5Y cells known as a reliable cellular model of Alzheimer's disease (AD). Especially, we examined whether ANS were more efficient than AP to reduce mitochondrial dysfunctions or bioenergetic decrease leading to neuronal cell death. Our results showed that the ANS BR 297 exhibits notable advantages over AP with regards to both protection of mitochondrial functions and reduction of oxidative stress. Indeed, under physiological conditions, BR 297 does not promote cell proliferation but efficiently ameliorates the bioenergetics by increasing cellular ATP level and mitochondrial respiration. Under oxidative stress situations, BR 297 treatment, which decreases ROS levels, improves mitochondrial respiration and cell survival, appears more potent than AP to protect control and APP-transfected cells against H2O2-induced death. Our findings lend further support to the neuroprotective effects of BR 297 emphasizing this analog as a promising therapeutic tool to counteract age- and AD-related bioenergetic deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. 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.

  1. 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.

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

    PubMed Central

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

    2009-01-01

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

  3. 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.

  4. 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.

  5. Experimental Smoke and Electromagnetic Analog Study of Induced Flow Field About a Model Rotor in Steady Flight Within Ground Effect

    NASA Technical Reports Server (NTRS)

    Gray, Robin B.

    1960-01-01

    Hovering and steady low-speed forward-flight tests were run on a 4-foot-diameter rotor at a ground height of 1 rotor radius. The two blades had a 2 to 1 taper ratio and were mounted in a see-saw hub. The solidity ratio was 0.05. Measurements were made of the rotor rpm, collective pitch, and forward-flight velocity. Smoke was introduced into the tip vortex and the resulting vortex pattern was photographed from two positions. Using the data obtained from these photographs, wire models of the tip vortex configurations were constructed and the distribution of the normal component of induced velocity at the blade feathering axis that is associated with these tip vortex configurations was experimentally determined at 450 increments in azimuth position from this electromagnetic analog. Three steady-state conditions were analyzed. The first was hovering flight; the second, a flight velocity just under the wake "tuck under" speed; and the third, a flight velocity just above this speed. These corresponded to advance ratios of 0, 0.022, and 0.030 (or ratios of forward velocity to calculated hovering induced velocity of approximately 0, 0.48, and 0.65), respectively, for the model test rotor. Cross sections of the wake at 450 intervals in azimuth angle as determined from the path of the tip vortex are presented graphically for all three cases. The nondimensional normal component of the induced velocity that is associated with the tip vortex as determined by an electromagnetic analog at 450 increments in azimuth position and at the blade feathering axis is presented graphically. It is shown that the mean value of this component of the induced velocity is appreciably less after tuck-under than before. It is concluded that this method yields results of engineering accuracy and is a very useful means of studying vortex fields.

  6. The inhibitory effect of alprazolam, a benzodiazepine, overrides the stimulatory effect of metyrapone-induced lack of negative cortisol feedback on corticotroph secretion in humans.

    PubMed

    Arvat, E; Maccagno, B; Ramunni, J; Di Vito, L; Giordano, R; Gianotti, L; Broglio, F; Camanni, F; Ghigo, E

    1999-08-01

    Alprazolam (ALP), a benzodiazepine that activates gamma-aminobutyric acid-ergic receptors, inhibits the activity of hypothalamo-pituitary-adrenal (HPA) axis, probably via inhibition of hypothalamic CRH and/or arginine vasopressin release. To further clarify the effects of ALP on the HPA axis in humans, in six normal young women (26-34 yr old) we studied the effects of 0.02 mg/kg ALP (administered orally at 0700 h) or placebo on ACTH, cortisol (F), and 11-deoxycortisol (S) levels assayed after placebo or metyrapone (MET; 0.04 g/kg administered orally at 2300 h the night before). After placebo administration, ACTH, F, and S levels showed a progressive decrease from 0700-1200 h (P < 0.03). At 0700 h, ACTH, F, and S levels before ALP overlapped with those after placebo. At 1200 h, ACTH, F, and S levels after ALP were lower than those after placebo (P < 0.03). MET pretreatment strongly increased ACTH (P < 0.03) and S (P < 0.02) while clearly inhibiting F (P < 0.03) levels at 0700 h. After MET, ACTH levels did not show any decrease up to 1200 h; similarly, S levels persisted similar up to 1200 h, whereas F levels at 1200 h were significantly increased (P < 0.03). At 0700 h, MET-induced ACTH and F levels before ALP overlapped with those after MET alone. The MET-induced ACTH levels at 1200 h were markedly inhibited by ALP (P < 0.05). At 1200 h after MET and ALP, a clear reduction of S levels (P < 0.02) and an insignificant F reduction were also found. In conclusion, our present data show that ALP inhibits basal and, much more, metyrapone-induced corticotroph secretion. These findings indicate that the inhibitory effect of central gamma-aminobutyric acid-ergic activation by ALP overrides the stimulatory effect of the MET-induced lack of negative F feedback on corticotroph secretion. These results also point toward potential contraindication of ALP administration in patients with suspected hypoadrenalism.

  7. 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

  8. 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.

  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. 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.

  11. Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

    PubMed

    Tewari-Singh, Neera; Jain, Anil K; Inturi, Swetha; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2012-01-01

    Chemical warfare agent sulfur mustard (HD) inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES)-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM) treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p<0.05) reversal in CEES-induced decrease in cell viability, apoptotic and necrotic cell death, DNA damage, and an increase in oxidative stress. Silibinin (1 mg) applied topically to mouse skin 30 min post-CEES exposure (2 mg), was effective in reversing CEES-induced increases in skin bi-fold (62%) and epidermal thickness (85%), apoptotic cell death (70%), myeloperoxidase activity (complete reversal), induction of iNOS, COX-2, and MMP-9 protein levels (>90%), and activation of transcription factors NF-κB and AP-1 (complete reversal). Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid)-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

  12. Glutamine dipeptide and cortisol change the liver glucose metabolism and reduce the severity of insulin-induced hypoglycaemia in untreated T1DM Swiss mice.

    PubMed

    Bataglini, Camila; Rezende, Diego G L; Primo, Marcos A; Gomes, Célia R G; Pedrosa, Maria M D; Godoi, Vilma A F

    2017-05-01

    Glutamine is conditionally essential in type 1 diabetes mellitus, and might be useful to counteract hypoglycaemia. To investigate the systemic and hepatic effects of counter-regulatory hormones and glutamine dipeptide (GDP) during hypoglycemic episodes. Diabetic Swiss mice made hypoglycaemic by insulin injection (1 U/kg) were given counter-regulatory hormones and/or GDP. Sixty minutes later, liver histology, liver glucose metabolism and plasma were assessed. Combined, cortisol and GDP improved the hypoglycemic profile. During liver perfusion, gluconeogenesis was possibly the major pathway leading to glucose release. Perfusion with gluconeogenic precursors after glycogen depletion by adrenaline increased liver glucose and urea release. The less severe hypoglycaemia could result from cortisol stimulating periportal gluconeogenesis and GDP inhibiting pericentral glycogenolysis, both favouring liver glucose release. At least some benefits of GDP and cortisol during hypoglycaemia came from their hepatic actions, and their use in diabetic patients should be explored.

  13. 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.

  14. 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.

  15. The impact of cortisol in steatotic and non-steatotic liver surgery.

    PubMed

    Cornide-Petronio, María Eugenia; Bujaldon, Esther; Mendes-Braz, Mariana; Avalos de León, Cindy G; Jiménez-Castro, Mónica B; Álvarez-Mercado, Ana I; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

    2017-10-01

    The intent of this study was to examine the effects of regulating cortisol levels on damage and regeneration in livers with and without steatosis subjected to partial hepatectomy under ischaemia-reperfusion. Ultimately, we found that lean animals undergoing liver resection displayed no changes in cortisol, whereas cortisol levels in plasma, liver and adipose tissue were elevated in obese animals undergoing such surgery. Such elevations were attributed to enzymatic upregulation, ensuring cortisol production, and downregulation of enzymes controlling cortisol clearance. In the absence of steatosis, exogenous cortisol administration boosted circulating cortisol, while inducing clearance of hepatic cortisol, thus maintaining low cortisol levels and preventing related hepatocellular harm. In the presence of steatosis, cortisol administration was marked by a substantial rise in intrahepatic availability, thereby exacerbating tissue damage and regenerative failure. The injurious effects of cortisol were linked to high hepatic acethylcholine levels. Upon administering an α7 nicotinic acethylcholine receptor antagonist, no changes in terms of tissue damage or regenerative lapse were apparent in steatotic livers. However, exposure to an M3 muscarinic acetylcholine receptor antagonist protected livers against damage, enhancing parenchymal regeneration and survival rate. These outcomes for the first time provide new mechanistic insight into surgically altered steatotic livers, underscoring the compelling therapeutic potential of cortisol-acetylcholine-M3 muscarinic receptors. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. 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

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

    PubMed

    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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

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

    USDA-ARS?s Scientific Manuscript database

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

  4. 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

  5. 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.

  6. 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.

  7. 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.

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

    SciTech Connect

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

    1994-06-01

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

  9. A Novel in Vitro Analog Expressing Learning-Induced Cellular Correlates in Distinct Neural Circuits

    ERIC Educational Resources Information Center

    Weisz, Harris A.; Wainwright, Marcy L.; Mozzachiodi, Riccardo

    2017-01-01

    When presented with noxious stimuli, "Aplysia" exhibits concurrent sensitization of defensive responses, such as the tail-induced siphon withdrawal reflex (TSWR) and suppression of feeding. At the cellular level, sensitization of the TSWR is accompanied by an increase in the excitability of the tail sensory neurons (TSNs) that elicit the…

  10. 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.

  11. 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

  12. 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.

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

    PubMed

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

    2016-07-25

    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.

  14. 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.

  15. 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.

  16. Time-dependent effects of cortisol on the contextualization of emotional memories.

    PubMed

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

    2013-12-01

    The inability to store fearful memories into their original encoding context is considered to be an important vulnerability factor for the development of anxiety disorders like posttraumatic stress disorder. Altered memory contextualization most likely involves effects of the stress hormone cortisol, acting via receptors located in the memory neurocircuitry. Cortisol via these receptors induces rapid nongenomic effects followed by slower genomic effects, which are thought to modulate cognitive function in opposite, complementary ways. Here, we targeted these time-dependent effects of cortisol during memory encoding and tested subsequent contextualization of emotional and neutral memories. In a double-blind, placebo-controlled design, 64 men were randomly assigned to one of three groups: 1) received 10 mg hydrocortisone 30 minutes (rapid cortisol effects) before a memory encoding task; 2) received 10 mg hydrocortisone 210 minutes (slow cortisol) before a memory encoding task; or 3) received placebo at both times. During encoding, participants were presented with neutral and emotional words in unique background pictures. Approximately 24 hours later, context dependency of their memories was assessed. Recognition data revealed that cortisol's rapid effects impair emotional memory contextualization, while cortisol's slow effects enhance it. Neutral memory contextualization remained unaltered by cortisol, irrespective of the timing of the drug. This study shows distinct time-dependent effects of cortisol on the contextualization of specifically emotional memories. The results suggest that rapid effects of cortisol may lead to impaired emotional memory contextualization, while slow effects of cortisol may confer protection against emotional memory generalization. © 2013 Society of Biological Psychiatry.

  17. 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.

  18. 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.

  19. Metaphit, an isothiocyanate analog of PCP, induces audiogenic seizures in mice.

    PubMed

    Debler, E A; Lipovac, M N; Lajtha, A; Zlokovic, B V; Jacobson, A E; Rice, K C; Reith, M E

    1989-06-08

    Metaphit induces audiogenic seizures in mice. The most severe clonic/tonic seizures occur 18-24 h after metaphit administration. After 48 h the incidence of the seizure episodes begin to diminish. These audiogenic seizures can be prevented by the administration of either PCP or MK-801 24 h after metaphit and 30 min prior to audio stimulation. These seizures may be due to a modulation of the PCP recognition site by metaphit which results in an enhanced probability that the NMDA/PCP ion channels are open.

  20. 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

  1. 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.

  2. 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. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

  3. 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.

  4. 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.

  5. 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

  6. 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.

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

    PubMed

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

    2016-12-12

    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.

  8. 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

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

    PubMed

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

    2015-09-29

    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 10(5).

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

    PubMed

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

    2012-01-01

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

  11. Ritanserin, a serotonin-S2 receptor antagonist, does not prevent 5-hydroxytryptophan-induced beta-EP, beta-LPH and cortisol secretion.

    PubMed

    Facchinetti, F; Martignoni, E; Nappi, G; Marini, S; Petraglia, F; Sandrini, G; Genazzani, A R

    1987-01-01

    Ritanserin, a new serotonin antagonist selective upon S2 receptor subclass is available. Thus, in order to better define the positive control of serotoninergic pathway on proopiomelanocortin (POMC)-related peptide release, a group of 7 healthy male volunteers has been submitted to a 5-hydroxytryptophane (5-OH-TP) test (200 mg p.o.) before and after 4 days Ritanserin pretreatment. Plasma beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol levels were measured hourly for 4 h after each 5-OH-TP loading. Hormonal levels were measured by specific RIAs on extracted (cortisol) and chromatographed (beta-EP and beta-LPH) plasma samples. Basal plasma concentrations of the three hormones were unchanged by Ritanserin pretreatment. Similarly, the integrated areas of beta-LPH, beta-EP and cortisol release in response to 5-OH-TP remained unaffected by the receptor blockade. These data confirm that serotonin-acting drugs are able to stimulate POMC-related peptide release and indicate that such interaction is not mediated through S2 receptor subclass.

  12. 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.

  13. 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.

  14. Genome-Wide Mutation Avalanches Induced in Diploid Yeast Cells by a Base Analog or an APOBEC Deaminase

    PubMed Central

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

    2013-01-01

    Genetic information should be accurately transmitted from cell to cell; conversely, the adaptation in evolution and disease is fueled by mutations. In the case of cancer development, multiple genetic changes happen in somatic diploid cells. Most classic studies of the molecular mechanisms of mutagenesis have been performed in haploids. We demonstrate that the parameters of the mutation process are different in diploid cell populations. The genomes of drug-resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning load of thousands of unselected mutations. Haploid mutants contained almost an order of magnitude fewer mutations. To explain this, we propose that the distribution of induced mutation rates in the cell population is uneven. The mutants in diploids with coincidental mutations in the two copies of the reporter gene arise from a fraction of cells that are transiently hypersensitive to the mutagenic action of a given mutagen. The progeny of such cells were never recovered in haploids due to the lethality caused by the inactivation of single-copy essential genes in cells with too many induced mutations. In diploid cells, the progeny of hypersensitive cells survived, but their genomes were saturated by heterozygous mutations. The reason for the hypermutability of cells could be transient faults of the mutation prevention pathways, like sanitization of nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the temporary inability of the destruction of the deaminase. The hypothesis on spikes of mutability may explain the sudden acquisition of multiple mutational changes during evolution and carcinogenesis. PMID:24039593

  15. 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.

  16. 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.

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

    PubMed

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

    2015-04-23

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

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

    PubMed

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

    2016-05-01

    The stress hormone cortisol is assumed to influence cognitive functions. While cortisol-induced alterations of declarative memory in particular are well-investigated, considerably less is known about its influence on executive functions. Moreover, most research has been focused on slow effects, and rapid non-genomic effects have not been studied. The present study sought to investigate the impact of acute cortisol administration as well as basal cortisol levels on cognitive flexibility, a core executive function, within the non-genomic time frame. Thirty-eight healthy male participants were randomly assigned to intravenously receive either cortisol or a placebo before performing a task switching paradigm with happy and angry faces as stimuli. Cortisol levels were measured at six points during the experiment. Additionally, before the experiment, basal cortisol measures for the cortisol awakening response were collected on three consecutive weekdays immediately following awakening and 30, 45, and 60min after. First and foremost, results showed a pronounced impact of acute and basal cortisol on reaction time switch costs, particularly for angry faces. In the placebo group, low basal cortisol was associated with minimal switch costs, whereas high basal cortisol was related to maximal switch costs. In contrast, after cortisol injection, basal cortisol levels showed no impact. These results show that cognitive flexibility-enhancing effects of acute cortisol administration are only seen in men with high basal cortisol levels. This result supports the context dependency of cortisol administration and shows the relevance of taking basal cortisol levels into account. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. 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.

  20. 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.

  1. Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures.

    PubMed

    Srithunyarat, Thanikul; Hagman, Ragnvi; Höglund, Odd V; Stridsberg, Mats; Olsson, Ulf; Hanson, Jeanette; Nonthakotr, Chalermkwan; Lagerstedt, Anne-Sofie; Pettersson, Ann

    2017-03-21

    Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs. Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 min after morphine administration. Blood samples were analyzed for CST, VS, and cortisol. Saliva volumes, however, were insufficient for analysis. Catestatin and cortisol concentrations, and CMPS-SF, and VAS scores differed significantly between dogs with fractures prior to morphine administration and healthy dogs. After morphine administration, dogs with fractures had significantly decreased CMPS-SF and VAS scores and, compared to healthy dogs, CST concentrations, CMPS-SF, and VAS scores still differed significantly. However, CST concentrations remained largely within the normal range. Absolute delta values for CST significantly correlated with delta values for CMPS-SF. Catestatin and cortisol did not differ significantly before and after morphine administration. Vasostatin concentrations did not differ significantly between groups. Catestatin and cortisol concentrations, CMPS-SF, and VAS scores differed significantly in the dogs with traumatic bone fractures compared to the healthy dogs

  2. 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.

  3. 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.

  4. Pharmacologic/pharmacokinetic evaluation of emesis induced by analogs of RSU 1069 and its control by antiemetic agents.

    PubMed

    Sebolt-Leopold, J S; Vincent, P W; Beningo, K A; Elliott, W L; Leopold, W R; Heffner, T G; Wiley, J N; Stier, M A; Suto, M J

    1992-01-01

    RB 6145, the ring-opened analog of RSU 1069, and PD 130908, the desoxy ring-opened analog of RSU 1069, were compared to RSU 1069 for their emetic potential in dogs. When RB 6145 and PD 130908 were administered intravenously at doses ranging from 20% to 50% of the mouse equivalent maximum tolerated dose (MTD), both analogs were less emetic than RSU 1069 on a molar basis. Furthermore, the 5HT3 antagonist ondansetron prevented emesis at doses as high as 75% of the MTD. The reactivity, and hence the emetic liability of these compounds, is thought to be mediated by formation of the corresponding aziridine intermediate. In mouse plasma, both analogs rapidly converted to two products, the reactive aziridine and a stable oxiazolidinone species formed upon reaction with bicarbonate in the blood. A positive correlation exists between the amounts of aziridine formed by these analogs and their emetic potential.

  5. The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via σ1 receptor activation: comparison with the effects of dextromethorphan

    PubMed Central

    Shin, Eun-Joo; Nah, Seung-Yeol; Kim, Won-Ki; Ko, Kwang Ho; Jhoo, Wang-Kee; Lim, Yong-Kwang; Cha, Joo Young; Chen, Chieh-Fu; Kim, Hyoung-Chun

    2005-01-01

    In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects. Dextromethorphan and dimemorfan are high-affinity ligands at σ1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan. Kainate (KA) administration (10 mg kg−1, i.p.) produced robust convulsions lasting 4–6 h in rats. Pre-treatment with dimemorfan (12 or 24 mg kg−1) reduced seizures in a dose-dependent manner. Dimemorfan pre-treatment also attenuated the KA-induced increases in c-fos/c-jun expression, activator protein (AP)-1 DNA-binding activity, and loss of cells in the CA1 and CA3 fields of the hippocampus. These effects of dimemorfan were comparable to those of dextromethorphan. The anticonvulsant action of dextromethorphan or dimemorfan was significantly counteracted by a selective σ1 receptor antagonist BD 1047, suggesting that the anticonvulsant action of dextromethorphan or dimemorfan is, at least in part, related to σ1 receptor-activated modulation of AP-1 transcription factors. We asked whether dimemorfan produces the behavioral side effects seen with dextromethorphan or dextrorphan (a phencyclidine-like metabolite of dextromethorphan). Conditioned place preference and circling behaviors were significantly increased in mice treated with phencyclidine, dextrorphan or dextromethorphan, while mice treated with dimemorfan showed no behavioral side effects. Our results suggest that dimemorfan is equipotent to dextromethorphan in preventing KA-induced seizures, while it may lack behavioral effects, such as psychotomimetic reactions. PMID:15723099

  6. 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.

  7. 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.

  8. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant

    PubMed Central

    Waisertreiger, Irina S.-R.; Menezes, Miriam R.; Randazzo, James; Pavlov, Youri I.

    2010-01-01

    Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis. Human inosine triphosphate pyrophosphatase (ITPA) hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6-hydroxyaminopurine (HAP) deoxynucleoside triphosphate) and thus regulates nucleotide pools and protects cells from DNA damage. We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA. A human polymorphic allele of the ITPA, 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP. The polymorphism has been associated with adverse reaction to purine base-analog drugs. The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant. The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs. PMID:20936128

  9. Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia.

    PubMed

    Karpman, Matthew S; Neculau, Madalina; Dias, Valerian C; Kline, Gregory A

    2013-10-01

    Insulin-induced hypoglycemia (IHT) is considered the gold standard test for evaluating the HPA axis. Serum free cortisol or its surrogate, salivary cortisol as opposed to total cortisol concentrations, offers a better reflection of the activation of HPA axis. Our study aimed to derive reference ranges for the normal salivary cortisol levels in healthy patients and patients with adrenal insufficiency. Serum cortisol concentrations, using the gold standard of IHT, and salivary cortisol were obtained. 36 patients referred to our outpatient endocrine testing unit for evaluation of adrenal function were included in the study. Most subjects had a history of suspected hypothalamic/pituitary disease causing adrenal insufficiency. We found a strong linear correlation between the serum and salivary cortisol concentrations in simultaneously collected samples (r=0.81, 95% CI 0.74-0.86, p<0.0001). The corresponding salivary cortisol equivalent to a serum cortisol of 500 nmol/L, using a linear-regression equation, was 16.7 nmol/L (95% CI 13.3-20.1 nmol/L, p=0.0001). A salivary cortisol of 13.3 nmol/L has a specificity of 89.3% to detect abnormal HPA function. Using the upper 95% CI result of salivary cortisol 20.1 yields a sensitivity of 87.5%. With the present assay, adrenal insufficiency may be diagnosed with reasonable confidence if a random salivary cortisol is lower than 13.3 nmol/L and excluded if a random salivary cortisol is higher than 20.1 nmol/L. Future studies should correlate these thresholds with clinical outcomes. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. 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. © 2016 Wiley Periodicals, Inc.

  11. 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.

  12. 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.

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

    PubMed Central

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

    2015-01-01

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

  14. 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…

  15. 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…

  16. 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

  17. 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.

  18. 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

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

    PubMed

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

    2009-12-01

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

  20. 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.

  1. Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.

    PubMed

    Hammad, Ayat S; Ravindran, Sreenithya; Khalil, Ashraf; Munusamy, Shankar

    2017-05-01

    Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells. Five amide-substituted piperine analogs were synthesized and their chemical structures were elucidated by pertinent spectroscopic techniques. An in vitro model of ER stress was developed using tunicamycin, and the compounds of interest were screened for their effect on cell viability, and the expression of ER chaperone GRP78, the pro-apoptotic ER stress marker CHOP, and apoptotic caspases 3 and 12 (via western blotting). Our findings indicate that exposure to tunicamycin (0.5 μg/mL) for 2 h induces the expression of GRP78 and CHOP, and apoptotic markers (caspase-3 and caspase-12) and causes a significant reduction in renal cell viability. Pre-treatment of cells with piperine and its cyclohexylamino analog decreased the tunicamycin-induced upregulation of GRP78 and CHOP and cell death. Taken together, our findings demonstrate that piperine and its analogs differentially regulate ER stress, and thus represent potential therapeutic agents to treat ER stress-related renal disorders. Graphical Abstract Piperine (PIP) reduces the expression of ER stress markers (GRP78 and CHOP) induced by pathologic stimuli and consequently decreases the activation of apoptotic caspase-12 and caspase-3; all of which contributes to its chemical chaperone and cytoprotective properties to protect

  2. Immunoassay or LC-MS/MS for the measurement of salivary cortisol in children?

    PubMed

    Bae, Yoon Ju; Gaudl, Alexander; Jaeger, Sonia; Stadelmann, Stephanie; Hiemisch, Andreas; Kiess, Wieland; Willenberg, Anja; Schaab, Michael; von Klitzing, Kai; Thiery, Joachim; Ceglarek, Uta; Döhnert, Mirko; Kratzsch, Juergen

    2016-05-01

    Dysregulation of the adrenal cortex has been assessed with measurement of salivary cortisol. So far salivary cortisol is routinely measured with immunoassay (IA). However, liquid chromatography-tandem mass spectrometry (MS) is known to offer better specificity. We compared the concentrations of salivary cortisol measured by MS and IA at basal and stress induced conditions and evaluated reasons for the difference in method-dependent cortisol results. Saliva samples (n=2703) were collected from 169 children (age range: 8-14 years; 81 healthy children; 55 with internalizing and 33 with externalizing disorders) under circadian conditions and during the Trier Social Stress Test for Children (TSST-C). Biochemical analyses were performed with MS for cortisol and cortisone, IA (IBL, RE62011) for cortisol, and enzyme kinetic assay for α-amylase. MS and IA showed mostly comparable results for circadian activity and TSST-C response with similar statistical power. However, IA measured cortisol concentrations about 2.39-fold higher than MS. We found that this difference in measured values between MS and IA was mainly due to different standardization of IA compared to MS. In addition, at cortisol IA concentration below 5 nmol/L, cross-reactivity with cortisone was found to contribute to the lower concordance between MS and IA. Immunoassay and LC-MS/MS were largely comparable in the interpretation of salivary cortisol dynamics in stress research. But the IA method revealed a restricted accuracy in the measuring range below 5 nmol/L.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Intracerebroventricular injection of L-serine analogs and derivatives induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks.

    PubMed

    Asechi, Mari; Tomonaga, Shozo; Tachibana, Tetsuya; Han, Li; Hayamizu, Kohsuke; Denbow, D Michael; Furuse, Mitsuhiro

    2006-06-03

    Four experiments were conducted to clarify the central functions of L-serine and its analogs on an acute stressful condition. Intracerebroventricular (i.c.v.) injection of L-serine (0.21, 0.42 and 0.84 micromol) attenuated stress responses in a dose-dependent fashion, as well as induced sleep, in Experiment 1. The effects of L- and D-serine in Experiment 2, those of L-serine, phosphoserine, acetylserine and L-cysteine in Experiment 3 and those of L-serine, glycine and lysophosphatidylserine in Experiment 4 were compared at an equimolar basis (0.84 micromol). D-Serine, proposed as an endogenous agonist of N-methyl-D-aspatate (NMDA) receptor, did not have sedative and hypnotic effects as observed with L-serine. In contrast, all the analogs and derivatives of L-serine had a sedative effect, although with a different manner in several behavioral markers of stress such as spontaneous activity and distress vocalizations. No significant changes in plasma corticosterone concentration were observed in any experiment. Taken together, the i.c.v. injection of L-serine analogs and its derivatives have sedative and hypnotic effects under an acute stressful condition, which does not involve the hypothalamic-pituitary-adrenal axis. In conclusion, L-serine may be effective in improving anxiety or sleep disorders induced by psychological stressor.

  9. A novel kynurenic acid analog (SZR104) inhibits pentylenetetrazole-induced epileptiform seizures. An electrophysiological study : special issue related to kynurenine.

    PubMed

    Demeter, Ildikó; Nagy, Károly; Gellért, Levente; Vécsei, László; Fülöp, Ferenc; Toldi, József

    2012-02-01

    The concentration of kynurenic acid (KYNA) in the cerebrospinal fluid, which is in the nanomolar range, is known to decrease in epilepsy. The experimental data suggest that treatment with L: -KYN dose dependently increases the concentration of the neuroprotective KYNA in the brain, which itself hardly crosses the blood-brain barrier. However, it is suggested that new synthetic KYNA analogs may readily cross the blood-brain barrier. In this study, we tested the hypothesis that a new KYNA analog administered systemically in a sufficient dose results in a decreased population spike activity recorded from the pyramidal layer of area CA1 of the hippocampus, and also provides protection against pentylenetetrazole-induced epileptiform seizures.

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

    USDA-ARS?s Scientific Manuscript database

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

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

    USDA-ARS?s Scientific Manuscript database

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

  12. 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.

  13. 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.

  14. No effect of free fatty acids on adrenocorticotropin and cortisol secretion in healthy young men.

    PubMed

    Mai, Knut; Bobbert, Thomas; Kullmann, Volker; Andres, Janin; Bähr, Volker; Maser-Gluth, Christiane; Rochlitz, Helmut; Spranger, Jochen; Diederich, Ssven; Pfeiffer, Andreas F H

    2006-08-01

    Free fatty acids (FFAs) affect anterior pituitary function. However, the effect of FFAs on corticotropin (ACTH) and cortisol in humans is controversial. Thus, we assessed the effect of a pronounced increase in circulating FFA levels induced by infusion of lipid/heparin on ACTH and cortisol secretion in young men. Eight healthy male volunteers who underwent a 10-hour overnight fast were investigated. A 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5 mL/min for 6 hours. A euglycemic hyperinsulinemic clamp was performed in 6 subjects 4 hours after the start of infusion. To assess steroid metabolism, we measured ACTH, cortisol, FFAs, and urinary steroids. Lipid infusion increased FFAs (6.06 +/- 0.52 vs 0.70 +/- 0.23 mmol/L; P < .005) and induced insulin resistance (glucose infusion rate, 4.08 +/- 2.15 vs 6.02 +/- 2.60 mg/kg per minute; P < .005). Serum cortisol and plasma ACTH decreased independent of lipid/heparin or saline/heparin infusion. In addition, we found no effect of hyperinsulinemia on ACTH and cortisol levels. There were no differences in urinary free cortisol, urinary free cortisone, 5beta-tetrahydrocortisol, 5alpha-tetrahydrocortisol, and tetrahydrocortisone. In conclusion, FFAs had no effect on basal ACTH and cortisol secretion in normal-weight young men. In addition, no alterations in urinary glucocorticoid metabolites were detected, suggesting unchanged cortisol metabolism during lipid infusion.

  15. 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

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

    PubMed

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

    2013-07-01

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

  17. Hair cortisol concentrations and cortisol stress reactivity predict PTSD symptom increase after trauma exposure during military deployment.

    PubMed

    Steudte-Schmiedgen, Susann; Stalder, Tobias; Schönfeld, Sabine; Wittchen, Hans-Ulrich; Trautmann, Sebastian; Alexander, Nina; Miller, Robert; Kirschbaum, Clemens

    2015-09-01

    Previous evidence on endocrine risk markers for posttraumatic stress disorder (PTSD) has been inconclusive. Here, we report results of the first prospective study to investigate whether long-term hair cortisol levels and experimentally-induced cortisol stress reactivity are predictive of the development of PTSD symptomatology in response to trauma during military deployment. Male soldiers were examined before deployment to Afghanistan and at a 12-month post-deployment follow-up using dimensional measures for psychopathological symptoms. The predictive value of baseline (i) hair cortisol concentrations (HCC, N=90) and (ii) salivary cortisol stress reactivity (measured by the Trier Social Stress Test, N=80) for the development of PTSD symptomatology after being exposed to new-onset traumatic events was analyzed. Baseline cortisol activity significantly predicted PTSD symptom change from baseline to follow-up upon trauma exposure. Specifically, our results consistently revealed that lower HCC and lower cortisol stress reactivity were predictive of a greater increase in PTSD symptomatology in soldiers who had experienced new-onset traumatic events (explaining 5% and 10.3% of variance, respectively). Longitudinal analyses revealed an increase in HCC from baseline to follow-up and a trend for a negative relationship between HCC changes and the number of new-onset traumatic events. Additional pre-deployment analyses revealed that trauma history was reflected in lower HCC (at trend level) and that HCC were negatively related to stressful load. Our data indicate that attenuated cortisol secretion is a risk marker for subsequent development of PTSD symptomatology upon trauma exposure. Future studies are needed to confirm our findings in other samples. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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.

  19. Relocation and Hair Cortisol Concentrations in New Zealand White Rabbits.

    PubMed

    Peric, Tanja; Comin, Antonella; Corazzin, Mirco; Montillo, Marta; Canavese, Federico; Stebel, Marco; Prandi, Alberto

    2017-01-01

    To investigate how long relocation modified hair cortisol concentrations in New Zealand white rabbits, 19 rabbits were subjected to a change in their breeding facility at the beginning of the trial and then were kept under stable environmental conditions. Hair samples were collected at the time of arrival to the nonhuman animal facility and at 40-day intervals from the same skin area for up to 440 days after the animals' arrival to the facility. A period effect on the hair cortisol concentration was found (p < .01). The transfer of the rabbits to the new facility might have induced an increase in the hypothalamic-pituitary-adrenal axis activity (p < .01). A second increase in hair cortisol concentration (p < .01) occurred at 320 days, after a change of personnel at the facility that occurred at 280 days, which was the only environmental change. The relocation of rabbits to the facility resulted in a stress response leading to elevated cortisol levels. The effect of relocation on mean cortisol concentrations was exhausted within 120 days when all environmental factors were kept stable.

  20. 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'.

  1. 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.

  2. 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

  3. 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.

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

    PubMed

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

    2016-10-01

    Maternally-derived hormones in oocytes, such as glucocorticoids (GCs), play a crucial role in embryo development in oviparous taxa. In fishes, maternal stressor exposure increases circulating and egg cortisol levels, the primary GC in fishes, as well as induces oxidative stress. Elevated egg cortisol levels modify offspring traits but whether maternal oxidative stress correlates with circulating and egg cortisol levels, and whether maternal/egg cortisol levels correlate with offspring oxidative stress have yet to be determined. The objective of this study was to examine the relationships among maternal and egg cortisol, and maternal and offspring oxidative stress to provide insight into the potential intergenerational effects of stressor exposure in sockeye salmon (Oncorhynchus nerka). Antioxidant concentration and oxidative stress were measured in maternal tissues (plasma, brain, heart and liver) as well as offspring developmental stages (pre-fertilization, 24h post-fertilization, eyed, and hatch), and were compared to both naturally-occurring and experimentally-elevated (via cortisol egg bath) levels of cortisol in eggs. Oxygen radical absorptive capacity of tissues from maternal sockeye salmon was measured spectrophotometrically and was not correlated with maternal or egg cortisol concentrations. Also, naturally-occurring and experimentally-elevated cortisol levels in eggs (to mimic maternal stress) did not affect oxidative stress or antioxidant capacity of the offspring. We conclude that the metrics of maternal stress examined in sockeye salmon (i.e., maternal/egg cortisol, maternal oxidative stress) are independent of each other, and that egg cortisol content does not influence offspring oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Increased cortisol awakening response and afternoon/evening cortisol output in healthy young adults with low early life parental care.

    PubMed

    Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Dagher, Alain; Pruessner, Jens C

    2011-03-01

    Growing evidence from animal and human studies suggests a profound and long-lasting influence of early life experiences--ranging from variations in parenting behavior to severe adversity--on hypothalamic-pituitary-adrenal axis function. The aim of the current investigation was to examine the association between naturally occurring variations in early life parental care and the cortisol awakening response (CAR), afternoon/evening cortisol output and key psychological variables in a sample of healthy young adults. Fifty-eight (19 male and 39 female) participants between 18 and 30 years of age completed psychological questionnaires and collected saliva at awakening, 30 min thereafter and at 3 p.m., 6 p.m., and 9 p.m. on three non-consecutive weekdays. Participants with low (compared to high) parental care experiences exhibited an increased CAR, increased afternoon/evening cortisol output, decreased self-esteem, and increased depressive symptomatology and anxiety. We suggest that the elevated CAR and afternoon/evening cortisol levels might reflect a biological correlate of adversity-induced vulnerability for psychopathology. This study is first to show an association between the retrospective perception of early life parental care and cortisol circadian rhythms in healthy young adults.

  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. 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…

  8. 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…

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Effects of aircraft noise exposure on saliva cortisol near airports in France.

    PubMed

    Lefèvre, Marie; Carlier, Marie-Christine; Champelovier, Patricia; Lambert, Jacques; Laumon, Bernard; Evrard, Anne-Sophie

    2017-08-01

    Saliva cortisol is a possible marker of noise-induced stress and could then mediate the relation observed between exposure to aircraft or road traffic noise and cardiovascular diseases. However, the association between transportation noise and cortisol levels is still unclear. The objective of the study was to investigate the variability of saliva cortisol concentration as an indicator of disturbed hypothalamus-pituitary-adrenal (HPA) axis regulation in relation to long-term aircraft noise exposure. Saliva samples were taken when awakening and before going to bed for 1244 participants older than 18 years of age. Information about health, socioeconomic and lifestyle factors was also collected by means of a face-to-face questionnaire performed at home by an interviewer. Aircraft noise exposure was assessed for each participant's home address using noise maps. Linear regression models were used to evaluate the effects of aircraft noise exposure on the morning and evening cortisol levels and on the daily variation of cortisol per hour. This study suggests a modification of the cortisol circadian rhythm in relation to aircraft noise exposure. This exposure was associated with a smaller variation of cortisol levels over the day, with unchanged morning cortisol levels, but higher cortisol levels in the evening. These findings provide some support for a psychological stress induced by aircraft noise exposure, resulting in HPA dysregulation and a flattened cortisol rhythm, thus contributing to cardiovascular diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. 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.

  17. 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

  18. 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.

  19. MC37, a new mono-carbonyl curcumin analog, induces G2/M cell cycle arrest and mitochondria-mediated apoptosis in human colorectal cancer cells.

    PubMed

    Liang, Baoxia; Liu, Ziyi; Cao, Yingnan; Zhu, Cuige; Zuo, Yinglin; Huang, Lei; Wen, Gesi; Shang, Nana; Chen, Yu; Yue, Xin; Du, Jun; Li, Baojian; Zhou, Binhua; Bu, Xianzhang

    2017-02-05

    (E)-1-(3'-fluoro-[1,1'-biphenyl-3-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one) (MC37), a novel mono-carbonyl curcumin analog, was previously synthesized in our laboratory as a nuclear factor kappa B (NF-κB) inhibitor with excellent cytotoxicity against several cancer cell lines. In this study, our further investigations showed that the potent growth inhibitory activity of MC37 in human colorectal cancer cells was associated with the arrest of cell cycle progression and the induction of apoptosis. As a multi-targeted agent, MC37 inhibited the intracellular microtubule assembly, altered the expression of cyclin-dependent kinase 1 (CDK1), and ultimately induced G2/M cell cycle arrest. Moreover, MC37 collapsed the mitochondrial membrane potential (MMP), increased the Bax/Bcl-2 ratio, activated the caspase-9/3 cascade, and finally led to cancer cells apoptosis, suggesting that the mitochondrial-mediated apoptotic pathway was involved in MC37-induced apoptosis. In conclusion, these observations demonstrated that mono-carbonyl curcumin analogs would serve as multi-targeted lead for promising anti-colorectal cancer agent development. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Inhibitory effect of ritanserin on the 5-hydroxytryptophan-mediated cortisol, ACTH and prolactin secretion in humans.

    PubMed

    Lee, M A; Nash, J F; Barnes, M; Meltzer, H Y

    1991-01-01

    Oral administration of the serotonin (5-HT) precursor L-5-hydroxytryptophan (5-HTP), 200 mg, significantly increased plasma cortisol levels in man. L-5-HTP had no significant effect on the plasma prolactin levels. A borderline effect of 5-HTP on plasma ACTH levels was found. Pretreatment with the 5-HT2/5-HT1c antagonist ritanserin (5 mg, PO, b.i.d. for 2 days) significantly inhibited 5-HTP-induced cortisol secretion. Ritanserin had no effect on the basal plasma cortisol or prolactin levels. These data are suggestive that 5-HTP stimulates cortisol secretion in man via 5-HT2/5-HT1c receptor mechanisms.

  1. 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.

  2. Impact of exogenous cortisol on the formation of intrusive memories in healthy women.

    PubMed

    Rombold, Felicitas; Wingenfeld, Katja; Renneberg, Babette; Schwarzkopf, Friederike; Hellmann-Regen, Julian; Otte, Christian; Roepke, Stefan

    2016-12-01

    Stress hormones such as cortisol are involved in modulating emotional memory. However, little is known about the influence of cortisol on the formation of intrusive memories after a traumatic event. The aim of this study was to examine whether cortisol levels during encoding and consolidation of an intrusion-inducing trauma film paradigm would influence subsequent intrusion formation. In an experimental, double-blind, placebo-controlled study a trauma film paradigm was used to induce intrusions in 60 healthy women. Participants received a single dose of either 20 mg hydrocortisone or placebo before watching a trauma film. Salivary cortisol and alpha-amylase as well as blood pressure were measured during the experiment. The consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions resulting from the trauma film were assessed throughout the following seven days. Hydrocortisone administration before the trauma film resulted in increased salivary cortisol levels but did not affect the consecutive number of intrusions, the vividness of intrusions, and the degree of distress evoked by the intrusions throughout the following week. These results indicate that pharmacologically increased cortisol levels during an experimental trauma film paradigm do not influence consecutive intrusive memories. Current data do not support a prominent role of exogenous cortisol on intrusive memories, at least in healthy young women after a relatively mild trauma equivalent. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. 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.

  4. 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

  5. Zinc Deprivation Mediates Alcohol-Induced Hepatocyte IL-8 Analog Expression in Rodents via an Epigenetic Mechanism

    PubMed Central

    Zhao, Yantao; Zhong, Wei; Sun, Xiuhua; Song, Zhenyuan; Clemens, Dahn L.; Kang, Y. James; McClain, Craig J.; Zhou, Zhanxiang

    2011-01-01

    Neutrophil infiltration caused by IL-8 production is a central mechanism in alcohol-induced hepatitis. This study was performed to examine if an epigenetic mechanism is involved in alcohol-induced IL-8 production. Mice were pair-fed an alcohol-containing liquid diet for 4 weeks. Alcohol exposure induced hepatitis as indicated by increased expression of keratinocyte-derived cytokine (mouse IL-8) and neutrophil infiltration. Alcohol exposure induced histone 3 hyperacetylation owing to inhibition of histone deacetylase (HDAC) in association with NF-κB activation. Cell culture studies showed that alcohol exposure induced IL-8 and cytokine-induced neutrophil chemoattractant-1 (CINC-1, rat IL-8) production in human VL-17A cells and rat H4IIEC3 cells, respectively, dependent on acetaldehyde production, oxidative stress, and zinc release. Zinc deprivation alone induced CINC-1 production and acted synergistically with lipopolysaccharide or tumor necrosis factor-α on CINC-1 production. Zinc deprivation induced histone 3 hyperacetylation at lysine 9 through suppression of HDAC activity. Zinc deprivation caused nuclear translocation of NF-κB, and reduced HDAC binding to NF-κB. Chromatin immunoprecipitation (ChIP) showed that zinc deprivation caused histone 3 hyperacetylation as well as increased NF-κB binding to the CINC-1 promoter. In conclusion, inactivation of HDAC caused by zinc deprivation is a novel mechanism underlying IL-8 up-regulation in alcoholic hepatitis. PMID:21708112

  6. 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.

  7. 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.

  8. 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).

  9. 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.

  10. 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.

  11. Cortisol broadens memory of a non-stressful social interaction.

    PubMed

    Wiemers, Uta S; Wolf, Oliver T

    2015-05-01

    Stress and its associated hormonal cascade are known to enhance long-term memory consolidation. Recently we have shown that central details of a stressful situation (Trier Social Stress Test; TSST) are remembered better than central details of a similar but non-stressful control condition (friendly Trier Social Stress Test; fTSST). We reasoned that since cortisol concentrations increase during stress (TSST) but remain low during the control condition (fTSST), a pharmacological increase in cortisol during the fTSST might be able to mimic the stress effects observed previously. The objective of the study was to assess the impact of a pharmacologically induced cortisol increase during the non-stressful friendly TSST on long-term memory for details presented during this event. In a double-blind between-group design, participants (final sample: 20 men and 13 women) either received hydrocortisone (20 mg) or a placebo and were then exposed to a non-stressful social interaction (fTSST). Affect, salivary cortisol, and salivary alpha-amylase (sAA) were assessed before and after the fTSST. Recognition memory for objects presented during this situation was assessed 1 day later. Positive affect and sAA increased in response to the friendly TSST in both groups. Hydrocortisone enhanced memory for peripheral objects of the situation in men but not in women. Memory for central objects was not affected by the hormone. The results suggest that in a non-stressful positive social environment, cortisol induces a broadening rather than a narrowing of memory. In addition, the findings provide preliminary evidence that this effect might be more prominent in men.

  12. Salivary but not plasma cortisone tracks the plasma cortisol response to exercise: effect of time of day.

    PubMed

    Del Corral, P; Schurman, R C; Kinza, S S; Fitzgerald, M J; Kordick, C A; Rusch, J L; Nadolski, J B

    2016-03-01

    The cortisol, cortisone, corticosterone, and CBG responses to exercise in the AM and PM have not been described. This study examined the response of these glucocorticoids and CBG to intense exercise in 12 endurance-trained men in plasma (Pl) and saliva (Sa). Each subject completed treadmill exercise in the morning and evening. Paired blood and Sa samples were obtained at rest before and after exercise. Significant time effect existed for Pl-cortisol and Sa-cortisol from baseline in the AM and PM (p < 0.01). Pl-cortisone and CBG significantly increased in the PM (p < 0.01). Pl-corticosterone increased in the AM and PM (p < 0.01). Unlike Pl-cortisone, Sa-cortisone was significantly higher in the AM compared to the PM, increasing in the AM and PM (All p < 0.01). Strong associations were found between Pl-cortisol and Sa-cortisol (r = 0.81, p < 0.0001), Pl-cortisol and Sa-cortisone (r = 0.81, p < 0.0001). (1) Intense EX induces a similar increase in Pl-cortisone (~90 %) and corticosterone (~200 %) in the AM and PM, whereas exercise increases CBG in the PM, but not in the AM; (2) vigorous exercise increases Sa-cortisone; (3) Sa-cortisone and cortisol are equally strongly correlated to Pl-cortisol, suggesting a significant role for Sa-cortisone as a novel marker of free cortisol during exercise.

  13. 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.

  14. 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

  15. 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

  16. Plasma adrenocorticotropin, cortisol and catecholamines response to various exercises.

    PubMed

    Nagata, S; Takeda, F; Kurosawa, M; Mima, K; Hiraga, A; Kai, M; Taya, K

    1999-07-01

    The responses of plasma adrenocorticotropin (ACTH), cortisol, noradrenaline and adrenaline in 5 Thoroughbred horses to an incremental exercise and 2 relative workload exercises, at 105 and 80% maximal oxygen consumption (VO2max), on a treadmill were examined. These hormone concentrations increased (P < 0.05) with each exercise and the maximal plasma concentrations of ACTH, cortisol were observed between 5 and 30 min after the end of the exercise, while maximal catecholamine concentrations occurred just at exhaustion time. The plasma ACTH, noradrenaline and adrenaline responses during exercise were more sensitive to the intensity of exercise than that of cortisol and showed a significant correlation with blood lactate concentrations (r = 0.605, P < 0.001 for ACTH; r = 0.718, P < 0.001 for noradrenaline; r = 0.738, P < 0.001 for adrenaline). The plasma cortisol response appeared to be connected with the duration of exercise (r = 0.71, P < 0.05). The recovery of these hormones was related to the exercise styles. These results suggest that the autonomic nervous system and the pituitary-adrenal axis of the horse are efficiently stimulated by various treadmill exercises, and these hormones may be used in the evaluation of exercise-induced stress.

  17. Cortisol in human milk predicts child BMI.

    PubMed

    Hahn-Holbrook, Jennifer; Le, Tran Bao; Chung, Anna; Davis, Elysia Poggi; Glynn, Laura M

    2016-12-01

    Breastfeeding has been linked to lower rates of childhood obesity. Human milk contains cortisol, known to regulate glucose storage and metabolism. The aim of this study was to to test the hypothesis that early exposure to cortisol in human breast milk helps to modulate infant body mass index (BMI) trajectories over the first 2 years of life. Growth curve modeling was used to examine whether infant exposure to cortisol in human milk at 3 months predicted changes in child body mass index percentile (BMIP) at 6, 12, and 24 months of age in 51 breastfeeding mother-child pairs. Infants exposed to higher milk cortisol levels at 3 months were less likely to exhibit BMIP gains over the first 2 years of life, compared with infants exposed to lower milk cortisol. By age 2, infants exposed to higher milk cortisol levels had lower BMIPs than infants exposed to lower milk cortisol. Milk cortisol was a stronger predictor of BMIP change in girls than boys. Cortisol exposure through human milk may help to program metabolic functioning and childhood obesity risk. Further, because infant formula contains only trace amounts of glucocorticoids, these findings suggest that cortisol in milk is a novel biological pathway through which breastfeeding may protect against later obesity. © 2016 The Obesity Society.

  18. DRAM Is Involved in Regulating Nucleoside Analog-Induced Neuronal Autophagy in a p53-Independent Manner.

    PubMed

    Gao, Ziyun; Shan, Junqi; Wang, Bishi; Qiao, Luxin; Chen, Dexi; Zhang, Yulin

    2017-03-06

    The widespread use of combined anti-retroviral therapy (cART) has not decreased the prevalence of HIV-1-associated neurocognitive disorder (HAND), a type of neurodegenerative disease, even though cART effectively inhibits virus colonization in the central nervous system. Therefore, anti-retroviral agents cannot be fully excluded from the pathogenesis of HAND. Our previous study reported that long-term nucleoside analogue (NA) exposure induced mitochondrial toxicity in the cortical neurons of HAND patients and mice, but the exact mechanism of NA-associated neurotoxicity has remained unclear. Alteration of autophagy can result in protein aggregation and the accumulation of dysfunctional organelles, which are hallmarks of some neurodegenerative diseases. In this study, we first found increased autophagy in cortical autopsy specimens of AIDS patients. We then found that a low dose of NAs could stimulate autophagy in primary cultured neurons, while a high dose of NAs could induce only neuronal apoptosis. The level of NA-induced Bcl-2 and Bax expressions determined whether neuronal autophagy or apoptosis occurred. Furthermore, the level of NA-induced neuronal apoptosis correlated with the dysfunction of cellular DNA polymerase gamma. Damage-regulated autophagy modulator (DRAM) overexpression was also involved in NA-induced neuronal autophagy. p53 played a role in the regulation of NA-induced neuronal apoptosis, but its role in NA-associated neuronal autophagy was uncertain. Our results suggest that DRAM is involved in the regulation of NA-induced neuronal autophagy in a p53-independent manner. Further research is needed to investigate the underlying mechanism.

  19. Tiron and trolox potentiate the autophagic cell death induced by magnolol analog Ery5 by activation of Bax in HL-60 cells.

    PubMed

    Kumar, Suresh; Kumar, Ajay; Pathania, Anup Singh; Guru, Santosh Kumar; Jada, Srinivas; Sharma, Parduman Raj; Bhushan, Shashi; Saxena, Ajit Kumar; Kumar, H M Sampath; Malik, Fayaz

    2013-05-01

    This study describes the mechanism of trolox and tiron induced potentiation of cytotoxicity caused by Ery5, an analog of magnolol, in human myeloid leukemia HL-60 cells. Ery5 induced cytotoxicity in HL-60 cells by involving activation of bax and cleavage of caspase 3, which contributed towards activation of both apoptotic and autophagic pathways. Trolox and tiron, even at non-toxic concentrations, contributed to the cytotoxicity of Ery5 by activation of autophagic proteins like ATG7, ATG12 and LC3-II. Z-VAD-fmk mediated reduction in the cytotoxicity and expression of autophagic proteins, further suggested that autophagy induced by Ery5 is largely dependent upon caspases. Interestingly, Ery5 induced autophagy was accompanied by the downregulation of PI3K/AKT pathway whereas, trolox and tiron strongly enhanced this effect. In addition to that treatment of cells with Ery5, trolox and tiron individually, displayed a marked upregulation of Bax. The involvement of Bax in trolox and tiron induced enhancement of the cytotoxicity of Ery5 was confirmed, when siRNA induced silencing of Bax led to increased viability of the cells and exerted a strong inhibitory effect on LC3-II accumulation and p62 degradation in case of cells treated by the combination of Ery5 with trolox or tiron. Additionally, an important role of PARP in Ery5 mediated cell death has been suggested by PARP silencing experiments, however, potentiation of autophagic cytotoxicity by trolox and tiron did not seem to be dependent on PARP-1. Therefore, Bax seems to play a vital role in trolox and tiron mediated potentiation of autophagic cell death by Ery5 in HL-60 cells.

  20. 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.

  1. 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

  2. The detection of cortisol in human sweat: implications for measurement of cortisol in hair.

    PubMed

    Russell, Evan; Koren, Gideon; Rieder, Michael; Van Uum, Stan H M

    2014-02-01

    Hair cortisol analysis has been shown to be an effective measure of chronic stress. Cortisol is assumed to incorporate into hair via serum, sebum, and sweat sources; however, the extent to which sweat contributes to hair cortisol content is unknown. Sweat and saliva samples were collected from 17 subjects after a period of intensive exercise and analyzed by salivary enzyme-linked immunosorbent assay (ELISA). Subsequently, an in vitro test on exposure of hair to hydrocortisone was conducted. Residual hair samples were immersed in a 50-ng/mL hydrocortisone solution for periods lasting 15 minutes to 24 hours, followed by a wash or no-wash condition. Hair cortisol content was determined using our modified protocol for a salivary ELISA. Postexercise control sweat cortisol concentrations ranged from 8.16 to 141.7 ng/mL and correlated significantly with the log-transformed time of day. Sweat cortisol levels significantly correlated with salivary cortisol concentrations. In vitro hair exposure to a 50-ng/mL hydrocortisone solution (mimicking sweat) for 60 minutes or more resulted in significantly increased hair cortisol concentrations. Washing with isopropanol did not affect immersion-increased hair cortisol concentrations. Human sweat contains cortisol in concentrations comparable with salivary cortisol levels. This study suggests that perfuse sweating after intense exercise may increase cortisol concentrations detected in hair. This increase likely cannot be effectively decreased with conventional washing procedures and should be considered carefully in studies using hair cortisol as a biomarker of chronic stress.

  3. 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. Copyright © 2012 John Wiley & Sons, Ltd.

  4. 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.

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

    PubMed Central

    Kong, In Chul

    2014-01-01

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

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

    PubMed

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

    2015-04-01

    Reduced space can lead to crowding in social animals. Crowding increases the risk of agonistic interactions that, in turn, may require additional physiological defensive coping mechanisms affecting health. To determine the stress induced from increased social density in a group of nineteen baboons living in an indoor/outdoor enclosure, saliva cortisol levels and rates of anxiety-related behavior were analyzed across two unique crowding episodes. Initially, mean salivary cortisol levels when animals were restricted to their indoor quarters were compared to those when they also had access to their larger outdoor enclosure. Then, mean cortisol levels were compared before, during, and after two distinct crowding periods of long and short duration. Crowding resulted in significantly elevated cortisol during crowding periods compared to non-crowded periods. Cortisol levels returned to baseline following two crowding episodes contrasting in their length and ambient climate conditions. These cortisol elevations indicate greater metabolic costs of maintaining homeostasis under social stress resulting from reduced space. Self-directed behavior, conversely, was not reliably elevated during crowding. Results suggest that the potential for negative social interactions, and/or the uncertainty associated with social threat can cause physiological stress responses detected by salivary cortisol. Self-directed behavioral measures of stress may constitute inadequate indicators of social stress in colony-housed monkeys or represent subjective emotional arousal unrelated to hypothalamic-pituitary adrenal axis activation. © 2015 Wiley Periodicals, Inc.

  7. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  9. 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.

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

    PubMed Central

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

    2016-01-01

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

  11. During a corticotropin-releasing hormone test in healthy subjects, administration of a beta-adrenergic antagonist induced secretion of cortisol and dehydroepiandrosterone sulfate and inhibited secretion of ACTH.

    PubMed

    Kizildere, Selda; Glück, Thomas; Zietz, Bettina; Schölmerich, Jürgen; Straub, Rainer H

    2003-01-01

    In chronic inflammatory diseases, serum levels of dehydroepiandrosterone (DHEA) sulfate (DHEAS) are low. Interestingly, several non-inflammatory diseases display similarly low levels of DHEAS which points to other inhibitory factors such as an activated sympathetic nervous system (SNS) (e.g. in patients with heart failure, fibromyalgia, or cancer cachexia). We aimed to identify the influence of the SNS tone on stimulated adrenal steroid secretion in 16 male and 12 female healthy subjects. One group were given oral propranolol 2 h before a corticotropin-releasing hormone (CRH) test, and levels of adrenocorticotropin (ACTH), cortisol, 17-hydroxyprogesterone (17OHP), androstenedione, DHEA, and DHEAS were measured. Propranolol treatment decreased heart rate (by 20%), diastolic blood pressure (by 20%), and plasma ACTH, and increased serum cortisol, serum DHEAS, and the molar ratio of cortisol/17OHP, cortisol/DHEA, and DHEAS/DHEA similarly in female and male subjects. A beta-adrenergic influence seems to decrease CRH-stimulated cortisol in relation to ACTH and 17OHP, and decreases DHEAS in relation to DHEA. Although other workers have found beta-adrenergic stimulation of steroid secretion in cultured adrenocortical cells, the overall systemic influence of the SNS via beta-adrenoceptors seems to inhibit adrenal steroids under unstimulated and stimulated conditions. Sympathetic hyperactivity may be a common denominator for low levels of DHEAS in inflammatory and non-inflammatory diseases.

  12. 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

  13. 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.

  14. 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.

  15. Cortisol boosts risky decision-making behavior in men but not in women.

    PubMed

    Kluen, Lisa Marieke; Agorastos, Agorastos; Wiedemann, Klaus; Schwabe, Lars

    2017-10-01

    Acute stress may escalate risky decision-making in men, while there is no such effect in women. Although first evidence links these gender-specific effects of stress to stress-induced changes in cortisol, whether elevated cortisol is indeed sufficient to boost risk-taking, whether a potential cortisol effect depends on simultaneous noradrenergic activation, and whether cortisol and noradrenergic activation exert distinct effects on risk-taking in men and women is unknown. In this experiment, we therefore set out to elucidate the impact of cortisol and noradrenergic stimulation on risky decision-making in men and women. In a fully-crossed, placebo-controlled, double-blind design, male and female participants received orally either a placebo, hydrocortisone, yohimbine, an alpha-2-adrenoceptor-antagonist leading to increased noradrenergic stimulation, or both drugs before completing the balloon analogue risk task, a validated measure of risk-taking. Overall, participants' choice was risk-sensitive as reflected in reduced responding in high- compared to moderate- and low-risk conditions. Cortisol, however, led to a striking increase in risk-taking in men, whereas it had no effect on risk-taking behavior in women. Yohimbine had no such effect and the gender-specific effect of cortisol was not modulated by yohimbine. Our data show that cortisol boosts risk-taking behavior in men but not in women. This differential effect of cortisol on risk-taking may drive gender differences in risky decision-making under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. 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.

  18. 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.

  19. Cortisol and DHEA in development and psychopathology.

    PubMed

    Kamin, Hayley S; Kertes, Darlene A

    2017-03-01

    Dehydroepiandrosterone (DHEA) and cortisol are the most abundant hormones of the human fetal and adult adrenals released as end products of a tightly coordinated endocrine response to stress. Together, they mediate short- and long-term stress responses and enable physiological and behavioral adjustments necessary for maintaining homeostasis. Detrimental effects of chronic or repeated elevations in cortisol on behavioral and emotional health are well documented. Evidence for actions of DHEA that offset or oppose those of cortisol has stimulated interest in examining their levels as a ratio, as an alternate index of adrenocortical activity and the net effects of cortisol. Such research necessitates a thorough understanding of the co-actions of these hormones on physiological functioning and in association with developmental outcomes. This review addresses the state of the science in understanding the role of DHEA, cortisol, and their ratio in typical development and developmental psychopathology. A rationale for studying DHEA and cortisol in concert is supported by physiological data on the coordinated synthesis and release of these hormones in the adrenal and by their opposing physiological actions. We then present evidence that researching cortisol and DHEA necessitates a developmental perspective. Age-related changes in DHEA and cortisol are described from the perinatal period through adolescence, along with observed associations of these hormones with developmental psychopathology. Along the way, we identify several major knowledge gaps in the role of DHEA in modulating cortisol in typical development and developmental psychopathology with implications for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Positive upshots of cortisol in everyday life

    PubMed Central

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

    2016-01-01

    Cortisol, the major physiological end-product of the hypothalamic-pituitary-adrenal (HPA) 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 two consecutive weekdays (n = 862 total samples). Utilizing multi-leveling 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. PMID:26950364

  1. Medical Clowns and Cortisol levels in Children Undergoing Venipuncture in the Emergency Department: A Pilot Study.

    PubMed

    Rimon, Ayelet; Shalom, Shelly; Wolyniez, Ido; Gruber, Alejandro; Schachter-Davidov, Anita; Glatstein, Miguel

    2016-11-01

    Medical clowns are increasingly used for diminishing pain and anxiety during painful procedures being performed on children in the hospital setting. Cortisol levels rise as a response to emotional distress. To investigate whether medical clown-assisted interventions to reduce child's distress during venipuncture have an effect on cortisol levels. During a 1 year period, children requiring blood work or intravenous access in the pediatric emergency department were prospectively randomized to either the presence or absence of a medical clown during the procedure. The child's distress was evaluated using the Faces Pain Scale - revised (FPS-R) for the 4-7 year age group and the visual analog scales (VAS) for those aged 8-15 years. Serum cortisol levels were measured in blood samples obtained by venipuncture. Fifty-three children aged 2-15 years were randomly assigned to the study group (with medical clown, n=29) or to the control group (without medical clown, n=24). Combined pain scores of the study group and control group were 2.2 and 7.5 respectively (P < 0.001). No difference in mean cortisol levels was found between the study group and the control group at all ages (16.4 µg/dl vs. 18.3 µg/dl, P = 0.65). In this pilot study, medical clowns reduced the distress from venipuncture in children. No effect on cortisol levels was observed.

  2. Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

    PubMed Central

    Orlander, Philip R.

    2011-01-01

    Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P < .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P < .0001). The mean ± SD free serum cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. Conclusions: Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily. Trial registry: ClinicalTrials.gov; No.: NCT00523198; URL: www.clinicaltrials.gov PMID:21816912

  3. 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.

  4. 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.

  5. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    PubMed

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

    2016-07-01

    Progesterone, an endogenous immunomodulator, suppresses human T-cell activation during pregnancy. A sustained Ca(2 +) influx is an important signal for T-cell proliferation after crosslinking of T-cell receptor/CD3 complexes by anti-CD3 antibodies or phytohemagglutinin (PHA). Progesterone targets cell membrane sites inducing rapid responses including elevated intracellular free calcium concentration ([Ca(2+)]i) and suppressed T-cell PHA-activated proliferation. Interestingly, both PHA and progesterone induce [Ca(2+)]i elevation, but it remains unclear whether the PHA-induced Ca(2+) influx is affected by progesterone leading to T-cell immunosuppression. Primary T-cells were isolated from human peripheral blood and the quench effect on intracellular fura-2 fluorescence of Mn(2+) was used to explore the responses to Ca(2+) influx with cell proliferation being determined by MTT assay. PHA-stimulated Ca(2+) influx was dose-dependently suppressed by progesterone and its agonist R5020, which correlated with PHA-activated T-cell proliferation inhibition. A similar dose-dependent suppression effect on cellular Ca(2+) influx and proliferation occurred with the TRPC channel inhibitor BTP2 and selective TRPC3 channel inhibitor Pyr3. In addition, two progesterone analogs, Org OD 02-0 and 20α-hydroxyprogesterone (20α-OHP), also produced dose-dependent suppression of Ca(2+) influx, but had no effect on proliferation. Finally, inhibition of PHA-activated T-cell proliferation by progesterone is further suppressed by 20α-OHP, but not by Org OD 02-0. Overall, progesterone and R5020 are able to rapidly decrease PHA-stimulated sustained Ca(2+) influx, probably via blockade of TRPC3 channels, which suppresses T-cell proliferation. Taken together, the roles of progesterone and its analogs regarding the rapid response Ca(2+) influx need to be further explored in relation to cytokine secretion and proliferation in activated T-cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. 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.

  8. 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

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

    PubMed Central

    Nakagawa, Kento; Obu, Takashi; Kanosue, Kazuyuki

    2014-01-01

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

  10. 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.

  11. Liraglutide, a glucagon-like peptide-1 analog, induce autophagy and senescence in HepG2 cells.

    PubMed

    Krause, Gabriele Catyana; Lima, Kelly Goulart; Dias, Henrique Bregolin; da Silva, Elisa Feller Gonçalves; Haute, Gabriela Viegas; Basso, Bruno Souza; Gassen, Rodrigo Benedetti; Marczak, Elisa Simon; Nunes, Rafaela Sole Bach; de Oliveira, Jarbas Rodrigues

    2017-08-15

    It has been reported that glucagon-like peptide-1 (GLP-1) agents have been associated with both the increased risk of cancer and inhibition of tumor growth and metastases. The aim of this study is to evaluate the effect of liraglutide on hepatocellular carcinoma cells - HepG2. Cytometry was used to evaluate mechanism related to decreased cell proliferation. Nuclear staining and morphometric analysis were also used to verify the process that was taking place after treatment with liraglutide, and in order to better understand the mechanism, TGF-β1 was performed. HepG2 cells decreased proliferation after liraglutide treatment without altering oxidative stress levels. Liraglutide was able to induce autophagy and senescence through the increase of TGF-β1 which possibly explains the growth decrease. We have demonstrated that liraglutide has an antiproliferative effect in HepG2 cells inducing autophagy and senescence by the increase of TGF-β1. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Chemopreventive effects of PBI-Se, a selenium-containing analog of PBIT, on AOM-induced aberrant crypt foci in F344 rats.

    PubMed

    Janakiram, Naveena B; Mohammed, Altaf; Ravillah, Durgadevi; Choi, Chang In; Zhang, Yuting; Desai, Dhimant; Amin, Shantu; Rao, Chinthalapally V

    2013-08-01

    Inducible nitric oxide synthase (iNOS) is a potential target for the treatment of inflammation and cancer. Previously, we showed that the selective iNOS inhibitor S,S'-1,4-phenylenebis(1,2-ethanediyl)bis-isothiourea (PBIT) caused significant inhibition of colon carcinogenesis induced by azoxymethane (AOM), although it did not completely abrogate NO production due to the exogenous bioavailability of NO and NO generation by eNOS in tumor tissues. To create an iNOS-targeting molecule that may have additional benefits, a novel isosteric analog of PBIT, PBI-Se, was developed, in which sulfur was replaced with selenium. Chemopreventive efficacy of PBI-Se was evaluated in an AOM-induced rat colon carcinogenesis model using aberrant crypt foci (ACF) as the endpoint. At 7 weeks of age, rats (12/group) were fed the control diet (AIN 76A) and then colonic ACF were induced with two AOM treatments. Three days later, rats were fed diets containing PBI-Se (0-20 ppm) for 8 weeks, and then ACF were evaluated histopathologically. Dietary administration of 10 or 20 ppm of PBI-Se significantly suppressed AOM-induced total colonic ACF formation (32 or 41%, p<0.002-0.0003), and multi-crypt (4 or more) aberrant foci (29 or 47%, p<0.01-0.0004), respectively. The inhibition by PBI-Se was dose-dependent and was half the dose of PBIT for inhibiting total ACF in rats. Both PBIT and PBI-Se induced dose-dependent apoptosis in CaCo2 cells and caused a significant decrease in the cell cycle proteins cyclin D1 (70%, p<0.0001) and iNOS (99%, p<0.0001). Treatment with PBIT (30 and 60 µM) and PBI-Se (2 and 4  µM) significantly decreased the LPS-induced cytokine interleukin-6 level. Incorporation of selenium into the structure of PBIT provided the agent with additional novel cytotoxic and immunologic properties. Results from the in vitro and in vivo bioassays suggest that PBI-Se could be developed further for the prevention and treatment of colon cancer.

  13. 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.

  14. Analog of midinfrared electromagnetically induced-transparency and slow rainbow trapping light based on graphene nanoribbon-coated silica substrate

    NASA Astrophysics Data System (ADS)

    Wei, Buzheng; Jian, Shuisheng

    2017-04-01

    A midinfrared band-tunable graphene-based plasmonic waveguide is analytically and numerically investigated to realize electromagnetically induced-transparency-like transmission and to slow rainbow trapping light. By applying different Fermi energy levels to the top and bottom graphene nanoribbons, a dynamic control of resonant wavelengths is thus obtained at the desired working regions. Plus, the structural size parameters play a significant role in modulating the resonant spectra and resonant depth. Combining the manipulation of the two sets of influential factors, the transparency window is therefore under control. Detailed investigations of the analytic mechanism of the device are made as well. Furthermore, the light signal that travels in the waveguide can be successfully slowed down to over 340 times the speed in a vacuum. If the nanoribbon width is gradiently distributed, the so-called rainbow trapping can be achieved. Hence, the device has potential applications in nanoimaging, sensing, integrated circuits, and light energy storage domains.

  15. When Gesture Becomes Analogy.

    PubMed

    Cooperrider, Kensy; Goldin-Meadow, Susan

    2017-07-01

    Analogy researchers do not often examine gesture, and gesture researchers do not often borrow ideas from the study of analogy. One borrowable idea from the world of analogy is the importance of distinguishing between attributes and relations. Gentner (, ) observed that some metaphors highlight attributes and others highlight relations, and called the latter analogies. Mirroring this logic, we observe that some metaphoric gestures represent attributes and others represent relations, and propose to call the latter analogical gestures. We provide examples of such analogical gestures and show how they relate to the categories of iconic and metaphoric gestures described previously. Analogical gestures represent different types of relations and different degrees of relational complexity, and sometimes cohere into larger analogical models. Treating analogical gestures as a distinct phenomenon prompts new questions and predictions, and illustrates one way that the study of gesture and the study of analogy can be mutually informative. Copyright © 2017 Cognitive Science Society, Inc.

  16. 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.

  17. 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. © 2016 Michigan Association for Infant Mental Health.

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

    PubMed Central

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

    2011-01-01

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

  19. Assessment of salivary free cortisol levels by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in patients treated with mitotane.

    PubMed

    Carrozza, Cinzia; Lapolla, Rosa; Gervasoni, Jacopo; Rota, Carlo Antonio; Locantore, Pietro; Pontecorvi, Alfredo; Zuppi, Cecilia; Persichilli, Silvia

    2012-01-01

    Mitotane is an adrenocytolytic agent used in adrenocortical carcinoma, inducing adrenal insufficiency, requiring replacement treatment. Such therapy is not easy to monitor because of mitotane interference. Salivary cortisol reflects a free fraction of plasma cortisol and may be useful in such patients. The aim of our study was to evaluate salivary cortisol by HPLC coupled to tandem-mass spectrometry (LC-MS/MS) and by an electrochemiluminescence immunoassay (ECLIA) in patients treated with mitotane. We enrolled 6 patients receiving mitotane and 2 Addison disease patients as negative controls and determined salivary cortisol rhythm. We also determined the salivary cortisol rhythm in 8 healthy subjects. Salivary samples (n=112) were assayed by ECLIA, using Roche Modular E170, and by LC-MS/MS. The mean values obtained by ECLIA were significantly higher than those obtained by LC-MS/MS in the mitotane group (p<0.001). In fact, in the group measured by LC-MS/MS, we observed several peaks eluting at a retention time different from the cortisol group, presumably due to cortisol-like analogues. In Addison disease, since steroidogenesis is absent, salivary cortisol values measured by the two methods did not show any significant difference (p=0.61). Salivary cortisol measured by LC-MS/MS is a selective method, excluding cortisol analogues accumulating in treated patients. Therefore, LC-MS/MS offers an effective system to monitor replacement therapy in mitotane treated patients.

  20. 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

  1. Salivary Cortisol Lower in Posttraumatic Stress Disorder

    PubMed Central

    Wahbeh, Helané; Oken, Barry S.

    2013-01-01

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

  2. 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

  3. 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.

  4. 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.

  5. 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

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

    PubMed

    Vaughan, O R; Davies, K L; Ward, J W; de Blasio, M J; Fowden, A L

    2016-11-01

    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. 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 < 0.05). Concomitantly

  7. 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.

  8. Everyday Discrimination and Diurnal Cortisol during Adolescence

    PubMed Central

    Huynh, Virginia W.; Guan, Shu-Sha Angie; Almeida, David M.; McCreath, Heather; Fuligni, Andrew J.

    2016-01-01

    Purpose To examine the associations of the frequency and type of everyday discrimination with diurnal cortisol and whether those associations depend upon adolescents’ ethnicity and gender. Methods Adolescents (N=292, Mage=16. 39 years, SD=.74; 58% female) reported the frequency of perceived everyday discrimination and whether they attributed that discrimination to race, gender, age, or height and weight. Five saliva samples were collected per day across 3 days and assayed for cortisol. Results Higher frequency of everyday discrimination was associated with greater total daily cortisol output (area under the curve; AUC), lower wake and bedtime levels of cortisol, and less of a decline in cortisol across the day. These associations generally did not depend upon ethnicity or gender and attributions for the discrimination were not as consequential as the actual frequency of any type of unfair treatment. Conclusion Everyday discrimination, regardless of its type, may contribute to heightened HPA activity among adolescents of different ethnic backgrounds and genders. PMID:26853614

  9. Expensive Egos: Narcissistic Males Have Higher Cortisol

    PubMed Central

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

    2012-01-01

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

  10. Salivary cortisol and psychosocial hazards at work.

    PubMed

    Maina, Giovanni; Palmas, Antonio; Bovenzi, Massimo; Filon, Francesca Larese

    2009-03-01

    Experimental and clinical evidence suggest that stress can lead to ill-health through the disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Studies to date have produced equivocal results likely due to different methodologies and failure to account for confounding factors. This investigation aimed to assess the relation between self-reported work-related stressors and salivary cortisol and to clarify the role of the potential confounders. Thirty-six call-handlers completed a self-administered job content questionnaire and collected seven daily salivary samples on two workdays and a weekend. The diurnal salivary cortisol output was expressed as cortisol awakening response (CAR), and cortisol output in the rest of the day. Salivary cortisol data were normalized by means of square root transformation. The generalized estimating equations method was used to assess the relation between job strain and cortisol levels after adjusting for gender, weekdays and adherence to the sampling schedule. Job strain significantly influenced the total amount of cortisol response to waking (high strain vs. low strain: 1.1 (0.3-2.0) nmol/L). The cortisol response to waking showed gender-specific differences [women excreting greater cortisol than men: 1.1 (0.3-1.9) nmol/L], and weekday differences [workdays vs. weekend: 1.0 (0.3-1.6) nmol/L]. Non-compliance with the sampling protocol was associated with lower salivary cortisol than in adherent subjects. Our results provide further evidence for the HPA axis involvement in the physiological response to work stress. The measure of the CAR showed to be the sensitive index to assess the physiological response to psychosocial factors. Gender, weekday, and protocol compliance were confounding factors.

  11. Noninvasive surrogate markers for plasma cortisol in newborn infants: utility of urine and saliva samples and caution for venipuncture blood samples.

    PubMed

    Okamura, Hisayoshi; Kinoshita, Masahiro; Saitsu, Hiroki; Kanda, Hiroshi; Iwata, Sachiko; Maeno, Yasuki; Matsuishi, Toyojiro; Iwata, Osuke

    2014-10-01

    Hypothalamus-pituitary-adrenal function is associated with important physiological/pathological events in neonates. Plasma/serum cortisol levels have been used to assess hypothalamus-pituitary-adrenal function. Several noninvasive surrogate markers have been used without sufficient validation. The objectives of the study were to investigate whether plasma cortisol levels are correlated with those in saliva and urine and whether these correlations are affected by procedural pain at blood sampling. Fifty neonates were recruited from a tertiary neonatal intensive care unit. Saliva and urine samples were collected shortly before routine clinical blood sampling. Cortisol levels were compared between plasma and noninvasive samples using a linear regression analysis for the entire study population and groups, whose blood was obtained via indwelling arterial catheters (group A) or by venipuncture (group V). Predictive values of salivary/urinary cortisol for low plasma cortisol levels less than 2.0 μg/dL were evaluated by receiver-operating characteristic analysis. Plasma cortisol showed linear correlations with salivary and urinary cortisol for the entire study population and patients in group A (all P < .0002) but not in group V. Areas under the curves of salivary and urinary cortisol to predict low plasma cortisol levels were 0.87 (95% confidence interval 0.78-0.97) and 0.84 (95% confidence interval 0.74-0.95), respectively. Cortisol levels from saliva or urine samples were shown to be useful surrogate markers for plasma cortisol levels in neonates. Caution is required in interpreting the findings of plasma cortisol levels in young patients when blood samples are obtained by venipuncture because procedural pain may induce alteration of cortisol levels.

  12. Chewing unflavored gum does not reduce cortisol levels during a cognitive task but increases the response of the sympathetic nervous system.

    PubMed

    Walker, Jessica; Hosiner, Andreas; Kergoat, Sophie; Walker, Joel M; Somoza, Veronika

    2016-02-01

    Stress might be caused by various lifestyle factors and physical challenges and can result in severe diseases. The body responds to stressful events by release of hormones, like cortisol, as well as reaction of the sympathetic nervous system. One strategy to counteract stress is chewing gum. The present study aimed at investigating the influence of mastication on biomarkers of stress during performance of a stress test. A two-armed cross-over study with 40 young male volunteers was performed. Hormone plasma concentrations were determined after an initial resting phase (2:30p.m.), immediately before (3:00p.m.) and two times after (3:20, 3:50p.m.) performance of a multitasking test using magnetic beads and ELISA methods. In addition, visual analog scales were used to rate subjective mood and the breathing and heart rates were monitored throughout the entire study period using a sensor chest belt. Performance of the stress test led to an increase in plasma cortisol concentrations from 223±23.3 to 325±38.4ng/ml (p=0.023) and caused changes in subjective mood ratings as well as breathing rates. Although chewing gum base had no impact on the plasma hormone concentrations, it induced a stronger elevation of average heart rates compared to not chewing (p=0.016). The effect of chewing gum on a mild stress load was less pronounced than in previous studies. Besides the detection of cortisol in saliva, not in plasma, in previous studies, flavored gum was used. Aroma active compounds might have substantially contributed to the beneficial effects of gum on biomarker of stress shown before. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 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.

  14. 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…

  15. 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.

  16. Prenatal cocaine exposure related to cortisol stress reactivity in 11-year-old children.

    PubMed

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

    2010-08-01

    Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school-aged children. 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. With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Children exposed to cocaine and who experienced domestic violence showed the strongest effects. The combination of prenatal cocaine exposure and an adverse postnatal environment could downregulate the hypothalamic-pituitary-adrenal axis resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  17. 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

  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. Cortisol enhances structural maturation of the hypoplastic fetal lung in sheep

    PubMed Central

    Boland, Rochelle; Joyce, Belinda J; Wallace, Megan J; Stanton, Heather; Fosang, Amanda J; Pierce, Richard A; Harding, Richard; Hooper, Stuart B

    2004-01-01

    Although exogenous corticosteroids advance structural maturation of the fetal lung, they can adversely affect fetal lung and body growth. Our aim was to determine whether cortisol, at physiological doses, can enhance structural maturation of the hypoplastic fetal lung without affecting fetal lung growth. Fetal sheep were divided into four groups (n = 5 for each) and lung hypoplasia (LH) was induced in two groups. Increasing doses of cortisol (1.5–4.0 mg) were infused into one group of fetuses with LH and one group without LH; the other two groups received saline. LH retarded structural development, reduced tropoelastin mRNA levels, reduced hydroxyproline and elastin contents, and increased active matrix metalloproteinase-2 (MMP-2) levels in the fetal lung. Cortisol infusions had no effect on fetal lung growth or body weights. In fetuses with LH, cortisol increased the percentage airspace, reduced the interalveolar wall thickness, increased alveolar number and reduced the increase in active MMP-2 levels. Thus, relatively low doses of cortisol can enhance structural maturation of the fetal lung without adversely affecting fetal lung growth. However, cortisol did not correct the abnormal deposition of elastin within the alveolar parenchyma associated with LH, indicating that secondary septal crest formation remained abnormal. PMID:14578477

  20. Stress and cortisol responses in men: differences according to facial symmetry.

    PubMed

    Borráz-León, Javier I; Cerda-Molina, Ana Lilia; Mayagoitia-Novales, Lilian

    2017-09-19

    Stress response is associated with increased activity in the hypothalamic-pituitary-adrenocortical axis. Chronic stress-induced elevation in cortisol may alter its own negative regulation with multiple long-term consequences for physical and psychological health. One of the most reliable physical traits associated with mental, apparent physical health, and competitiveness is the degree of facial fluctuating asymmetry. However, to our knowledge there are no studies regarding the relationship between cortisol levels, facial symmetry and male competitiveness, and how cortisol changes after a stressful test depending on these traits. Here, a group of 100 college men were photographed to obtain their facial asymmetry levels. They then, answered the perceived stress scale and the intrasexual competition test and donated two saliva samples (pre-and post-test sample) to measure the change in their cortisol levels after a stressful test. We found that basal cortisol levels were positively correlated with both perceived stress and competitiveness, but not with facial fluctuating asymmetry. Cortisol levels increased in most symmetrical men after a short stressful test, but it decreased in most asymmetrical men. The results suggest differences in endocrine responses according to facial fluctuating asymmetry in men and how these responses could be related to the maintenance of social status.

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

    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/cm2. 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.

  3. 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.

  4. 3-O-[N-(p-fluorobenzenesulfonyl)-carbamoyl]-oleanolic acid, a semisynthetic analog of oleanolic acid, induces apoptosis in breast cancer cells.

    PubMed

    Akl, Mohamed R; Elsayed, Heba E; Ebrahim, Hassan Y; Haggag, Eman G; Kamal, Amel M; El Sayed, Khalid A

    2014-10-05

    Oleanolic acid (OA), a pentacyclic triterpene acid widely distributed in food and traditional herbal remedies, exhibits diverse therapeutic effects. OA has been subjected to various chemical modifications to optimize its anticancer effect. Among other analogs, 3-O-[N-(p-fluorobenzenesulfonyl)-carbamoyl]-oleanolic acid (PFOA) was semisynthesized from OA. This study evaluates the cytotoxic effects of PFOA on MDA-MB-231, MCF-7, BT-474, and T-47D human breast cancer cells. Acute treatment of PFOA inhibited breast cancer cell viability in a dose-dependent manner. Treatment of PFOA at cytotoxic doses significantly induced apoptosis in cancer cells as shown by flow cytometry analysis. Activation of apoptosis in MCF-7 and BT-474 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8 and PARP-1, whereas apoptosis in MDA-MB-231 cells was initiated by the activation of caspase-9, caspase-3 and PARP-1. The mechanism of apoptosis induction in T-47D involves activation of PARP-1. PFOA decreased the expression of EGFR, HER-2, MET and ERα in human breast cancer cell lines. These findings suggest that PFOA inhibits cell growth, activates apoptosis, and decreases the expression of key proteins involved in progression of breast cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

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

    2016-04-10

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

  6. 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

  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. 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.

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

    PubMed Central

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

    2014-01-01

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

  10. Cortisol response to an induction of negative affect among adolescents with and without loss of control eating.

    PubMed

    Radin, Rachel M; Shomaker, Lauren B; 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

    2016-12-01

    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. 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 min relative to film administration, and state mood ratings were reported before and after the film. Adolescents with LOC had greater increases in negative affect during the experimental paradigm in both conditions (ps > 0.05). Depressive symptoms, but not LOC, related to a greater cortisol response in the sad film condition (ps > 0.05). Depressive symptoms and state LOC were related to different aspects of eating behaviour, independent of film condition or cortisol response (ps > 0.05). 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. © 2015 World Obesity Federation.

  11. 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

  12. 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.

  13. Evaluation of Salivary Cortisol Changes and Psychological Profiles in Patients with Recurrent Aphthous Stomatitis.

    PubMed

    Rezaei, Fatemeh; Aminian, Maziar; Raygani, Asad Vaisi

    2017-01-01

    Some studies suggest that psychological condition and stress can play role in the development of recurrent aphthous stomatitis (RAS). The purpose of this study was to evaluate salivary cortisol changes and psychological conditions in patients with RAS. Twenty-seven patients (13 males and 14 females, mean age of 32.8 (±10.2) years) with minor RAS and 27 age- and sex-matched controls without RAS participated in this study. The concentration of cortisol (nanomole/L) was measured in samples of unstimulated saliva from patients and controls two times; once during the presence of active lesions and once again when the lesions had healed by immunologic assay. The Hospital Anxiety and Depression Scale was employed to determine psychological condition. Visual analog scale for pain severity was recorded for patients with active lesions episode. Data were analyzed by the SPSS software (version 18.0) using paired and unpaired t-tests and Pearson correlation coefficient. Salivary cortisol level was lower in patients during active lesions (12.4 ± 5.1) and healing (10.5 ± 3.9) episodes compared to the controls (13.1 ± 3.6) (P = 0.583, P = 0.015; respectively). There was no significant difference in salivary cortisol between active lesions and healing episodes (P = 0.943). Anxiety and depression represented no significant differences between active lesions and healing episodes (P > 0.05). Anxiety and depression levels in patients were significantly higher than in controls (P < 0.05). Pain severity in active lesions was not significantly correlated to salivary cortisol level, and anxiety or depression scores (P > 0.05). The findings showed that occurrence of RAS was associated with anxiety and depression but not with alterations of salivary cortisol level.

  14. Detection of FITC-cortisol via modulated supraparticle lighthouses.

    PubMed

    Petkus, Matthew M; McLauchlin, Melissa; Vuppu, Anil K; Rios, Lynnette; Garcia, Antonio A; Hayes, Mark A

    2006-03-01

    Hormones are important bioactive compounds in blood and tissue that vary in concentration in response to stress and certain disease states. Establishing the changes in physiological hormone concentrations over time can lead to more effective diagnoses and perhaps a better understanding of the evolution of stress and disease. To monitor concentration over time, the sampling must be rapid and noninvasive; specimens such as saliva that require little effort to collect are preferred. However, more sensitive assay techniques are needed when compared to blood analysis since free hormone concentration in saliva is only a small fraction of the concentration in circulating blood. In this work, magnetic field-induced structures of paramagnetic particles are used as a solid substrate to demonstrate improved detection limits for a separation-free assay of cortisol. Once formed, the structures are subjected to a rotating magnetic field and this leads to two important features. First is the ability to utilize frequency and phase filtering (lock-in amplification) for the signal generated from surface-bound labeled species. Second is the improved mass transport of the antigen to the surface of the rotating structures. These two unique capabilities result in a quantifiable signal at a relatively low target antigen concentration. This method has been demonstrated with the detection of fluorescein isothiocyanate-labeled cortisol (FITC-cortisol) at a concentration of 300 pM.

  15. Biomimetic Analogs for Collagen Biomineralization

    PubMed Central

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

    2011-01-01

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

  16. 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)

  17. 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)

  18. 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)

  19. Effect of sodium valproate on naloxone-stimulated ACTH and cortisol release in humans.

    PubMed

    Torpy, D J; Grice, J E; Hockings, G I; Crosbie, G V; Walters, M M; Jackson, R V

    1995-01-01

    1. Gamma-aminobutyric acid (GABA) and endogenous opioids each inhibit hypothalamic CRH secretion. In humans, the opioid antagonist, naloxone, stimulates the release of CRH, and so of ACTH and cortisol, while alprazolam, an indirect GABAA agonist, blocks naloxone-induced ACTH and cortisol secretion. Sodium valproate (SV) inhibits ACTH release in response to CRH, metyrapone and substance P. We hypothesized that, if this action is GABAA-mediated, SV should also inhibit naloxone-stimulated ACTH release. 2. We studied five healthy volunteers in randomized, double-blind, placebo-controlled afternoon studies with SV 400 mg, given 180 min before i.v. naloxone 125 micrograms/kg bodyweight. Plasma concentrations of ACTH, cortisol and SV were measured at intervals during the experiments. 3. SV had no effect on the mean integrated ACTH and cortisol responses to naloxone; ACTH: 165 +/- 21 versus 284 +/- 40 pmol.min per L, P = 0.08; cortisol: 10.5 +/- 1.9 versus 12.8 +/- 1.2 nmol.min per L-3, P = 0.14, placebo/nal versus SV/nal respectively. Basal ACTH and cortisol levels were also not significantly altered by SV (P > 0.30). Mean SV levels were not significantly different between SV/nal and SV/placebo studies (P > 0.50). 4. In conclusion, SV had no effect on naloxone-induced ACTH and cortisol release in normal humans at the dose and plasma drug concentrations studied. This contrasts with the potent inhibitory effect of alprazolam, and suggests that the effect of SV on the human hypothalamic-pituitary-adrenal axis may not be through a GABAA-mediated mechanism. Alternatively, higher plasma SV levels or more sustained exposure to SV may be necessary to inhibit hypothalamic secretion of CRH.

  20. Work stress and recovery measured by urinary catecholamines and cortisol excretion in long distance coach drivers

    PubMed Central

    Sluiter, J. K.; van der Beek, A. J.; Frings-Dresen, M. H.

    1998-01-01

    OBJECTIVES: To evaluate coach drivers' work stress during work and in the course of recovery from work by measurement of urinary catecholamines and cortisol. METHODS: The urinary excretion rate of adrenaline, noradrenaline, and cortisol of 10 coach drivers was studied during a long distance trip of three days and two consecutive days off. Each driver was asked to provide seven urine samples on the working days and six urine samples on the days off. The second day off was considered as the baseline. RESULTS: An occupationally induced disturbance of the circadian rhythmicity was found for adrenaline and noradrenaline but not for cortisol. The mean excretion rates of adrenaline on the first working day and most samples on all working days were higher than the baseline. For both adrenaline and noradrenaline the mean excretion rates on the first day off were lower than the baseline. For cortisol, the mean excretion rate on all working days was higher than the baseline. A trend towards accumulation of cortisol excretion from the first working day to the third working day was found. A backward shift in peak concentrations was found for adrenaline and noradrenaline on the second working day, as was a forward shift in peak concentration of cortisol on both days off. CONCLUSIONS: Long distance coach drivers showed occupationally induced reactivity in rates of urinary excretion of adrenaline, noradrenaline, and cortisol. After the outward journey the rates of excretion of catecholamines did not return to baseline values. The course of recovery in adrenaline excretion after the journey showed a new phenomenon, which has been called "fatigue debt". It is recommended that longer resting times in shuttle bus trips and fixed days off after these kind of trips should be planned. Extensive future research should be focused on the additional relations between fatigue debt and health complaints.   PMID:9764101

  1. Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

    PubMed

    Admon, Roee; Treadway, Michael T; Valeri, Linda; Mehta, Malavika; Douglas, Samuel; Pizzagalli, Diego A

    2017-08-16

    The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response (n = 10), moderate-response (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability.SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how

  2. Testosterone, cortisol, and human competition.

    PubMed

    Casto, Kathleen V; Edwards, David A

    2016-06-01

    Testosterone and cortisol figure prominently in the research literature having to do with human competition. In this review, we track the history of this literature, concentrating particularly on major theoretical and empirical contributions, and provide commentary on what we see as important unresolved issues. In men and women, athletic competition is typically associated with an increase in testosterone (T) and cortisol (C). Hormone changes in response to non-athletic competition are less predictable. Person (e.g., power motivation, mood, aggressiveness, social anxiety, sex, and baseline levels of T and C) and context (e.g., whether a competition is won or lost, the closeness of the competition, whether the outcome is perceived as being influenced by ability vs. chance, provocations) factors can influence hormone responses to competition. From early on, studies pointed to a positive relationship between T and dominance motivation/status striving. Recent research, however, suggests that this relationship only holds for individuals with low levels of C - this is the core idea of the dual-hormone hypothesis, and it is certain that the broadest applications of the hypothesis have not yet been realized. Individuals differ with respect to the extent to which they embrace competition, but the hormonal correlates of competitiveness remain largely unexplored. Although rapid increases in both T and C associated with competition are likely adaptive, we still know very little about the psychological benefits of these hormonal changes. Administration studies have and will continue to contribute to this inquiry. We close with a discussion of what, we think, are important methodological and mechanistic issues for future research. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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

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

    PubMed

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

    2016-06-01

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

  5. 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.

  6. 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.

  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. Acetaminophen analog N-acetyl-m-aminophenol, but not its reactive metabolite, N-acetyl-p-benzoquinone imine induces CYP3A activity via inhibition of protein degradation.

    PubMed

    Santoh, Masataka; Sanoh, Seigo; Ohtsuki, Yuya; Ejiri, Yoko; Kotake, Yaichiro; Ohta, Shigeru

    2017-05-06

    Cytochrome P450 (CYP) 3A subfamily members are known to metabolize various types of drugs, highlighting the importance of understanding drug-drug interactions (DDI) depending on CYP3A induction or inhibition. While transcriptional regulation of CYP3A members is widely understood, post-translational regulation needs to be elucidated. We previously reported that acetaminophen (APAP) induces CYP3A activity via inhibition of protein degradation and proposed a novel DDI concept. N-Acetyl-p-benzoquinone imine (NAPQI), the reactive metabolite of APAP formed by CYP, is known to cause adverse events related to depletion of intracellular reduced glutathione (GSH). We aimed to inspect whether NAPQI rather than APAP itself could cause the inhibitory effects on protein degradation. We found that N-acetyl-l-cysteine, the precursor of GSH, and 1-aminobenzotriazole, a nonselective CYP inhibitor, had no effect on CYP3A1/23 protein levels affected by APAP. Thus, we used APAP analogs to test CYP3A1/23 mRNA levels, protein levels, and CYP3A activity. We found N-acetyl-m-aminophenol (AMAP), a regioisomer of APAP, has the same inhibitory effects of CYP3A1/23 protein degradation, while p-acetamidobenzoic acid (PAcBA), a carboxy-substituted form of APAP, shows no inhibitory effects. AMAP and PAcBA cannot be oxidized to quinone imine forms such as NAPQI, so the inhibitory effects could depend on the specific chemical structure of APAP. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2008-07-01

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

  10. 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

  11. [Changes in plasma cortisol and ACTH caused by diazepam, bromazepam, triazolam, and alprazolam in oral premedication].

    PubMed

    Rodríguez-Huertas, F; Carrasco, M S; García-Baquero, A; Coq, F D; Freire, J

    1992-01-01

    Benzodiazepines relieve anxiety and modify the endocrine response to surgical-anesthetic stress. The aim of this study was to evaluate the effects of four benzodiazepines on preoperative secretion of cortisol and ACTH. We studied 60 patients programmed for abdominal surgery. Patients were randomly allocated into six groups of treatment: control group (placebo), diazepam 10 mg, triazolam 0.5 mg, alprazolam 0.5 mg, bromazepam 6 mg, and bromazepam 12 mg. Blood samples for cortisol and ACTH measurements were obtained at five different stages of the anesthetic-surgical procedure: baseline, preanesthesia, anesthesia, surgery, and postoperative phase. Diazepam and bromazepam (6 and 12 mg) lessened the increase in plasmatic cortisol induced by preanesthesia and anesthesia in control patients. Triazolam attenuated the cortisol response only during preanesthesia. Administration of 12 mg of bromazepam decreased ACTH levels during preanesthesia and anesthesia with respect to the control group. Benzodiazepines failed to modify cortisol and ACTH levels during surgery and during the immediate postoperative period. The most marked attenuation of adrenocortical response was achieved with 12 mg of bromazepam and the less marked lessening was induced by 0.5 mg of alprazolam.

  12. 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.

  13. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Pregnancy Anxiety and Prenatal Cortisol Trajectories

    PubMed Central

    Kane, Heidi S.; Schetter, Christine Dunkel; Glynn, Laura M.; Hobel, Calvin J.; Sandman, Curt A.

    2014-01-01

    Pregnancy anxiety is a potent predictor of adverse birth and infant outcomes. The goal of the current study was to examine one potential mechanism whereby these effects may occur by testing associations between pregnancy anxiety and maternal salivary cortisol on 4 occasions during pregnancy in a sample of 448 women. Higher mean levels of pregnancy anxiety over the course of pregnancy predicted steeper increases in cortisol trajectories compared to lower pregnancy anxiety. Significant differences between cortisol trajectories emerged between 30 to 31 weeks of gestation. Results remained significant when adjusted for state anxiety and perceived stress. Neither changes in pregnancy anxiety over gestation, nor pregnancy anxiety specific to only a particular time in pregnancy predicted cortisol. These findings provide support for one way in which pregnancy anxiety may influence maternal physiology and contribute to a growing literature on the complex biological pathways linking pregnancy anxiety to birth and infant outcomes. PMID:24769094

  15. Fetal motor activity and maternal cortisol

    PubMed Central

    DiPietro, Janet A.; Kivlighan, Katie T.; Costigan, Kathleen A.; Laudenslager, Mark L.

    2009-01-01

    The contemporaneous association between maternal salivary cortisol and fetal motor activity was examined at 32 and 36 weeks gestation. Higher maternal cortisol was positively associated with the amplitude of fetal motor activity at 32 weeks, r(48) = .39, p < .01, and 36 weeks, r(77)=.27, p < .05, and the amount of time fetuses spent moving at 32 weeks during the 50 minute observation period, r(48) = 33, p < .05. Observation of periods of unusually intense fetal motor activity were more common in fetuses of women with higher cortisol, Mann-Whitney U = 58.5. There were no sex differences in fetal motor activity, but the associations between maternal cortisol and fetal motor amplitude and overall movement were significantly stronger for male than female fetuses. PMID:19630038

  16. Cortisol and Corticotrophin in Burned Patients,

    DTIC Science & Technology

    1982-04-01

    BASIL A. PRUITT, JR., M.D., AND ARTHUR D. MASON, JR., M.D. < In a study of 36 men burned in a fire, based on sequential early morning samples, plasma ...cortisol concentration was elevated in proportion to burn size. Plasma corticotrophin (ACTH) was not correlated with burn size, suggesting that factors...in proportion to burn size. Although plasma cortisol Was positively correlated with metabolic rate and with temperature, this appeared to result from a

  17. 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.

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

    PubMed

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

    2014-10-01

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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Neurotoxicology of Synthetic Cathinone Analogs.

    PubMed

    Angoa-Pérez, Mariana; Anneken, John H; Kuhn, Donald M

    The present review briefly explores the neurotoxic properties of methcathinone, mephedrone, methylone, and methylenedioxypyrovalerone (MDPV), four synthetic cathinones most commonly found in "bath salts." Cathinones are β-keto analogs of the commonly abused amphetamines and display pharmacological effects resembling cocaine and amphetamines, but despite their commonalities in chemical structures, synthetic cathinones possess distinct neuropharmacological profiles and produce unique effects. Among the similarities of synthetic cathinones with their non-keto analogs are their targeting of monoamine systems, the release of neurotransmitters, and their stimulant properties. Most of the literature on synthetic cathinones has focused on describing their properties as psychostimulants, their behavioral effects on locomotion, memory, and potential for abuse, whereas descriptions of their neurotoxic properties are not abundant. The biochemical gauges of neurotoxicity induced by non-keto analogs are well studied in humans and experimental animals and include their ability to induce neuroinflammation, oxidative stress, excitotoxicity, temperature alterations as well as dysregulation of neurotransmitter systems and induce changes in monoamine transporters and receptors. These neurotoxicity gauges will serve as parameters to discuss the effects of the four previously mentioned synthetic cathinones alone or in combination with either another cathinone or with some of their non-keto analogs. Bath salts are not a defined combination of drugs and may consist of one synthetic cathinone compound or combinations of more cathinones. Furthermore, this review also presents some of the mechanisms that are thought to underlie this toxicity. A better understanding of the cellular and molecular mechanisms involved in the synthetic cathinones-induced neurotoxicity should contribute to generate modern therapeutic approaches to prevent or attenuate the adverse consequences of use of these

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

    PubMed

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

    2015-02-01

    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. 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. 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. Hypothalamic-pituitary-adrenal (HPA) axis reactivity to psychological stressors and the relationship between HPA axis reactivity and children's internalizing and externalizing

  5. 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

  6. 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

  7. Bayesian analogy with relational transformations.

    PubMed

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

    2012-07-01

    How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

  8. Reduced nocturnal ACTH-driven cortisol secretion during critical illness

    PubMed Central

    Boonen, Eva; Meersseman, Philippe; Vervenne, Hilke; Meyfroidt, Geert; Guïza, Fabian; Wouters, Pieter J.; Veldhuis, Johannes D.

    2014-01-01

    Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness. PMID:24569590

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

    PubMed Central

    2013-01-01

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

  10. Term neonates with infection and shock display high cortisol precursors despite low levels of normal cortisol.

    PubMed

    Khashana, Abdelmoneim; Ojaniemi, Marja; Leskinen, Markku; Saarela, Timo; Hallman, Mikko

    2016-02-01

    Neonatal therapy-resistant septic shock is a common problem in middle and low-income countries. We investigated whether newborn infants with infection and therapy-resistant hypotension showed evidence of abnormal levels of cortisol or cortisol precursors. A total of 60 term or near term neonates with evidence of infection were enrolled after informed consent. Of these, 30 had an infection and refractory shock and 30 had an infection without shock. There were no detectable differences between the groups in the length of gestation, birth weight or gender distribution. Serum was obtained during days four and 14 after birth. Cortisol and cortisol precursor concentrations were analysed using liquid chromatography-tandem mass spectrometry. The cortisol concentrations were low considering the expected responses to stress and they did not differ between the groups. The infants with infection and shock had higher serum dehydroepiandrosterone (DHEA) levels than those without shock (319.0 ± 110.3 μg/dL, versus 22.3 ± 18.3 μg/dL; p < 0.0001) and they also had higher 17-hydroxy-pregnenolone, pregnenolone and progesterone concentrations. There were no detectable differences in the levels of 17-hydroxy-progesterone, 11-deoxy-cortisol, cortisol or cortisone. Septic newborn infants with therapy-resistant hypotension had very high DHEA levels, suggesting that 3-beta-hydroxysteroid dehydrogenase activity limited the rate of cortisol synthesis. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  11. Developmental origins of flatter cortisol rhythms: socioeconomic status and adult cortisol activity.

    PubMed

    Desantis, Amy S; Kuzawa, Christopher W; Adam, Emma K

    2015-01-01

    Low socioeconomic status (SES) is associated with increased psychosocial stress among low-income persons, which could contribute to differences in activity of the HPA axis (assessed by diurnal cortisol profiles). The current article investigates associations of SES from different developmental stages with cortisol profiles. Using data from a large, socioeconomically diverse birth cohort (N = 1,490) in Cebu, Philippines, the current study compares the relative and joint contributions of SES from five developmental periods, between the prenatal/birth period and early adulthood, to adult cortisol, and examines the effects of chronic exposure to low SES. Chronically low SES from infancy through early adulthood predicts the highest bedtime cortisol levels, lowest cortisol awakening responses (CARs), lowest total cortisol levels across the day (area under curve or AUC), and the flattest cortisol rhythms between wake up and bedtime, a profile associated with poorer health. Results indicate that cumulative economic strain (between the prenatal period and early adulthood) predicts flatter cortisol rhythms more consistently than SES from any particular period. Interventions focusing on the psychosocial stressors associated with economic deprivation during any period from infancy to adulthood may be helpful, but targeting interventions across multiple periods may have the greatest impact. Interventions aimed at improving economic conditions between infancy and early adulthood may have implications for long-term changes in HPA axis functioning. © 2015 Wiley Periodicals, Inc.

  12. Effect of Home Cage Bedding in the Induction Chamber on Serum Cortisol and Corticosterone Levels in Response to Isoflurane-induced Anesthesia in C57BL/6J Mice.

    PubMed

    Reiter, Cara P; Christy, Amanda C; Olsen, Cara H; Bentzel, David E

    2017-03-01

    Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to induction of anesthesia. Here we evaluated the potential for familiar surroundings to reduce the adrenocortical response of mice during anesthesia induction with isoflurane. However, adding bedding from the animals' home cage to the induction chamber failed to significantly reduce serum cortisol or corticosterone levels in male and female C57BL/6J mice. These results indicate that familiar surroundings do not appear sufficient to reduce the adrenocortical response of mice during anesthesia induction with isoflurane.

  13. Cortisol concentrations in blood and urine of horses.

    PubMed

    Ralston, J M; Stenhouse, A M; Stenhouse, N S; Buck, G J; Lucks, S F; Reynoldson, J A; Bolton, J R

    1988-01-01

    A survey of the concentrations of cortisol in blood and urine samples taken from thoroughbred and standardbred horses after racing is presented. Statistical analysis showed the only significant difference between thoroughbred and standardbred horses was a higher cortisol concentration in thoroughbred urine. Urine volume and pH had no significant influence on the urinary cortisol concentration, however 9.5% of the urinary cortisol variation could be explained due to the influence of plasma cortisol concentration. The results of cortisol and ACTH administrations are also shown and compared with the survey results.

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

    PubMed

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

    2016-04-01

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

  15. Analog Frame Store Memory.

    DTIC Science & Technology

    1980-01-15

    information in analog form for periods up to ten (i0)seconds. The storage element is a state-of-the-art monolithic charge coupled device (CCD) which...Analog Field Storage Device The Analog Field Storage Device is a solid state monolithic array operating on the "charge coupled" principle. It consists...the implementation of the corrective action. A three-month slip in delivery of the full system will result with integration test taking place in June

  16. Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion.

    PubMed

    Douyon, Liselle; Schteingart, David E

    2002-03-01

    Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is

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